ASCO Guidelines Podcast Series podkast

ASCO Guidelines Podcast Series

American Society of Clinical Oncology (ASCO)

The ASCO Guidelines Podcast Series features interviews with panelists of recently published American Society of Clinical Oncology Clinical Practice Guidelines products highlighting key recommendations from the publication. Music:“Journeys” by Scott Buckley – www.scottbuckley.com.au, used under CC:BY.

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  • ASCO Guidelines Podcast Series podkast

    Immunotherapy in Patients with Locally Advanced Esophageal Carcinoma: ASCO Guideline Rapid Recommendation Update

    8:45

    An interview with Dr. Manish Shah from New York Hospital and Weill Cornell Medicine, co-chair on “Immunotherapy in Patients with Locally Advanced Esophageal Carcinoma: ASCO Guideline Rapid Recommendation Update.” He discusses the results of the Checkmate 577 trial and the updated recommendation of the Treatment of Locally Advanced Esophageal Carcinoma Guideline. For more information, visit www.asco.org/gastrointestinal-cancer-guidelines.   TRANSCRIPT [MUSIC PLAYING]   SPEAKER: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. BRITTANY HARVEY: Hello, and welcome to the ASCO Guidelines Podcast Series, brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at ASCO.org/podcasts. My name is Brittany Harvey, and today I'm interviewing Dr. Manish Shah from New York Hospital and Weill Cornell Medicine in New York, NY, co-chair of the Locally Advanced Esophageal Carcinoma guideline expert panel and lead author on the Immunotherapy in Patients with Locally Advanced Esophageal Carcinoma: ASCO Guideline Rapid Recommendation Update. Thank you for being here, Dr. Shah. MANISH SHAH: Absolutely. Thank you very much for having me. BRITTANY HARVEY: First, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline is available online. Dr. Shah, do you have any relevant disclosures that are directly related to this guideline? MANISH SHAH: Yes, so I do have relationships with many of the companies that make checkpoint inhibitors. And in fact, we are being supported by Bristol Myers Squibb on a first-line study of chemotherapy with nivolumab. We've also been supported by Merck on a pre-operative study of chemotherapy with radiation and pembrolizumab. BRITTANY HARVEY: Thank you for that information. Then so what prompted this rapid update to the Treatment of Locally Advanced Esophageal Carcinoma: ASCO Guideline? MANISH SHAH: Yes, so recently there was a landmark study that was practice-changing in the space, published in the New England Journal of Medicine by Ronan Kelly and colleagues. And this was the report of CheckMate 577, the use of adjuvant nivolumab in resected esophageal or gastroesophageal junction carcinoma. And this was a positive study that led to important changes in practice. And we felt that this was worthy and worthwhile of getting it out there to the community. BRITTANY HARVEY: Great. Then based off this new data from CheckMate 577 on nivolumab, what is the updated recommendation? MANISH SHAH: Sure. So previously, the data available was that patients who receive chemotherapy and radiation and then went on to receive surgery, that those patients with esophageal cancer had no further treatment recommendations. This study, CheckMate 577, actually examined nivolumab in that context. So patients who received chemotherapy and radiation and then underwent surgery, if they had some residual disease at the time of the surgical resection, even if they had a major response but there was some residual cancer in the surgical specimen, patients were eligible for randomization. And about 800 patients were randomized, 2 to 1, to receive nivolumab versus placebo in this context. And the primary endpoint in the study was disease-free survival. And patients who received nivolumab had a median disease-free survival of 22.4 months compared to placebo, which was the previous standard of care. The median disease-free survival in that group was 11.0 months, so almost a doubling of the disease-free survival. The hazard ratio was 0.69. And that was highly significant, with a p value of 0.001. So there was a 31% improvement in reducing the risk of recurrence with adjuvant nivolumab. So based on that trial, we have updated the guideline to recommend adjuvant nivolumab for patients who have received chemotherapy and radiation and surgery, and then had some residual disease in the surgical specimen. A key distinction is that about 20% to 30% of patients will have had a pathologic complete response. These patients were not eligible for the trial. And so at this time, patients who have had a complete response, the current guidelines remain the same, where there's no further treatment indicated. BRITTANY HARVEY: OK, it seems like this study provided a strong signal to update that recommendation. I appreciate you going through the details of that study, and particularly the patients that were eligible to participate. So then, how will this guideline impact patients with locally advanced esophageal cancer? MANISH SHAH: Yeah, I think that this is a key thing. Because 70% to 75% of patients have residual disease at the time of resection. And still, even if you've had a major pathologic response, the risk of recurrence for many patients is still high, greater than 50%. Of note also I'd highlight that the study included adenocarcinoma and squamous cell cancer. And the results were positive in both groups. So based on that, I think that this will be highly impactful for a majority of patients with esophageal cancer, both adenocarcinoma and squamous cell cancer, who, as I said, underwent chemoradiation and surgery and had residual disease in the surgical pathologic specimen. BRITTANY HARVEY: That's good to hear that this will have a positive impact for these patients. So then what are the outstanding clinical questions regarding treatment of these patients? MANISH SHAH: Yeah, so I think that there are a lot of outstanding questions. I think one question which is currently being studied is the use or integration of checkpoint inhibition therapy prior to surgery. So that's being examined in an inter-group study in the United States, as well as several company-sponsored studies across the globe. And a concept there is that, if you're giving chemotherapy with radiation and a checkpoint inhibitor all combined, you might be able to have even the higher benefit from activation of the immune system against the cancer than in the adjuvant setting where you're trying to treat microscopic minimal disease. So that's one question. And the other key question, which was actually raised by the clinical trial itself was the CPS scoring system. So CPS means Combined Positive Score. This is a way to examine the level of PD-L1 expression in the tumor and its microenvironment. And it's not a great biomarker, but it's the best biomarker available. And it is predictive of who would benefit. So patients who have a higher CPS score are more likely to benefit from a checkpoint inhibitor. A post hoc analysis of this study suggested that tumors that had a CPS score of less than 5 had less benefit. So although the FDA approval for adjuvant nivolumab was independent of the CPS score, I think, with time, we'll have more information on the potential impact of CPS or other biomarkers on which patients really may benefit from adjuvant therapy. So I think, on the positive end, patients now have options. And I think they're clinically significant and meaningful. But it does, as you point out, highlight new questions that will be answered in due course. BRITTANY HARVEY: Great. And we'll look forward to the results of those studies that address some of those questions. So thank you for your efforts to issue this rapid update and for taking the time to speak with me today, Dr. Shah. MANISH SHAH: Oh, absolutely. It was a pleasure to be here. Thanks so much, Brittany. BRITTANY HARVEY: And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast Series. To read the full guideline, go to www.ASCO.org/gastrointestinal-cancer-guidelines. If you have enjoyed what you've heard today, please rate and review the podcast, and be sure to subscribe so you never miss an episode. [MUSIC PLAYING]
  • ASCO Guidelines Podcast Series podkast

    Adjuvant PARP Inhibitors in Patients with High-risk Early-Stage HER2-Negative Breast Cancer and Germline BRCA Mutations: ASCO Hereditary Breast Cancer Guideline Rapid Recommendation Update

    15:46

    An interview with Dr. Nadine Tung and Dr. Dana Zakalik, co-chairs on ”Adjuvant PARP Inhibitors in Patients with High-risk Early-Stage HER2-Negative Breast Cancer and Germline BRCA Mutations: ASCO Hereditary Breast Cancer Guideline Rapid Recommendation Update.” They discuss the results and impact of the OlympiA trial, the updated recommendation, and outstanding questions on the use of PARP inhibitors in the adjuvant setting. For more information, visit www.asco.org/breast-cancer-guidelines.   TRANSCRIPT [MUSIC PLAYING] ANNOUNCER: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. BRITTANY HARVEY: Hello and welcome to the ASCO Guidelines Podcast Series, brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content, and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at podcast.ASCO.org. My name is Brittany Harvey, and today I'm interviewing Dr. Nadine Tung from Beth Israel Deaconess Medical Center in Boston, Massachusetts, and Dr. Dana Zakalik from Beaumont Health in Royal Oak, Michigan, co-chairs of the Management of Hereditary Breast Cancer Guideline Expert Panel and this rapid recommendation update, Adjuvant PARP Inhibitors in Patients With High-Risk Early-Stage HER2-Negative Breast Cancer and Germline BRCA Mutations: ASCO Guideline Recommendation Update. Thank you for being here, Dr. Tung and Dr. Zakalik. DR. ZAKALIK: Thank you for having us. DR. TUNG: Thank you so much. Pleasure to be here. BRITTANY HARVEY: First, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online. Dr. Tung, do you have any relevant disclosures that are directly related to this guideline topic? DR. TUNG: I do receive research funding from AstraZeneca, as I run a trial using a PARP inhibitor in breast cancer. BRITTANY HARVEY: Thank you. And Dr. Zakalik, do you have any relevant disclosures? DR. ZAKALIK: I do not. BRITTANY HARVEY: Thank you. Then let's get into the meat of this rapid recommendation update. So, Dr. Tung, what prompted this rapid update to a recommendation from the Management of Hereditary Breast Cancer Guideline? DR. TUNG: The OlympiA Trial, which was presented at ASCO this past June and published the same day in the "New England Journal of Medicine." OlympiA was a large Phase III trial, which demonstrated that a year of adjuvant olaparib, a PARP inhibitor, significantly improved both invasive disease-free survival by nearly 9%, and distant disease-free survival by a similar improvement, in germline BRCA mutation carriers with HER2-negative breast cancer and a high risk of recurrence. Overall survival was numerically better with olaparib, but it didn't yet reach significant improvement as a stringent p-value was required for this early reporting. And I say early reporting because the trial was reported early after the first event-driven interim analysis showed a benefit with olaparib. 1,800 patients had been enrolled with a median follow up of 2 and 1/2 years at the reporting. But the follow up was 3 and 1/2 years for the first 900 patients enrolled, known as the maturity cohort. And it was comforting that the significant improvement in invasive disease-free survival and distant disease-free survival was also seen when just looking at that maturity cohort. So for those who might think that it's too early and that these benefits might not hold up with longer follow up, it's very comforting that in that maturity cohort with longer follow up, the results were really the same. And last year, ASCO published guidelines on managing patients with hereditary breast cancer, including women with inherited BRCA mutations, meaning a pathogenic or likely pathogenic variant. At that time, PARP inhibitors were recommended only for BRCA carriers with metastatic disease, based on the OlympiAD and EMBRACE trials. So when OlympiA was published, we felt the need to update the guidelines to recommend olaparib in the early-stage setting for some germline BRCA carriers. BRITTANY HARVEY: So then, based off this new data from the OlympiA trial, Dr. Zakalik, what is the updated recommendation from the guideline expert panel? DR. ZAKALIK: The updated recommendation states that for patients with early-stage, HER2-negative breast cancer with a high risk of recurrence, and who carry a germline BRCA1 or 2 mutation, one year of adjuvant olaparib should be offered after completion of adjuvant or neoadjuvant chemotherapy and local treatment, including radiation therapy. And this data was specific to a high risk of recurrence subgroup of these patients, defined as, for those with triple-negative breast cancer having a tumor over two centimeters, or with any involved lymph nodes, or for those who received neoadjuvant chemo, any residual disease in the triple-negative setting was sufficient to qualify. For patients with hormone receptor positive disease, these were high-risk patients for recurrence, again, and that was defined as having at least four positive lymph nodes, or any residual disease following neoadjuvant therapy. But in addition, having a clinical stage and pathologic stage estrogen receptor status and tumor grade, otherwise called the CPS+EG score, of greater than or equal to three, which is really defined as looking at estrogen receptor status grade and clinical and pathologic stage. So again, a high-risk group for risk of recurrence was included in this study. And again, in order to apply these findings, we have to be mindful of patients who meet these inclusion criteria as being high-risk for recurrence. Again, both in the triple-negative hormone receptor-positive setting, if they met these criteria, there was a significant benefit in terms of outcome in lowering the risk of recurrence. BRITTANY HARVEY: I appreciate you going through that recommendation. So then, given that updated recommendation. Dr. Tung, what should clinicians know as they implement the use of adjuvant olaparib into clinical practice? DR. TUNG: For those who have not used olaparib, it's worth saying that it's an oral medication. Typically patients take two pills twice a day. And it's important to be familiar with the side effects. I would say that generally, olaparib is well-tolerated. But it can have side effects. And the two most common are nausea, and then anemia. So for the nausea, we use the typical antiemetics we would use for any chemotherapy. And it's worth saying to patients who do have nausea that quite often, that lessens with time. It decreases. So I would say nausea's one of the side effects. Some patients can have fatigue, although I don't think that's all that common. And anemia is the other one. And we do check bloodwork monthly for patients on olaparib. The anemia can come suddenly, even after months of really not having any. And grade 3 anemia was probably the most common, grade 3 or higher, toxicity that was seen in OlympiA, although it's only 9% of patients that had grade 3 or higher anemia. But I would say those are the two side effects to look for most. And then I think one other thing that's worth saying is that for the BRCA carriers with triple-negative breast cancer, currently our standard therapy for patients who have residual disease after neoadjuvant chemotherapy is capecitabine. But olaparib should not be given with capecitabine. There is no safety data for that. So oncologists are going to need to choose between what I think is our standard therapy right now, capecitabine, and olaparib. And there's no data directly comparing these two medications in the early-stage setting. But in the metastatic setting in BRCA carriers, in both OlympiAD and EMBRACE, olaparib was compared to chemotherapy. And olaparib with superior. And in both of those studies, about half the women in the chemotherapy arms received capecitabine. And olaparib, again was superior. So olaparib may be the better choice in the early-stage setting. But I can't say that there's any direct data. But the message would be not to give them together. And I think it would be better probably not to give capecitabine first and then olaparib, because there's some data that the earlier you give a PARP inhibitor the better. BRITTANY HARVEY: Those are important notes for clinicians and particularly for safety. So then building on that, Dr. Zakalik, how will this update impact patients with breast cancer? DR. ZAKALIK: This data will significantly impact the therapeutic options that we have for patients with high-risk disease in the setting of a BRCA germline mutation. And that will happen in the sense that patients who have these certain specific features that render them high-risk will now be able to be offered a very impactful therapy that has been shown in this landmark study to significantly decrease their risk of recurrence. And these are patients who otherwise would face a significant risk of potentially facing a recurrence in the future. So the outcomes we anticipate to be dramatically improved for patients who have triple-negative or high-risk hormone receptor-positive breast cancer in the setting of a BRCA germline mutation. But furthermore, whereas genetic testing in the past was predominantly focused on identifying individuals who are at high risk for developing breast cancer so that we can offer early detection or prevention options, this is the first time that we're able to broadly apply the benefit of molecular genetic testing for hereditary risk to therapy for patients with early nonmetastatic breast cancer. So as clinicians who see patients with breast cancer, it is further made more important to recognize what the guidelines are for genetic testing. To think of whether a patient meets criteria that are currently outlined for genetic testing, as this will have a significant potentially major impact on patients' outcome. And already in the clinic, we have been focused on recognizing who may have a BRCA mutation. Obviously, this data will make that even more important, because this therapy is so beneficial for patients. And I think going forward, it will fuel a discussion of possibly reevaluating who gets genetic testing, now that it's particularly important not to miss patients who have BRCA mutations when they develop breast cancer. So I think that physicians who are in the clinic will not only have a therapeutic option, but also will be hopefully recognizing more patients who have a BRCA mutation in that the therapy is so markedly better now with this new data. And in the future, we may possibly expand our guidelines for testing. And I think that remains to be determined, based on a number of factors that go into this decision. BRITTANY HARVEY: Well then, you've both touched on this a bit, regarding outstanding questions for both genetic testing and the use of capecitabine. But finally, Dr. Tung, given this recent study and guideline update, what are the outstanding questions regarding the use of PARP inhibitors in the adjuvant setting? DR. TUNG: Right. We have already listed a couple. The capecitabine question is one that I won't repeat. And I think who gets tested would be another one that Dana just mentioned. I think a big one, as of yesterday, is immune therapy. Yesterday, the FDA approved pembrolizumab, based on the KEYNOTE-522 study for patients with triple-negative breast cancer. And that population in KEYNOTE was very similar to the one in OlympiA for BRCA carriers, namely patients with T2 tumors, or involved axillary lymph nodes. So for BRCA carriers, we're going to have to make some decisions here, namely, should they receive pembrolizumab and olaparib together, for those who have residual disease after neoadjuvant chemotherapy. I think everyone right now is digesting KEYNOTE-522 and this FDA approval. And so that's something that will have to be worked out. I know in other diseases there is safety data for the combination of pembrolizumab and olaparib. But again, I think that's something that we're all going to have to sort out. I don't think there's going to be any data forthcoming immediately about the use of pembro, olaparib, and the combination, et cetera for our patients. So that's a big one I think another question that comes up is, how long after a BRCA carrier finishes their chemotherapy and local therapy are they eligible to take olaparib? What about patients that finished six months ago, or a year ago, or longer? And again, I don't think there are any data for that, and we're going to have to use some clinical judgment. There was precedent for this kind of question when adjuvant trastuzumab was approved and in 2005, when the adjuvant trials demonstrating such an impressive benefit for trastuzumab were announced and published. I remember that we were administering trastuzumab to patients who'd completed their chemotherapy within the last year. So I think for many, that may be a timeline that makes sense. But again, there are no data. So still questions, and we're going to as always have to use some clinical judgment. And others, Dana, that you can think of? DR. ZAKALIK: No. I think this is tremendously exciting new data. It really provides hope for patients who are young, often, when they're diagnosed. Because hereditary breast cancer tends to manifest itself at a young age. And so for our women in the prime of their life, when they have high risk and develop breast cancer, I think this just really gives us tremendous hope and opportunity for improving the lives and saving lives in the future of patients who have high-risk disease. Very exciting data. DR. TUNG: Yeah, I agree completely. I think the investigators are really to be congratulated. This was a very large study. 1,800 BRCA carriers, international study. Very hard to do with a situation, a disease that's relatively uncommon. Only 3% to 5% of all breast cancer. So really a terrific effort with a significant, major impact for our BRCA carriers with breast cancer. BRITTANY HARVEY: Definitely. This is an exciting update for patients with breast cancer. And we'll look forward to hearing more research about those outstanding questions that you mentioned. So I want to thank you both for your efforts to update this guideline recommendation so quickly, and provide evidence-based recommendations for both clinicians and patients. And thank you for taking the time to speak with me today, Dr. Zakalik and Dr. Tung. DR. ZAKALIK: Thank you. DR. TUNG: My pleasure. BRITTANY HARVEY: And thank you to all of our listeners for tuning in to the ASCO Guidelines Podcast Series. For more information, visit www.ASCO.org/breast-cancer-guidelines. If you have enjoyed what you heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. [MUSIC PLAYING]
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    Endocrine Treatment and Targeted Therapy for Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer Guideline Update

