OncLive Insights

Dr. Neeraj Agarwal (Huntsman Cancer Institute) and Dr. Alicia Morgans (Dana-Farber Cancer Institute) examine EZH2 inhibition as an investigational strategy in androgen receptor pathway inhibitor (ARPI)-resistant metastatic castration-resistant prostate cancer (mCRPC). The discussion explores the canonical and non-canonical roles of EZH2 in prostate cancer biology, including its function as a histone methyltransferase and as a co-activator of the androgen receptor (AR), and the rationale for combining EZH2 inhibitors with enzalutamide. The experts review early-phase efficacy and safety data for mevrometostat plus enzalutamide and detail the design of the phase 3 MEVPRO-1 and MEVPRO-2 trials, including patient populations, eligibility, endpoints, and dosing. Practical guidance is provided on adverse event management, trial referral pathways, patient communication about investigational therapy, and contextualizing mevrometostat among other EZH2-directed strategies. Tailored for genitourinary oncologists, urologists, and the multidisciplinary team.

In this OncLive® My Treatment Approach program, Wade Iams, MD, MSCI, is joined by Matthew Gumbleton, MD, PhD, and Estelamari Rodriguez, MD, MPH, for an in-depth discussion on navigating the evolving first-line treatment landscape in EGFR-mutant metastatic non–small cell lung cancer. The panel reviews key evidence from pivotal phase III trials, including MARIPOSA and FLAURA2, comparing combination strategies such as amivantamab plus lazertinib and chemotherapy plus osimertinib against osimertinib monotherapy. Topics include CNS disease management, TP53 co-mutation as a high-risk feature, and practical strategies for managing dermatologic toxicity, VTE prophylaxis, and dose modifications. Two illustrative patient cases anchor the discussion, highlighting how disease burden, molecular profile, patient priorities, and logistical considerations together shape individualized treatment decisions in clinical practice.

In this OncLive Insights program, Anwaar Saeed, MD, and Daniel Ahn, MD, review the treatment landscape for refractory non-MSI-high metastatic colorectal cancer, discuss the biologic rationale for combining multi-kinase inhibition with immune checkpoint blockade, and examine efficacy, safety, and clinical positioning data from the phase 3 STELLAR 303 trial of zanzalintinib plus atezolizumab, along with future directions including the STELLAR 316 study in minimal residual disease.

Dr. Nicole Shonka of Nebraska Medicine and Dr. Robert Chong of UCLA Health discuss the evolving care of high-grade glioma in adults and children, focusing on the distinction between glioblastoma, isocitrate dehydrogenase (IDH) wild-type, and diffuse midline glioma (DMG), H3 K27-altered, under the 2021 World Health Organization (WHO) classification. They review imaging clues, essential molecular workup, and the August 2025 accelerated US Food and Dr.ug Administration (FDA) approval of dordaviprone (Modeyso) for recurrent H3 K27M-mutant DMG in patients 1 year of age and older. Discussion covers dordaviprone’s mechanism, the 22% overall response rate (ORR) from a 5-trial integrated analysis, weekly oral dosing and safety, sequencing at progression, response assessment with Response Assessment in Neuro-Oncology (RANO) 2.0, and patient communication.

Dr. Marin Xavier from Scripps Cancer Center and Dr. Raji Shameem from Orlando Health Cancer Institute discussed evolving second-line treatment strategies for chronic lymphocytic leukemia (CLL) following prior covalent BTK inhibitor therapy. The discussion emphasized how recent clinical trial data, particularly the BRUIN CLL-321 study, have reshaped sequencing decisions with pirtobrutinib (LOXO-305) now approved for second-line treatment after covalent BTK inhibitor exposure.

Two patient scenarios illustrated common scenarios: disease progression with acquired resistance mutations (BTK C481S, TP53) and treatment intolerance due to cardiac toxicities. The CLL-321 trial demonstrated pirtobrutinib’s efficacy with 14-month median progression-free survival versus 8.7 months for investigator's choice, including sustained benefits in venetoclax-exposed and TP53-aberrant populations.

