Overall survival from tebentafusp versus nivolumab plus ipilimumab in first-line metastatic uveal melanoma: a propensity score-weighted analysis.

Autor:	Piulats JM; Institut Català d'Oncologia, Barcelona; Cancer Immunotherapy Group, OncoBell, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Barcelona; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain. Electronic address: jmpiulats@iconcologia.net., Watkins C; Clarostat Consulting Ltd, Cheshire, UK., Costa-García M; Cancer Immunotherapy Group, OncoBell, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Barcelona., Del Carpio L; Institut Català d'Oncologia, Barcelona; Cancer Immunotherapy Group, OncoBell, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Barcelona., Piperno-Neumann S; Institut Curie, Paris, France., Rutkowski P; Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland., Hassel JC; University Hospital Heidelberg, Heidelberg, Germany., Espinosa E; Hospital Universitario La Paz, CIBERONC, Madrid., de la Cruz-Merino L; Oncology Department, Virgen Macarena University Hospital, Department of Medicine, School of Medicine, University of Seville, Seville, Spain., Ochsenreither S; Charité-Comprehensive Cancer Center, Berlin, Germany., Shoushtari AN; Memorial Sloan Kettering Cancer Center, New York; Weill Cornell Medical College, New York., Orloff M; Sidney Kimmel Cancer Center, Thomas Jefferson University Hospital, Philadelphia., Salama AKS; Duke University, Durham, USA., Goodall HM; Immunocore, Abingdon, UK., Baurain JF; Institut Roi Albert II Cliniques Universitaires St-Luc, UCLouvain, Brussels, Belgium., Nathan P; Mount Vernon Cancer Centre, Northwood, UK.
Jazyk:	angličtina
Zdroj:	Annals of oncology : official journal of the European Society for Medical Oncology [Ann Oncol] 2024 Mar; Vol. 35 (3), pp. 317-326. Date of Electronic Publication: 2023 Dec 02.
DOI:	10.1016/j.annonc.2023.11.013
Abstrakt:	Background: Tebentafusp demonstrated a superior overall survival (OS) benefit [hazard ratio (HR) 0.51] compared to investigator's choice (82% pembrolizumab) in a randomized, phase III trial (IMCgp100-202; N = 378) in untreated metastatic uveal melanoma (mUM). The 1-year OS rates for tebentafusp and pembrolizumab were 73% and 59%, respectively. In the single-arm GEM1402 (N = 52), the 1-year OS rate for nivolumab plus ipilimumab (N+I) in mUM was 52%. Due to limitations in conducting randomized trials in mUM, we compared OS on tebentafusp or pembrolizumab (IMCgp100-202) to N+I (GEM1402) in untreated mUM using propensity scoring methods. Patients and Methods: Analyses were adjusted using propensity score-based inverse probability of treatment weighting (IPTW), balancing age, sex, baseline lactate dehydrogenase (LDH), baseline alkaline phosphatase, disease location, Eastern Cooperative Oncology Group status, and time from primary diagnosis to metastasis. OS was assessed using IPT-weighted Kaplan-Meier and Cox proportional hazard models. Sensitivity analyses using alternative missing data and weights methods were conducted. Results: The primary IPTW analysis included 240 of 252 patients randomized to tebentafusp from IMCgp100-202 and 45 of 52 N+I-treated patients from GEM-1402. Key baseline covariates, including LDH, were generally well balanced before weighting. The IPTW-adjusted OS favored tebentafusp, HR 0.52 [95% confidence interval (CI) 0.35-0.78]; 1-year OS was 73% for tebentafusp versus 50% for N+I. Sensitivity analyses showed consistent superior OS for tebentafusp with all IPTW HRs ≤0.61. IPTW analysis of pembrolizumab versus N+I showed no significant difference in OS (HR 0.72; 95% CI 0.50-1.06). Conclusions: Tebentafusp was previously shown to provide an OS benefit compared to checkpoint inhibitors or chemotherapy in untreated mUM. Propensity score analysis demonstrated a similar OS benefit for tebentafusp compared with N+I. These data further support tebentafusp as the standard of care in previously untreated human leukocyte antigen (HLA)-A∗02:01+ adult patients with mUM. (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
Databáze:	MEDLINE
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