    16:19

    An interview with Dr. Harold Burstein from Dana Farber Cancer Institute in Boston, MA, chair on “Endocrine Treatment and Targeted Therapy for Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer: ASCO Guideline Update.” This guideline updates recommendations on use of alpelisib, and the role of biomarkers and CDK4/6 inhibitors. Read the guideline at asco.org/breast-cancer-guidelines. Suggest a topic for guideline development at surveymonkey.com/r/ascoguidelinesurvey.   TRANSCRIPT [MUSIC PLAYING] SPEAKER: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. [MUSIC PLAYING] BRITTANY HARVEY: Hello and welcome to the ASCO Guidelines podcast series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at podcasts.asco.org. My name is Brittany Harvey. And today I'm interviewing Dr. Harold Burstein from Dana-Farber Cancer Institute in Boston, Massachusetts, chair and lead author on endocrine treatment and targeted therapy for hormone receptor-positive HER2 negative metastatic breast cancer ASCO guideline update. Thank you for being here, Dr. Burstein. HAROLD BURSTEIN: Glad to be with you. BRITTANY HARVEY: First I'd like to note that ASCO takes great care in the development of its guidelines in ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online with the publication of the guideline in the Journal of Clinical Oncology. Dr. Burstein, do you have any relevant disclosures that are related to this guideline topic? HAROLD BURSTEIN: I do not. BRITTANY HARVEY: Great, thank you. Then let's delve into the content of this guideline. So first, what prompted the update of this guideline and what is the focus of this update? HAROLD BURSTEIN: So this guideline focuses on metastatic breast cancer, and in particular, estrogen receptor-positive HER2 negative metastatic breast cancer. Worldwide in 2021, actually breast cancer became the most commonly diagnosed cancer in the world, excepting superficial skin cancers. And so it is a true global health problem. And the most common type of breast cancer is estrogen receptor-positive HER2 negative breast cancer, which accounts for 70% to 75% of all cancer diagnoses in the breast cancer space, and as a consequence, also accounts for 70% to 75% of the cases of metastatic breast cancer. So it's really important from a public health point of view and a quality point of view, both in the United States and globally, to have current up-to-date guidance for the management of this most common form of breast cancer that we have. In addition, there have been several innovations in the way of targeted therapies that are coming into place for advanced ER-positive breast cancer. And increasingly, we are using genomic tests to help us understand how best to treat patients with advanced ER-positive breast cancer. So those two initiatives-- the interest in genomic testing and the use of targeted therapies-- all warranted and justified an update to the guidelines. BRITTANY HARVEY: Great. Thank you for reviewing that landscape of where we are in clinical practice for this guideline. So then I'd like to review the key recommendations that this guideline addresses. So first, should alpelisib be given to post-menopausal women and to male patients with hormone receptor-positive HER2 negative PIK3CA-mutated advanced or metastatic breast cancer? HAROLD BURSTEIN: So alpelisib, as you indicated, is a new drug. It is now FDA approved. And it is a protein kinase targeted inhibitor. And it goes after the PIK3CA-mutated tumors. And in a seminal study called the SOLAR-1 study, there was randomization to endocrine therapy alone with fulvestrant or endocrine therapy plus alpelisib for ER-positive HER2 negative breast cancer. And that study showed two important things. First was that in women whose tumors did not have a PIK3CA mutation, there was no benefit for alpelisib. However, in the women whose tumors did have a PIK3CA mutation, there was an improvement in progression-free survival with the use of this targeted drug alpelisib. So based on that, the guidelines now incorporate alpelisib into the treatment algorithm. And as a corollary, it means that all patients who have ER-positive metastatic breast cancer now need testing of the tumor to see if they have a PIK3CA mutation because that's going to guide therapy. In the guideline, we now suggest that this be a standard thing to do-- to test all tumors for PIK3CA mutation. And in those cases where there is a PIK3CA mutation to add alpelisib-based therapy with endocrine treatment typically in second or subsequent lines of therapy. BRITTANY HARVEY: Great. And thank you for reviewing the evidence base behind that recommendation. So next, what is recommended regarding the role of biomarkers in treatment selection for patients with hormone receptor-positive metastatic breast cancer? HAROLD BURSTEIN: So there are two different ways of thinking about biomarkers. One is traditional biomarkers, such as estrogen receptor, progesterone receptor, and HER2. Those are familiar to all clinicians who have been dealing with breast cancer. The second is to think about some of the newer technologies, including tumor genomic sequencing and the kind of mutational analysis we just discussed with the PIK3CA mutations. So in the breast cancer space, there are some important innovations in that latter genomic or genetic testing. One, of course, is the PIK3CA mutation testing that we now recommend for all cancers. That can be done on the primary tumor, or it can be done on cell-free or circulating tumor DNA samples from the bloodstream in most cases. The other kind of testing we do relates to ESR1 mutations. And one of the reasons that tumors become resistant to aromatase inhibitors is that they acquire mutations in the estrogen receptor itself, so-called ESR1 activating mutations. Those mutations mean that the estrogen receptor is on even in the absence of estrogen. And that accounts for probably 50% to 60% of the resistance that we see in treatment with aromatase inhibitors. So the panel really struggled with this because, on the one hand, this is not a uniformly accepted way to decide how to treat patients. On the other hand, there are a lot of data that women whose tumors have ESR1 mutations get negligible benefit from ongoing use of aromatase inhibitor therapy. So this recommendation fell into sort of our practice suggestions, which is that if you have the information on ESR1, then it probably is the case that there's very little, if any, role for ongoing aromatase inhibitor treatment. This fell short of the highest level in endorsement because, first, it's not a uniformly tested assay. And secondly, it's important to remember that these tumors can still benefit from ongoing anti-estrogen therapy with different anti-estrogens like fulvestrant. And finally, and perhaps this is the most practical issue, the way you become ESR1 mutated is usually through exposure to aromatase inhibitors. And if you've already had a patient with extensive exposure to AIs, and they need ongoing anti-estrogen therapy in the metastatic setting, it usually means you're switching treatment anyway. So that's an example of where we're sort of on the frontier of thinking about dynamic changes in the tumor as a way to select treatment for ER-positive metastatic disease. BRITTANY HARVEY: Great. That's helpful for a clinical interpretation of the recommendations and incorporating these into practice. So the final question that was addressed in this focused update was, what is the role of CDK4/6 inhibitors in the treatment of patients with hormone receptor-positive metastatic breast cancer? HAROLD BURSTEIN: So CDK4/6 inhibitors are another tyrosine kinase inhibitor class of drugs that has really emerged as an important part of first-line therapy for ER-positive metastatic disease. There have been multiple randomized trials looking at either first-line therapy with an aromatase inhibitor with or without a CDKI4/6 inhibitor, or second-line treatment typically with fulvestrant with or without a CDKI4/6 inhibitor in the metastatic setting. And the panel was able to update the guidance here based on the maturation of multiple randomized trials, as well as extensive subset analyses that have been performed by investigators associated with the individual pharmaceutical-led studies and by the FDA itself. So here are some important takeaways. The first is that in long-term follow-up, these drugs as a class are improving overall survival for women with ER-positive HER2 negative metastatic breast cancer. And for that reason, they are a very important part of the standard armamentarium for ER-positive disease. It's important to say that they also delay the onset of need for chemotherapy, and in general, are associated with a very well preserved quality of life. So this is a big win for patients with ER-positive metastatic breast cancer. We typically recommend them in the first-line setting. So if a patient has de novo metastatic disease, then they should get an endocrine therapy such as an aromatase inhibitor with a CDK4/6 inhibitor. If they've previously had adjuvant aromatase inhibitor treatment or recur while on adjuvant endocrine therapy, we often move to fulvestrant plus a CDKI4/6 inhibitor. Both settings have shown substantial benefit for this class of drugs. It's important that clinicians understand the side effects of these drugs. Neutropenia and diarrhea are common side effects associated with the various drugs. And because of the prevalence of ER-positive metastatic disease, it's really important for clinicians and all those who care for advanced breast cancer patients to know how to manage those side effects carefully. The panel discussed controversial issues, I suppose you might say, in the management. What about patients who have truly minimal metastatic disease? There aren't a lot of data on how best to think about those patients. And we all can imagine on a case-by-case basis an individual who might not need a CDK4/6 inhibitor at a given moment in time. But what was impressive when we pulled all the data was that in subset analyses, it's really hard to find a group of patients that does not benefit from the incorporation of these drugs. So that included premenopausal women who also get concurrent ovarian suppression and then endocrine therapy plus the CDK4/6 inhibitor. It included women with bone-only metastatic disease. It included women whose tumors were ER-positive but PR negative, or had other variations in ER expression. It included patients who had less rather than more metastatic cancer, including visceral disease. So in the literature, one is hard-pressed to see a subset that does not benefit meaningfully from this class of drugs. So we really wanted to reiterate in the algorithms just how important these are. They should be the standard first-line treatment for metastatic disease either paired with an AI or with fulvestrant. And so one of the other nice things that the update gave us was the opportunity to put in some fresh sort of algorithm flow sheets. I would very much encourage people to look at that. They make fantastic PowerPoint or downloadable Twitter documents if you are so inclined. But it's very clear the way the treatment should flow, which is the initial therapy is endocrine treatment plus a CDK4/6 inhibitor. While the patients are getting that, we typically test for PIK3CA mutations. In second line, if it's a PIK3CA mutated, you have the option of using alpelisib. You also might consider an older drug for PIK3CA wild type tumors called everolimus. We reiterated that recommendation in the guideline. Finally, one more thing to touch on that is emerging in the guidelines we generated and in the parallel guideline process for the ASCO guidance on chemotherapy-resistant or refractory breast cancer is the importance of genetic testing all patients who have metastatic breast cancer to look for the possibility of a BRCA1 or BRCA2 deleterious mutation, because there now is FDA approval for PARP inhibitors in the setting of metastatic disease. And one of the interesting things is that as we test more and more, we're seeing that not all the patients who are found to have a BRCA1 or 2 mutation meet the classic criteria for genetic testing-- strong family history, or say, triple-negative breast cancer. So it's really important to test, because that class of drugs, the PARP inhibitors, can be immensely helpful in women with ER-positive metastatic disease when they harbor a BRCA1 or 2 mutation. One of the things the guideline panel wrestled with and ended up putting into the sort of clinical discussion, as opposed to the strong guidance, was the 1% of patients who have PALB2 mutations. So PALB2 mutation, another hereditary predisposing factor for breast cancer. Most tumors that arise in PALB2 mutation carriers are in fact estrogen receptor positive. And a very small study, now published in the JCO, has suggested that those patients have a very high likelihood of response to PARP inhibitors. Because there were only like 15 patients in that cohort, we didn't feel that this warranted clear endorsement in the guidelines. But at the same time, everyone on the panel acknowledges that this is an active drug in that rare subset of tumors with PALB2 mutations in addition to the BRCA1 or 2 mutations. So the takeaway here is that genetic testing should be standard for all patients with advanced metastatic breast cancer to see if the patient is a candidate for a PARP inhibitor-based therapy. BRITTANY HARVEY: Definitely. Well, thank you for reviewing all of those updated recommendations and highlighting some of the ones that were still relevant to this guideline. HAROLD BURSTEIN: Work in progress. BRITTANY HARVEY: Yeah, definitely. And then finally, what is the importance of this guideline update? And how will it impact both clinical practice and what does it mean for patients? HAROLD BURSTEIN: Well, I think guidelines like this have multiple purposes. The first is to sort of describe the state of the art. And while breast cancer is a very common disease, and most clinicians who take care of a lot of cancer patients will see a lot of advanced breast cancer, I think it's still helpful to articulate the rationale for these treatment recommendations. And one of the great things about the ASCO guideline process is the thoroughness of the literature review, the thoroughness of the search to make sure we're including all important publications, and the thoughtfulness that the panel, which includes experts, patient advocates, quality of life expertise, all those things bring to bear on really thinking through what makes sense and what does not for our patients based on the best science available. So I think it is an important activity to really sort of benchmark where we're at. The second thing we've tried to do in the guideline is to introduce areas of nuanced discussion, because not every patient is the same. And I think for those who are interested and take the time to read the guideline, there really is a very nice discussion about how our panel thought about when best to use this approach and when to use a different approach. Third, there's extensive discussion of the side effects and the appropriate management of the side effects. These are drugs that do carry risks. And while by oncology standards, many of them are, quote, "well tolerated," unquote, there's no doubt that there are side effects to these drugs. And it's important for clinical teams to know how to manage them. Finally, I think by putting forward all the evidence, you make clear to investigators, to drug companies, to patients and advocates, and others who are involved in the review of new drugs what the benchmarks are and what the criteria should be for designing clinical trials and for approving new drugs. And I think we've done a nice job of framing that discussion quite handsomely in this guideline and to all of the ASCO guidelines. BRITTANY HARVEY: Great. Well, thank you so much for your work on this guideline update and for taking the time to speak with me today, Dr. Burstein. HAROLD BURSTEIN: Happy to join you and thanks very much. BRITTANY HARVEY: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast series. To read the full guideline, go to www.asco.org/breast cancer guidelines. Additionally, our annual survey for guideline topics is open for submissions. Suggest a topic for guideline development at SurveyMonkey.com /r/ascoguidelinesurvey. The link is also available in the episode notes of this podcast. If you've enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. [MUSIC PLAYING]
  • ASCO Guidelines Podcast Series podkast

