Subcutaneous Versus Intravenous Amivantamab, Both in Combination With Lazertinib, in Refractory Epidermal Growth Factor Receptor–Mutated Non–Small Cell Lung Cancer: Primary Results From the Phase III PALOMA-3 Study

作者：Natasha B. Leighl, Hiroaki Akamatsu, Sun Min Lim, Ying Cheng, Anna Rachel Minchom, Melina Elpi 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 Pablo Korbenfeld, Mor Tal Moskovitz, Ji‐Youn Han, Mariam P. 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 Mirosław Kowalski, Mehmet Alı Nahıt Şendur, John Xie, Debopriya Ghosh, Ali A. Alhadab, Nahor Haddish‐Berhane, Pamela L. Clemens, Patricia A. Lorenzini, Remy B. Verheijen, Mohamed Gamil, Joshua Michael Bauml, Mahadi Ali Baig, Antonio Passaro, for the PALOMA-3 Investigators, Hiroaki Akamatsu, Mariam P. Alexander, Annalen Bleckmann, Federico Cappuzzo, Ying Cheng, Byoung Chul Cho, Timuçin Çil, Alexis Benjamin Cortot, Pongwut Danchaivijitr, Till‐Oliver Emde, Dilek Erdem, Enriqueta Felip, F. Estevinho, Maria Lurdes Ferreira, Flavio Ferreira da Silva, Maria del Rosario Garcia Campelo, Laurent Greillier, Alastair Greystoke, Ji‐Youn Han, Ping‐Chih Hsu, Jen‐Yu Hung, Mei Ji, Thomas John, Rohit Joshi, Young‐Chul Kim, Masashi Kondo, Ernesto Pablo Korbenfeld, Dariusz Mirosław Kowalski, Se‐Hoon Lee, Natasha B. Leighl, Juan Li, Sheng-Hao Lin, Baogang Liu, Caigang Liu, John Seng-Hooi Low, Melina Elpi Marmarelis, Bartomeu Massutí, Anna R. Minchom, Sara Moore, Mor Moskovitz, Adnan M. Nagrial, Danny Nguyen, Silvia Novello, Yuichiro Ohe, Mustafa Özgüroğlu, Özgür Özyılkan, Antonio Passaro, Nir Peled, Naiyarat Prasongsook, Angel Qin, Elisa F. Ramos, Joshua K. Sabari, Jorge Salinas, Rachel E. Sanborn, Mehmet Alı Nahıt Şendur, Felipe José Silva Melo Cruz, Alexander I. Spira, Thatthan Suksombooncharoen, Motohiro Tamiya, Jiunn Liang Tan, Encarnação Teixeira, R R Tota, Damien Urban, Alain Vergnenégre, Pei Jye Voon, V. Wainsztein, Jialei Wang, Thomas Wehler, James Chih‐Hsin Yang, Hiroshige Yoshioka, Alona Zer, Yanqiu Zhao, Bogdan A. Żurawski · 发表于：Journal of Clinical Oncology · 年份：2024 · DOI：10.1200/jco.24.01001 · 被引用次数：129 · 研究领域：Lung Cancer Treatments and Mutations、Lung Cancer Research Studies、Peptidase Inhibition and Analysis

PURPOSE Phase III studies of intravenous amivantamab demonstrated efficacy across epidermal growth factor receptor ( EGFR )–mutated advanced non–small cell lung cancer (NSCLC). A subcutaneous formulation could improve tolerability and reduce administration time while maintaining efficacy. PATIENTS AND METHODS Patients with EGFR -mutated advanced NSCLC who progressed after osimertinib and platinum-based chemotherapy were randomly assigned 1:1 to receive subcutaneous or intravenous amivantamab, both combined with lazertinib. Coprimary pharmacokinetic noninferiority end points were trough concentrations (C trough ; on cycle-2-day-1 or cycle-4-day-1) and cycle-2 area under the curve (AUC D1-D15 ). Key secondary end points were objective response rate (ORR) and progression-free survival (PFS). Overall survival (OS) was a predefined exploratory end point. RESULTS Overall, 418 patients underwent random assignment (subcutaneous group, n = 206; intravenous group, n = 212). Geometric mean ratios of C trough for subcutaneous to intravenous amivantamab were 1.15 (90% CI, 1.04 to 1.26) at cycle-2-day-1 and 1.42 (90% CI, 1.27 to 1.61) at cycle-4-day-1; the cycle-2 AUC D1-D15 was 1.03 (90% CI, 0.98 to 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 to 0.92; nominal P = .02). Fewer patients in the subcut...