OncLive Insights

Dr. Jonathan Riess from UC Davis Comprehensive Cancer Center moderated a discussion with Dr. Mary Jo Fidler from Rush University Medical Center and Dr. Matthew Gumbleton from Huntsman Cancer Institute on first-line treatment selection and proactive toxicity management for patients with EGFR-mutated non-small cell lung cancer (NSCLC).

With two combination regimens now demonstrating overall survival benefit over osimertinib monotherapy, including amivantamab-lazertinib (MARIPOSA) and osimertinib plus carboplatin-pemetrexed (FLAURA2), the discussion addresses how to individualize frontline EGFR-mutated NSCLC treatment selection based on TP53 co-mutation status, CNS metastases, and patient-specific factors. The COCOON dermatologic prophylaxis protocol, COPERNICUS study design, subcutaneous amivantamab, dose modification strategies, and patient education frameworks are covered in depth. Two clinical scenarios illustrate shared decision-making for a never-smoking woman with TP53 co-mutation and a patient with CNS metastases, with closing practice pearls emphasizing frontline treatment intensification for the majority of patients with EGFR-mutated advanced NSCLC.

Two medical oncologists recording at the 2026 World Conference on Lung Cancer (WCLC) in Seoul use new evidence as a way into 2 biomarkers in non-small cell lung cancer (NSCLC). The program covers what EGFR and KRAS G12C results tell a clinician beyond treatment selection, the EGFR result at progression and the updated HARMONi overall survival analysis, AMIGO-1 and COPERNICUS data, EGFR and central nervous system disease, KRAS G12C in practice and neoadjuvant NAUTIKA1 data, broad molecular profiling from diagnosis, and closing clinical pearls.

Edgardo Santos, MD, FACP, FASCO, of Starling Oncology, and Wade Iams, MD, MSCI, of Tennessee Oncology, work through how they choose among first-line options for EGFR exon 19 deletion and L858R advanced non–small cell lung cancer. Both favor a combination regimen over third-generation tyrosine kinase inhibitor monotherapy, citing the overall survival advantage seen with amivantamab plus lazertinib in MARIPOSA and with platinum-based chemotherapy plus osimertinib in FLAURA2. Dr Santos cites 3-year intracranial progression-free survival of 36% with the combination vs 18% with osimertinib in MARIPOSA as the reason he favors it when brain metastases are present. Dr Iams describes the pragmatic COPERNICUS study, which pairs every-4-week subcutaneous amivantamab with prophylactic anticoagulation and enhanced dermatologic prophylaxis, and reports rash falling from roughly 50% to 60% down to 20% to 30%. Dr Santos details his day 1 order set, and across 2 cases the faculty weigh brain metastases, chronic kidney disease, prior thrombosis, travel distance, and patient preference.

Dr. Roy Herbst from Dartmouth Cancer Center and Dr. Samuel Kareff from Lynn Cancer Institute discuss how emerging long-term survival data are reshaping treatment decisions across the continuum of EGFR-mutated non-small cell lung cancer (NSCLC), from the adjuvant setting through metastatic disease management.

Two clinical scenarios are discussed. The first presents a patient with resected early-stage EGFR exon 19 deletion NSCLC who received immunotherapy before molecular results returned, illustrating the pitfalls of acting on PD-L1 status alone and the importance of completing next-generation sequencing before initiating systemic therapy. The second presents a patient with metastatic EGFR-mutated NSCLC and central nervous system metastases, exploring frontline combination therapy selection, local consolidative therapy considerations, post-progression biopsy strategy, and resistance mechanisms including small cell transformation and MET amplification. The 8-year ADAURA overall survival data, adjuvant osimertinib treatment adherence strategies, neoadjuvant approaches, and future directions including vaccines and leptomeningeal disease management are discussed throughout.

This OncLive® Insights program explores evolving approaches to the management of multiple myeloma across frontline and early relapse settings, with a focus on practical considerations for advanced practice providers. Jill Burke, NP, and Tanika Pittman, APRN, discuss the growing role of quadruplet regimens in newly diagnosed multiple myeloma, including patient selection, treatment goals, multidisciplinary assessment, and strategies for educating patients and caregivers. The discussion also addresses treatment duration, toxicity monitoring, infection prevention, supportive care, adherence, shared decision-making, and the role of minimal residual disease assessment in communicating treatment response. Faculty share practical perspectives on anti-CD38 therapy administration, subcutaneous delivery options, clinic workflow, and reducing treatment burden. The conversation then transitions to early relapse, highlighting individualized treatment selection, sequencing considerations, and preparation for teclistamab plus daratumumab, including step-up dosing, safety monitoring, infection risk, and care coordination. The program concludes with practical clinical pearls on the evolving role of APPs in multiple myeloma care.

