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
Issued Date
2024-01-01
Resource Type
ISSN
0732183X
eISSN
15277755
Scopus ID
2-s2.0-85201012855
Pubmed ID
38857463
Journal Title
Journal of Clinical Oncology
Rights Holder(s)
SCOPUS
Bibliographic Citation
Journal of Clinical Oncology (2024)
Suggested Citation
Leighl N.B., Akamatsu H., Lim S.M., Cheng Y., Minchom A.R., Marmarelis M.E., Sanborn R.E., Chih-Hsin Yang J., Liu B., John T., Massutí B., Spira A.I., Lee S.H., Wang J., Li J., Liu C., Novello S., Kondo M., Tamiya M., Korbenfeld E., Moskovitz M., Han J.Y., Alexander M., Joshi R., Felip E., Voon P.J., Danchaivijitr P., Hsu P.C., Silva Melo Cruz F.J., Wehler T., Greillier L., Teixeira E., Nguyen D., Sabari J.K., Qin A., Kowalski D., Nahit Şendur M.A., Xie J., Ghosh D., Alhadab A., Haddish-Berhane N., Clemens P.L., Lorenzini P., Verheijen R.B., Gamil M., Bauml J.M., Baig M., Passaro A. 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. Journal of Clinical Oncology (2024). doi:10.1200/JCO.24.01001 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/101392
Title
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
Author(s)
Leighl N.B.
Akamatsu H.
Lim S.M.
Cheng Y.
Minchom A.R.
Marmarelis M.E.
Sanborn R.E.
Chih-Hsin Yang J.
Liu B.
John T.
Massutí B.
Spira A.I.
Lee S.H.
Wang J.
Li J.
Liu C.
Novello S.
Kondo M.
Tamiya M.
Korbenfeld E.
Moskovitz M.
Han J.Y.
Alexander M.
Joshi R.
Felip E.
Voon P.J.
Danchaivijitr P.
Hsu P.C.
Silva Melo Cruz F.J.
Wehler T.
Greillier L.
Teixeira E.
Nguyen D.
Sabari J.K.
Qin A.
Kowalski D.
Nahit Şendur M.A.
Xie J.
Ghosh D.
Alhadab A.
Haddish-Berhane N.
Clemens P.L.
Lorenzini P.
Verheijen R.B.
Gamil M.
Bauml J.M.
Baig M.
Passaro A.
Akamatsu H.
Lim S.M.
Cheng Y.
Minchom A.R.
Marmarelis M.E.
Sanborn R.E.
Chih-Hsin Yang J.
Liu B.
John T.
Massutí B.
Spira A.I.
Lee S.H.
Wang J.
Li J.
Liu C.
Novello S.
Kondo M.
Tamiya M.
Korbenfeld E.
Moskovitz M.
Han J.Y.
Alexander M.
Joshi R.
Felip E.
Voon P.J.
Danchaivijitr P.
Hsu P.C.
Silva Melo Cruz F.J.
Wehler T.
Greillier L.
Teixeira E.
Nguyen D.
Sabari J.K.
Qin A.
Kowalski D.
Nahit Şendur M.A.
Xie J.
Ghosh D.
Alhadab A.
Haddish-Berhane N.
Clemens P.L.
Lorenzini P.
Verheijen R.B.
Gamil M.
Bauml J.M.
Baig M.
Passaro A.
Author's Affiliation
Siriraj Hospital
Osaka International Cancer Institute
Janssen Vaccines & Prevention B.V.
Fudan University Shanghai Cancer Center
Ankara Yildirim Beyazit University
Sichuan Cancer Hospital and Institute
Chang Gung University College of Medicine
National Taiwan University Hospital
Janssen Research & Development
Maria Sklodowska-Curie National Research Institute of Oncology
National Cancer Center, Gyeonggi
Fujita Health University School of Medicine
NYU Langone Health
Istituto Europeo di Oncologia
Princess Margaret Cancer Centre
University of Melbourne
Centre de Recherche en Cancérologie de Marseille
Wakayama Medical University
Medical University of South Carolina
Universitat Autònoma de Barcelona
Penn Medicine
Rabin Medical Center Israel
Harbin Medical University
Samsung Medical Center, Sungkyunkwan university
Yonsei University College of Medicine
Providence Health System in Oregon
University of Michigan Rogel Cancer Center
Università degli Studi di Torino
Royal Marsden Hospital
Sarawak General Hospital
China Medical University Shenyang
Universitätsklinikum Gießen und Marburg, Standort Gießen
City of Hope National Med Center
Hospital Britanico de Buenos Aires
Dr. Balmis General University Hospital
Hospital CUF Descobertas
Conservation Council SA
Jilin Cancer Hospital
Virginia Cancer Specialists
Instituto Brasileiro de Controle do Câncer
Osaka International Cancer Institute
Janssen Vaccines & Prevention B.V.
Fudan University Shanghai Cancer Center
Ankara Yildirim Beyazit University
Sichuan Cancer Hospital and Institute
Chang Gung University College of Medicine
National Taiwan University Hospital
Janssen Research & Development
Maria Sklodowska-Curie National Research Institute of Oncology
National Cancer Center, Gyeonggi
Fujita Health University School of Medicine
NYU Langone Health
Istituto Europeo di Oncologia
Princess Margaret Cancer Centre
University of Melbourne
Centre de Recherche en Cancérologie de Marseille
Wakayama Medical University
Medical University of South Carolina
Universitat Autònoma de Barcelona
Penn Medicine
Rabin Medical Center Israel
Harbin Medical University
Samsung Medical Center, Sungkyunkwan university
Yonsei University College of Medicine
Providence Health System in Oregon
University of Michigan Rogel Cancer Center
Università degli Studi di Torino
Royal Marsden Hospital
Sarawak General Hospital
China Medical University Shenyang
Universitätsklinikum Gießen und Marburg, Standort Gießen
City of Hope National Med Center
Hospital Britanico de Buenos Aires
Dr. Balmis General University Hospital
Hospital CUF Descobertas
Conservation Council SA
Jilin Cancer Hospital
Virginia Cancer Specialists
Instituto Brasileiro de Controle do Câncer
Corresponding Author(s)
Other Contributor(s)
Abstract
PURPOSEPhase 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 METHODSPatients 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.RESULTSOverall, 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.CONCLUSIONSubcutaneous amivantamab-lazertinib demonstrated noninferiority to intravenous amivantamab-lazertinib, offering a consistent safety profile with reduced IRRs, increased convenience, and prolonged survival.