    Chemotherapy and Targeted Therapy for Patients with Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer That is Either Endocrine-Pretreated or Hormone Receptor-Negative Guideline Update

    11:21

    An interview with Dr. Beverly Moy from Massachusetts General Hospital, co-chair on “Chemotherapy and Targeted Therapy for Patients With HER2-Negative Metastatic Breast Cancer That is Either Endocrine-Pretreated or Hormone Receptor-Negative: ASCO Guideline Update.” Updated guidance addresses optimal sequence of therapy & indications for treatment regimens. Read the guideline at asco.org/breast-cancer-guidelines. Suggest a topic for guideline development at surveymonkey.com/r/ascoguidelinesurvey.   TRANSCRIPT [MUSIC PLAYING] SPEAKER: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. [MUSIC PLAYING] BRITTANY HARVEY: Hello and welcome to the ASCO Guidelines podcast series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at podcast.asco.org. My name is Brittany Harvey. And today I'm interviewing Dr. Beverly Moy from Massachusetts General Hospital in Boston, Massachusetts, co-chair and lead author on chemotherapy and targeted therapy for patients with HER2 negative metastatic breast cancer that is either endocrine pre-treated or hormone receptor negative ASCO guideline update. Thank you for being here, Dr. Moy. BEVERLY MOY: Thanks for having me, Brittany. BRITTANY HARVEY: First, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online with the publication of the guideline in the Journal of Clinical Oncology. Dr. Moy, do you have any relevant disclosures that are directly related to this guideline topic? BEVERLY MOY: I do not have any relevant disclosures related to this guideline topic. BRITTANY HARVEY: Great. Thanks so much. Then let's get into what this update covers. So first, what prompted the update of this ASCO guideline and what does the scope of this guideline update? BEVERLY MOY: So this guideline update was developed to address both chemotherapy and targeted therapy for women with advanced HER2 negative breast cancer that is either endocrine pre-treated or hormone receptor negative. So it really focuses on chemo and targeted therapy. The original ASCO clinical treatment guideline was published in 2014 and really focused on chemotherapy, since that was generally the standard of care at that time. Since 2014, however, there have been several important new therapies that have become available based on robust evidence from numerous clinical trials. These include, but are not limited to, BOLERO-6 and PEARL trials for hormone receptor positive HER2 negative metastatic breast cancer, the ASCENT and EMBRACE trials for triple negative metastatic breast cancer, and the EMBRACA trial for metastatic breast cancer associated with germline BRCA1 or 2 mutations. So it really was important to update the guideline in a fairly urgent matter. BRITTANY HARVEY: Great. Well, then this guideline addresses four overarching clinical questions. For each of these, I'd like to review the key recommendations for our listeners. So starting with question one, is there an optimal sequence of chemotherapy and/or targeted therapy for patients with triple negative metastatic breast cancer either with or without BRCA1 or BRCA2 germline mutations? BEVERLY MOY: So clinical question one really focused on patients with metastatic triple negative breast cancer. So for patients with metastatic triple negative disease, the first key question is, what is the Programmed cell Death Ligand 1, or what we call PD-L1 status? If the disease is PD-L1 positive, then patients may be offered first line therapy with an immune checkpoint inhibitor plus chemotherapy. And that's a very important development. If the disease, however, is PD-L1 negative, patients should be offered single agent chemotherapy rather than combination chemotherapy, unless they have symptomatic or immediately life-threatening disease, and you really need to get a response more quickly. In those cases, combination chemotherapy can be used. After the first line, if patients with metastatic triple negative breast cancer have received at least two prior therapies, then they should be offered treatment with the new antibody drug conjugate called sacituzumab govitecan, which is a very exciting development in the treatment of metastatic triple negative breast cancer. If the patient has a germline BRCA1 or 2 mutation and has metastatic triple negative disease and have been previously treated with chemotherapy, then they may be offered treatment with an oral PARP inhibitor rather than chemotherapy, also a very exciting development that this guideline update addresses. BRITTANY HARVEY: Great. Thank you for reviewing those recommendations for triple negative metastatic breast cancer. So then next for clinical question two, what are the indications for chemotherapy versus endocrine therapy in endocrine pre-treated estrogen receptor positive metastatic breast cancer? BEVERLY MOY: So clinical question two focuses on women or patients with metastatic hormone receptor positive breast cancer who have developed progressive disease on a prior endocrine therapy with or without targeted therapy. So really is focusing on patients with metastatic hormone receptor positive breast cancer that have become fairly resistant to endocrine therapy alone. These patients may be offered treatment with either endocrine therapy with or without a targeted therapy or single agent chemotherapy. Brittany, I think it's important for listeners to realize that there is another important clinical practice guideline update that's being released simultaneously with this guideline. And that one is called endocrine therapy and targeted therapy for hormone receptor positive metastatic breast cancer. This other guideline update will describe in detail recommendations for the various targeted therapies that can be used with endocrine therapy, such as CDK4/6 inhibitors, PI 3-kinase inhibitors, and others. So I encourage everyone to read this guideline as well. Importantly, both guidelines state that treatment choice should be based on individualized patient and provider assessment of preferences, risks, and benefits. BRITTANY HARVEY: Great. And thank you for pointing out that companion guideline. Listeners can also listen to a podcast episode with Dr. Burstein on that particular guideline, which will be available in our podcast feed. So then next, what are the key recommendations for the third question in the guideline, which is, is there an optimal sequence of non-endocrine agents for patients with hormone receptor positive but HER2 negative metastatic breast cancer who are no longer benefiting from endocrine therapy, either with or without BRCA1 or BRCA2 germline mutations? BEVERLY MOY: So this third question really focuses on patients with hormone receptor positive HER2 negative disease and the optimal sequence. Essentially what we recommend is that germline BRCA1 or 2 patients with metastatic hormone receptor positive HER2 negative breast cancer who are no longer benefiting from endocrine therapy, those patients may be offered an oral PARP inhibitor in the first through third line setting rather than chemotherapy. And that is evidence that is evolving and important, and that's what the guideline recommends at this time. BRITTANY HARVEY: Great. And then clinical question four was the last question addressed in this guideline update. And what did the panel say regarding at what point should a patient be transitioned to hospice or best supportive care only? BEVERLY MOY: So this obviously is an incredibly important question for clinicians and oncologists to consider. The current literature and evidence does not allow us, at this time, to make a firm recommendation regarding at which point a patient's care should be transitioned to hospice or best supportive care only. When to transition is a decision that really needs to be shared between the patient and clinician in the context of an ongoing conversation regarding goals of care. The conversation of that integration of supportive care and eventual consideration of hospice care really should start early in the management of metastatic breast cancer. And these conversations have to occur throughout. I would also refer listeners to other important clinical treatment guidelines on the ASCO website about incorporation of palliative and supportive care for patients with metastatic cancer. I think those are incredibly valuable guidelines. BRITTANY HARVEY: And then you've touched on this a bit as you've talked about the recommendations, but in your view, what is the importance of this guideline update? And how will these updated recommendations impact both clinicians and patients? BEVERLY MOY: I think that this is an extremely important guideline update. It provides really important clinical guidance about the new use of immune checkpoint inhibitors, which really is the first time immune checkpoint inhibitors are clearly recommended for the treatment of breast cancer. It also provides important clinical guidance about this new antibody drug conjugate, sacituzumab govitecan, and PARP inhibitors for the treatment of metastatic breast cancer. These are all important and effective new treatments for breast cancer. And every clinician should be aware of their optimal uses. I will point out that many unanswered questions remain. And that was really an exciting part of doing this guideline update to look at these unanswered questions, such as what we described earlier, the optimal time to transition to best supportive care only and the widespread use of molecular tumor profiling. As treatments get more complicated and the entire oncology community are increasingly tasked to absorb new data, ASCO guidelines are enormously helpful in giving people an easy to access tool that takes into account the latest data. BRITTANY HARVEY: Great. Thank you so much for your work on this guideline update and for taking the time to speak with me today, Dr. Moy. BEVERLY MOY: Thank you. BRITTANY HARVEY: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast series. To read the full guideline, go to www.asco.org/breast cancer guidelines. Additionally, our annual survey for guideline topics is open for submissions. Suggest a topic for guideline development at surveymonkey.com /r/ascoguidelinesurvey. The link is also available in the episode notes of this podcast. If you've enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss episode. [MUSIC PLAYING]
  • ASCO Guidelines Podcast Series podkast

