EGFR-mutated NSCLC: Evolving Treatment Landscape

At ASCO 2025, experts in thoracic oncology gathered to discuss advances in EGFR-mutant non-small cell lung cancer (NSCLC), particularly first-line treatment strategies. Patients with EGFR mutations often present with unique characteristics—many are younger, fitter, and highly informed—which requires a nuanced and personalized treatment approach. Key goals at diagnosis include achieving a rapid and deep response, maximizing durability of benefit, and preserving quality of life over years of treatment. This makes early toxicity management and patient education essential to optimize outcomes.

The treatment landscape has significantly expanded. Osimertinib monotherapy remains a widely used standard due to its ease of administration and favorable progression-free survival (PFS) of about 19 months. However, two new combination regimens have entered practice. One pairs osimertinib with chemotherapy (carboplatin and pemetrexed), supported by the FLAURA2 trial showing a hazard ratio of 0.65 for improved PFS. The other combines amivantamab, a bispecific EGFR/MET antibody, with lazertinib, a third-generation EGFR TKI, as studied in the MARIPOSA trial. Both regimens offer extended disease control, prompting oncologists to consider patient-specific factors when choosing among these options.

Despite the progress, several unmet needs remain. Clinicians still lack clear guidance on which patients benefit most from intensified combinations versus monotherapy, especially among those with lower disease burden or asymptomatic presentations. Additionally, current data heavily focus on classical EGFR mutations (exon 19 deletions and L858R), leaving a gap in evidence for rarer or atypical mutations. Moving forward, further research is needed to refine treatment selection, improve outcomes for underrepresented mutation subtypes, and explore strategies like chemotherapy de-escalation or incorporation of novel agents to reduce toxicity while preserving efficacy.