Yang James Chih-Hsin, Lu Shun, Hayashi Hidetoshi, Felip Enriqueta, Spira Alexander I, Girard Nicolas, Kim Yu Jung, Lee Se-Hoon, Ostapenko Yurii, Danchaivijitr Pongwut, Liu Baogang, Alip Adlinda, Korbenfeld Ernesto, Mourão Dias Josiane, Besse Benjamin, Passaro Antonio, Lee Ki-Hyeong, Xiong Hailin, How Soon-Hin, Cheng Ying, Chang Gee-Chen, Yoshioka Hiroshige, Thomas Michael, Nguyen Danny, Ou Sai-Hong Ignatius, Mukhedkar Sanjay, Prabhash Kumar, D'Arcangelo Manolo, Alatorre-Alexander Jorge, Vázquez Limón Juan Carlos, Alves Sara, Stroyakovskiy Daniil, Peregudova Marina, Şendur Mehmet Ali Nahit, Yazici Ozan, Califano Raffaele, Gutiérrez Calderón Vanesa, de Marinis Filippo, Kim Sang-We, Gadgeel Shirish M, Owen Scott, Xie John, Sun Tao, Mehta Jaydeep, Venkatasubramanian Raja, Ennis Mariah, Fennema Elizabeth, Daksh Mahesh, Roshak Amy, Man Julie, Knoblauch Roland E, Bauml Joshua M, Baig Mahadi, Shah Sujay, Sethi Seema, Cho Byoung Chul
National Taiwan University Cancer Center, National Taiwan University Hospital, Taipei, Taiwan.
Department of Medical Oncology, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
N Engl J Med. 2025 Oct 30;393(17):1681-1693. doi: 10.1056/NEJMoa2503001. Epub 2025 Sep 7.
Previous results from this phase 3 trial showed that progression-free survival among participants with previously untreated (epidermal growth factor receptor)-mutated advanced non-small-cell lung cancer (NSCLC) was significantly improved with amivantamab-lazertinib as compared with osimertinib. Results of the protocol-specified final overall survival analysis in this trial have not been reported.
We randomly assigned, in a 2:2:1 ratio, participants with previously untreated -mutated (exon 19 deletion or L858R substitution), locally advanced or metastatic NSCLC to receive amivantamab-lazertinib, osimertinib, or lazertinib. Overall survival (assessed in an analysis of the time from randomization to death from any cause) in the amivantamab-lazertinib group as compared with the osimertinib group was a key secondary end point. Additional end points included safety.
A total of 429 participants each were assigned to receive amivantamab-lazertinib or osimertinib. Over a median follow-up of 37.8 months, amivantamab-lazertinib led to significantly longer overall survival than osimertinib (hazard ratio for death, 0.75; 95% confidence interval, 0.61 to 0.92; P = 0.005); 3-year overall survival was 60% and 51%, respectively. At the clinical cutoff date, 38% of participants in the amivantamab-lazertinib group and 28% in the osimertinib group were still receiving the assigned treatment. Adverse events of grade 3 or higher were more common with amivantamab-lazertinib (in 80% of participants) than with osimertinib (in 52%), particularly skin-related events, venous thromboembolism, and infusion-related events; these findings were consistent with the established safety profile of each treatment. No new safety signals were observed with additional follow-up.
Amivantamab-lazertinib led to significantly longer overall survival among participants with previously untreated -mutated advanced NSCLC than osimertinib but was associated with an increased risk of adverse events of grade 3 or higher. (Funded by Janssen Research and Development; MARIPOSA ClinicalTrials.gov number, NCT04487080.).
这项3期试验之前的结果显示，与奥希替尼相比，在先前未接受过治疗的（表皮生长因子受体）突变的晚期非小细胞肺癌（NSCLC）参与者中，阿美凡他单抗-拉泽替尼显著改善了无进展生存期。该试验中方案规定的最终总生存期分析结果尚未报告。
我们以2:2:1的比例将先前未接受过治疗的（外显子19缺失或L858R替代）、局部晚期或转移性NSCLC参与者随机分配，分别接受阿美凡他单抗-拉泽替尼、奥希替尼或拉泽替尼治疗。阿美凡他单抗-拉泽替尼组与奥希替尼组的总生存期（在从随机分组到因任何原因死亡的时间分析中评估）比较是关键的次要终点。其他终点包括安全性。
每组共有429名参与者被分配接受阿美凡他单抗-拉泽替尼或奥希替尼治疗。在中位随访37.8个月时，阿美凡他单抗-拉泽替尼组的总生存期显著长于奥希替尼组（死亡风险比，0.75；95%置信区间，0.61至0.92；P = 0.005）；3年总生存率分别为60%和51%。在临床截止日期时，阿美凡他单抗-拉泽替尼组38%的参与者和奥希替尼组28%的参与者仍在接受指定治疗。3级或更高等级的不良事件在阿美凡他单抗-拉泽替尼组（80%的参与者）中比在奥希替尼组（52%）中更常见，特别是皮肤相关事件、静脉血栓栓塞和输液相关事件；这些发现与每种治疗既定的安全性特征一致。额外随访未观察到新的安全信号。
对于先前未接受过治疗的（突变）晚期NSCLC参与者，阿美凡他单抗-拉泽替尼组的总生存期显著长于奥希替尼组，但与3级或更高等级不良事件风险增加相关。（由杨森研发公司资助；MARIPOSA 临床试验注册号，NCT04487080。）