    Telehealth in Oncology: Standards and Practice Recommendations

    12:43

    An interview with Dr. Robin Zon from Michiana Hematology Oncology in Mishawaka, IN, co-chair on “Telehealth in Oncology: ASCO Standards and Practice Recommendations.” The standards address telehealth implementation, doctor-patient relationships, roles of advanced practice providers & allied health professionals, multidisciplinary cancer conferences, and teletrials. Read the standards at www.asco.org/standards. Suggest a topic for standards development at www.surveymonkey.com/r/standardssurvey.   TRANSCRIPT [MUSIC PLAYING] SPEAKER: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. [MUSIC PLAYING] BRITTANY HARVEY: Hello and welcome to the ASCO Guidelines Podcast Series, brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content, and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at podcasts.asco.org. My name is Brittany Harvey, and today I'm interviewing Dr. Robin Zon from Michiana Hematology Oncology in Mishawaka, Indiana, co-chair on the "Telehealth in Oncology: ASCO Standards and Practice Recommendations." Thank you for being here Dr. Zon. ROBIN ZON: Thank you so very much for having me here with you, to discuss this very important topic and work, which was undertaken by an expert panel of ASCO incredible volunteers and ASCO staff lead, Erin Kennedy. BRITTANY HARVEY: Great. Then first I'd like to note that ASCO takes great care in the development of its standards and ensuring that the ASCO conflict of interest policy is followed. The full conflict of interest information for the expert panel is available online with the publication of the standards in the JCO Oncology Practice. Dr. Zon, do you have any relevant disclosures that are directly related to these standards? DR. ROBIN ZON: No. I do not have any relationships to disclose related to the subject. BRITTANY HARVEY: Thank you. Then let's get into the content of these telehealth standards. So first, can you give us a general overview of the purpose and scope of these standards for telehealth in oncology? DR. ROBIN ZON: Well, absolutely. The service background, pre-pandemic, telehealth was utilized less than 1% of the time for oncology ambulatory visits. With, of course, a subsequent rapid adoption of digital health, in response to the public health emergency. This uptake of technology intervention was then further facilitated by the Centers for Medicare and Medicaid Services increased flexibility and reimbursement for these services. In response to the COVID-19 pandemic, ASCO published an interim policy statement on telemedicine. The signal is positions on emerging policy issues, as well as the road to recovery report, which presented ASCO's recommendations for modifying pre-pandemic policies and practices to improve high-quality patient care, wherein ASCO membership identified a need for more detailed oncology-based telemedicine. So these standards were created in response to this need. It is important to note that these standards include an endorsement of existing general guidelines as published by the American Medical Association Telehealth Implementation Playbook and the American Telemedicine Association's Quickstart Guide. BRITTANY HARVEY: That background and context is helpful for our listeners. So, then these standards, reading through them, they address six questions. I'd like to review the key points in each section for our listeners. So the first section, which patients should be seen via telehealth versus in-person? And what are the important implementation considerations for oncology telehealth visits? DR. ROBIN ZON: Those are great questions, Brittany. Generally speaking, patients should always have the option for in-person visits when feasible. But when appropriate infrastructure and personnel are available, telehealth visits are suitable for treatment or long term management visits, in addition to family conferences, genetic counseling, second opinion evaluations, consent form discussions for pre-research trial participation, or when care access issues exist. I would refer the audience to the bottom line box which highlights the 18 described visits, as well as the preferred in-person consultation recommendations. So from an operations standpoint, the standards include recommendations for practices to develop their own policies and procedures for these types of visits, frequency of visits, and documentation requirements for all clinical visits. Additionally, patients need to be oriented to the technology being utilized and have real time access to troubleshoot and support, if there are technology issues. The panel strongly advocated the quality of care should be equivalent to in-person visits. Thus to support this concept, the standards include, key performance indicators evaluation, policies for interventions delivered asynchronously, automated reminders, and inclusion of patients and caregivers involvement, if new technologic interventions are developed. BRITTANY HARVEY: Great. I think those specifics you outlined will be helpful both for clinicians and practices, as they implement telehealth. So then, how should the establishment of the physician-patient relationship occur within the context of telehealth in oncology. DR. ROBIN ZON: Well, both state and federal policies permitting telemedicine to cross state lines, should include a provision requiring that the doctor-patient relationship be established, prior to provision of any telemedicine services. As a reminder to the listener, the ASCO position statement, Telemedicine Cross-State Licensure, was recently approved by the Board of Directors and references a valid doctor-patient relationship as outlined by the American Medical Association. This includes establishment of relationship by face-to-face examination or consultation with another physician, who has an ongoing doctor-patient relationship with the patient, or meets the standards of establishing a doctor-patient relationship, if included, in clinical practice guidelines developed by a major medical specialty society. I would refer the audience then to this ASCO position statement, for a much more detailed discussion regarding this topic. Importantly, the doctor-patient relationship should include the usual follow-up and care responsibilities and include opportunity for in-person visits at the physical location of the physician practice. BRITTANY HARVEY: Then following those recommendations for the physician-patient relationship, what is the guidance for when patients may see an advanced practice provider? DR. ROBIN ZON: Well, the panel recommends that practices follow established standards, policies, and algorithms that govern when Advanced Practice Providers, also known as APPs, or physicians should conduct the televisit based on the disease, treatment, or decision inflection point. However, the panel advises that practices should also review and comply with state and local regulations, for advanced practice provider supervision, including on how the APPs and physicians form teams. BRITTANY HARVEY: Understood. And then further, in addition to those, what is the role of allied health professionals in oncology-specific telehealth interventions? DR. ROBIN ZON: And just to orient the audience, when we refer to allied health professionals, we are referring to health professionals who are valued oncology team members. But they're distinct from physicians and nurses. That said, the expert panel referred to the Clinical Oncology Society of Australia, also known as COSA, Tele-oncology Guidelines, which provides guidance for oncology telehealth in rural and remote Australia. This evidence base was the largest for allied health professionals supportive interventions, delivered by both telephone and video conferencing. So due to the strength of the COSA evidence base, the expert panel endorses these recommendations, and refers to the utilization of telephone-based support systems, computerized screening, hybrid tele-practice systems, and video conferencing, as instruments for allied services delivery. BRITTANY HARVEY: Great. And then the standards went into specifics regarding multidisciplinary cancer conferences. So how should discussion occur at virtual multidisciplinary cancer conferences, compared to in-person MCC meetings? DR. ROBIN ZON: Well, as many of you know, many practices, in both academia and community settings, consider cancer conferences, which we also refer to as tumor boards, as essential for high quality patient care. Therefore, virtual cancer conferences replace these face-to-face meetings. The expert panel endorses the recommendations by the University of Pittsburgh Medical Center, for implementation of a virtual cancer conference. These include finalization of the agenda, one day in advance, secure video conferencing software, prioritizing complicated cases, and documentation and evaluation guidance. The expert panel also suggests that practices follow institutional guidelines, allowing the discussion to be directed by the presenter. And that there be no recording of the conference taking place without prior legal review. BRITTANY HARVEY: Once again I find those specifics will be very helpful and explicit for clinicians. So then the last question that was addressed in these standards, how can telehealth be incorporated into clinical trials in oncology? DR. ROBIN ZON: Well, utilization of telehealth and clinical trials are recommended, as a method for increasing recruitment, while reducing patient burden. Importantly, I want to emphasize that the expert panel endorses these recommendations prevail, beyond COVID-19 pandemic restrictions. This includes consideration for a hub and spoke model for patient enlistment. As well as recommendations to facilitate the conduct of teletrials, which are modifications intended to reduce risk during the pandemic, but also results in increased accessibility, reduced costs, and are less time-consuming. BRITTANY HARVEY: Thank you for reviewing all of those key statements that were highlighted in the standards. So then, in your view, Dr. Zon, what is the importance of these standards to clinicians, and how will their implementation impact clinical practice? DR. ROBIN ZON: Well, as I mentioned earlier, telehealth was very uncommonly utilized in cancer care, prior to the pandemic. However, with the soaring use of this intervention, there was a noted gap specific to oncology standards beyond the general telehealth guidance. These standards, then, are designed to assist the cancer care team in delivering the highest quality patient care, similar to the face-to-face quality care the oncologists strive to provide on a daily basis. Furthermore, what we have witnessed, from both the practice responses and the convening of many experts in the delivery of telecare, is the flexibility to swiftly change and harness innovation among our colleagues worldwide. Telehealth, then, has the potential to improve care beyond the pandemic. And these standards serve as a roadmap for telecare best practices to continue to develop and address the needs for rural communities, patients with poor access to care, increase overall clinical trial participation, support patient education, and become one strategy, in a toolbox of other strategies, to help narrow the gap in disparate care. BRITTANY HARVEY: Great. And then you've started to touch on this already, and talking about access to telehealth and how that impacts patients. But finally, how will these standards affect patients? DR. ROBIN ZON: With regards to patients, what we learned from this evidence review, is that patient satisfaction is high. And they appreciate the convenience, flexibilities, and time and cost savings, as a result of telehealth options. I can share from my own practice that my patients were very grateful that we were able to provide telecare during the pandemic, and even now, as restrictions lessen, they're very thankful to have that opportunity. Many oncology patients want this option to continue for the future, and do not believe their clinical care was compromised. However, oncology patient-reported outcomes and ongoing patient satisfaction evaluations must continue, along with the assessment of how the continuing challenges of broadband access, lack of technologic devices, or even familiarity with some technology, may serve as barriers to this care model. These standards are meant to assure the same high quality care for patients who choose to use this intervention, as they would if it were in person. BRITTANY HARVEY: Definitely. Well, thank you for your work on these evidence-based standards directed at delivering high quality and accessible oncology care. And thank you for taking the time to speak with me today Dr. Zon. DR. ROBIN ZON: And thank you so very much for this opportunity. BRITTANY HARVEY: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast series. To read the standards go to www.asco.org/standards. Additionally, our annual survey for standard topics is open for submissions suggest a topic for standard development at www.surveymonkey.com/r/standardssurvey. Our standards survey. The link is also available in the episode notes of this podcast. If you have enjoyed what you heard today, please rate and review the podcast, and be sure to subscribe, so you never miss an episode. [MUSIC PLAYING]
  • ASCO Guidelines Podcast Series podkast

    Salivary Gland Hypofunction and/or Xerostomia Induced by Non-Surgical Cancer Therapies: ISOO/MASCC/ASCO Guideline