Treatment of EGFR-mutated advanced non-small cell lung cancer has moved well past a single tyrosine kinase inhibitor, and the decisions have grown correspondingly harder. This series works through them in sequence. It opens with risk stratification, including how often TP53 co-mutations appear and what they should change, then examines the clinical and molecular factors that determine whether a patient starts on monotherapy or a combination, weighing tumor burden and metastatic sites against age, comorbidities, and what a patient is willing to accept. Second-line discussion covers platinum rechallenge, the choice between datopotamab deruxtecan and amivantamab plus chemotherapy in the absence of a head-to-head trial, and what emerging antibody-drug conjugate combinations would need to demonstrate to change practice. Later segments turn to the toxicities that actually interrupt treatment, the multidisciplinary support required to manage them, and the testing, trial access, and reimbursement barriers that shape care outside academic centers.

Dr. Sandip Patel (UC San Diego, Moores Cancer Center) and Dr. Deborah Doroshow (Tisch Cancer Center, Icahn School of Medicine at Mount Sinai) take a practical look at how treatment selection and sequencing are evolving in advanced EGFR-mutated non-small cell lung cancer (NSCLC). The discussion covers frontline regimen selection between osimertinib monotherapy, FLAURA2, and MARIPOSA, including the role of clinical features, ctDNA, CNS metastases, TP53 co-mutation, and treatment burden. The experts review subcutaneous amivantamab and the COCOON regimen, sequential planning across lines, second-line options including COMPEL and MARIPOSA-2, the role of Dato-DXd and ADC toxicity management, MET-directed resistance, and key takeaways on precision diagnostics and treatment tolerability. Tailored for community and academic oncologists, BCOPs, and the multidisciplinary thoracic oncology team.

In this OncLive® Insights program, Dr. Joshua Richter and Dr. Doris Hansen discuss the evolving role of CAR T-cell therapy in early relapsed/refractory multiple myeloma, with a focus on treatment sequencing, patient selection, bridging therapy, and emerging cellular therapy approaches. The experts examine how the expanding availability of BCMA-directed CAR T-cell therapies and bispecific antibodies is influencing treatment decisions at first relapse, including considerations around using CAR T-cell therapy earlier in the disease course. They discuss the importance of early referral to cellular therapy centers, appropriate patient selection, and disease control before CAR T-cell infusion. The conversation also explores how bridging therapy can help optimize patients for treatment, including strategies to balance disease control, T-cell fitness, efficacy, and toxicity risk. Dr. Richter and Dr. Hansen further address treatment sequencing following CAR T-cell therapy and consider emerging approaches such as dual-target CAR T-cell therapies, GPRC5D-directed cellular therapies, in vivo CAR T-cell platforms, and allogeneic CAR T-cell therapies.

Three transplant physicians examine unmet needs in allogeneic stem cell transplantation, review Precision-T data, and discuss patient selection, reduced-intensity conditioning, and GVHD prevention and management strategies.

This OncLive® Insights program explores how real-world evidence (RWE) is shaping the use of CAR T-cell therapy in relapsed or refractory large B-cell lymphoma (LBCL). Dr. Megan Melody, Dr. Miguel-Angel Perales, and Dr. Nirav Shah discuss the evolving role of the three FDA-approved CD19-directed CAR T-cell therapies, including their positioning across the second- and later-line settings and how RWE complements pivotal clinical trial data. The panel examines how clinicians can use real-world data to assess CAR T-cell candidacy beyond traditional trial eligibility criteria, considering age, comorbidities, performance status, disease burden, geriatric vulnerabilities, and practical support systems. The discussion also addresses timely referral, bridging therapy, site-of-care considerations, outpatient delivery, and post-infusion logistics. Throughout the program, the experts highlight how RWE can support individualized treatment decisions and help clinicians identify the right patient for CAR T-cell therapy at the right time.

