Critical Decision Points When Selecting EGFR-Targeted Therapy for NSCLC

Panelists discuss how, when discussing frontline regimens for EGFR-mutated non–small cell lung cancer (NSCLC), the NCCN-recommended options include osimertinib monotherapy for its targeted approach with lower toxicity; amivantamab/lazertinib combination for potentially deeper responses in specific mutations; and osimertinib with platinum-doublet chemotherapy for more aggressive disease requiring enhanced tumor control.

Panelists discuss how disease-related factors like central nervous system (CNS) involvement or specific metastatic sites can guide treatment selection, favoring agents with CNS penetration or targeted efficacy. Mutational factors, such as TP53 comutations, may impact therapy response. Patient-related aspects, including age and comorbidities, influence tolerability and regimen choice.

Panelists discuss how medical professionals use shared decision-making by aligning treatment options with patient values, discussing benefits, risks, and preferences. Patients often prioritize longest progression-free survival (PFS), lowest toxicity, and shortest infusion time. Collaborative discussions ensure personalized, evidence-based care.

Panelists discuss how medical professionals balance maximizing progression-free survival with preserving future treatment options by considering disease biology, resistance mechanisms, and patient factors. At first progression, the NCCN recommends continuing current therapy or switching to amivantamab with a platinum doublet, based on mutation status, prior response, toxicity, and patient preferences.

Panelists discuss how medical professionals consider continuing osimertinib with second-line and subsequent therapies based on disease progression, resistance mechanisms, and patient response. It may be combined with other agents or switched depending on clinical trials, biomarkers, and overall treatment goals to optimize outcomes.

Panelists discuss how, if the MARIPOSA trial shows an overall survival advantage exceeding 1 year, the amivantamab-lazertinib combination may see increased frontline use. Subsequent therapy options could include chemotherapy, targeted therapies based on resistance mechanisms, or clinical trials for emerging treatments.

Panelists discuss how various strategies have been developed to enhance the tolerability of intravenous amivantamab, including premedication, step-up dosing, and infusion rate adjustments. Adoption into clinical practice varies, with many institutions integrating these approaches to mitigate infusion-related reactions and improve patient outcomes.

Panelists discuss how emerging therapies like patritumab (a HER3-directed antibody-drug conjugate [ADC]), datopotamab (a TROP2 ADC), and ivonescimab (a PD-1/VEGF bispecific) show distinct toxicity profiles compared with existing treatments, potentially influencing earlier use. Balancing efficacy gains against toxicity risks remains critical in optimizing EGFR-mutated non–small cell lung cancer (NSCLC) treatment.