    15:58

    An interview with Dr. Valeria Mercadante from University College London, Dr. Siri Beier Jensen from Aarhus University, and Dr. Douglas Peterson from UConn Health, authors on “Salivary Gland Hypofunction and/or Xerostomia Induced by Non-Surgical Cancer Therapies: ISOO/MASCC/ASCO Guideline.” This guideline provides evidence-based recommendations for interventions to prevent, minimize, and manage salivary gland hypofunction and xerostomia in patients receiving nonsurgical cancer therapy. Read the full guideline at www.asco.org/supportive-care-guidelines. Suggest a topic for guideline development at www.surveymonkey.com/r/ascoguidelinesurvey.   TRANSCRIPT [MUSIC PLAYING]   SPEAKER: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. [MUSIC PLAYING]   BRITTANY HARVEY: Hello, and welcome to the ASCO Guidelines Podcast Series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at podcasts.asco.org. My name is Brittany Harvey, and today I'm interviewing Dr. Valeria Mercadante from University College London and University College London Hospitals Trust in London, United Kingdom, Dr. Siri Beier Jensen from Aarhus University in Aarhus, Denmark, and Dr. Douglas Peterson from the School of Dental Medicine and Neag Comprehensive Cancer Center UConn Health in Farmington, Connecticut, authors on "Salivary Gland Hypofunction and/or Xerostomia Induced by Non-Surgical Cancer Therapies: International Society of Oral Oncology, Multinational Association of Supportive Care in Cancer, and American Society of Clinical Oncology Guideline." Thank you for being here, Dr. Mercadante, Dr. Beier Jensen, and Dr. Petersen. DR. VALERIA MERCADANTE: Thank you. It's a pleasure to be here. DR. DOUGLAS PETERSON: Thank you. DR. SIRI BEIER JENSEN: Thank you. BRITTANY HARVEY: First, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online with the publication of the guideline in the Journal of Clinical Oncology. Dr. Mercadante, do you have any relevant disclosures that are directly related to this guideline topic? DR. VALERIA MERCADANTE: No, I do not have any relevant disclosure. BRITTANY HARVEY: Thank you. And Dr. Beier Jensen, do you have any relevant disclosures that are directly related to this guideline? DR. SIRI BEIER JENSEN: No, I have no conflicts to declare related to this guideline topic. BRITTANY HARVEY: Thank you. And finally, Dr. Peterson, do you have any relevant disclosures that are related to this guideline topic? DR. DOUGLAS PETERSON: No. No related conflicts to declare. BRITTANY HARVEY: Thank you. Then let's delve into some of the content of the guideline. First, Dr. Mercadante, can you give us an overview of this guideline's scope and purpose? DR. VALERIA MERCADANTE: Of course. These clinical practice guidelines focus on the prevention and management of salivary gland hypofunction and xerostomia due to non-surgical cancer therapies. This is something we are deeply passionate about because nonsurgical cancer therapies, including all type of radiation regimens, chemotherapy, and biological cancer therapy, can damage the glands in our mouth that produce saliva, resulting in xerostomia, which we define as patient-reported subjective sensation of dryness and salivary gland hypofunction, which we define as reduced salivary flow rate as measured objectively. And this condition may last for several months or may become permanent. And because saliva serves so many important function, xerostomia may lead to a range of other symptoms that can impact patient quality of life. And therefore, ASCO, MASCC, and ISOO decided to update the findings of their two previous systematic reviews published in 2010 and provide a practical, evidence-based approach in a multidisciplinary setting to address this important topic. BRITTANY HARVEY: Great. Thank you for that background. So then I'd like to review the key recommendations of this guideline. This guideline covers two clinical questions, one on prevention and one on management. So Dr. Peterson, starting with prevention, what are the key recommendations regarding pharmacologic and non-pharmacologic interventions for the prevention of salivary gland hypofunction and/or xerostomia induced by non-surgical cancer therapies? DR. DOUGLAS PETERSON: Thank you, Brittany. As you've noted, the guideline is framed in the context of two clinical questions, prevention, and then followed by the management once the condition has occurred. Relative to prevention, there were eight recommendations, all of which were directed to reducing the risk of salivary gland hypofunction and/or xerostomia in patients with head and neck cancer. And as with other ASCO guidelines, each of these recommendations was in turn supported by text directed to literature review and analysis and clinical interpretation. So let me just briefly highlight the eight recommendations on prevention. Recommendation 1.1 was that intensity-modulated radiation therapy, IMRT, should be used to spare major and minor salivary glands from a higher dose of radiation. This was a very strong, well-evidenced recommendation. The evidence quality was high. The strength of the recommendation was strong. Recommendation 1.2 is that other radiation modalities that limit cumulative dose to an irradiated volume of major and minor salivary glands as one or more effectively than IMRT may be offered. Recommendation 1.3 reads that acupuncture may be offered during radiation therapy for head and neck cancer to reduce the risk of developing the symptom of xerostomia. Recommendation 1.4, systemic administration of the sialogogue bethanechol may be offered during radiation therapy for head and neck cancer. Recommendation 1.5-- and this is an important different type of recommendation-- vitamin E or other antioxidants should not be used to reduce the risk of radiation-induced salivary gland hypofunction and xerostomia. And this is because of the potential adverse impact of these antioxidants on cancer-related outcomes and the lack of evidence of benefit. In addition to those five recommendations, there were three recommendations for which the evidence was insufficient. In the panel's view, it was important to delineate these three recommendations in the context of current clinical practice as well as opportunities for future research that we'll talk about in a little bit. The three recommendations for which there was insufficient evidence are 1.6. -- The panel was unable to make a recommendation for or against the use of submandibular gland transfer administered before head and neck cancer treatment. This limitation is due to the current amount of evidence associated with this surgical intervention, submandibular gland transfer, in relation to ever-evolving contemporary radiation modalities. Recommendation 1.7-- evidence remains insufficient for a recommendation for or against use of the following three interventions during radiotherapy for head and neck cancer. The three interventions are oral pilocarpine, amifostine in association with contemporary radiation modalities, and low-level laser therapy. And then, finally, Recommendation 1.8-- the evidence remains insufficient for or against the use of several interventions, including selected radiation technology, for example, boost radiation or hyper or hypofractionated radiation therapy, Transcutaneous Electrical Nerve Stimulation or TENS, human epidermal growth factor, and selected complementary medicines. And again, the evidence is insufficient in the panel's view for a recommendation for or against these and several other interventions that are listed in the guideline. So I'll now turn the microphone back to Brittany. BRITTANY HARVEY: Great. Thank you for reviewing those prevention recommendations and explaining the evidence that supported those as well. That's very helpful. So following that, Dr. Beier Jensen, what are the key recommendations on pharmacologic and non-pharmacologic interventions for the management of salivary gland hypofunction and/or xerostomia induced by non-surgical cancer therapies? DR. SIRI BEIER JENSEN: The key recommendations for the management of salivary gland hypofunction and xerostomia induced by cancer therapies are based on the principles of stimulation of the salivary reflex and lubrication of the oral tissues of, say, the mucosa and the teeth. The recommendations 2.2, 2.3, 2.4, and 2.5 address this stimulatory approach. If there is residual secretory capacity of the salivary glands, stimulation of natural saliva secretion may be provided by chewing or taste stimuli. This can be regular use of sugar-free lozenges, sugar-free candies, or sugar-free non-acidic chewing gum. In patients who have their natural teeth, it's important to be aware that if acidic candies are used to stimulate saliva secretion, then it should be a special nonerosive preparation for dentate patients that will say that they do not dissolve the tooth substance. Pharmacological stimulation is also an option by prescription medication such as oral pilocarpine and cevimeline in countries where this is available. This may result in systemic adverse effects that limit use in some patients. So the gustatory and masticatory salivary reflex stimulation, Recommendation 2.2, the evidence-based quality was intermediate, and the strength of the recommendation was moderate. And for the pharmacological stimulation by pilocarpine and cevimeline, it was evidence-based, high-quality, and strong recommendation strength. For patients who have salivary gland hypofunction or xerostomia induced by radiation therapy for head and neck cancer, stimulation of saliva secretion may also be provided by acupuncture, transcutaneous electrical stimulation, or acupuncture-like transcutaneous electrical stimulation, although the evidence base here is less strong than for the other stimulatory management options mentioned. This is addressed in Recommendation 2.4 and 2.5. If the residual secretory capacity of the salivary glands is low or maybe even nonexistent, then regular lubrication of the oral mucosa and teeth is of relevance. This is addressed in Recommendation 2.1. Such lubrication may be provided by topical application of mucosal lubricants and saliva substitutes, which are agents directed at ameliorating xerostomia and other salivary gland hypofunction-related symptoms. It is of importance to notice that available stimulatory and lubricating options all provide transitory increased salivary flow rates and transitory relief from xerostomia. If you would like to review the specific recommendations, they can be found in the manuscript. BRITTANY HARVEY: Great. Thank you for reviewing those recommendations on the management of salivary gland hypofunction and/or xerostomia. So Dr. Peterson, you mentioned this earlier, but there are some cases in the guideline in which evidence was insufficient to make recommendations. And you went through a few of these areas. So what areas of future research did the panel discuss? DR. DOUGLAS PETERSON: Thanks, Brittany. The panel worked very carefully to relate the quality of evidence to strength of each of the recommendations. In addition to providing important context regarding clinical prevention and treatment of xerostomia salivary hypofunction, novel directions for future research were therefore identified. And I'll just briefly delineate these future directions. Studies directed to the continued, rapidly-evolving radiation technology such as proton therapy and volumetric modulated art therapy or VMAT, as well as the length of time after this treatment is completed, for example, one to five years after completion of treatment, these studies are needed to assess the relationship of this rapidly-evolving technology to the long-term adverse oral events such as salivary gland hypofunction and xerostomia as well as advanced dental disease and osteoradionecrosis as well. Importantly, and the panel spent quite a bit of time deliberating this, ethical considerations must continue to be paramount in the study designs. And this is pertinent relative to this guideline. An important issue is that implementation of randomized clinical trials comparing current and novel radiation therapy modalities is typically precluded for ethical reasons. So this is a barrier to address, and the panel wanted to call attention to the scientific and clinical community. In addition to the radiation technology itself, two additional future research directions also represent potential strategic advances in the field as well. First, radiosensitivity of parotid gland stem cells. For example, it has been recently shown that not all constituents of the parotid gland are equally radiosensitive because of an unequal distribution of the stem cells within the gland. This and related biologic concepts should be incorporated in future randomized controlled trials of head and neck cancer patients. Secondly, novel regenerative medicine options may be used to spare, optimize, or restore salivary gland function after treatment. The guideline addresses these innovative treatment approaches in the context of both the current state of the science as well as opportunities for future research. I'll turn the microphone back to Brittany. BRITTANY HARVEY: Great. Thank you, Dr. Peterson, for reviewing those areas where additional research would be helpful. So next, in your view, Dr. Mercadante, what is this guideline's importance and how will it affect clinicians? DR. VALERIA MERCADANTE: Thank you for this question. We believe these guidelines offer an opportunity for any clinician involved in non-surgical cancer therapies-- oncologists, dentists, dental specialists, dental hygienists, oncology nurses, clinical researchers, advanced practitioners. We all have an essential role in supporting our patients for the entire journey by optimizing symptoms management and improve our patients quality of life. These guidelines thus suggest a preventative and treatment course, but we've also delineated what we feel is common practice between experts and what areas would need further research to provide, as Dr. Peterson beautifully described, an ethical framework for future studies in this field. BRITTANY HARVEY: Great. Thank you so much. So finally, Dr. Beier Jensen, how will these guideline recommendations impact patients? DR. SIRI BEIER JENSEN: Well, for patients who live with these complications during cancer treatment or as [INAUDIBLE] of cancer therapies, these guideline recommendations on prevention and management of salivary gland hypofunction and xerostomia will enable them evidence-based and with the help of professional health care providers to support the natural functions of saliva and promote their oral comfort and health. BRITTANY HARVEY: Great. Well, thank you all, Dr. Mercadante, Dr. Beier Jensen, and Dr. Peterson for taking the time to work on this guideline and produce evidence-based recommendations for clinicians and patients. And thank you for taking the time to speak with me today. DR. BEIER JENSEN: Thank you. DR. DOUGLAS PETERSON: Thank you. BRITTANY HARVEY: And thank you to all of our listeners for tuning into the ASCO Guidelines podcast series. To read the full guideline, go to www.asco.org/supportive-care-guidelines.  Additionally, our annual survey for guideline topics is open for submissions. Suggest a topic for guideline development at www.SurveyMonkey.com/r/ascoguidelinesurvey by August 1st. The link is also available in the episode notes of this podcast. If you've enjoyed what you've heard today, please rate and review the podcast, and be sure to subscribe so you never miss an episode. [MUSIC PLAYING]
  • ASCO Guidelines Podcast Series podkast

    Management of the Axilla in Early-Stage Breast Cancer: OH (CCO) and ASCO Guideline

