Subcutaneous versus Intravenous Amivantamab, both in Combination with Lazertinib, in Refractory EGFR-mutated NSCLC: Primary Results from the Phase 3 PALOMA-3 Study
- Author(s)
- Leighl, NB; Akamatsu, H; Lim, SM; Cheng, Y; Minchom, AR; Marmarelis, ME; Sanborn, RE; Chih-Hsin Yang, J; Liu, B; John, T; Massutí, B; Spira, AI; Lee, SH; Wang, J; Li, J; Liu, C; Novello, S; Kondo, M; Tamiya, M; Korbenfeld, E; Moskovitz, M; Han, JY; Alexander, M; Joshi, R; Felip, E; Voon, PJ; Danchaivijitr, P; Hsu, PC; Silva Melo Cruz, FJ; Wehler, T; Greillier, L; Teixeira, E; Nguyen, D; Sabari, JK; Qin, A; Kowalski, D; Nahit Şendur, MA; Xie, J; Ghosh, D; Alhadab, A; Haddish-Berhane, N; Clemens, PL; Lorenzini, P; Verheijen, RB; Gamil, M; Bauml, JM; Baig, M; Passaro, A;
- Journal Title
- Journal of Clinical Oncology
- Publication Type
- Online publication before print
- Abstract
- PURPOSE: 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. PATIENTS AND METHODS: 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 (C(trough); on cycle-2-day-1 or cycle-4-day-1) and cycle-2 area under the curve (AUC(D1-D15)). Key secondary endpoints were objective response rate (ORR) and progression-free survival (PFS). Overall survival (OS) was a predefined exploratory endpoint. RESULTS: Overall, 418 patients underwent randomization (subcutaneous group, n=206; intravenous group, n=212). Geometric mean ratios of C(trough) for subcutaneous to intravenous amivantamab were 1.15 (90% CI, 1.04-1.26) at cycle-2-day-1 and 1.42 (90% CI, 1.27-1.61) at cycle-4-day-1; the cycle-2 AUC(D1-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. CONCLUSION: Subcutaneous amivantamab-lazertinib demonstrated noninferiority to intravenous amivantamab-lazertinib, offering a consistent safety profile with reduced infusion-related reactions, increased convenience, and prolonged survival.
- Department(s)
- Medical Oncology
- Publisher's Version
- https://doi.org/10.1200/jco.24.01001
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2024-08-06 05:29:21
Last Modified: 2024-08-06 05:31:19