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.
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Leighl Natasha B, Akamatsu Hiroaki, Lim Sun Min, Cheng Ying, Minchom Anna R, Marmarelis Melina E, Sanborn Rachel E, Chih-Hsin Yang James, Liu Baogang, John Thomas, Massutí Bartomeu, Spira Alexander I, Lee Se-Hoon, Wang Jialei, Li Juan, Liu Caigang, Novello Silvia, Kondo Masashi, Tamiya Motohiro, Korbenfeld Ernesto, Moskovitz Mor, Han Ji-Youn, Alexander Mariam, Joshi Rohit, Felip Enriqueta, Voon Pei Jye, Danchaivijitr Pongwut, Hsu Ping-Chih, Silva Melo Cruz Felipe José, Wehler Thomas, Greillier Laurent, Teixeira Encarnação, Nguyen Danny, Sabari Joshua K, Qin Angel, Kowalski Dariusz, Şendur Mehmet Ali Nahit, Xie John, Ghosh Debopriya, Alhadab Ali, Haddish-Berhane Nahor, Clemens Pamela L, Lorenzini Patricia, Verheijen Remy B, Gamil Mohamed, Bauml Joshua M, Baig Mahadi, Passaro Antonio, PALOMA-3 Investigators
Аннотация
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 (Ctrough; on cycle-2-day-1 or cycle-4-day-1) and cycle-2 area under the curve (AUCD1-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 Ctrough 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 AUCD1-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.