Besse Benjamin, Goto Koichi, Wang Yongsheng, Lee Se-Hoon, Marmarelis Melina E, Ohe Yuichiro, Bernabe Caro Reyes, Kim Dong-Wan, Lee Jong-Seok, Cousin Sophie, Ichihara Eiki, Li Yongsheng, Paz-Ares Luis, Ono Akira, Sanborn Rachel E, Watanabe Naohiro, de Miguel Maria Jose, Helissey Carole, Shu Catherine A, Spira Alexander I, Tomasini Pascale, Yang James Chih-Hsin, Zhang Yiping, Felip Enriqueta, Griesinger Frank, Waqar Saiama N, Calles Antonio, Neal Joel W, Baik Christina S, Jänne Pasi A, Shreeve S Martin, Curtin Joshua C, Patel Bharvin, Gormley Michael, Lyu Xuesong, Chen Jun, Chu Pei-Ling, Mahoney Janine, Trani Leonardo, Bauml Joshua M, Thayu Meena, Knoblauch Roland E, Cho Byoung Chul
Paris-Saclay University, Institut Gustave Roussy, Villejuif, France.
National Cancer Center Hospital East, Kashiwa, Japan.
J Thorac Oncol. 2025 May;20(5):651-664. doi: 10.1016/j.jtho.2024.12.029. Epub 2025 Jan 2.
Treatment options for patients with EGFR-mutated NSCLC with disease progression on or after osimertinib and platinum-based chemotherapy are limited.
CHRYSALIS-2 cohort A evaluated amivantamab plus lazertinib in patients with EGFR exon 19 deletion- or L858R-mutated NSCLC with disease progression on or after osimertinib and platinum-based chemotherapy. Primary end point was investigator-assessed objective response rate (ORR). The patients received 1050 mg of intravenous amivantamab (1400 mg if ≥ 80 kg) plus 240 mg of oral lazertinib.
In cohort A (N = 162), the investigator-assessed ORR was 28% (95% confidence interval [CI]: 22-36). The blinded independent central review-assessed ORR was 35% (95% CI: 27-42), with a median duration of response of 8.3 months (95% CI: 6.7-10.9) and a clinical benefit rate of 58% (95% CI: 50-66). At a median follow-up of 12 months, 32 of 56 responders (57%) achieved a duration of response of more than or equal to 6 months. Median progression-free survival by blinded independent central review was 4.5 months (95% CI: 4.1-5.8); median overall survival was 14.8 months (95% CI: 12.2-18.0). Preliminary evidence of central nervous system antitumor activity was reported in seven patients with baseline brain lesions and no previous brain radiation or surgery. Exploratory biomarker analyses using next-generation sequencing of circulating tumor DNA revealed responses in patients with and without EGFR- or MET-dependent resistance. The most frequent adverse events were rash (grouped term; 81%), infusion-related reaction (68%), and paronychia (52%). The most common grade greater than or equal to 3 treatment-related adverse events were rash (grouped term; 10%), infusion-related reaction (9%), and hypoalbuminemia (6%).
For patients with limited treatment options, amivantamab plus lazertinib demonstrated an antitumor activity with a safety profile characterized by EGFR- or MET-related adverse events, which were generally manageable.
对于在奥希替尼及铂类化疗期间或之后病情进展的表皮生长因子受体（EGFR）突变的非小细胞肺癌（NSCLC）患者，治疗选择有限。
CHRYSALIS-2队列A评估了氨武单抗联合拉泽替尼用于EGFR基因19外显子缺失或L858R突变的NSCLC患者，这些患者在奥希替尼及铂类化疗期间或之后病情进展。主要终点是研究者评估的客观缓解率（ORR）。患者接受1050mg静脉注射氨武单抗（体重≥80kg者为1400mg）加240mg口服拉泽替尼。
在队列A（N = 162）中，研究者评估的ORR为28%（95%置信区间[CI]：22 - 36）。盲法独立中央审查评估的ORR为35%（95%CI：27 - 42），中位缓解持续时间为8.3个月（95%CI：6.7 - 10.9），临床获益率为58%（95%CI：50 - 66）。在中位随访12个月时，56例缓解者中有32例（57%）达到了6个月或更长时间的缓解持续时间。盲法独立中央审查评估的中位无进展生存期为4.5个月（95%CI：4.1 - 5.8）；中位总生存期为14.8个月（95%CI：12.2 - 18.0）。7例有基线脑转移灶且既往未接受过脑部放疗或手术的患者报告了中枢神经系统抗肿瘤活性的初步证据。使用循环肿瘤DNA的下一代测序进行的探索性生物标志物分析显示，有或没有EGFR或MET依赖性耐药的患者均有缓解。最常见的不良事件是皮疹（合并术语；81%）、输液相关反应（68%）和甲沟炎（52%）。最常见的≥3级治疗相关不良事件是皮疹（合并术语；10%）、输液相关反应（9%）和低白蛋白血症（6%）。
对于治疗选择有限的患者，氨武单抗联合拉泽替尼显示出抗肿瘤活性，其安全性特征为EGFR或MET相关不良事件，这些不良事件通常是可控的。
