S16 Ep35: T-DXd Trials Transform Treatment for HER2-Positive Breast Cancer: With Sara Nunnery, MD, MSCI; and Kelly E. McCann, MD, PhD

In this podcast, experts Narjust Florez, MD, FASCO; David Carbone, MD, PhD; and Edward Garon, MD, MS; discuss the use of KRAS-, NRG1-, MET-, and ROS1-targeting agents to transform patient care in advanced non–small cell lung cancer (NSCLC).

In today’s episode, we sat down with John Marshall, MD, and Christopher Lieu, MD, to discuss the clinical relevance of KRAS G12C and pan-RAS inhibitors in the management of pancreatic and colorectal cancers. Dr Marshall is chief of Hematology and Oncology, a professor of medicine and oncology, and director of the Otto J Ruesch Center for the Cure of Gastrointestinal Cancers at the Georgetown Lombardi Comprehensive Cancer Center in Washington, DC. Dr Lieu is a professor of medicine, associate director for Clinical Research, and co-director of Gastrointestinal Medical Oncology at the University of Colorado Anschutz and the University of Colorado Cancer Center in Aurora. In our exclusive interview, the experts highlighted historical challenges in targeting RAS mutations, as well as recent breakthroughs. They also emphasized the importance of testing early for biomarkers like Claudin 18.2, PD-L1, HER2, and microsatellite instability in patients with gastroesophageal cancers. Furthermore, the experts discussed the need to use targeted therapies early in treatment to avoid treatment resistance, and noted the potential of novel RAS inhibitors and immunotherapies. Their conversation also touched on the importance of rebiopsy and the challenges of obtaining sufficient tissue for biomarker analysis.

Breast Cancer Briefing, hosted by Sara Nunnery, MD, MSCI, a breast medical oncologist and the director of Breast Cancer Research at Tennessee Oncology in Nashville, is a podcast series that breaks down the latest news in breast cancer research, one conversation at a time.In today's episode, filmed live onsite at the 43rd Annual Miami Breast Cancer Conference, Dr Nunnery sat down with Kelly E. McCann, MD, PhD, a breast medical oncologist in the University of California system.Their conversation centered around the evolving HER2-positive breast cancer treatment paradigm. The experts highlighted that although this disease was once associated with a poor prognosis, targeted therapies like trastuzumab (Herceptin) have revolutionized management, making these cancers highly curable.They noted the role of fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu), an antibody-drug conjugate (ADC) that delivers chemotherapy directly to cancer cells and uses a bystander effect to kill neighboring malignant cells. The phase 3 DESTINY-Breast11 trial (NCT05113251) evaluated T-DXd in the neoadjuvant setting for patients with high-risk, HER2-positive early breast cancer. Results showed significantly higher pathological complete response rates with T-DXd followed by docetaxel, trastuzumab, and pertuzumab (Perjeta) compared with standard chemotherapy. Responses were even more pronounced in patients with hormone receptor–negative disease.Furthermore, they spotlighted the phase 3 DESTINY-Breast05 trial (NCT04622319), which examined T-DXd as adjuvant therapy for high-risk patients with residual HER2-positive disease. In this study, T-DXd generated an improvement in invasive disease–free survival compared with standard ado-trastuzumab emtansine (Kadcyla). They noted that a significant benefit of T-DXd is its ability to cross the blood-brain barrier, offering the potential for preventing brain metastases. However, the experts expressed caution regarding interstitial lung disease, a potentially fatal adverse effect associated with T-DXd. Because of this risk, patients who receive T-DXd require frequent, expensive CT monitoring, which Nunnery and McCann explained can pose logistical and insurance challenges in standard practice.Although adjuvant T-DXd has been added to the National Comprehensive Cancer Network Clinical Practice Guidelines for HER2-positive breast cancer, the neoadjuvant regimen has not yet been included, likely awaiting more mature survival data. Both oncologists conclude that although ADC-associated toxicities require vigilant management, these treatment advancements provide powerful new tools for potentially curing high-risk patients with HER2-positive breast cancer.

In today’s episode, Jae Park, MD, discussed all things CAR T-cell therapy in acute lymphoblastic leukemia (ALL), touching on topics like where this treatment modality fits into the ALL paradigm, how it affects clinical practice, and how to go about selecting between the multiple FDA-approved options. Dr Park is the chief of the Cellular Therapy Service at Memorial Sloan Kettering Cancer Center in New York, New York. In our exclusive interview, Dr Park began with a conversation about the November 2024 FDA approval of obecabtagene autoleucel (obe-cel; Aucatzyl) and the October 2021 FDA approval of brexucabtagene autoleucel (brexu-cel; Tecartus) for patients with ALL. He explained how these CAR T-cell therapies fit into the ALL treatment paradigm for patients who have relapsed disease. After weighing how the safety and efficacy of each therapy stack up against others, Dr Park then discussed analyses that have come out after the obe-cel approval and their effect on obe-cel usage. Dr Park pointed out real-world studies presented at the 2025 ASH Annual Meeting, as well as analyses of the phase 1/2 FELIX trial (NCT04404660), which supported the approval of obe-cel. Finally, Dr Park looked ahead to the future of CAR T-cell therapies for ALL, noted in which settings he believes this class of agents will see the most use, and explained how to make treatment selections between therapies like brexu-cel and obe-cel.  