    13:18

    An interview with Dr. Muriel Brackstone from London Health Sciences Centre and Dr. Tari King from Dana Farber and Brigham and Women’s Cancer Center, authors on “Management of the Axilla in Early-Stage Breast Cancer: OH (CCO) and ASCO Guideline.” This guideline addresses management & timing of surgical and radiotherapeutic treatment of the axilla in early breast cancer. Read the guideline at asco.org/breast-cancer-guidelines. Suggest a topic for guideline development at surveymonkey.com/r/ascoguidelinesurvey.   TRANSCRIPT [MUSIC PLAYING] SPEAKER: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. [MUSIC PLAYING] BRITTANY HARVEY: Hello, and welcome to the ASCO Guidelines podcast series, brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at podcast.asco.org. My name is Brittany Harvey, and today I am interviewing Dr. Muriel Brackstone from London Health Sciences Center in London, Ontario and Dr. Tari King from Dana-Farber and Brigham and Women's Cancer Center in Boston, Massachusetts, authors on "Management of the Axilla in Early-Stage Breast Cancer" Ontario Health (Cancer Care Ontario) and American Society of Clinical Oncology Guideline." Thank you for being here Dr. Brackstone and Dr. King. DR. MURIEL BRACKSTONE: Thank you. DR. TARI KING: Thank you for having us. BRITTANY HARVEY: First, I'd like to note that we take great care in the development of our guidelines in both the ASCO and Ontario Health Cancer Care Ontario program and evidence-based care. Conflict of interest policies were followed for this guideline. The full conflict of interest information for this guideline panel is available online with the publication of the guideline in the Journal of Clinical Oncology. Dr. Brackstone, do you have any relevant disclosures that are directly related to this guideline topic? DR. MURIEL BRACKSTONE: No, I don't have any conflicts to disclose. BRITTANY HARVEY: Thank you. And Dr. King, do you have any relevant disclosures that are directly related to this guideline topic? DR. TARI KING: No, I do not have any relevant disclosures. BRITTANY HARVEY: Great, thank you. Then let's get into some of the content of this guideline. So first, Dr. Brackstone, can you give us a general overview of what this guideline covers? DR. MURIEL BRACKSTONE: Sure. This guideline reviews how best to diagnose and treat any lymph node spread in breast cancer patients with early-stage disease. It also reviews the role of radiation and surgery in treating the axilla to reduce the risk of regional cancer recurrence in these patients. BRITTANY HARVEY: Great, thank you. Then I'd like to review some of the key recommendations that this guideline covers. So this guideline addresses five specific objectives. So I'd like it if we could go through each of those. So for each of these objectives, could you give an overview of those high level recommendations? First, Dr. King, the first objective is about which patients with early-stage breast cancer require auxiliary staging. DR. TARI KING: Yes, thank you. So I think the two main takeaway points from this objective-- the first is that sentinel lymph node biopsy really is the standard of care for axillary staging for all breast cancer patients when it is felt that information about the lymph node status is necessary. So this really is in the majority of patients that we see and care for with early-stage breast cancer. We want to know the status of the axillary lymph nodes. That's important in our subsequent treatment recommendations. And there's really no role for axillary lymph node dissection as a staging procedure any longer. Sentinel lymph node biopsy is the staging procedure of choice. Now, there are some patient populations, however, where we may decide that we don't need the information from the axillary lymph nodes to make subsequent treatment recommendations. And one particular group which is called out in this guideline is for those women who are over the age of 70 with early-stage, again, clinically node-negative hormone receptor-positive, HER2-negative breast cancer, where the information from the sentinel lymph node biopsy is not going to alter subsequent systemic therapy recommendations. And this is really based on several lines of work demonstrating that omitting sentinel node in these older women, again, with hormone receptor-positive, HER2-negative breast cancer, does not negatively impact their long term outcomes. And so this is an opportunity for us to tailor our approach to a particular patient population without having a negative impact. BRITTANY HARVEY: Great, thank you, and thank you for reviewing for which patients this is specifically targeted to. So then for the second objective, Dr. Brackstone, is further auxiliary treatment indicated for women with early-stage breast cancer who did not receive neoadjuvant chemotherapy and are sentinel lymph node-negative at diagnosis? DR. MURIEL BRACKSTONE: No. We use this guideline to confirm that in patients who have early-stage disease and go to surgery first, so they're not having neoadjuvant chemotherapy. And in those patients, if their sentinel lymph node excision for staging is negative, that no further axillary surgery is required. Now, with regards to axillary radiation, it may be considered in the subset of patients whose breast cancer risk is high for recurrence-- so the triple negative subtype, patients who are under 50 years of age, or those with medial tumors. BRITTANY HARVEY: OK. And then Dr. King, for the third objective, which axillary strategy is indicated for women with early-stage breast cancer who did not receive neoadjuvant chemotherapy and are pathologically sentinel lymph node-positive at diagnosis after a clinically known negative presentation? DR. TARI KING: Thank you. Yes, so this recommendation really addresses a very large population of our breast cancer patients. Those that present with clinical T1 and T2 but node-negative early-stage breast cancer, we take them to the operating room. We perform a sentinel biopsy, and about 20% to 30% of them will actually end up having positive lymph nodes. And traditionally, we thought that we needed to do axillary lymph node dissection in the setting of positive nodes. But we now have multiple clinical trials that have addressed this question. And we now know that it is safe to avoid lymph node dissection in women found to have one or two positive sentinel nodes. We've had trials that have compared lymph node dissection to axillary radiotherapy or lymph node dissection to observation alone. And with either of those strategies, we've seen excellent local control in the women who have not undergone lymph node dissection. And so it really provides us, again, an opportunity to dial back or tailor our therapies to the patient's individual disease burden. Now, certainly, patients that have more than one or two positive nodes, and the guideline specifically states how to manage patients with three or more positive nodes. And those patients do need additional axillary treatment, either in the form of lymph node dissection or lymph node dissection plus axillary radiotherapy and in some scenarios. Also, the guideline is very clear to define that there are some differences in the level of recommendation for women undergoing breast-conserving surgery and found to have one or two positive nodes as opposed to women undergoing mastectomy and found to have positive nodes. So certainly, we have the larger body of data in the breast-conserving therapy group, but the guideline is very clear to also highlight the data that is available for the mastectomy group. And again, the overall recommendation is that not everybody with positive nodes needs additional lymph node dissection. And that we have alternatives which we know minimize the morbidity of our treatments. BRITTANY HARVEY: Great. Thank you for addressing the evidence base behind both of those recommendations as well. So following that, Dr. Brackstone, for the fourth objective, what axillary treatment is indicated? And what is the best timing of axillary treatment for women with early-stage breast cancer? And when is neoadjuvant chemotherapy used? DR. MURIEL BRACKSTONE: Right. So this guideline was really used to formalize a recommendation against repeating the sentinel lymph node biopsy procedure twice in patients, before and after chemotherapy. We really found that the risk of false negativity in a repeat procedure was too high. So for patients who are having neoadjuvant chemotherapy-- so patients with higher risk cancers-- the axillary ultrasound is useful to guide a biopsy of any suspicious lymph nodes to document if they're positive. If the clinical exam and the ultrasound are both negative, then the sentinel lymph node excision should be done at the time of surgery after chemotherapy. If they do have a positive lymph node that's confirmed by biopsy before their chemotherapy, and those lymph nodes respond really well to chemotherapy and are no longer palpable, then their staging can occur by sentinel lymph node procedure at the time of surgery. And that avoids what we have standardly done up to now, which is the axillary dissection and the risk of lymphedema that comes with that. If the sentinel lymph nodes are negative when you're doing your surgery after neoadjuvant chemotherapy, then we are recommending that no axillary lymph node dissection is required. If any of the lymph nodes are positive after neoadjuvant chemotherapy through the sampling technique, then a completion axillary lymph node dissection is still recommended, at least for now, until the results of some ongoing clinical trials looking at avoiding axillary node dissection are completed, which will be in the next several years. In both of those scenarios, however, locoregional radiation is still recommended. BRITTANY HARVEY: Great, thank you for providing some clarity around those specific scenarios. So then finally, Dr. King, regarding the fifth and last objective, what are the best methods for identifying sentinel nodes? DR. TARI KING: Thank you. Yes, so this objective encompasses several different clinical scenarios as well. The first being, when you are performing a sentinel lymph node biopsy procedure, do you need to use single tracer or do you need to use dual tracers to help you identify the lymph nodes? We know that in the up upfront surgery setting that you can absolutely identify the nodes with a very low false-negative rate with a single tracer. And this guideline highlights that single tracer is appropriate in patients who are undergoing upfront surgery. The guideline suggests that the physicians start with radiocolloid, and if there is a good signal, then blue dye can be omitted. In contrast, though, in patients that are receiving neoadjuvant chemotherapy, the data there supports really that the use of dual tracer is important and improves the identification rate, as well as decreases the false-negative rate of the procedure. This recommendation also includes guidance on when ultrasound should be used. As you just heard from Dr. Brackstone that they do recommend ultrasound prior to neoadjuvant chemotherapy. But in patients undergoing upfront surgery, again, with early-stage disease, clinically node-negative disease, the guidelines states that preoperative axillary ultrasound staging is not recommended. But in anybody who has suspicious or potentially abnormal nodes, then preoperative axillary ultrasound is recommended to confirm nodal status. And then finally, it is important to note that nodal staging cannot be solely performed with axillary ultrasound. So sentinel lymph node biopsy is still, again, indicated even if the ultrasound is negative. There are many clinical trials going on around the world right now to address that question. But right now, the evidence still certainly supports that we cannot rely on a negative axillary ultrasound, and sentinel lymph node biopsy should be performed. BRITTANY HARVEY: Great. Well, thank you both for reviewing those key recommendations around the objectives. So then Dr. Brackstone, in your view, what is the importance of this guideline? And how will it both impact clinicians and patients? DR. MURIEL BRACKSTONE: Thank you. I would say for clinicians that the guideline was written in an effort to collate all of the clinical trial data and the variable practice patterns across institutions in an effort to standardize treatment. In order to deescalate therapies that don't improve patient outcomes. And hopefully, provide some clarity for clinicians who treat breast cancer. For patients, I would say that deescalating treatments that are entrenched as standard, but where data demonstrates no known significant disease-free survival or overall survival benefit, that these are important because patients can suffer long term side effects from treatments, such as lymphedema, that could potentially be avoided if they're not clinically indicated. BRITTANY HARVEY: Great. Thank you both so much for your work on these evidence-based recommendations. And for taking the time to give a summary to our listeners, Dr. Brackstone and Dr. King. DR. TARI KING: Thank you. BRITTANY HARVEY: And thank you to all of our listeners for tuning into the ASCO Guidelines podcast series. To read the full guideline, go to www.asco.org/breast-cancer-guidelines.  Additionally, our annual survey for guideline topics is open for submissions. Suggest a topic for guideline development at www.surveymonkey.com/r/ascoguidelinesurvey by August 1. The link is also available in the episode notes of this podcast. If you have enjoyed what you've heard today, please rate and review the podcast, and be sure to subscribe so you never miss an episode. [MUSIC PLAYING]
  • ASCO Guidelines Podcast Series podkast

    Oncology Medical Home: ASCO and COA Standards

    19:15

    An interview with Kim Woofter, RN from Advanced Centers for Cancer Care and John V. Cox, DO, MBA from UT Southwestern Medical Center, co-chairs on “Oncology Medical Home: ASCO and COA Standards.” They review the standards for the OMH model, which is a system of care delivery that features coordinated, efficient, accessible, evidence-based care and includes a process for measurement of outcomes to facilitate continuous quality improvement. For more information, visit www.asco.org/standards.   TRANSCRIPT   [MUSIC PLAYING] SPEAKER: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.   BRITTANY HARVEY: Hello, and welcome to the ASCO Guidelines Podcast Series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at podcast.asco.org.   My name is Brittany Harvey, and today I'm interviewing Kim Woofter, RN from the Advanced Centers for Cancer Care in South Bend, Indiana, and John Cox, DO, MBA, from UT Southwestern Medical Center in Dallas, Texas, co-chairs on Oncology Medical Homes, American Society of Clinical Oncology, and Community Oncology Alliance Standards. Thank you for being here, Ms. Woofter and Dr. Cox.   JOHN COX: You bet.   KIM WOOFTER: Thank you for having us.   BRITTANY HARVEY: I'd like to note that ASCO takes great care in the development of its standards and ensuring that the ASCO conflict of interest policy is followed. The full conflict of interest information for the expert panel is available online with the publication of the standards in JCO Oncology Practice. Ms. Woofter, do you have any relevant disclosures that are directly related to these standards?   KIM WOOFTER: No, I don't have anything to disclose.   BRITTANY HARVEY: Thank you. And Dr. Cox, do you have any relevant disclosures that are related to these standards?   JOHN COX: I do not.   BRITTANY HARVEY: Great. Then let's talk a little bit about these standards. So first, can you give us a general overview of the purpose and scope of these standards for the Oncology Medical Home or OMH model?   KIM WOOFTER: Sure. I'll start this one out. The purpose was to collaboratively define a care delivery system with a standardized set of expectations and goals, and it all centered around the delivery of high quality, cost-effective care. And one of the reasons this is so important to all of us right now is to be ready for value-based care. We all need to really have a care delivery system that's patient-centric and has a standardized set for all of us to follow. Dr. Cox, do you see this any differently, or what would you have to say?   JOHN COX: No, I think you've said it well, Kim. I think one of the challenges we all have when we talk about Oncology Medical Home or a system of care is to be challenged to address that question in a simple answer. I would give the predicate that we have had a blossoming of the complexity of oncology care in our science, yet one of the thorny issues that faces oncology practice is how do we equitably and efficiently provide quality oncology care.   And if you were to challenge many clinicians to define how they provide quality oncology care, you get diverse opinions about that. The Oncology Medical Home certification program and the system of care that Kim highlighted attempts to put forward a comprehensive set of standards that helps us define what quality oncology care looks like and to answer those questions in care delivery.   BRITTANY HARVEY: Great. Then, given that scope, what are the key statements made by the expert panel in these standards?   JOHN COX: I'll take a stab at that, but also offer a little bit of insight into the development of Oncology Medical Home. We actually had some 20 years of history with different medical home certification programs to draw on, including significant contributions by oncologists who have worked in different programs to help define what Oncology Medical Home is. So when we took on this project, a collaborative project between ASCO and the Community Oncology Alliance, COA, we drew upon that great history of previous certification programs.   These programs focused on different aspects of care delivery, including aspects that are focused on improving patient engagement and access to practice, ensuring that evidence-based medicine is provided in a practice, looking at how quality is measured and how that feedback is given to practices and how that feedback is used to have quality improvement programs, focusing on palliative and end-of-life care, and addressing one of the unique features of medical oncology delivery, which is the delivery of chemotherapy and how we do that safely. So this was a very comprehensive set of standards. Kim, I don't know if you want to add to this.   KIM WOOFTER: No, I think you stated that very well. And the piece that I really love about this project, and what we focused heavily on, is the equitable delivery of care. We all fundamentally believe that every cancer patient deserves and has the right to high quality, cost-effective care, and this was just the baseline. And I think Dr. Cox explained it very well, that one of the key elements is the quality improvement process, or the re-evaluation continually of how we deliver care, the outcomes of care, the patient satisfaction with that care.   So as we developed this, we knew this was just the foundation. This is the starting point. We've brought some unity around the discussion. We've used evidence to come up with these standards and really defined what's gone on prior to this time. And what's exciting is this is just the beginning of what will evolve over the years to come.   BRITTANY HARVEY: Great. It sounds like this is a really comprehensive document. So I'm reading through the standards. It looks like there's a little bit of a deeper dive on two subcomponents of the OMH model-- first, clinical pathways, and second, survivorship care plans. How do the standards address these two?   JOHN COX: Oh, I'll dive in first again. And not to step on Kim at all about this, but many of the listeners to this podcast will be very familiar with ASCO guideline development. And the traditional clinical guidelines are completely infused and based on an evaluation of what the evidence base is. Care delivery is a bit more complex. Much of care delivery focuses on best practices that have been learned in practice through trial and error-- observation, if you will.   So many of the standards that are in Oncology Medical Home certifications are really based on best practices. However, we knew that we would be challenged to evaluate those standards that had significant cost or significant resource dedication in a practice. If we were going to build those aspects of a certification program forward as being a best practice in a care delivery model, we would need to justify, or at least examine, what evidence base is present to show that it had value.   Two of the most consequential standards that are going to require significant resource development by any practice is the measurement of evidence base through a pathway program. The other one was the significant discussion that has been around survivorship and survivorship care plans. So those two areas of the standards we took a deep dive in in this process. Kim, do you want to add to this?   KIM WOOFTER: Yeah. I really appreciate Dr. Cox's description. He's spot on, as always. I think having managed to practice myself for many, many years, the struggle with the implementation of a clinical pathway program and survivorship care plans or for survivorship program have always been somewhat difficult. And what I love about the standards is we clearly define that pathways are no longer a homegrown list of what I like to do or how I like to treat. It is absolutely evidence-based. Your pathways have to truly reflect the importance of clinical research and what that has done to lead up to the intelligence of that delivery.   What I think is so important, too, is ASCO still did a little bit of work and set the pathway for us on this in that it needs to be a comprehensive list. It needs to have systematic review. We have to demonstrate adherence to pathways and also document when somebody goes off a pathway. And I think that's very important as you manage a practice and as you prepare for this delivery system. It's no longer what we do in the back room. It's very well-defined and very measurable.   As far as survivor care plans, I love that we have migrated a little bit on this standard. I think the nation has migrated. Over the years-- and I'll include the COC in this discussion. Originally, it was check the box, have a survivorship care plan and a visit to explain what the future would look like. And we now know that isn't the best way to handle survivorship.   Patient satisfaction and outcomes are much better when we have a survivorship program. And that's what the standard calls out. It is not just a care plan or a piece of paper. It is support. It is ongoing evaluation of the patient. It's integration with the primary care and when to transition back to primary care. So what's exciting is it is now a program versus just a care plan.   BRITTANY HARVEY: Thank you both for explaining the evidence-based reasoning behind those two components. So then you've both noted earlier the importance of these standards for quality oncology care. So why are these standards important, and how will their implementation impact clinicians?   KIM WOOFTER: I'll jump in to why I think they're important-- and I think the whole industry, the whole ecosystem of oncology care thinks they're important-- is we need standardization. We need real, evidence-based standardization. And we need to prepare ourselves in all settings-- community oncology practice settings, academic settings-- for the value-based care that we're going to be required to deliver every day, all day. And clinicians, I believe, will embrace this. They'll embrace this because it's taken away some of the ambiguity of what care delivery should look like, and it levels the playing field, if you will.   It also helps with the dialogue with patients and their employers. I think we could all argue that patients and employers are the ultimate payers. And they now have a mechanism by which they can evaluate, am I getting the highest quality, most affordable care? And these Oncology Medical Home standards will be the foundation for that discussion. And I'm excited that everyone will be involved in that discussion. So I think that's why they're very important.   BRITTANY HARVEY: Great. And then, finally, how will these standards impact patients?   JOHN COX: Well, I think our whole goal in delivering efficient and quality oncology care is to be very patient focused. I would underline that this entire concept of an Oncology Medical Home is built around a patient centered care. So every standard that this program identifies has the patient at the center of care. And I think anybody who reads through the standards can see that every aspect of this is focused on some issue that they can relate to patients in their practice stumbling over.   We have this wonderful technology of care. But right now, I would challenge oncology practice universally that as our science has become more complex, patients are having to jump through more hoops to get that quality care. Specialization breeds fragmentation. What we want this program to do is to define what a oncology practice must do to help that patient have a coordinated care approach for all aspects of their cancer journey.   And I want to come back and just put a coda, a real strong statement, is this is a care delivery system. We are trying to take as comprehensive view of the delivery of oncology practice in the certification program as we can. It's not intended to parse. It's intended to focus on the patient and to provide a comprehensive system of care.   The other challenge is we know that the only way there can be efficient and easily accessible practices that can provide this kind of care is that they be adequately funded. And though this certification program does not speak to funding directly-- this is about the quality of care delivery-- we wanted to build a program that payers in industry could look at and build their reimbursement systems around. We hope that as new reimbursement models, alternative payment models come to bare, that if practices are pursuing this certification program, they will be able to meet the demands of the payer and apply this toward a comprehensive, meeting the standards of any alternative payment program.   And to that end, I really want to defer maybe a little more discussion of this to Kim. Kim, we sort of present two ends of the barbell, if you will, of care delivery. I, a practitioner, Kim is on the point of the sword in dealing with her practice about the reimbursement issues and contracting. So when we talk about this, what is the impact for patients?   Part of that is recognizing that patients have insurance. They have employers. They have people who are paying for this care. And that's really important to address. Kim, I'm long-winded. Maybe I'm trying to wrap too much into this answer. But I'll let you add to the issues of reimbursement and how this affects patients.   KIM WOOFTER: Well, thank you, Dr. Cox. You're never too long-winded. I always love to hear you speak, and your insight is spot on. And I think, from a patient's perspective, what's exciting about this program is it engages and empowers patients right from the beginning. You'll see, very well spelled out in the standards, that one of the requirements is that you educate that patient about what an Oncology Medical Home really means, what the components are. And that empowerment of the patient allows them to be part of the voice for quality oncology.   As we work with their payers, their employers, the patient themselves understand the value of what we are doing in collaboration. They understand that we provide them access, 24/7 access, you'll see, as part of the requirement. And they understand very well and can help us communicate to everybody in the ecosystem that this comprehensive package is what gives them the highest quality, allows them, like I said, the most access. It allows them safe chemo delivery. And as they communicate that, it will become the desired standard.   The patient is absolutely the ultimate winner here. Everything we do as clinicians and administrators is based around the patient. Outcomes, satisfaction, end-of-life initiatives. And I believe by putting this comprehensively and well-defined into one set of standards, we have helped the patient to achieve that goal.   BRITTANY HARVEY: Well, it sounds like these standards will have a real positive impact for patients and quality oncology care delivery. So I want to thank you both for your work on the development of these Oncology Medical Home standards and for taking the time to speak with me today, Dr. Cox and Ms. Woofter.   KIM WOOFTER: It was our pleasure.   JOHN COX: It's our pleasure.   BRITTANY HARVEY: And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast Series. To read the standards, go to www.asco.org/standards. If you have enjoyed what you've heard today, please rate and review the podcast. And be sure to subscribe so you never miss an episode.   [MUSIC PLAYING]
  • ASCO Guidelines Podcast Series podkast

