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.
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.)