Welcome to OncLive On Air®! I’m your host today, Ashling Wahner.OncLive On Air is a podcast from OncLive®, which provides oncology professionals with the resources and information they need to provide the best patient care. In both digital and print formats, OncLive covers every angle of oncology practice, from new technology to treatment advances to important regulatory decisions.In today’s episode, Marina Baretti, MD, discussed the real-world utilization of tissue-free circulating tumor DNA (ctDNA) monitoring in cholangiocarcinoma (CCA). Baretti is an assistant professor and the Jiasheng Chair in Hepato-Biliary Cancer Research at Johns Hopkins University School of Medicine, as well as co-director of the Liver and Biliary Cancer Multidisciplinary Clinic at the Sidney Kimmel Comprehensive Cancer Center in Baltimore, Maryland. In the exclusive interview, Dr Baretti discussed multiple potential roles for ctDNA testing in CCA management, including the detection of minimal residual disease following curative-intent surgery, longitudinal monitoring of treatment response in advanced disease, and identification of emergent resistance mechanisms with targeted therapy.Baretti also reviewed findings from a small real-world observational analysis of 44 patients, in which a tissue-free ctDNA assay demonstrated high sensitivity, detecting variant allele frequencies as low as 0.2% and identifying actionable alterations in most patients; ctDNA dynamics also correlated with response and enabled early detection of resistance alterations, including secondary FGFR2 mutations, prior to radiographic progression in select cases.Lastly, Baretti contextualized these findings within the broader treatment landscape by reviewing data from the phase 2 FIGHT-202 trial (NCT02924376), which supported the FDA approval of pemigatinib (Pemazyre) in patients with previously treated CCA harboring FGFR2 fusions or rearrangements. Real-world data have confirmed the efficacy and safety of this agent observed in clinical trials, reinforcing the importance of comprehensive molecular profiling._____That’s all we have for today! Thank you for listening to this episode of OncLive On Air. Check back throughout the week for exclusive interviews with leading experts in the oncology field.For more updates in oncology, be sure to visit www.OncLive.com and sign up for our e-newsletters.OncLive is also on social media. On X and BlueSky, follow us at @OncLive. On Facebook, like us at OncLive, and follow our OncLive page on LinkedIn.If you liked today’s episode of OncLive On Air, please consider subscribing to our podcast on Apple Podcasts, Spotify, and many of your other favorite podcast platforms,* so you get a notification every time a new episode is posted. While you are there, please take a moment to rate us!Thanks again for listening to OncLive On Air.*OncLive On Air is available on: Apple Podcasts, Spotify, CastBox, Podcast Addict, Podchaser, RadioPublic, and TuneIn.This content is a production of OncLive; this OncLive On Air podcast episode is supported by funding, however, content is produced and independently developed by OncLive.

