Dr Cho on First-Line Amivantamab Plus Lazertinib in EGFR-Mutant NSCLC

Byoung Chul Cho, MD, PhD, professor, Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea, discusses key findings from the phase 3 MARIPOSA study (NCT04487080) of first-line amivantamab-vmjw (Rybrevant) plus lazertinib (Laclaza) vs osimertinib (Tagrisso) in EGFR-mutant locally advanced or metastatic non–small cell lung cancer (NSCLC).

The MARIPOSA study enrolled patients with treatment-naïve locally advanced or metastatic NSCLC with either EGFR exon 19 deletions or L858R mutations. Patients were stratified by EGFRstatus. Patients were randomly assigned to receive the EGFR-MET bispecific antibody amivanatamab in combination with lazertinib, a CNS-penetrant, 3rd-generation EGFR TKI; osimertinib plus placebo; or lazertinib plus placebo.

The trial met its primary end point of improved progression-free survival (PFS) by blinded independent review with amivantamab plus lazertinib vs osimertinib, Cho begins. Median PFS with this combination was 23.7 months vs 16.6 months with osimertinib monotherapy, translating to a 30% reduction of the risk of progression or death. Unlike previous trials in EGFR-mutant lung cancer, the trial required serial brain MRIs for all patients, potentially leading to more frequent detection of progression, Cho notes. Accordingly, investigators measured extracranial PFS by BICR, and observed a 9-month improvement in median PFS with the amivantamab and lazertinib combination vs osimertinib monotherapy, he details. Additionally, time to second progression was notably enhanced with amivantamab plus lazertinib.

Although median overall survival (OS) was not estimable for both arms at the time of the analysis, Cho states that early interim OS data suggested a trend favoring the amivantamab combination over osimertinib, with a hazard ratio of 0.8 (P = .11). This indicates the potential for improved survival outcomes with the combination therapy, he says.

Overall, the study establishes amivantamab plus lazertinib as a potential first-line standard of care for patients with EGFR-mutant advanced NSCLC, with significant improvements in PFS and a favorable safety profile, Cho concludes.