韩国延世大学医学院Byoung C. Cho团队研究了埃万妥单抗联合拉泽替尼治疗初治EGFR突变晚期NSCLC的疗效与安全性。相关论文于2024年6月26日发表在《新英格兰医学杂志》上。

在既往未经治疗或奥西替尼预处理的表皮生长因子受体（EGFR）突变的晚期非小细胞癌症（NSCLC）患者中，埃万妥单抗加拉泽替尼（埃万妥单抗-拉泽替尼）显示出临床意义和持久的抗肿瘤活性。

在一项3期国际随机试验中，研究组以2:2:1的比例，将先前未经治疗的EGFR突变（外显子19缺失或L858R）、局部晚期或转移性NSCLC患者分配接受埃万妥单抗-拉泽替尼（以开放标签方式）、奥西替尼（以盲法方式）或拉泽替尼（盲法方式，评估治疗成分的作用）。通过盲法独立中心审查评估，与奥西替尼组相比，主要终点是埃万妥单抗-拉泽替尼组的无进展生存率。

总体而言，1074名患者接受了随机分组（429名患者接受埃万妥单抗-拉泽替尼治疗，429名患者使用奥西替尼治疗和216名患者接受拉泽替尼治疗）。埃万妥单抗-拉泽替尼组的中位无进展生存期明显长于奥西替尼组（23.7个月vs.16.6个月；疾病进展或死亡的风险比为0.70；95%置信区间[CI]为0.58-0.85；P<0.001）。埃万妥单抗-拉泽替尼组86%的患者（95%CI，83至89）和奥西替尼组85%的患者（95%CI，81至88）观察到客观缓解；在确定缓解的患者中（埃万妥单抗-拉泽替尼组336例，奥西替尼组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）。在一项计划的中期总生存率分析中，与奥西替尼相比，埃万妥单抗-拉泽替尼的死亡风险比为0.80（95%CI，0.61至1.05）。主要不良事件是EGFR相关的毒性作用。埃万妥单抗-拉泽替尼组因治疗相关不良事件而停用所有药物的发生率为10%，奥西替尼为3%。

研究结果表明，埃万妥单抗-拉泽替尼作为EGFR突变的晚期NSCLC的一线治疗显示出优于奥西替尼的疗效。

附：英文原文

Title: Amivantamab plus Lazertinib in Previously Untreated EGFR-Mutated Advanced NSCLC

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

Issue&Volume: 2024-06-26

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.

DOI: NJ202406260000002

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2403614