S16 Ep40: FDA Approval Insights: Zongertinib for HER2 TKD–Mutated NSCLC: With Julia Rotow, MD; and Martin Dietrich, MD, PhD

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 Neil M. Iyengar, MD, an associate professor and co-director of Breast Medical Oncology in the Department of Hematology and Medical Oncology at the Emory University School of Medicine, as well as the director of Survivorship Services at the Winship Cancer Institute of Emory University in Atlanta, Georgia.Their conversation centered around lifestyle and medical interventions pertinent to breast cancer survivorship. Dr Iyengar explained that although endocrine therapies can be life-saving, they disrupt estrogen signaling, which can lead to cardiometabolic dysfunction, including increased risks for diabetes, heart disease, and bone health issues. He noted that weight gain associated with these treatments is often tied to the induction of a post-menopausal state, which disrupts energy homeostasis and promotes inflammation.A key theme of the conversation was Dr Iyengar’s explanation of a "drug development paradigm" for lifestyle changes. Rather than offering generic advice, his research focuses on precision lifestyle interventions, treating diet and exercise as prescribed medical therapies with specific "doses". He highlighted that body mass index (BMI) is an insufficient tool for risk stratification, as high body fat despite a normal BMI is a significant risk factor for cancer recurrence.The discussion also covered the rising use of GLP-1 receptor agonists to manage metabolic health. These drugs replicate natural hormones to maintain glycemic balance and reduce hunger. Dr Iyengar addressed the black box warning for thyroid cancer associated with this class of drugs, noting that although the data are mixed, the protective benefits against obesity-related cancers appear to outweigh the risks. Finally, he emphasized that exercise is a critical tool for managing treatment adverse effects like fatigue, noting that although starting is difficult, the "return on investment" for patient health is immense.

Welcome to OncLive On Air®! I’m your host today, Kyle Doherty.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, we spoke with David Morris, MD, FACS, and Alan H. Bryce, MD. Dr Morris is the president of Urology Associates, PC, in Nashville, Tennessee. Dr Bryce is a medical oncologist and the chief clinical officer of City of Hope Cancer Center Phoenix in Arizona.In our exclusive interview, Drs Morris and Bryce discussed the clinical implications of the FDA’s full approval of rucaparib (Rubraca) for BRCA mutation–associated metastatic castration-resistant prostate cancer (mCRPC), including the notable data that supported the regulatory decision and how this agent fits into the mCRPC treatment paradigm.

From Discovery to Delivery: Charting Progress in Gynecologic Oncology, hosted by Ursula A. Matulonis, MD, brings expert insights into the most recent breakthroughs, evolving standards, and emerging therapies across gynecologic cancers. Dr Matulonis is chief of the Division of Gynecologic Oncology and the Brock-Wilcon Family Chair at the Dana-Farber Cancer Institute, as well as a professor of medicine at Harvard Medical School, both in Boston, Massachusetts.In this episode, Dr Matulonis sat down with guest Katharine M. Esselen, MD, MBA. Dr Esselen is an attending gynecologic oncologist at Beth Israel Deaconess Medical Center and an assistant professor of obstetrics, gynecology, and reproductive biology at Harvard Medical School in Boston. Drs Matulonis and Esselen explored the growing effect of financial toxicity in gynecologic oncology, emphasizing how economic burden can influence access to care, treatment adherence, and patient outcomes. Dr Esselen, whose research focuses on patient-centered outcomes and value-based care, highlighted that financial toxicity extends beyond direct medical costs to include indirect burdens such as lost wages, childcare needs, transportation, and basic living expenses. To address these challenges, Dr Esselen and her colleagues developed a financial navigation program at Beth Israel Deaconess Medical Center. This initiative includes systematic screening for financial concerns and dedicated support from a financial navigator who connects patients with resources such as insurance optimization, transportation assistance, and financial aid programs. Implementation of this program significantly increased identification of at-risk patients and improved access to supportive services.Importantly, Drs Matulonis and Esselen emphasized that financial toxicity is not only a quality-of-life issue but also a clinical one. Studies show that patients experiencing high financial burden are more likely to delay or forgo care and less likely to adhere to prescribed treatments, which may ultimately affect survival outcomes. Drs Matulonis and Esselen concluded the discussion by outlining the steps that can be taken to reduce financial burden on patients, underscoring the need for proactive screening, multidisciplinary support, and systemic change.

In this podcast, experts Carrie L. Kitko, MD; Miguel-Angel Perales, MD; and Amandeep Salhotra, MD, discuss GVHD prophylaxis strategies and therapies to address treatment-naive and steroid-refractory chronic GVHD.

