Dr Gadgeel on Longer-Term Data for Amivantamab Plus Lazertinib in EGFR+ NSCLC

Shirish M. Gadgeel, MD, head, Division of Hematology/Oncology, associate director, Patient Experience and Clinical Care, Henry Ford Health, discusses longer-term follow-up data from the phase 3 MARIPOSA study (NCT04487080), which evaluated the combination of amivantamab-vmjw (Rybrevant) plus lazertinib (Lazcluze) vs osimertinib (Tagrisso) monotherapy for first-line treatment of patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) harboring EGFR exon 19 deletions or exon 21 L858R mutations.

Prior data from the study supported the August 2024 FDA approval of amivantamab plus lazertinibfor the first-line treatment of adult patients with locally advanced or metastatic NSCLC harboring EGFR exon 19 deletions or exon 21 L858R substitution mutations, as detected by an FDA-approved test.

At the 2024 IASLC World Conference on Lung Cancer, Gadgeel presented additional data with a median follow-up of 31.1 months.

Findings showed the 3-year intracranial progression-free survival (PFS) rate was 38% in the combination arm (n = 178) compared with 18% in the osimertinib arm (n = 173). The median intracranial PFS was 24.9 months (95% CI, 20.1-34.7) in the amivantamab/lazertinib arm vs 22.2 months (95% CI, 18.4-26.1) in the osimertinib arm (HR, 0.82; 95% CI, 0.62-1.09; P = .165).

Moreover, the median intracranial duration of response was not evaluable (NE; 95% CI, 21.4-NE) in patients receiving amivantamab and lazertinib vs 24.4 months (95% CI, 22.1-31.2) in those treated with osimertinib. Notably, 51% of responders treated with the combination maintained their response at three years compared with 0% in the osimertinib group.

All patients treated with amivantamab plus lazertinib (n = 429) experienced a median time to treatment discontinuation of 26.3 months (95% CI, 22.3-30.4) vs 22.6 months (95% CI, 20.3-24.5) for those given osimertinib (n = 429; HR, 0.80; 95% CI, 0.68-0.96; P = .014).

Updated overall survival (OS) data indicated a widening survival benefit favoring the combination therapy. At 2 years, OS rates were 75% and 70% for the amivantamab/lazertinib and osimertinib groups, respectively. At 3 years, these rates were 61% and 53%, respectively. The median OS was NE (95% CI, NE-NE) in the combination arm vs 37.3 months (95% CI, 32.5-NE) in the osimertinib arm (HR, 0.77; 95% CI, 0.61-0.96; P = .019).

A future prespecified final analysis will be conducted to confirm these findings, and ongoing follow-up is critical to further elucidate the survival benefits of this combination in EGFR-mutated advanced NSCLC, Gadgeel concludes.