SCI
13 July 2024
Subcutaneous versus Intravenous Amivantamab, both in Combination with Lazertinib, in Refractory EGFR-mutated NSCLC: Primary Results from the Phase 3 PALOMA-3 Study
(Journal of Clinical Oncology, IF: 42.1)
Natasha B. Leighl, Hiroaki Akamatsu, Sun Min Lim, Ying Cheng, Anna R. Minchom, Melina E. Marmarelis, Rachel E. Sanborn, James Chih-Hsin Yang, Baogang Liu, Thomas John, Bartomeu Massutí, Alexander I. Spira, Se-Hoon Lee, Jialei Wang, Juan Li, Caigang Liu, Silvia Novello, Masashi Kondo, Motohiro Tamiya, Ernesto Korbenfeld, Mor Moskovitz, Ji-Youn Han, Mariam Alexander, Rohit Joshi, Enriqueta Felip, Pei Jye Voon, Pongwut Danchaivijitr, Ping-Chih Hsu, Felipe José Silva Melo Cruz, Thomas Wehler, Laurent Greillier, Encarnação Teixeira, Danny Nguyen, Joshua K. Sabari, Angel Qin, Dariusz Kowalski, Mehmet Ali Nahit Şendur, John Xie, Debopriya Ghosh, Ali Alhadab, PharmD, Nahor Haddish-Berhane, Pamela L. Clemens, Patricia Lorenzini, Remy B. Verheijen, Mohamed Gamil, Joshua M. Bauml, Mahadi Baig, Antonio Passaro, for the PALOMA-3 Investigators
CORRESPONDENCE TO: Natasha.Leighl@uhn.ca
Phase 3 studies of intravenous amivantamab demonstrated efficacy across EGFR-mutated advanced non-small cell lung cancer (NSCLC). A subcutaneous formulation could improve tolerability and reduce administration time while maintaining efficacy.
静脉注射Amivantamab单抗的3期研究证明了其对EGFR突变的晚期肺癌（NSCLC）的疗效。皮下制剂可以提高耐受性，减少给药时间，同时保持疗效。
Patients with EGFR-mutated advanced NSCLC who progressed following osimertinib and platinum-based chemotherapy were randomized 1:1 to receive subcutaneous or intravenous amivantamab, both combined with lazertinib. Co-primary pharmacokinetic noninferiority endpoints were trough concentrations (Ctrough; on cycle-2-day-1 or cycle-4-day-1) and cycle-2 area under the curve (AUCD1-D15). Key secondary endpoints were objective response rate (ORR) and progression-free survival (PFS). Overall survival (OS) was a predefined exploratory endpoint.
对经奥西替尼和铂类化疗后肿瘤进展的EGFR突变的晚期NSCLC患者进行1:1的随机分组，接受皮下或静脉注射Amivantamab单抗治疗，两者均与Lazertinib联合治疗。共同主要的药代动力学非劣效性终点是波谷浓度（Ctrough；第2周期第1天或第4周期第1天时）和第2周期曲线下面积（AUCD1-D15）。主要次要终点是客观有效率（ORR）和无进展生存率（PFS）。总生存期（OS）是一个预先确定的探索终点。
Overall, 418 patients underwent randomization (subcutaneous group, n=206; intravenous group, n=212). Geometric mean ratios of Ctrough for subcutaneous to intravenous amivantamab were 1.15 (90% CI, 1.04-1.26) at cycle-2-day-1 and 1.4 (90% CI, 1.27-1.61) at cycle-4-day-1; the cycle-2 AUCD1-D15 was 1.03 (90% CI, 0.98- 1.09). ORR was 30% in the subcutaneous and 33% in the intravenous group; median PFS was 6.1 and 4.3 months, respectively. OS was significantly longer in the subcutaneous versus intravenous group (hazard ratio for death, 0.62; 95% CI, 0.42- 0.92; nominal P=0.02). Fewer patients in the subcutaneous group experienced infusion-related reactions (13% versus 66%) and venous thromboembolism (9% versus 14%) versus the intravenous group. Median administration time for first infusion was reduced to 4.8 minutes (range, 0-18) for subcutaneous amivantamab from 5 hours (range, 0.2- 9.9) for intravenous amivantamab. During cycle-1-day-1, 85% and 52% of patients in the subcutaneous and intravenous groups, respectively, considered treatment convenient; end-of-treatment rates were 85% and 35%, respectively.
总体而言，418名患者接受了随机分组（皮下用药组，n=206；静脉用药组，n=212）。皮下注射与静脉注射Amivantamab单抗的Ctrough几何平均比值在第1个周期第2天为1.15（90%CI，1.04-1.26），在第1周期第4天为1.4（90%CCI，1.27-1.61）；第2周期 AUCD1-D15为1.03（90%CI，0.98-1.09）。皮下注射组ORR为30%，静脉注射组ORR为33%；中位PFS分别为6.1个月和4.3个月。皮下注射组的OS明显长于静脉注射组（死亡风险比为0.62；95%可信区间为0.42-0.92；标称P=0.02）。与静脉注射组相比，皮下注射组出现输液相关反应（13%对比66%）和静脉血栓栓塞（9%对比14%）的患者更少。首次输注的中位给药时间从静脉注射的5小时（范围0.2-9.9）减少到皮下注射的4.8分钟（范围0-18）。在第1周期第一天期间，皮下组和静脉组分别有85%和52%的患者认为该治疗方式方便；治疗完成率分别为85%和35%。
Subcutaneous amivantamab-lazertinib demonstrated noninferiority to intravenous amivantamab-lazertinib, offering a consistent safety profile with reduced infusion-related reactions, increased convenience, and prolonged survival.
与静脉注射的Amivantamab联合Lazertinib相比，皮下注射Amivantamab联合Lazertinib显示出非劣效性，提供了一致的安全性，减少了输液相关反应，增加了便利性，延长了生存期。