    Assessment of Adult Women with Ovarian Masses and Treatment of Epithelial Ovarian Cancer Resource Stratified Guideline

    15:22

    An interview with Dr. Zeba Aziz from Hameed Latif Hospital in Lahore, Pakistan, Dr. William Burke from Stony Brook University Hospital in Stony Brook, NY, and Dr. Keiichi Fujiwara from Saitama Medical University International Medical Center in Saitama, Japan, authors on "Assessment of Adult Women with Ovarian Masses and Treatment of Epithelial Ovarian Cancer: ASCO Resource Stratified Guideline." This guideline provides recommendations in three resource-constrained settings on diagnosis and staging of adult women with ovarian masses and treatment of patients with epithelial ovarian (including fallopian tube and primary peritoneal) cancer. Read the full guideline at www.asco.org/resource-stratified-guideline.   TRANSCRIPT ASCO: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. BRITTANY HARVEY: Hello, and welcome to the ASCO Guidelines podcast series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content, and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at podcast.asco.org. My name is Brittany Harvey, and today, I'm interviewing Dr. Zeba Aziz from Hameed Latif Hospital in Lahore, Pakistan, Dr. William Burke from Stony Brook University Hospital in Stony Brook, New York, and Dr. Keiichi Fujiwara from Saitama Medical University International Medical Center in Saitama, Japan, authors on Assessment of Adult Women with Ovarian Masses in Treatment of Epithelial Ovarian Cancer: ASCO Resource Stratified Guideline. Thank you for being here, Doctors Aziz, Burke, and Fujiwara. First, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online with the publication of the guideline and the Journal of Clinical Oncology, Global Oncology. Dr. Burke, do you have any relevant disclosures that are directly related to this guideline topic? DR. WILLIAM BURKE: I do not. BRITTANY HARVEY: And Dr. Fujiwara, do you have any relevant disclosures that are related to this guideline topic? DR. KEIICHI FUJIWARA: Yes. I have the consultancy for the PARP inhibitors development. BRITTANY HARVEY: Thank you. And then Dr. Aziz, do you have any relevant disclosures that are related to this guideline? DR. ZEBA AZIZ: No, I don't. BRITTANY HARVEY: Thank you. OK, so first, Dr. Burke, can you give us a general overview of what this guideline covers? DR. WILLIAM BURKE: Sure, Brittany. The purpose of this guideline is to provide expert guidance in treatment of adult women 18 years and older with epithelial ovarian cancer, including fallopian tube and primary peritoneal cancer, to clinicians, public health leaders, patients, and policymakers in a resource-constrained setting. To do this, ASCO has established a process for development of resource stratified guidelines, which includes a mixed methods of evidence-based guideline development, adaptation of the clinical practice guidelines to other organizations, and formal expert consensus. This guideline summarizes the results of this process and presents resource-stratified recommendations. The recommendation of this guideline centers around the four key clinical questions pertaining to the care of women with ovarian cancer. BRITTANY HARVEY: Great. And then, as you just mentioned, this is a resource-stratified guideline. So Dr. Fujiwara, can you tell our listeners about the four-tier resource stratification used for the development of this guideline? DR. KEIICHI FUJIWARA: Oh, yes. So we have the four tiers resource stratification, which were basic, limited, enhanced, and maximum. So for the basic, it's the core resources or fundamental services that are absolutely necessary for any public health or primary health care systems to function. So the basic levels of this typically are applied in our single clinical interactions. For the limited, so this is the second tier resources or services that are intended to produce major improvements in outcomes such as, for instance, cost-effectiveness, and are attainable with a limited financial means and modest infrastructures. So the limited level of service may involve single or multiple interactions. And the third  tier is enhanced. The third tier resources or services that are optional, that are important, enhance the level of resources should produce further improvements in the outcome and to increase the number of the quality of options in the individual choices. Lastly, the fourth tier is a maximal, so high-level or state of the art resources, or services that may be used or are available in some high-resource countries, and/or may be recommended for the high resource setting guidelines that do not adapt to resource constraints, but that nonetheless should be considered for a lower priority than those resources or services listed in the other categories on the basis of extreme cost and/or impracticality for the broad use of the resource-limited environment. BRITTANY HARVEY: Great. Thank you for going over those. So next, I'd like to review the key recommendations of this guideline. This guideline addresses four overarching clinical questions. So first, Dr. Aziz, what are the key diagnostic and staging recommendations for patients with symptoms of epithelial ovarian cancer? DR. ZEBA AZIZ: Thanks, Brittany. Basically, as pointed out, we have three levels. The basic level usually involves one or two encounters, and at the basic level, the doctor makes a clinical assessment of a suspected ovarian mass, takes a good history and physical, and the family history is also important at the same time. At the basic level, one can do a chest X-ray and an ultrasound to confirm the suspicion, and then the doctor should ideally send the patient to a limited or an enhanced level-- wherever the patient can go. At the limited and enhanced level, again, you have to do diagnostics, which include a CT scan and an MRI if it's available and feasible. You can do the biomarker studies for CA125 and CEA level, and to make a diagnosis, you can do a CT-guided biopsy. You can also do a cell cytology and if a cell block preparation can be made through cell block. Very rarely, if need be, and if you think that you need to make a diagnosis and you can't do anything else, laparoscopy can be done. Once the diagnosis is made, you then go for staging. And the staging is usually done when you're doing a CT scan and you do an abdominal and pelvic CT scan. You do a CT scan of the chest if you think it's needed. Otherwise, a chest ray will suffice. And then you go forward and get a diagnostic workup done and send it to the surgeon for either and decide on a multidisciplinary with a neoadjuvant or surgical assessment testing. BRITTANY HARVEY: Great. Then so next, Dr. Fujiwara, what are the overarching recommendations for surgery with women with stage one to four epithelial ovarian cancer? DR. KEIICHI FUJIWARA: Yes. So the purpose of the surgery is to diagnose, stage, and/or for treatment. So we strongly recommended the ovarian cancer surgery should be performed by trained gynecological oncologists or surgeons with oncologists' surgical expertise. If it is not suitable, we strongly recommend to refer those patients to the highest-resourced level center with an oncology surgical care capacity. For the staging purpose, where the feasible patients with a presumed early stage ovarian cancer should undergo surgical staging by train surgeons. In basic setting, surgical staging is not feasible. Thus, it is not recommended. For the treatment purpose of the women with advanced ovarian cancer, which is a stage three or four, should receive optimal surgical debulking to remove all visible disease to improve overall survival by trained surgeons. BRITTANY HARVEY: Great. And then Dr. Burke, what are the key recommendations for optimal adjuvant and systemic therapy for patients with stage one to four epithelial ovarian cancer? DR. WILLIAM BURKE: Sure. Well, one of the most important things is that access to appropriate evidence-based chemotherapy agents, contraindications to chemotherapy, and potential side effects of chemotherapy should be evaluated and managed in every patient. Basic resource settings that most likely lack the capacity to provide safe administration of chemotherapy should refer patients to a higher level center for evaluation. Limited settings without skilled capacity should refer patients to settings with access to specialized care. Some other notes include that clinicians should be able to document pathology and stage to determine eligibility for adjuvant chemotherapy. If pathology confirmation is not possible due to patient or resource limitation, alternatives can be discussed. Clinicians should not administer systemic treatment, adjuvant chemotherapy, to patients with ovarian low malignant potential tumors or early stage, microinvasive borderline tumors, independent of stage. Combination chemotherapy with paclitaxel and carboplatin is the standard of care for adjuvant therapy in ovarian cancer. However, single agent carboplatin may be utilized due to resource limitation or patient characteristics. Only in enhanced settings, highly selected cases can be assessed for appropriate evidence based intraperitoneal chemotherapy following optimal debulking, where there are resources and expertise to manage the toxicities. BRITTANY HARVEY: Great. And then the last overarching clinical question-- Dr. Aziz, what is recommended for patients with recurrent epithelial ovarian cancer? DR. ZEBA AZIZ: You know, with recurrent ovarian epithelial cancer is a tough option, especially in patients residing in the low-middle income countries. Supportive care treatment should be started together with whatever we have to do. So there are three options. There's one patient who presents with a rising CA125 with no evidence of disease and asymptomatic. We can elect to follow these patients, and it's easier to follow them until they become symptomatic or they have evidence of disease. If you have small volume disease which is resectable, you send them to an enhanced level setting, ideally where surgery can be done. Then you also look at patients and divide them into platinum resistant or platinum sensitive. If they're platinum sensitive, you can give a platinum-containing regimen, but if they're platinum resistant, you can put them on a non-platinum chemotherapy-- a single agent or whatever-- but these patients are tough to manage in that part of the world. BRITTANY HARVEY: Definitely. Well, thank you all for reviewing each of those key recommendations. The full recommendations are available in the guideline, but those are some important highlights. Thank you very much. So Dr. Burke, in your view, what is the importance of this guideline, and how will it change practice? DR. WILLIAM BURKE: Sure. Well, I think the importance of this guideline is that it globally targets health care providers, including gynecologic oncologists, surgeons, nurses, and palliative care clinicians, as well as non-medical community members, including patients, caregivers, and members of advocacy groups, providing them with resource-stratified clinical guidelines, recommendations that can be implemented across many health settings. The guideline will hopefully raise awareness among frontline practitioners, and provide guidance to provide adequate services in the face of varied and sometimes limited resources we see throughout the world. BRITTANY HARVEY: Great. And Dr. Aziz, how do you envision that these guidelines can be applied in low and middle income regions? DR. ZEBA AZIZ: These are extremely important guidelines for our part of the world. Remember that there are about 70 low-middle income countries, and all these countries-- and within each country-- there's marked variability in training of physicians who encounter cancer patients. There's also difficulty by the patients in accessing a few tertiary care centers, cancer care centers which are present, and most of all, financial implications, because you have to go there, you have to stay there, you have to get your chemotherapy, and this is true for the marginalized population. You also have to remember that more than 50% of our patients are treated in a limited resource setting, and the availability of enhanced resources are very difficult for them. And these limited settings are in public sector hospitals, where the doctors-- some of the doctors are very good, but the physicians or surgeons are overworked. They have resources ranging from minimal to moderate, depending on the funds available. And because they're overworked and there are few working hours, detailed counseling of the patient is infrequent because there are a large number of patients there. And the majority of surgeries, which is the cornerstone of ovarian cancer, is done by the postgraduate fellows who are there. Sometimes the senior consultants do surgeries, but most of the time, it is done by them. First time chemotherapy is easier to deliver because it does not have any expensive medicines. There are a lot of generics for carboplatin and taxanes regimen available, so it's not a major problem. But treating the side effects, again, becomes very expensive, and the patients have to come back and forth. The relapsed disease is very difficult to treat because we don't have too many options there and it is expensive. We've also seen that patients who are treated at an enhanced level do much better. Their survival outcomes are better, the supportive care treatment is better, and the progression-free survival is also better. BRITTANY HARVEY: Great. Thank you for reviewing that information. And then finally, Dr. Fujiwara, Dr. Aziz touched on this a bit on how it impacts patients, but how else do you view that these guideline recommendations will affect patients? DR. KEIICHI FUJIWARA: Yes. As Dr. Aziz said and Dr. Burke said, this guideline is written for the patients around the world in a different medical environment. So I think that it is very useful resource of information for patients to receive the best ovarian cancer treatment that suits the actual situation of each country or regions. BRITTANY HARVEY: Great. Well, thank you all for your work on these important guidelines. It sounds like they're going to have a real impact globally, and so I really appreciate both all of your work on these guidelines, and also for taking the time to speak with me today, Dr. Aziz, Dr. Burke, and Dr. Fujiwara. DR. ZEBA AZIZ: Thank you, Brittany. BRITTANY HARVEY: And thank you to all of our listeners for tuning in to the ASCO Guidelines Podcast Series. To read the full guideline, go to www.asco.org/resource-stratified-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO guidelines available on iTunes or the Google Play store. If you have enjoyed what you've heard today, please rate and review the podcast, and be sure to subscribe so you never miss an episode.
  • ASCO Guidelines Podcast Series podkast

