Helena A. Yu, MD

Experts discuss the persistent challenges in EGFR-mutated non–small cell lung cancer , including central nervous system (CNS) progression and treatment sequencing, emphasizing the urgent need for more transformative strategies beyond current combination regimens, greater inclusion of complex patient populations in trials, and the critical role of comprehensive biomarker testing and shared decision-making in delivering personalized, future-forward care.

Experts discuss the expanding treatment landscape for EGFR-mutated non–small cell lung cancer (NSCLC), highlighting emerging strategies beyond tyrosine kinase inhibitors (TKIs)—including novel immunotherapy combinations and antibody-drug conjugates (ADCs)—with particular interest in bispecific antibodies and TROP2-directed ADCs that may offer new options for patients progressing on targeted therapy, despite ongoing challenges in translating immune-based approaches into consistent survival gains.

Experts discussed how, despite several new third-generation EGFR tyrosine kinase inhibitors (TKIs) in development, the real progress in treating EGFR-mutant lung cancer is likely to come from combination therapies rather than new monotherapies, emphasizing the need for treatments that deliver meaningful improvements over current standards rather than just incremental changes.

Resistance management in EGFR-mutant lung cancer relies on both liquid and tissue biopsies to guide therapy, with careful interpretation of molecular findings and multidisciplinary collaboration essential to balancing precision medicine advances against patient safety and evidence-based care.

Experts shared that while amivantamab combined with chemotherapy in MARIPOSA- 2 can cause challenging toxicities, careful dose adjustments, premedication, and vigilant monitoring help manage adverse effects and support continued treatment.

Experts highlight evolving evidence that continuing EGFR tyrosine kinase inhibitors (TKIs) with chemotherapy after progression may improve outcomes, but emphasize that treatment sequencing decisions must be personalized based on emerging data, patient factors, and drug availability.

Experts discuss the promise of subcutaneous (SubQ) amivantamab in improving logistical efficiency and reducing infusion-related reactions in the MARIPOSA regimen, while emphasizing that chronic toxicities persist regardless of administration route, underscoring the ongoing need for proactive monitoring, supportive care, and close clinical oversight.

Experts discuss the cumulative toxicities of pemetrexed in the FLAURA2 regimen, emphasizing the need for personalized, flexible approaches to maintenance therapy duration that balance ongoing efficacy with tolerability, guided by patient-specific factors and real-world clinical experience.

Experts discuss the critical role of toxicity management in deciding whether to use amivantamab/lazertinib up-front or in later lines, highlighting the need for intensive supportive care, coordinated care teams, and structured patient education to navigate the regimen’s unique and often burdensome adverse effect profile.

Experts discuss the comparative merits of FLAURA2 and MARIPOSA frontline regimens for EGFR-mutant non–small cell lung cancer, noting similar survival benefits but highlighting key differences in toxicity profiles, supportive care demands, and real-world practicality that make individualized patient counseling essential to treatment selection.

Experts discuss the vital role of shared decision-making in lung cancer treatment, emphasizing personalized, ongoing conversations that align therapy choices with patients’ values, quality-of-life considerations, and life circumstances to support informed and compassionate care.

Experts discuss a key finding from FLAURA2 showing that many patients never reach second-line therapy, reinforcing the importance of delivering the most effective treatment—such as combination therapy—up-front, particularly when patients are fit, as real-world barriers and rapid progression may limit later opportunities for intervention.

Experts discuss the slow but growing real-world adoption of combination therapy for EGFR-mutant non–small cell lung cancer (NSCLC) despite strong FLAURA2 survival data, citing factors such as clinical inertia, comfort with monotherapy, and regional practice variations, while anticipating broader uptake as confidence, education, and infrastructure catch up with the evolving standard of care.

Experts discuss the gap between current clinical guidelines and emerging trial data in EGFR-mutant lung cancer, highlighting calls to elevate combination therapies in treatment recommendations following robust survival benefits, while underscoring the continued importance of individualized care and patient-centered flexibility in frontline decision-making.

Experts discuss the evolving role of combination therapy in frontline treatment for EGFR-mutated metastatic lung cancer, emphasizing that while survival data from FLAURA2 support broader use beyond traditionally defined high-risk groups, real-world factors and patient preferences continue to necessitate individualized, shared decision-making.

Experts discuss emerging consensus around the value of combination therapy in EGFR-mutated metastatic NSCLC, highlighting practice-changing overall survival data from FLAURA2 and emphasizing how intensified upfront treatment may now redefine the standard of care despite added complexity and toxicity.

Panelists discuss how despite recent advances in first-line treatments, unmet needs remain. These include better personalized care, community education, understanding resistance mechanisms, central nervous system (CNS) metastases management, and development of novel therapies such as antibody-drug conjugates.

Panelists discuss how a 45-year-old anxious patient who refused chemotherapy was successfully treated with amivantamab plus lazertinib along with prophylactic management strategies for potential adverse effects.

Panelists discuss how a 56-year-old patient with high-risk disease features was successfully treated with osimertinib plus chemotherapy, achieving excellent response before eventually discontinuing pemetrexed maintenance while continuing osimertinib.

Panelists discuss how the FLAURA2 pemetrexed exposure subanalysis showed that patients could benefit from the regimen even if they didn't complete the full maintenance period as prescribed in the trial.

Panelists discuss how FLAURA2 maintenance therapy strategies involve monitoring patients for toxicities and implementing dose modifications or schedule adjustments to improve tolerability.

Panelists discuss how quality-of-life (QoL) considerations and individual toxicity profiles significantly impact first-line (1L) treatment decisions, with different regimens having distinct adverse effect profiles.

Panelists discuss how disease characteristics such as central nervous system (CNS) metastases can influence treatment decisions, with both FLAURA2 and MARIPOSA trials showing superior outcomes for patients with brain metastases when using combination therapies.

Panelists discuss how patient-centered factors are crucial in shared decision-making for first-line (1L) treatment, with a potential default approach of offering combination therapy with an option to choose osimertinib monotherapy.

Panelists discuss how explaining survival benefits to patients must be tailored to individual goals and expectations, with many patients having specific life milestones they hope to reach.

Panelists discuss how treatment choice involves weighing quality of life against treatment burden, considering factors such as hospital visits for infusions vs oral medications at home.

Panelists discuss how health care providers and patients view survival differently, with providers being more data driven and patients focusing on living with minimal symptoms and maintaining quality of life.

Panelists discuss how overall survival is an important but not the only consideration in treatment decision-making, with factors such as patient characteristics, disease burden, and quality of life also being critical.

Panelists discusses how the MARIPOSA trial demonstrated significant survival improvement with amivantamab plus lazertinib versus osimertinib alone in EGFR-mutant NSCLC, showing a hazard ratio of 0.75 and an expected 12-month survival benefit that could potentially change the natural history of this disease.

Panelists discuss the increasing complexity in treatment decision-making for EGFR-mutant non–small cell lung cancer (NSCLC) with multiple frontline options now available.