Dr Gadgeel on Long-Term Data With Amivantamab/Lazertinib in EGFR+ Advanced NSCLC

Shirish M. Gadgeel, MD, head, Division of Hematology/Oncology, associate director, Patient Experience and Clinical Care, Henry Ford Health, discusses three-year follow-up data from the phase 3 MARIPOSA study (NCT04487080), evaluating the combination of amivantamab-vmjw (Rybrevant) plus lazertinib (Lazcluze) vs osimertinib (Tagrisso) for first-line treatment of EGFR-positive advanced non–small cell lung cancer (NSCLC).

On August 20, 2024, the FDA approved amivantamab plus lazertinibin patients with locally advanced or metastatic EGFR-mutant NSCLC based on prior findings from MARIPOSA. The updated analysis that was presented at the 2024 IASLC World Conference on Lung Cancer was conducted with a median follow-up of 31.1 months.

The results showed that the intracranial progression-free survival (PFS) rate at three years was significantly higher in the combination arm (38%) compared with the osimertinib group (18%). Moreover, the median intracranial duration of response was not estimable in patients receiving amivantamab and lazertinib, while it was 24.4 months in those treated with osimertinib. Notably, 51% of patients on the combination therapy who initially responded maintained their intracranial response at three years, compared with 0% in the osimertinib group.

The study also assessed post-progression end points, revealing that the combination of amivantamab and lazertinib was associated with longer time to treatment discontinuation, time to subsequent treatment, and improved PFS2 compared with osimertinib, Gadgeel explains.

Updated overall survival (OS) data indicated a widening survival benefit favoring the combination therapy. At two years, OS rates were 74% and 69% for the amivantamab/lazertinib and osimertinib groups, respectively. At three years, this difference increased to 61% vs 53%, respectively. This shows an 8% improvement in survival favoring the combination, compared with the 5% improvement that was observed in the study’s 2-year follow-up presentation at the 2023 ESMO Congress.

Although these findings suggest that amivantamab plus lazertinib offers improved long-term outcomes over osimertinib, particularly regarding intracranial efficacy and OS, the results are still preliminary. Gadgeel concludes that a prespecified final analysis will be conducted to confirm these observations, and ongoing follow-up is critical to further elucidate the survival benefits of this combination in EGFR-mutant advanced NSCLC.