Zosia Piotrowska, MD, MHS

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 implementing the new standard of combination therapies requires thorough patient education, prophylactic management of toxicities, and multidisciplinary support to optimize outcomes for patients with EGFR-mutant lung cancer.

Panelists discuss how optimizing treatment duration, using local therapy for oligometastatic disease, and understanding the limitations of current biomarkers are important considerations in developing effective sequencing strategies for EGFR-mutant lung cancer.

Panelists discuss how central nervous system (CNS) progression presents unique challenges in treatment decision-making, highlighting the importance of brain imaging surveillance and considering approaches that maintain CNS disease control while addressing systemic progression.

Panelists discuss how many patients never receive second-line therapy, emphasizing the critical importance of selecting the optimal first-line treatment and monitoring patients closely to identify progression early.

Panelists discuss how subsequent therapy after initial disease progression should consider patient symptomatology, biomarker testing through tissue or liquid biopsies, and potential treatment options including MET-targeted approaches or chemotherapy combinations.

Panelists discuss how quality of life considerations, including prophylactic medications to prevent dermatologic toxicities and infusion-related reactions, are crucial when implementing EGFR-targeted therapies, especially the MARIPOSA regimen.

Panelists discuss how the overall survival benefit from the MARIPOSA regimen (amivantamab plus lazertinib) with a hazard ratio of 0.75 and projected survival improvement exceeding 1 year represents a significant advancement that must be weighed against toxicity concerns.

Panelists discuss how conversations with patients about treatment options have become more complex and nuanced, requiring thorough explanation of efficacy data and adverse effects while adapting to each patient’s level of understanding and involvement.

Panelists discuss how the treatment landscape for EGFR-mutant non–small cell lung cancer has evolved with new combination therapies like osimertinib plus chemotherapy (FLAURA2) and amivantamab plus lazertinib (MARIPOSA) challenging osimertinib monotherapy as the standard of care.

Zosia Piotrowska, MD, MHS, discusses the importance of differentiating between HER2 alterations among patients with non–small cell lung cancer.

Zosia Piotrowska, MD, MHS, discusses disease factors that guide treatment decision-making and sequencing for patients with HER2-mutated NSCLC.

The panel examines which patient populations might benefit most from treatment with datopotamab deruxtecan (Dato-DXd), sacituzumab govitecan, and patritumab deruxtecan (HER3-DXd). Additionally, they explore potential sequencing strategies for these antibody-drug conjugates in second-line and later treatment settings.

Benjamin Levy, MD, compares the common toxicities associated with datopotamab deruxtecan (Dato-DXd), sacituzumab govitecan, and patritumab deruxtecan (HER3-DXd), and shares practical tips for managing these toxicities in the clinical setting to optimize patient care and minimize adverse effects.

Julia Rotow, MD, highlights and discusses other notable antibody-drug conjugate (ADC) data presented at the American Society of Clinical Oncology (ASCO) 2024 annual meeting, providing insights into the potential impact of these findings on the evolving treatment landscape for non-small cell lung cancer (NSCLC).