Dr. Eric Singhi (MD Anderson) and Dr. Chinmay Jani (University of Miami) as they explore biomarker-driven management in advanced NSCLC. The session emphasizes best practices in biomarker testing, optimal timing, tissue-based versus ctDNA approaches, and the value of repeat testing at progression, while addressing real-world institutional barriers to comprehensive molecular profiling. The experts dissect how key biomarkers inform treatment sequencing and decision-making, including KRAS mutation subtypes and their therapeutic implications, STK11 and MTAP as modifiers of immunotherapy response, the evolution of EGFR resistance, and emerging targets such as TROP2. The discussion also covers unmet needs, notably MET amplification as a resistance mechanism after osimertinib and how serial liquid biopsies and complex genomic patterns may be integrated into clinical choice. Tailored for community and academic oncologists and multidisciplinary teams, the program aims to sharpen precision biomarker strategies in everyday practice for better patient outcomes.

Dr. Pankit Vachhani from the University of Alabama at Birmingham and Dr. Firas El Chaer from Miami Cancer Institute discussed key considerations in managing polycythemia vera (PV), including thrombotic risk assessment and treatment decision-making across the disease course. The discussion emphasized moving beyond traditional binary risk stratification (age >60 years, prior thrombosis) to comprehensive assessment incorporating white blood cell count control, symptom burden, and disease-modifying therapy selection.

Two real-world patient scenarios illustrated evolving management approaches: a 54-year-old initially low-risk patient requiring frequent phlebotomies despite hydroxyurea, and a 68-year-old with progressive splenomegaly and rising white blood cell counts despite hematocrit control. Both cases demonstrated hydroxyurea resistance/intolerance requiring treatment escalation.

Clinical Considerations:

• Frequent phlebotomies (>3 annually) indicate cytoreductive therapy failure requiring reassessment
• White blood cell count >11,000 represents independent thrombotic risk factor necessitating treatment optimization
• Symptom burden assessment using MPN10/MPNSAF tools guides therapy decisions
• ROPEG interferon alfa-2b and ruxolitinib offer event-free survival advantages as second-line therapies
• Hematocrit <45% represents minimum control standard, not comprehensive disease management goal

This program will examine how the evolving first-line landscape, informed by clinical trial evidence and emerging data, is shaping expectations around response, durability, and long-term outcomes. Expert panelists will discuss how clinicians interpret key trial results, integrate multiple therapeutic options into practice, and navigate treatment selection across diverse patient populations. The session will also explore real-world considerations, sequencing strategies, and ongoing clinical trials that may influence future approaches to care.

Explore evolving clinical considerations in relapsed and refractory multiple myeloma, drawing on recent clinical trial data, real-world evidence, and insights from major scientific meetings, including ASH 2025.

Dr. Anand Patel from the University of Chicago and Dr. Cecilia Arana Yi from Mayo Clinic Phoenix discussed the evolving treatment landscape for relapsed/refractory NPM1-mutated acute myeloid leukemia (AML). The conversation emphasized comprehensive disease re-characterization at relapse, including repeated molecular testing, fitness assessment, and transplant candidacy evaluation to guide treatment selection between intensive chemotherapy, lower-intensity approaches, or targeted therapies.

Key discussions centered on menin inhibitors (revumenib and ziftomenib) as breakthrough targeted therapies, demonstrating 23% to 25% complete remission rates in heavily pretreated patients with manageable toxicity profiles. The speakers highlighted differentiation syndrome as the primary adverse effect requiring proactive monitoring and cytoreductive strategies using hydroxyurea for high white blood cell counts.

