Luis E Raez, MD, FASCO, FACP

Luis E. Raez, MD, and Suresh S. Ramalingam, MD, FACP, FASCO, sit down with Chandler Park, MD, FACP, and Eric K. Singhi, MD, to discuss the latest abstracts in lung cancer presented during the International Association for the Study of Lung Cancer 2025 World Conference on Lung Cancer.

Panelists discussed that despite advances in targeted therapies for EGFR-mutant lung cancer, challenges remain around defining meaningful clinical endpoints, improving access to molecular testing and treatments, expanding trial eligibility for high-risk patients, exploring curative approaches in select cases, and emphasizing personalized strategies with ongoing patient-centered care and education.

Panelists discussed that consolidation osimertinib after chemoradiation significantly improves progression-free survival in unresectable stage III EGFR-mutant NSCLC, neoadjuvant osimertinib plus chemotherapy shows promise in early-stage disease, and new antibody-drug conjugates offer effective, better-tolerated options after progression on osimertinib and chemotherapy.

Panelists discussed that although a HER3-targeted ADC showed limited benefit and lost FDA approval, emerging therapies like new ADCs, bispecific antibodies, and personalized sequencing based on molecular testing are expanding treatment options for EGFR-mutant NSCLC resistant to TKIs.

Luis E. Raez, MD, FACP, FASCO, dives into evolving practices in molecular testing for patients with lung cancer.

Panelists discuss that when patients progress after frontline osimertinib without histologic transformation or secondary drivers, treatment options include switching to chemotherapy combined with targeted agents like anti-MET antibodies, considering toxicity and patient tolerance, while molecular testing guides sequencing decisions—especially in cases with MET amplification—and that after newer combination regimens, biopsy and personalized approaches remain essential for optimizing therapy and managing side effects.

Panelists discuss that after progression on frontline therapy, treatment decisions hinge on prior regimens, progression patterns, and detailed molecular profiling—including tissue biopsy to detect transformations and resistance mechanisms like MET or HER2 alterations—with sequencing strategies tailored accordingly and clinical trial enrollment encouraged for patients without clear targets.

Panelists discuss that managing systemic progression in EGFR-mutant lung cancer requires thorough molecular profiling via tissue and liquid biopsies to identify resistance mechanisms like histologic transformation and MET amplification, with comprehensive testing guiding next-line targeted therapies or clinical trial enrollment to optimize patient outcomes.

Panelists discuss that resistance to frontline osimertinib is diverse, involving on-target mutations like C797S, MET amplification, and small cell transformation, highlighting the need for tissue biopsies alongside liquid biopsies to guide treatment, and note that newer combination therapies such as Mariposa may reduce certain resistance mutations and alter tumor evolution, offering hope for improved outcomes.

Panelists discuss that the Cocoon trial’s four-part prophylactic regimen—including oral antibiotics, clindamycin topical treatment, nail toxicity prevention, and ceramide-based lotions—significantly reduces skin toxicities like scalp rashes in EGFR inhibitor therapies, emphasizing the importance of patient and provider education to ensure adherence and improve treatment tolerability.

Panelists discuss that the skipper regimen—a prophylactic dexamethasone schedule started days before infusion—has significantly reduced infusion-related reactions from about 66% to 22%, improving patient comfort and clinic workflow while emphasizing ongoing education and early management to ensure safety.

Panelists discuss that chemotherapy plus osimertinib requires managing early hematologic toxicities and EGFR-related rash and diarrhea with close monitoring, while the bispecific antibody regimen involves proactive prevention of infusion reactions, anticoagulation for VTE risk, and intensive rash management to support treatment adherence and patient quality of life.

Panelists discuss the evolving safety profiles of first-line EGFR-mutated lung cancer treatments, highlighting that chemotherapy combinations cause expected hematologic toxicities and fatigue, while bispecific antibody regimens bring unique challenges such as infusion reactions, more severe rashes and diarrhea, peripheral edema, and a notably increased risk of venous thromboembolism that warrants prophylactic anticoagulation and careful patient monitoring.

Panelists discuss the critical role of regular brain MRI monitoring in EGFR-mutant lung cancer, balancing timely detection of intracranial progression with the risks of early radiation; they emphasize individualized treatment sequencing guided by progression patterns and resistance profiling through biopsies and liquid biopsies to optimize patient outcomes.

Panelists discuss the evolving management of CNS metastases in EGFR-mutant lung cancer, highlighting how third-generation TKIs and combination regimens from the FLORA and Mariposa trials delay CNS progression and reduce new brain metastases, supporting a shift away from upfront radiation in asymptomatic patients.

Panelists discuss how the availability of three frontline options for EGFR-mutant NSCLC has complicated treatment selection, prompting highly individualized, hour-long consultations that balance disease biology, patient values, and the trade-offs between monotherapy and combination regimens.

Panelists discuss the Mariposa trial’s landmark overall survival benefit with amivantamab plus lazertinib over osimertinib monotherapy in EGFR-mutant NSCLC, marking a paradigm shift toward durable survival and reinforcing the value of optimized patient selection and adherence to combination regimens.

Panelists discuss how the FLAURA2 trial has reshaped EGFR-mutant NSCLC treatment by demonstrating meaningful progression-free survival gains with osimertinib plus chemotherapy, while emphasizing the importance of protocol adherence, long-term outcome potential, and the ongoing pursuit of curative strategies.

Panelists discuss evolving first-line strategies for EGFR-mutant NSCLC, highlighting the expanding role of combination regimens, CNS efficacy, and the need for personalized treatment selection and toxicity management, especially in younger, well-informed patients.