In today’s episode, we spoke with Ticiana Leal, MD, about variability in community practice and evolving treatment strategies for patients with small cell lung cancer (SCLC). Dr Leal is a professor and director of the Thoracic Medical Oncology Program in the Department of Hematology and Medical Oncology at Emory University School of Medicine, as well as the medical director of the Clinical Trials Office at Winship Cancer Institute in Atlanta, Georgia.In our exclusive interview, Dr Leal began by discussing how SCLC management can differ widely across community settings according to how patients present. Leal emphasized the importance of quickly confirming a patient’s diagnosis and initiating treatment to avoid missing the critical window where chemotherapy could provide meaningful clinical benefit. However, Leal noted that the field still lacks predictive biomarkers to guide treatment selection. Accordingly, current strategies, including chemoimmunotherapy, maintenance approaches, and second-line options like tarlatamab-dlle (Imdelltra) and lurbinectedin (Zepzelca) are largely chosen based on clinical factors such as disease burden, comorbidities, and patient preferences.The conversation then shifted to the challenge of treating patients who may not meet traditional clinical trial eligibility criteria due to poor performance status, comorbidities, or social vulnerabilities. Leal stated that a multidisciplinary approach, including collaboration with supportive care teams, is essential to optimize outcomes for these patients. She noted that potential solutions to restrictive trial eligibility criteria may include decentralizing trials, improving collaboration between academic and community centers, and providing additional patient support such as transportation and care navigation services.Looking ahead, Leal emphasized the need for community practices to prepare for emerging therapies, including antibody-drug conjugates and novel immunotherapy approaches. Successfully integrating these treatments into everyday practice will require education, infrastructure development, and multidisciplinary collaboration, Leal imparted.

In today’s episode, we spoke with Julia Rotow, MD, and Martin Dietrich, MD, PhD. Dr Rotow is the clinical director of the Lowe Center for Thoracic Oncology and director of clinical research at Dana-Farber Cancer Institute, as well as an assistant professor of medicine at Harvard Medical School in Boston, Massachusetts. Dr Dietrich is a medical oncologist with The US Oncology Network Cancer Care Centers of Brevard and an assistant professor of internal medicine at the University of Central Florida College of Medicine in Orlando.In our exclusive interview, Drs Rotow and Dietrich discussed the significance of the accelerated FDA approval of zongertinib (Hernexeos) for patients with HER2 TKD–mutated non–small cell lung cancer (NSCLC). They highlighted how this approval addresses a longstanding unmet need in a patient population that historically relied on chemotherapy-based approaches.They noted that the introduction of zongertinib into the frontline setting represents a meaningful shift toward upfront biomarker-driven care, aligning HER2-positive disease with other oncogene-driven lung cancers where targeted therapies are used upfront.The discussion also focused on efficacy findings from the pivotal phase 1b Beamion LUNG-1 trial (NCT04886804). In previously untreated patients with HER2 TKD mutations, zongertinib generated an objective response rate of 76% (95% CI, 65%-85%). The treatment also showed encouraging durability, with 64% of responders having a duration of response (DOR) lasting at least 6 months and 44% of responders having a DOR lasting at least 12 months. Regarding safety, Rotow and Dietrich explained that zongertinib was designed as a HER2-selective inhibitor, potentially minimizing off-target EGFR-related toxicities. The most common adverse effects included low-grade diarrhea, rash, and liver enzyme elevations, with interstitial lung disease occurring infrequently. Notably, no significant signal for cardiac toxicity was observed, distinguishing zongertinib from some other HER2-directed therapies. Finally, the experts underscored the importance of comprehensive biomarker testing to identify HER2 alterations and ensure that patients can benefit from these expanding targeted treatment options.

In today’s episode, we spoke with Misty D. Shields, MD, PhD, about the realities of treating patients with small cell lung cancer (SCLC) in the community setting and how emerging therapies are shaping care delivery. Dr Shields is a translational medical oncologist at Indiana University Health in Indianapolis. In our exclusive interview, Dr Shields highlighted the urgency associated with SCLC treatment, an aggressive malignancy that often presents with rapid symptom onset and widespread metastases. The conversation also underscored the importance of multidisciplinary care. This approach is especially critical in light of expanded treatment options such as chemoimmunotherapy regimens, second-line therapies including tarlatamab-dlle (Imdelltra) and lurbinectedin (Zepzelca), along with clinical trials evaluating antibody-drug conjugates and radioligand therapies.From a practical standpoint, integrating these therapies into the community setting presents logistical challenges. Shields noted that although immunotherapy has been rapidly adopted since its introduction into standard care around 2019, newer agents require additional infrastructure. Education gaps remain another key issue. The growing availability of clinical trials and new treatment strategies makes it essential to guide patients through potential care pathways, helping them understand options across the first-line, maintenance, and relapsed settings.Looking ahead, molecular characterization may play a larger role in shaping treatment strategies. Ongoing research efforts, including cooperative group studies, aim to determine whether these subtypes can guide more personalized treatment approaches in the future. The discussion concluded with a call for continued infrastructure development in community oncology. 

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.