This OncLive Insights program brings together Dr. Hans Lee, Dr. Muhamed Baljevic, and Dr. Prashant Kapoor to discuss the rapidly evolving treatment landscape in multiple myeloma and its implications for clinical practice. The panel examines how advances in quadruplet regimens, CAR T-cell therapy, bispecific antibodies, and emerging immune-based approaches are reshaping treatment strategies across newly diagnosed and relapsed/refractory multiple myeloma. The discussion explores treatment sequencing, continuous versus fixed-duration therapy, de-escalation, MRD-guided decision-making, and the balance between disease control, treatment-related toxicity, quality of life, and patient preferences. The experts also address supportive care and strategies to mitigate infections and cytokine release syndrome, approaches to improving access to T-cell-engaging therapies in community settings, and considerations for sequencing therapies after BCMA-directed treatment. Looking ahead, the panel considers emerging targets, trispecific antibodies, in vivo CAR T-cell approaches, CELMoDs, and other developments that may further transform multiple myeloma management.

Eric Whitman, MD, and Gino K. In, MD, MPH, discuss how they select and sequence immunotherapy in advanced cutaneous squamous cell carcinoma, from high-risk resected disease through unresectable disease, using two patient cases to illustrate how comorbidities and transplant status shape treatment decisions.

This OncLive® Insights program examines the evolving role of supportive care in extensive-stage small cell lung cancer (ES-SCLC), with a focus on the clinical burden of chemotherapy-induced myelosuppression (CIM) and its impact on treatment delivery, patient outcomes, and quality of life. Megan May, PharmD, moderates a multidisciplinary discussion with Taylor Praska, PharmD, and Amanda Edmond, PA-C, who explore the challenges associated with hematologic toxicities and the limitations of traditional reactive supportive care approaches. The panel discusses the scientific rationale for proactive myeloprotection, including the mechanism of action and clinical evidence supporting trilaciclib, while reviewing its potential role in preserving bone marrow function during platinum-etoposide-containing chemotherapy. Practical insights are shared on patient selection, treatment planning, workflow integration, multidisciplinary collaboration, and patient education, alongside emerging real-world evidence evaluating hospitalization rates, healthcare resource utilization, and quality-of-life outcomes. Throughout the discussion, the faculty emphasize individualized supportive care strategies that help maintain treatment continuity, minimize chemotherapy-related complications, and optimize the overall care experience for patients with ES-SCLC.

In this OncLive® Insights program, Dr. Joshua Richter and Dr. Marco Davila provide an evidence-based discussion on the evolving management of relapsed/refractory multiple myeloma (RRMM), with a focus on optimizing treatment selection, sequencing, and personalized patient care. The conversation explores how recent clinical evidence is influencing earlier integration of advanced therapies, while emphasizing patient identification, disease risk assessment, and individualized treatment planning. Dr. Richter and Dr. Davila discuss practical considerations that extend beyond efficacy data, including appropriate timing of referral to specialized centers, multidisciplinary collaboration, bridging therapy, and coordination between community and academic practices. Through case-based discussions, they examine real-world approaches to managing patients with standard-risk and high-risk disease, highlighting factors that influence therapeutic decision-making across different clinical scenarios. The program also addresses patient quality of life, caregiver engagement, and remaining challenges in improving access to innovative therapies, providing clinicians with practical, balanced insights for delivering personalized care to patients with relapsed/refractory multiple myeloma.

In this OncLive® News Network program, Dr. Mark Socinski and Dr. Susan Scott discuss the evolving treatment landscape for patients with EGFR-mutant non-small cell lung cancer (NSCLC), highlighting recent advances that are reshaping treatment selection across the continuum of care. The discussion explores emerging clinical evidence supporting first-line treatment strategies, interpretation of progression-free and overall survival outcomes, and considerations for treatment sequencing following disease progression. Drs. Socinski and Scott also examine patient- and disease-specific factors that influence therapeutic decision-making, approaches to managing treatment-related adverse events, and practical strategies for maintaining treatment continuity in clinical practice. Additional topics include mechanisms of resistance, molecular reassessment at progression, the role of emerging therapies, multidisciplinary care, and the impact of treatment complexity, access, and financial burden on patient-centered management of EGFR-mutant NSCLC, with an emphasis on translating evolving evidence into everyday clinical practice.

