Article
Author: Liu, Caigang ; Leighl, Natasha ; Cappuzzo, Federico ; Haddish-Berhane, Nahor ; Alhadab, Ali ; Teixeira, Encarnação ; Moskovitz, Mor ; Ozyilkan, Ozgur ; Özgüroğlu, Mustafa ; Lee, Se-Hoon ; Han, Ji-Youn ; Zer, Alona ; Felip, Enriqueta ; Wehler, Thomas ; Bleckmann, Annalen ; Greillier, Laurent ; Joshi, Rohit ; Alexander, Mariam ; Seng-Hooi Low, John ; Chih-Hsin Yang, James ; Ohe, Yuichiro ; Cortot, Alexis ; Suksombooncharoen, Thatthan ; Wainsztein, Vanina ; Lorenzini, Patricia ; Nguyen, Danny ; da Silva, Flavio Ferreira ; Cheng, Ying ; Silva Melo Cruz, Felipe José ; Emde, Till-Oliver ; Liang Tan, Jiunn ; Gamil, Mohamed ; Xie, John ; Lin, Sheng-Hao ; Kowalski, Dariusz ; Prasongsook, Naiyarat ; Wang, Jialei ; Şendur, Mehmet Ali Nahit ; Clemens, Pamela L. ; Spira, Alexander I. ; Massutí, Bartomeu ; Zurawski, Bogdan ; Leighl, Natasha B. ; Nahit Sendur, Mehmet Ali ; Ghosh, Debopriya ; Sanborn, Rachel E. ; Qin, Angel ; Voon, Pei Jye ; Passaro, Antonio ; Tota, Rajanikar ; Urban, Damien ; Salinas, Jorge ; Peled, Nir ; Moore, Sara ; Sabari, Joshua K. ; Yoshioka, Hiroshige ; Zhao, Yanqiu ; Hsu, Ping-Chih ; Ramos, Elisa F. ; Bauml, Joshua M. ; Lurdes Ferreira, Maria ; Akamatsu, Hiroaki ; Korbenfeld, Ernesto ; Danchaivijitr, Pongwut ; Estevinho, Fernanda ; Minchom, Anna R. ; Erdem, Dilek ; Garcia Campelo, Maria del Rosario ; Baig, Mahadi ; Teixeira, Encarnacao ; Vergnenègre, Alain ; Verheijen, Remy B. ; Greystoke, Alastair ; Kim, Young-Chul ; Liu, Baogang ; José Silva Melo Cruz, Felipe ; Cho, Byoung Chul ; Cil, Timucin ; Hung, Jen-Yu ; Lim, Sun Min ; Ji, Mei ; Novello, Silvia ; John, Thomas ; Nagrial, Adnan ; Sendur, Mehmet Ali Nahit ; Marmarelis, Melina E. ; Kondo, Masashi ; Tamiya, Motohiro ; Li, Juan
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 subcutaneous group experienced infusion-related reactions (IRRs; 13%
v
66%) and venous thromboembolism (9%
v
14%) versus the intravenous group. Median administration time for the first infusion was reduced to 4.8 minutes (range, 0-18) for subcutaneous amivantamab and to 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; the end-of-treatment rates were 85% and 35%, respectively.
CONCLUSIONSubcutaneous amivantamab-lazertinib demonstrated noninferiority to intravenous amivantamab-lazertinib, offering a consistent safety profile with reduced IRRs, increased convenience, and prolonged survival.