Overall survival for amivantamab plus lazertinib versus osimertinib as first-line treatment in Asian participants with EGFR-mutant advanced NSCLC: A MARIPOSA subset analysis

Lung Cancer. 2026 Apr:214:109305. doi: 10.1016/j.lungcan.2026.109305. Epub 2026 Feb 4.

Abstract

Background: Approximately 60 % of lung cancer cases occur in Asia, indicating an epidemiological disparity and need for effective therapies. Amivantamab-lazertinib is approved for first-line EGFR-mutated advanced non-small cell lung cancer (NSCLC) in many countries. In the protocol-specified final overall survival (OS) analysis of MARIPOSA (NCT04487080), amivantamab-lazertinib showed a statistically significant and clinically meaningful improvement in OS versus osimertinib (HR, 0.75; P = 0.005) among all participants. We evaluated OS for amivantamab-lazertinib versus osimertinib in Asian participants.

Patients and methods: Participants with previously untreated EGFR-mutated, locally advanced/metastatic NSCLC were randomized 2:2:1 to receive amivantamab-lazertinib, osimertinib, or lazertinib (for evaluating contribution of components). Self-identified Asian race was a stratification factor. OS was a key secondary endpoint.

Results: Of 1074 randomized participants, 629 self-identified as Asian (amivantamab-lazertinib:250; osimertinib:251; lazertinib:128). At a median follow-up of 38.7 months, amivantamab-lazertinib significantly prolonged OS versus osimertinib among Asian participants. Median OS was not reached (NR; 95 % CI, NR-NR) for amivantamab-lazertinib versus 38.4 months (95 % CI, 35.1-NR) for osimertinib (HR, 0.74; 95 % CI, 0.56-0.97; nominal P = 0.026). Assuming exponential distribution of OS in both arms, amivantamab-lazertinib is projected to prolong median OS among Asian participants by > 12 months versus osimertinib. At 36 months, 61 % and 53 % were alive in the amivantamab-lazertinib and osimertinib arms. Safety profile was consistent with the overall population.

Conclusions: Consistent with the overall population, amivantamab-lazertinib significantly improved OS versus osimertinib among Asian participants with previously untreated EGFR-mutated advanced NSCLC, making it the first regimen to improve survival among Asian patients.

Keywords: Amivantamab plus lazertinib; Asian; EGFR TKI; EGFR-mutated NSCLC; Overall survival.

Publication types

  • Randomized Controlled Trial
  • Clinical Trial, Phase III

MeSH terms

  • Acrylamides* / administration & dosage
  • Acrylamides* / therapeutic use
  • Adult
  • Aged
  • Aged, 80 and over
  • Aniline Compounds* / administration & dosage
  • Aniline Compounds* / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Asian People / genetics
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / mortality
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • ErbB Receptors / genetics
  • Female
  • Humans
  • Indoles
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / mortality
  • Lung Neoplasms* / pathology
  • Male
  • Middle Aged
  • Mutation*
  • Pyrimidines
  • Treatment Outcome

Substances

  • osimertinib
  • ErbB Receptors
  • Aniline Compounds
  • Acrylamides
  • EGFR protein, human
  • Indoles
  • Pyrimidines