SCI

29 June 2024

Amivantamab plus Lazertinib in Previously Untreated EGFR-Mutated Advanced NSCLC 

(NEJM, IF: 74.7)

  • Byoung C, Cho,Shun, Lu,Enriqueta, Felip et al. Amivantamab plus Lazertinib in Previously Untreated EGFR-Mutated Advanced NSCLC.[J] .N Engl J Med, 2024, 0: 0.

BACKGROUND 背景

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). 

Amivantamab 加 Lazertinib （amivantamab-lazertinib） 在既往未经治疗或奥希替尼预处理的 EGFR（表皮生长因子受体）突变晚期非小细胞肺癌 （NSCLC） 患者中显示出具有临床意义和持久的抗肿瘤活性。

 

METHODS方法

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. 

在一项 3 期国际随机试验中，我们以 2：2：1 的比例分配既往未经治疗的 EGFR 突变（外显子 19 缺失或 L858R）、局部晚期或转移性 NSCLC 患者接受 amivantamab-lazertinib（以开放标签方式）、osimertinib（以盲法方式）或 lazertinib（以盲法方式，以评估治疗成分的贡献）。主要终点是amivantamab-lazertinib组与osimertinib组相比的无进展生存期，通过盲法独立中心评价进行评估。

 

RESULTS 结果

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. 

总体而言，1074 例患者接受了随机分组（429 例接受 amivantamab-lazertinib，429 例接受osimertinib治疗，216 例接受 lazertinib 治疗）。amivantamab-lazertinib组的中位无进展生存期显著长于osimertinib组（23.7个月 vs. 16.6个月;疾病进展或死亡风险比为0.70;95%置信区间[CI]为0.58-0.85;P<0.001）。amivantamab-lazertinib组86%的患者（95%CI，83-89）和osimertinib组85%的患者（95%CI，81-88）观察到客观缓解;在确诊缓解的患者中（amivantamab-lazertinib组为336例，osimertinib组为314例），中位缓解持续时间分别为25.8个月（95%CI，20.1至无法估计）和16.8个月（95%CI，14.8至18.5）。在一项计划中，与osimertinib相比，amivantamab-lazertinib的中期总生存期分析显示，死亡风险比为0.80 （95% CI， 0.61-1.05）。主要不良事件是EGFR相关毒性反应。amivantamab-lazertinib组因治疗相关不良事件而停药的发生率为10%，osimertinib组为3%。

 

CONCLUSIONS 结论

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.).

amivantamab-lazertinib作为EGFR突变晚期NSCLC的一线治疗效果优于osimertinib。由Janssen研发部资助；马里波萨ClinicalTrials.gov注册号，NCT04487080。