Panelists discuss clinical decision-making in EGFR-mutated non-small cell lung cancer, focusing on how emerging data are shaping treatment selection, risk–benefit assessment, and sequencing across lines of therapy, including monotherapy versus combination strategies, key efficacy and safety considerations, biomarker testing such as MET alterations, the emerging role of TROP2-directed antibody–drug conjugates, and the impact of subcutaneous administration on treatment burden and patient experience, with the goal of providing practical, evidence-informed insights to support clinical decision-making.

Dr. Irene Kang from City of Hope Orange County and Dr. Megan Kruse from Cleveland Clinic reviewed transformative advances in HER2- and TROP2-directed antibody drug conjugates (ADCs) across breast cancer subtypes. The discussion emphasized 2025 and 2026 as a boom period with ADCs expanding from later-line HER2-positive therapy to cornerstone treatments across hormone receptor-positive, triple-negative, and early-stage disease settings.

Key clinical updates included DESTINY-Breast09 challenging the CLEOPATRA standard in first-line HER2-positive metastatic disease, brain metastases management advances through DESTINY-Breast12, and early-stage integration via DESTINYBreast-05 and -11. TROP2-targeted therapy selection focused on toxicity differentiation between sacituzumab govitecan and datopotamab deruxtecan, with practical scheduling and side effect management considerations driving decisions.

Triple-negative breast cancer advances featured ASCENT-04 establishing sacituzumab govitecan plus pembrolizumab as first-line standard for PD-L1-positive disease, whereas ASCENT-03 and TROPION-Breast02 provided options for PD-L1-negative patients. Future priorities include developing alternative payload ADCs, investigating combination strategies, and understanding resistance mechanisms through ongoing translational research and real-world sequencing studies to optimize treatment paradigms.

In this discussion, experts will focus on the evolving management of smoldering multiple myeloma, with emphasis on how advances in risk stratification are influencing clinical decision-making. We will review the evidence for early therapeutic intervention versus active monitoring, drawing from recent clinical trials and guideline recommendations. The experts will also address practical considerations for applying these data in real-world practice, including patient selection, safety, and implications for long-term treatment sequencing, with the goal of providing a balanced, evidence-based perspective on patient care.

This expert-led oncology program features Dr. Edgardo Santos and Dr. Gilberto Lopes, who provide a clinicalvly focused discussion on therapeutic advances in HER2-mutated non–small cell lung cancer (NSCLC). Drawing from a recent workshop, the discussion synthesizes emerging clinical trial data, evolving treatment paradigms, and real-world decision-making considerations in this molecular subset of NSCLC. The faculty contextualize HER2 as a distinct actionable driver, emphasizing differences from HER2-positive breast cancer and outlining implications for biomarker testing, sequencing strategies, and patient selection.

Key themes include the integration of HER2-targeted antibody-drug conjugates (ADCs), interpretation of efficacy and safety data, and challenges in optimizing first-line versus later-line therapy. Drs. Santos and Lopes also explore CNS activity, resistance mechanisms, and future directions in clinical research. The program is designed to support oncologists in translating rapidly evolving HER2 NSCLC data into evidence-based clinical practice.

This OncLive Insights program featured Drs. Lori Muffly and Jae Park discussing CAR T-cell therapy evolution in relapsed/refractory acute lymphoblastic leukemia (ALL). Key topics included individualized treatment sequencing considering prior therapy history, disease burden, and transplant candidacy rather than algorithmic approaches. The physicians addressed common concerns about inotuzumab veno-occlusive disease risk and CAR T-transplant sequencing, emphasizing that CAR T should not be limited to non-transplant candidates.

Durability assessment varies by product, with minimal residual disease negativity and B-cell aplasia serving as indicators for 4-1BB-containing products, whereas persistence monitoring provides additional guidance. Toxicity profiles differ significantly between brexucabtagene autoleucel (brexucel) and obecabtagene autoleucel (obe-cel), with the latter demonstrating substantially lower severe cytokine release syndrome and neurotoxicity rates, expanding treatment candidacy.

