Frontline Treatment Selection in EGFR-Mutated Non-Small Cell Lung Cancer: Monotherapy Versus Combination Strategies

Dr. Ticiana Leal introduces the discussion on treatment selection and sequencing in EGFR-mutated advanced non-small cell lung cancer (NSCLC), emphasizing that biomarker testing results must be available before initiating any frontline treatment discussion. With osimertinib monotherapy, osimertinib plus chemotherapy, and amivantamab plus lazertinib all now guideline-recommended, she reviews the comparative efficacy data driving patient discussions.

In the FLAURA trial, osimertinib monotherapy achieved median progression-free survival (PFS) of 18.9 months and median overall survival (OS) of 38.6 months. In FLAURA2, adding chemotherapy to osimertinib improved median PFS to 25.5 months and median OS to 47.5 months, with 4-year survival probability of 49% versus 41% for monotherapy and an updated OS hazard ratio of 0.7; these benefits were consistent across EGFR exon 19 deletion and L858R subgroups and regardless of baseline brain metastases. In MARIPOSA, amivantamab plus lazertinib achieved median PFS of 23.7 months with OS not yet reached but projected to exceed 1 year of improvement (hazard ratio 0.75), with benefit maintained across high-risk prognostic subgroups.

Dr. Leal notes that although osimertinib monotherapy retains NCCN Category 1 and ASCO preferred status, over 90% of patients have at least 1 high-risk feature associated with greater relative benefit from combination therapy. She reserves monotherapy primarily for patients without high-risk features, with lower disease burden, or with a strong personal preference for a less intensive regimen, while emphasizing that treatment decisions require balanced discussion incorporating patient goals and quality of life alongside efficacy data.