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

Leighl, NB; Akamatsu, H; Lim, SM; Cheng, Y; Minchom, AR; Marmarelis, ME; Sanborn, RE; Chih-Hsin Yang, J; Liu, B; John, T; Massut&#237;, 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; Şendur, MAN; Xie, J; Ghosh, D; Alhadab, A; Haddish-Berhane, N; Clemens, PL; Lorenzini, P; Verheijen, RB; Gamil, M; Bauml, JM; Baig, M; Passaro, A; PALOMA-3 Investigators

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; Şendur, MAN; Xie, J; Ghosh, D; Alhadab, A; Haddish-Berhane, N; Clemens, PL; Lorenzini, P; Verheijen, RB; Gamil, M; Bauml, JM; Baig, M; Passaro, A; PALOMA-3 Investigators;
Details: Publication Year 2024-10-20,Volume 42,Issue #30,Page 3593-3605
Journal Title: Journal of Clinical Oncology
Publication Type: Research article
Abstract: 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. CONCLUSION: Subcutaneous amivantamab-lazertinib demonstrated noninferiority to intravenous amivantamab-lazertinib, offering a consistent safety profile with reduced IRRs, increased convenience, and prolonged survival.
Publisher: American Society of Clinical Oncology
Keywords: Humans; *Carcinoma, Non-Small-Cell Lung/drug therapy/genetics/pathology/mortality; Male; Female; *Lung Neoplasms/drug therapy/genetics/mortality/pathology; Middle Aged; *ErbB Receptors/genetics; Aged; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use/administration &; dosage/pharmacokinetics/adverse effects; Adult; Injections, Subcutaneous; Aged, 80 and over; Mutation; Acrylamides/administration & dosage; Progression-Free Survival; Administration, Intravenous
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: 2024-10-23 05:59:33

Last Modified: 2024-10-23 05:59:43