Future directions focus on moving CAR T-cells to earlier treatment lines as definitive therapy, reducing chemotherapy exposure duration. Emerging innovations include CD7 CARs for T-cell ALL addressing critical unmet needs, and in vivo CAR development improving patient access through reduced hospitalization and collection requirements while maintaining efficacy.

In this OncLive My Treatment Approach discussion, expert panelists review the practical integration of bispecific antibodies into the management of relapsed or refractory B-cell lymphomas, with a focus on real-world implementation, safety management, and care coordination. The conversation explores how clinicians discuss treatment goals with patients, including expected response rates, durability of benefit, and quality-of-life considerations associated with immunotherapy-based approaches.

Panelists outline key operational considerations for administering bispecific antibodies, including infusion-center preparation, staff training, and multidisciplinary coordination among physicians, pharmacists, nurses, and emergency care teams. A substantial portion of the discussion addresses safety management, particularly the recognition and treatment of cytokine release syndrome and neurologic toxicities, as well as strategies for infection prevention and monitoring.

The experts also emphasize the importance of communication between academic and community practices to maintain continuity of care as patients transition between treatment settings. Finally, the panel discusses emerging data and ongoing clinical trials evaluating bispecific antibodies in combination regimens and earlier lines of therapy, highlighting their growing role in the lymphoma treatment landscape.

This OncLive® Insights program explored emerging innovations in biomarker-driven care for non–small cell lung cancer (NSCLC), with a focus on quantitative continuous scoring (QCS) technology and the TROP2 normalized membrane ratio (NMR) as potential tools to improve patient selection for TROP2-directed antibody-drug conjugates (ADCs). The discussion highlighted the importance of comprehensive molecular testing using tissue and liquid next-generation sequencing alongside immunohistochemistry within a multidisciplinary workflow. Traditional TROP2 expression methods have limited predictive value, as clinical benefit appears to depend not only on surface expression but also on intracellular processing and drug internalization. TROP2 NMR, a computational pathology-derived metric incorporating membrane and cytoplasmic localization, has demonstrated promising retrospective associations with improved outcomes. Experts emphasized the need for prospective validation, standardization, and scalable implementation. If confirmed, QCS-based approaches could expand beyond TROP2 to other biomarkers, supporting a broader transition toward digital, quantitative pathology and more precise, biology-driven treatment decisions.

This discussion focuses on the evolving role of first line maintenance therapy in extensive stage small cell lung cancer, with focused discussion of the phase 3 IMforte trial evaluating atezolizumab plus lurbinectedin. Faculty review efficacy data, safety considerations, patient selection, management of brain metastases, and case based decision making to contextualize how maintenance strategies are being integrated into contemporary practice.

This OncLive Insights program reviews the rapidly expanding role of antibody-drug conjugates (ADCs) across the breast cancer continuum and their growing impact on clinical decision-making. In early-stage HER2-positive disease, emerging data from DESTINY-Breast trials support the movement of trastuzumab deruxtecan into neoadjuvant and adjuvant settings for selected high-risk patients, while highlighting the need for careful toxicity monitoring. In metastatic HER2-positive disease, ADCs are moving into the first-line setting with evolving strategies for treatment duration and maintenance. For hormone receptor–positive HER2-low disease, ADCs have redefined classification and earlier treatment sequencing, with additional agents providing options after chemotherapy. In metastatic triple-negative breast cancer, multiple ADCs, either alone or combined with immunotherapy, are reshaping first-line care. Across subtypes, key challenges include optimal sequencing, cumulative toxicity management, and patient selection. Looking ahead, next-generation ADCs, biomarker-driven strategies, and treatment de-escalation approaches are expected to further personalize therapy and improve outcomes.