Two Onc Docs, hosted by Samantha A. Armstrong, MD, and Karine Tawagi, MD, is a podcast dedicated to providing current and future oncologists and hematologists with the knowledge they need to ace their boards and deliver quality patient care. Dr Armstrong is a hematologist/oncologist and assistant professor of clinical medicine at Indiana University Health in Indianapolis. Dr Tawagi is a hematologist/oncologist and assistant professor of clinical medicine at the University of Illinois in Chicago.In this episode, OncLive On Air® partnered with Two Onc Docs to spotlight the most practice-informing data to come out of the 2026 Genitourinary Cancers Symposium.In prostate cancer, the phase 3 PEACE-3 trial (NCT02194842) demonstrated a clear overall survival (OS) benefit with the combination of radium-223 and enzalutamide (Xtandi) compared with enzalutamide alone in patients with metastatic castration-resistant prostate cancer (mCRPC). The phase 2 BRCAAway trial (NCT03012321) showed that for patients with mCRPC with BRCA1/2 or ATM mutations, combination therapy with olaparib (Lynparza) and abiraterone led to a longer median progression-free survival (PFS) than sequential treatment. Additionally, the POSEIDON meta-analysis indicated that short-term hormone therapy is adequate for most patients with prostate cancer receiving postoperative radiotherapy, as longer durations did not improve OS.In bladder cancer, the phase 3 KEYNOTE-B15 trial (NCT04700124) showed that neoadjuvant enfortumab vedotin-ejfv (Padcev) combined with pembrolizumab (Keytruda) significantly improved OS and event-free survival vs neoadjuvant chemotherapy in cisplatin-eligible patients with muscle-invasive bladder cancer, despite notable toxicities like skin and ocular adverse effects. Furthermore, the phase 2 RC48G001 trial (NCT04879329) found that disitamab vedotin (RC48) generated responses in patients with metastatic urothelial carcinoma, including those with HER2-low expression.Regarding renal cell carcinoma (RCC), the phase 3 LITESPARK-011 trial (NCT04586231) showed a PFS benefit with belzutifan plus lenvatinib vs cabozantinib in the second-line setting. In the adjuvant setting, the phase 3 LITESPARK-022 study (NCT05239728) demonstrated that adding belzutifan (Welireg) to pembrolizumab improved disease-free survival vs placebo plus pembrolizumab in patients with resected clear cell RCC.Finally, regarding testicular cancer, a phase 2 trial (NCT04876456) of cabozantinib showed meaningful activity in patients with relapsed/refractory germ cell tumors. Drs Armstrong and Tawagi noted that this marks the first nonchemotherapy agent to demonstrate such clinical benefit in this population, providing a new option for patients who have exhausted traditional treatment regimens.

In today’s episode of OncLive On Air®, Jonathan Trent, MD, PhD, and Neeta Somaiah, MD, sat down to discuss the evolving role of circulating tumor DNA (ctDNA) testing in gastrointestinal stromal tumors (GIST), as well as the importance of identifying both initial drivers of disease and secondary resistance mechanisms when approaching frontline treatment selection and overall therapeutic sequencing.Trent is a professor of medicine, associate director of Clinical Research, and director of the Sarcoma Medical Research Program at the University of Miami Miller School of Medicine, in Florida. Somaiah is a professor and chair of the Department of Sarcoma Medical Oncology in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center in Houston.Drs Trent and Somaiah began their discussion by highlighting the rarity of GIST, underscoring the importance of evaluation at specialized sarcoma centers and comprehensive molecular testing to identify driver alterations.Somaiah then reviewed the molecular landscape of GIST, noting that approximately 70% to 80% of tumors harbor activating mutations in the KIT gene, while additional cases involve rarer alterations such as BRAF or NTRK fusions. Of note, resistance to imatinib (Gleevec) frequently emerges through secondary mutations in KIT exons 13 or 17, which can influence sensitivity to subsequent TKIs.ctDNA testing may help detect these resistance mechanisms, particularly at progression or when tissue is limited, enabling clinicians to refine sequencing strategies, both experts explained. They also discussed how mutation-informed approaches may guide treatment selection, including emerging strategies such as combining sunitinib (Sutent) with bezuclastinib to address resistant clones involving KIT exon 13 or 17 alterations.This content is a production of OncLive; this OncLive On Air podcast episode is supported by funding, however, content is produced and independently developed by OncLive.

In today’s episode, we welcomed Wendy Stock, MD, to discuss key recommendations from the ASH 2026 Guidelines for Frontline Management of Acute Lymphoblastic Leukemia (ALL) in Adolescents and Young Adults, which were published in February. Stock is the Anjuli Seth Nayak Professor of Medicine at University of Chicago Medicine and co-leader of the Clinical and Experimental Therapeutics research program at the University of Chicago Medicine Comprehensive Cancer Center in Illinois.In our exclusive interview, Dr Stock explained how specialists, including hematologists, adolescent/young adult (AYA) psychosocial care specialists, pharmacists, methodologists, and patient representatives, contributed to the formation of the ASH AYA ALL guidelines, discussed key recommendations in the guidelines supported by evidence, and detailed how these guidelines can aid in AYA ALL management.

In today’s episode, we spoke with Colin Vale, MD. Dr Vale is an assistant professor in the Department of Hematology and Medical Oncology at the Emory University School of Medicine in Atlanta, Georgia.In our exclusive interview, Dr Vale discussed data from a phase 2 trial (NCT03263572) evaluating blinatumomab (Blincyto) plus ponatinib (Iclusig) in patients with Philadelphia chromosome–positive B-cell acute lymphoblastic leukemia. In addition to underscoring the findings and their clinical significance, Vale expanded on how the combination can improve patient quality of life by helping patients avoid procedures like allogeneic stem cell transplant.

In this podcast, experts Naval Daver, MD; Courtney DiNardo, MD; and Eunice Wang, MD; discuss the rationale for treatment with menin inhibitors—and the data showing their efficacy and safety—in acute myeloid leukemia (AML).