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, Natasha B. (Princess Margaret Cancer Centre (Toronto, Canadà))
Akamatsu, Hiroaki (Wakayama Medical University)
Lim, Sun Min (Yonsei University College of Medicine (Seoul, Corea del Sud))
Cheng, Ying (Jilin Cancer Hospital (Chanbgchun, Xina))
Minchom, Anna R.
Marmarelis, Melina E. (The Royal Marsden Hospital and The Institute of Cancer Research (Sutton, Regne Unit))
Sanborn, Rachel E.
Chih-Hsin Yang, James (University of Pennsylvania)
Liu, Baogang (University Hospital of Giessen and Marburg (Alemanya))
John, Thomas (Harbin Medical University Cancer Hospital)
Massutí, Bartomeu (Alicante University Dr. Balmis Hospital)
Spira, Alexander I. (Virginia Cancer Specialists)
Lee, Se-Hoon (Sungkyunkwan University School of Medicine (Seoul, República de Corea))
Wang, Jialei (Fudan University Shanghai Cancer Center (Shanghai, Xina))
Li, Juan (Sichuan Cancer Hospital)
Liu, Caigang (Shengjing Hospital of China Medical University (Shenyang, Xina))
Novello, Silvia (University of Turin)
Kondo, Masashi (Fujita Health University School of Medicine (Toyoake, Japó))
Tamiya, Motohiro (Osaka International Cancer Institute)
Korbenfeld, Ernesto (British Hospital of Buenos Aires-Central British Hospital)
Moskovitz, Mor (Davidoff Cancer Center (Petah Tikva, Israel))
Han, Ji-Youn (National Cancer Center (Goyang, República de Corea))
Alexander, Mariam (Medical University of South Carolina)
Joshi, Rohit (Medical University of South Carolina)
Felip, Enriqueta (Vall d'Hebron Institut d'Oncologia)
Voon, Pei Jye (Cancer Research (Adelaide, Australia))
Danchaivijitr, Pongwut (Sarawak General Hospital (Kuching, Malàsia))
Hsu, Ping-Chih (Chang Gung University College of Medicine (Taoyuan, Taiwan))
Silva Melo Cruz, Felipe José (Instituto Brasileiro de Controle do Câncer)
Wehler, Thomas (University Hospital of Giessen and Marburg (Alemanya))
Greillier, Laurent
Teixeira, Encarnação (Aix Marseille University (França))
Nguyen, Danny (City of Hope National Medical Center (Duarte, Estats Units d'Amèrica))
Sabari, Joshua K. (New York University Langone Health)
Qin, Angel (University of Michigan Rogel Cancer Center)
Kowalski, Dariusz (Maria Sklodowska-Curie National Research Institute of Oncology (Warsaw, Poland))
Şendur, Mehmet Ali Nahit (Ankara Yıldırım Beyazıt University)
Xie, John (Janssen Research & Development (Raritan, Estats Units d'Amèrica))
Ghosh, Debopriya (Janssen Research & Development (Raritan, Estats Units d'Amèrica))
Alhadab, Ali (Janssen Research & Development (San Diego, Estats Units d'Amèrica))
Haddish-Berhane, Nahor (Janssen Research & Development ( Leiden, Estats Units d'Amèrica))
Clemens, Pamela L. (Janssen Research & Development, Spring Housen (Estats Units d'Amèrica))
Lorenzini, Patricia (Janssen Research & Development (Raritan, Estats Units d'Amèrica))
Verheijen, Remy B. (Janssen Research & Development (Leiden, Holanda))
Gamil, Mohamed (Janssen Research & Development (Spring Housen, Estats Units d'Amèrica))
Bauml, Joshua M. (Janssen Research & Development (Spring Housen, Estats Units d'Amèrica))
Baig, Mahadi (Janssen Research & Development (San Diego, Estats Units d'Amèrica))
Passaro, Antonio (European Institute of Oncology IRCCS (Milano, Itàlia))
Universitat Autònoma de Barcelona. Departament de Cirurgia

Data:	2024
Resum:	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 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; on cycle-2-day-1 or cycle-4-day-1) and cycle-2 area under the curve (AUC). Key secondary end points were objective response rate (ORR) and progression-free survival (PFS). Overall survival (OS) was a predefined exploratory end point. Overall, 418 patients underwent random assignment (subcutaneous group, n = 206; intravenous group, n = 212). Geometric mean ratios of C 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 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. Subcutaneous amivantamab-lazertinib demonstrated noninferiority to intravenous amivantamab-lazertinib, offering a consistent safety profile with reduced IRRs, increased convenience, and prolonged survival. PALOMA-3 shows noninferior PK, efficacy, better safety, and faster administration subcutaneous versus IV amivantamab.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	Journal of clinical oncology, Vol. 42 (june 2024) , p. 3593-3605, ISSN 1527-7755

DOI: 10.1200/JCO.24.01001
PMID: 38857463

29 p, 1.9 MB

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