This program focuses on integrating emerging oral selective estrogen receptor degraders (SERDs) into the treatment of ER-positive, HER2-negative metastatic breast cancer. Drs. Jason Mouabbi and Aditya Bardia review current and investigational agents such as elacestrant, imlunestrant, camizestrant, giredestrant, and others, emphasizing differences in tolerability and side-effect profiles. Oral SERDs are generally better tolerated than traditional endocrine therapies, with side effects ranging from gastrointestinal discomfort to bradycardia and visual disturbances, highlighting the importance of aligning therapy choice with patient lifestyle and preferences. Combination strategies with targeted therapies, including CDK4/6 inhibitors and everolimus, show enhanced efficacy but require careful consideration of overlapping toxicities. Using a case-based approach, the program demonstrates practical decision-making, including sequencing, monitoring with scans, tumor markers, and plasma-based genotyping, and underscores the role of patient-centered care. The overarching takeaway is the critical importance of molecular testing to identify ESR1 and other actionable mutations, enabling personalized, effective, and safe therapy selection.

Experts review recent evidence shaping prostate cancer care, including emerging survival data, sion outcomes, and findings across biochemical recurrence and metastatic castration-sensitive prostate cancer.

Experts discuss practical management considerations, including patient selection for monotherapy, long term tolerability, fatigue management strategies, and the role of exercise in supporting patients on therapy.

Experts explore how alterations within the PI3K/AKT/PTEN pathway influence treatment decisions in HR+/HER2-negative advanced breast cancer, and we will take a focused look at strategies for managing key adverse events associated with therapies targeting this pathway, including diarrhea, hyperglycemia, and rash.

Experts integrate perspectives from medical oncology, pharmacy, and advanced practice nursing to review practical approaches to patient education, monitoring, and supportive care, along with considerations that support treatment adherence and improve patient experience.

Breast cancer experts discuss how long-term data from the monarchE and NATALEE trials inform patient selection, drug choice, and real-world use of adjuvant CDK4/6 inhibitors in high-risk HR-positive, HER2-negative early breast cancer.

Experts examine the evolving role of TROP2 in non–small cell lung cancer, highlighting the limitations of conventional IHC and the potential of quantitative continuous scoring (QCS) and normalized membrane ratio (NMR) as more reliable, predictive biomarkers for TROP2-directed antibody–drug conjugates.

This OncLive Insights program features Drs. Sandip Patel and Jonathan Riess in an in-depth discussion on current and emerging strategies for managing HER2-mutated non-small cell lung cancer (NSCLC). The experts review the evolving diagnostic landscape, emphasizing the importance of comprehensive molecular testing, both tissue and plasma, to identify HER2 mutations and HER2 IHC 3+ overexpression. They examine the clinical integration of targeted therapies including trastuzumab deruxtecan (T-DXd), zongertinib, and the recently reported sevabertinib, highlighting their efficacy, safety profiles, and roles across lines of therapy. Key challenges are addressed, such as CNS metastases, sequencing uncertainty, toxicity monitoring, and the need for resistance-based treatment strategies. The discussion concludes with a forward-looking perspective on next-generation HER2 inhibitors, ADC development, CNS-penetrant agents, and opportunities to advance care through clinical trials and real-world evidence.

This OncLive Insights program features Dr Hatim Husain and Dr Surbhi Singhal discussing how genomic testing guides modern lung cancer care from diagnosis through treatment selection and monitoring. The panel reviews the roles of tissue biopsy, liquid biopsy, and next generation sequencing, highlighting how timing, test choice, and test limitations affect clinical decisions. Using real world examples, they show how molecular profiling, ctDNA, and emerging biomarkers help personalize therapy, track resistance, and improve patient outcomes, while also addressing cost, access, and future directions in precision oncology.

In this OncLive® PV Insights program, expert faculty discuss recent advances in the management of polycythemia vera, with a focus on expanding the definition of disease control beyond hematologic parameters. The conversation highlights evolving perspectives on symptom burden, thrombotic risk, iron regulation, and emerging therapies, including insights from recent clinical trials. Faculty also explored how clinicians can integrate patient experience, functional outcomes, and molecular insights into real world treatment decisions to improve long term patient outcomes in PV.