    Appropriate Systemic Therapy Dosing for Obese Adult Patients with Cancer Guideline Update

    14:43

    An interview with Dr. Jennifer Griggs from University of Michigan and Dr. Gary Lyman from Fred Hutchinson Cancer Research Center & University of Washington, co-chairs on “Appropriate Systemic Therapy Dosing for Obese Adult Patients with Cancer: ASCO Guideline Update.” This guideline updates recommendations on appropriate dosing of systemic antineoplastic agents – including cytotoxic chemotherapy, checkpoint inhibitors, and targeted therapies – for obese adults with cancer. Read the full guideline at www.asco.org/supportive-care-guidelines.   TRANSCRIPT [MUSIC PLAYING] SPEAKER: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.   BRITTANY HARVEY: Hello, and welcome to the ASCO Guidelines podcast series, brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows, including this one at podcasts.asco.org. My name is Brittany Harvey, and today I'm interviewing Dr. Jennifer Griggs from the University of Michigan and Dr. Gary Lyman from Fred Hutchinson Cancer Research Center and University of Washington, co-chairs on appropriate systemic therapy dosing for obese adult patients with cancer ASCO guideline update. Thank you for being here, Dr. Griggs and Dr. Lyman.   DR. GARY LYMAN: Thank you, Brittany.   DR. JENNIFER GRIGGS: Thanks for having us.   BRITTANY HARVEY: First, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online with the publication of the guideline in the Journal of Clinical Oncology. Dr. Griggs, do you have any relevant disclosures that are directly related to this guideline topic?   DR. JENNIFER GRIGGS: No, I don't.   BRITTANY HARVEY: And Dr. Lyman, do you have any relevant disclosures related to this guideline?   DR. GARY LYMAN: I have no relevant disclosures to this guideline.   BRITTANY HARVEY: Great. Thank you, both. Then let's get into the substance of this guideline update.   So Dr. Lyman, can you explain what prompted an update to this guideline on appropriate dosing for obese adult patients with cancer last published in 2012, and what is the scope of this update?   DR. GARY LYMAN: Thank you, Brittany. Yes, this is an update of a previous guideline, several years old, that was prompted by evidence that there was wide variation in how chemotherapies at that time were being dosed, particularly in the overweight and obese population. Some were capping the dose, some were giving the full weight-based dosing, and all sorts of permutations in between. So that guideline was greeted, I think quite favorably, and, in fact, led to changes in clinical practice in many institutions and I believe also in the cooperative group research networks.   Since that time, however, a whole array of new therapies have come along. These, we'll talk about briefly in this podcast, include the novel targeted therapies based on molecular targets, as well as the new checkpoint inhibitors, and other monoclonal antibody therapies, where the dosing issues, in general, are different for many of these agents. And specifically for patients who are overweight and obese, we thought it was important that we update this guideline, review the evidence in total appropriate to the dosing of these new agents in overweight and obese patients, and make updated recommendations that would be more relevant to that practice of oncology in 2021.   BRITTANY HARVEY: Great. Thank you for explaining the previous version of the guideline and for explaining the expanded scope. So given that, I'd like to review those key recommendations made in this guideline. So Dr. Griggs, what are the recommendations regarding dosing of cytotoxic chemotherapy in obese adults with cancer?   DR. JENNIFER GRIGGS: With rare exception, we recommend, and the evidence supports, using actual body weight when we calculate doses. So whether it's just per kilogram, milligrams per kilogram for example, or per meter squared, using body surface area, we recommend that the actual body weight of the patient be used with no compromise or capping, no maximizing the dose as if it were calculated using 2 meter squared for example. There's no evidence that that's necessary to avoid side effects, and, in fact, there's increasing evidence that doing so, that limiting the doses in patients, is associated with decreased benefit of the treatment.   Since the original guideline came out, there's been no convincing evidence that has made us change our recommendation. So again, in brief, we recommend that actual body weight be used in calculating the target dose for cytotoxic chemotherapy.   BRITTANY HARVEY: Great. Thank you. That's very clear for clinicians. So Dr. Lyman, you mentioned this in your introduction to the scope of this guideline, what are the recommendations for dosing of checkpoint inhibitors and targeted therapy in obese adults with cancer?   DR. GARY LYMAN: Well, Brittany, these are the new agents that I referred to in the introduction that have appeared in broad usage in oncology and other disciplines since our 2012 guideline recommendation. Many of these are monoclonal antibodies, and they just generally have a wider therapeutic index and distribute an extracellular fluid and plasma with less correlation with body size descriptors, such as weight or body surface area. They may be, in fact, in some cases are amenable to fixed dosing schedules.   So this has all led to a whole array of new agents approved by the FDA for cancer therapies that are being dosed on a wide variety of means, some based on dosing like we have done for classical chemotherapy that Dr. Griggs discussed using body surface area, in some cases body weight, and then some being dosed base on fixed dosing-- fixed size regardless of the body size that the patient represents. So it gets a little complicated, because currently the monoclonal antibodies and many of these therapies are dosed in different ways, versus fixed dosing is recommended for some of the immunotherapies, alemtuzumab, afatinib, as well as targeted therapies like pertuzumab, which are relatively recent.   And then weight-based dosing, milligram per kilogram, is used for other checkpoint inhibitors, like ipilumumab, as well as other monoclonals like bevacizumab and trastuzumab among others. And then again some were still dosing based on body surface area, such as rituximab and cetuximab. So the bottom line is these agents will be dosed and the approved dosing by the FDA will generally be based on the schedule and dosing that was used in the pivotal clinical trials. And different companies in different disease areas have chosen different ways of dosing these.   So for us, with this guideline, and this is true of overweight and obese patients in particular, we recommend dosing these agents based on the FDA approved dose and schedule for that agent. But be aware, as I indicated, that it will vary from agent to agent and category of agent from one to the other. Because of the convenience and perhaps some safety issues related to fixed dosing, additional data has been submitted to the FDA for some agents, nivolumab, for instance, and pembrolizumab, to suggest that a different dosing schema, fixed dose schema can be used, and that has led to a modification in those dosing recommendations.   So even if you think you know, if you're not using these agents day in and day out, you really should check and make sure you're using the currently recommended dosing. And final point is, in the overweight and obese patient, any dose modification because of adverse events or scheduling changes should be applied independent of the patient's obesity or overweight status. In other words, any dose modification that you would apply a healthy weight patient is the same type of dose modification you should apply in the overweight and obese patient and not modify solely based on the patient's weight or obesity status.   BRITTANY HARVEY: Definitely. Great. That was actually going to be my next question. So Dr. Griggs, do you have anything to add about for obese adult patients with cancer who experience high grade toxicity-- should clinicians modify dosing and schedules differently than they would for non obese patients?   DR. JENNIFER GRIGGS: Well, as Dr. Lyman says, the same with checkpoint inhibitors and targeted therapies, we don't recommend and the evidence doesn't support making changes in a different way. That is, there's no interaction between obesity status and the recommendation through dose modification. So in a patient who has severe toxicity related to chemotherapy as well as the targeted agents and checkpoint inhibitors, we recommend that standard dose modifications be made, and moreover that if the patient does better that one consider dose escalation again, if there were for example another concurrent illness that might have contributed in part to the toxicity. So if that other factor resolves, let the dose be increased again to try to maintain that relative intensity dose over time that we consider ideal.   BRITTANY HARVEY: Great. Thank you for reviewing that for the cytotoxic agents in addition to the immune checkpoint inhibitors and targeted therapies. So then, Dr. Lyman, the last clinical question of this guideline-- how should body surface area be calculated?   DR. GARY LYMAN: Well, this is the issue alluding to when I mentioned that there could be safety concerns with these complex calculations. And we tried to make it simple in the guidelines. There are multiple BSA-- Body Surface Area-- calculators out there. You can search them on the web, you can go to textbooks, and there's a whole range of them.   And we actually looked at this. This goes back to the original guideline, and it holds true today, that if you compare that the dose calculated by these different calculators, it's very close to one another. So our bottom line recommendation-- if you're going to use body surface area for calculating the dose of conventional cytotoxic therapy or any of these other agents where that dosing approach is recommended, any of these calculators are going to give you a safe and hopefully effective dose of the therapy. And we don't prefer or recommend one over the other.   Again, there are many on the web. Many institutions have their preferred and may even have embedded the calculator within the EMR or computer order entry system. Many prefer the Mosteller, the Du Bois, the Boyd, there's a whole variety of these, but all of them will generally yield very similar calculations. We haven't mentioned, and just to point out, as most oncologist know certainly, is one drug group, a specific agent, carboplatin is dosed differently. And for carboplatin, we calculate the dose based on a target area under the curve and GFR, so that the Calvert formula calculates the dose differently for carboplatin. And that's for historical as well as pharmacologic reasons.   So again, as Dr. Griggs mentioned, for classical chemotherapy, body surface area is the most common one. But any of the approved calculators or available calculators will give you essentially the same dosing recommendation. And I would follow what's recommended by your institution.   BRITTANY HARVEY: OK. Well, thank you both for reviewing the key recommendations in this guideline update. So finally, Dr. Griggs, in your view, why is this guideline update important, and how will it impact both clinicians and patients with cancer?   DR. JENNIFER GRIGGS: Dr. Lyman and I have viewed this as a really important guideline and guideline update. Because, as we know, the prevalence of obesity is increasing and obesity is associated with an increase in the risk of cancer-- many cancers, not all. And moreover, people who are obese tend to have worse outcomes. And so to try to level out and keep people from systematically what we consider underdosing people who are obese with chemotherapy is very likely to improve outcomes for an important group of our patients.   In addition, the update, because it's been updated now since 2012, we have more evidence that what we're recommending, what the evidence has supported thus far historically and in trials, is actually safe. There's been no signals, in other words, that the original guideline needed to be altered for certain patients or drugs. And now, with this update, we're pretty confident, based on what we know from the FDA and clinical trials, that using actual body weight is not just appropriate, but it's also recommended. So it's an important issue for the population and for our patients, and it's important for clinicians to have the confidence to use actual body weight when calculating anticancer drug doses.   BRITTANY HARVEY: Great. Thank you, both, for all the work you did to update this evidence-based guideline and thank you for taking the time today to speak with me on the podcast, Dr. Griggs and Dr. Lyman.   DR. GARY LYMAN: Thank you, Brittany.   DR. JENNIFER GRIGGS: Thanks, Brittany. We want to thank our co-authors on the guidelines, as well as the ASCO staff for their tremendous work.   DR. GARY LYMAN: Yes, we couldn't do it without all of them, and it's a tremendous team effort.   BRITTANY HARVEY: Definitely. We thank them all as well. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast series. To read the full guideline, go to www.asco.org/supportive-care-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app, available on iTunes or the Google Play store. If you have enjoyed what you've heard today, please rate and review the podcast, and be sure to subscribe so you never miss an episode.   [MUSIC PLAYING]

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