Amivantamab plus Lazertinib in Previously UntreatedEGFR-Mutated Advanced NSCLC

  • Cho, Byoung C. M.D., Ph.D.
  • Lu, Shun M.D., Ph.D.
  • Felip, Enriqueta M.D., Ph.D.
  • Spira, Alexander I. M.D., Ph.D.
  • Girard, Nicolas M.D., Ph.D.
  • Lee, Jong-Seok M.D., Ph.D.
  • Lee, Se-Hoon M.D., Ph.D.
  • Ostapenko, Yurii M.D., Ph.D.
  • Danchaivijitr, Pongwut M.D.
  • Liu, Baogang M.D.
  • Alip, Adlinda M.D.
  • Korbenfeld, Ernesto M.D.
  • Dias, Josiane Mourão M.D.
  • Besse, Benjamin M.D., Ph.D.
  • Lee, Ki-Hyeong M.D.
  • Xiong, Hailin M.D.
  • How, Soon-Hin M.D.
  • Cheng, Ying M.D.
  • Chang, Gee-Chen M.D., Ph.D.
  • Yoshioka, Hiroshige M.D., Ph.D.
  • Yang, James C.-H. M.D., Ph.D.
  • Thomas, Michael M.D.
  • Nguyen, Danny M.D.
  • Ou, Sai-Hong I. M.D., Ph.D.
  • Mukhedkar, Sanjay M.D.
  • Prabhash, Kumar M.D., D.M.
  • D'Arcangelo, Manolo M.D.
  • Alatorre-Alexander, Jorge M.D.
  • Vázquez Limón, Juan C. M.D.
  • Alves, Sara M.D.
  • Stroyakovskiy, Daniil M.D.
  • Peregudova, Marina M.D., Ph.D.
  • Şendur, Mehmet A.N. M.D., Ph.D.
  • Yazici, Ozan M.D.
  • Califano, Raffaele M.D.
  • Calderón, Vanesa Gutiérrez M.D.
  • de Marinis, Filippo M.D.
  • Passaro, Antonio M.D., Ph.D.
  • Kim, Sang-We M.D., Ph.D.
  • Gadgeel, Shirish M. M.D., Ph.D.
  • Xie, John Ph.D.
  • Sun, Tao Ph.D.
  • Martinez, Melissa M.S.
  • Ennis, Mariah M.S.
  • Fennema, Elizabeth M.A.
  • Daksh, Mahesh Ph.D.
  • Millington, Dawn M.S.
  • Leconte, Isabelle Ph.D.
  • Iwasawa, Ryota Ph.D.
  • Lorenzini, Patricia M.S.
  • Baig, Mahadi M.D.
  • Shah, Sujay M.D.
  • Bauml, Joshua M. M.D.
  • Shreeve, Martin S. M.D., Ph.D.
  • Sethi, Seema D.O.
  • Knoblauch, Roland E. M.D., Ph.D.
  • Hayashi, Hidetoshi M.D., Ph.D.
New England Journal of Medicine 391(16):p 1486-1498, October 24, 2024. | DOI: 10.1056/NEJMoa2403614

ABSTRACT

BACKGROUND

Amivantamab plus lazertinib (amivantamab-lazertinib) has shown clinically meaningful and durable antitumor activity in patients with previously untreated or osimertinib-pretreated EGFR (epidermal growth factor receptor)-mutated advanced non-small-cell lung cancer (NSCLC).

METHODS

In a phase 3, international, randomized trial, we assigned, in a 2:2:1 ratio, patients with previously untreated EGFR-mutated (exon 19 deletion or L858R), locally advanced or metastatic NSCLC to receive amivantamab-lazertinib (in an open-label fashion), osimertinib (in a blinded fashion), or lazertinib (in a blinded fashion, to assess the contribution of treatment components). The primary end point was progression-free survival in the amivantamab-lazertinib group as compared with the osimertinib group, as assessed by blinded independent central review.

RESULTS

Overall, 1074 patients underwent randomization (429 to amivantamab-lazertinib, 429 to osimertinib, and 216 to lazertinib). The median progression-free survival was significantly longer in the amivantamab-lazertinib group than in the osimertinib group (23.7 vs. 16.6 months; hazard ratio for disease progression or death, 0.70; 95% confidence interval [CI], 0.58 to 0.85; P<0.001). An objective response was observed in 86% of the patients (95% CI, 83 to 89) in the amivantamab-lazertinib group and in 85% of those (95% CI, 81 to 88) in the osimertinib group; among patients with a confirmed response (336 in the amivantamab-lazertinib group and 314 in the osimertinib group), the median response duration was 25.8 months (95% CI, 20.1 to could not be estimated) and 16.8 months (95% CI, 14.8 to 18.5), respectively. In a planned interim overall survival analysis of amivantamab-lazertinib as compared with osimertinib, the hazard ratio for death was 0.80 (95% CI, 0.61 to 1.05). Predominant adverse events were EGFR-related toxic effects. The incidence of discontinuation of all agents due to treatment-related adverse events was 10% with amivantamab-lazertinib and 3% with osimertinib.

CONCLUSIONS

Amivantamab-lazertinib showed superior efficacy to osimertinib as first-line treatment in EGFR-mutated advanced NSCLC. (Funded by Janssen Research and Development; MARIPOSA ClinicalTrials.gov number, NCT04487080.)

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