Sandip Patel, MD, and Chul Kim, MD, review ASCO data on TP53 co-mutations, the TOP study, frontline therapy selection, and treatment sequencing strategies for patients with EGFR-mutated advanced non-small cell lung cancer.

This OncLive® Insights program features Dr. Sonya Reid and Dr. Allison DiPasquale discussing the evolving role of genomic testing in early-stage hormone receptor-positive, HER2-negative breast cancer and its integration into contemporary clinical practice. The faculty examine how multigene assays complement traditional clinicopathologic factors to support individualized treatment planning, improve risk stratification, and guide adjuvant therapy decisions. The discussion reviews the clinical impact of landmark studies, including TAILORx and RxPONDER, and explores how these data have influenced treatment recommendations for node-negative and node-positive disease. Dr. Reid and Dr. DiPasquale also share practical perspectives on incorporating genomic testing into multidisciplinary care, interpreting recurrence scores, selecting and applying available genomic assays in different clinical scenarios, communicating results with patients, and balancing evidence-based recommendations with real-world clinical decision-making. The program concludes with key insights into the future of precision medicine and ongoing research aimed at further personalizing treatment for patients with early-stage breast cancer.

In this program moderator Dr. Eric Winer and expert Dr. Ruta Rao address specific clinical questions regarding the optimal management of high-risk patients. The core inquiries focus on how to select appropriate candidates for adjuvant CDK4/6 inhibitor therapy, exploring the balance between strict trial eligibility criteria and real-world clinical judgment. The discussion addresses questions regarding the optimal timing of treatment initiation following surgery or chemotherapy, and how treatment delays alter clinical decisions. The faculty also discuss how to interpret and compare efficacy data from major trials, specifically examining how differences in trial design and treatment duration affect patient care. Significant focus is placed on patient safety, detailing how to monitor and manage toxicities like neutropenia and gastrointestinal issues through dose modifications to support long-term adherence. Finally, the conversation uses targeted questions within case-based scenarios, contrasting early and delayed treatment starts, to explore how physicians can individualize risk assessments, navigate ongoing clinical uncertainties, and balance recurrence risk reduction with patient quality of life.

In this OncLive® My Treatment Approach program filmed at the 2026 ASCO Annual Meeting, Drs. Daniel Ahn and Midhun Malla examine the evolving first-line treatment landscape for metastatic pancreatic ductal adenocarcinoma. The discussion opens with how the FDA approval of NALIRIFOX has reshaped treatment selection and how clinicians differentiate it from FOLFIRINOX across mechanism of action, tolerability, and long-term survival outcomes from the NAPOLI 3 trial. Two patient cases ground the evidence in clinical reality, a 67-year-old male with KRAS G12D and liver metastases and a 54-year-old female with germline BRCA2 and KRAS G12V, exploring dose modification strategies, UGT1A1 considerations, performance status preservation, and molecularly informed sequencing. The program closes with a forward-looking discussion of the landmark RASolute 302 results for daraxonrasib presented at this meeting, the emerging KRAS-targeted sequencing story, and practical implementation guidance for community oncologists managing this challenging disease.

Dr. Timothy Cloughesy from UCLA and Dr. Ugur Sener from Mayo Clinic discuss the evolving treatment landscape for IDH-mutant gliomas, focusing on vorasidenib, the first FDA-approved targeted therapy for grade 2 IDH-mutant gliomas.

The INDIGO trial demonstrated remarkable efficacy with vorasidenib versus placebo, showing a hazard ratio of 0.4 and extending median progression-free survival from 11.1 to 27.7 months at initial analysis. Updated data presented at ASCO 2026 reveals even more encouraging results with estimated progression-free survival reaching 44 months and only 28% of patients requiring subsequent radiation or chemotherapy.

Key discussion points include patient selection criteria, optimal timing for treatment initiation, duration of therapy, and practical management considerations. The panelists emphasize that IDH-mutant gliomas represent a distinct disease entity affecting younger patients who typically present with seizures and face decades of disease management.

The program addresses real-world clinical scenarios through case-based discussions, highlighting the paradigm shift from watchful waiting to early targeted intervention, particularly for astrocytomas which demonstrate more aggressive behavior than oligodendrogliomas.

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.