Margetuximab Versus Trastuzumab in Patients With Previously Treated HER2-Positive Advanced Breast Cancer (SOPHIA): Final Overall Survival Results From a Randomized Phase 3 Trial

Rugo HS, Im SA, Cardoso F, Cortes J, Curigliano G, Musolino A, Pegram MD, Bachelot T, Wright GS, Saura C, Escrivá-de-Romaní S, De Laurentiis M, Schwartz GN, Pluard TJ, Ricci F, Gwin WR, Levy C, Brown-Glaberman U, Ferrero JM, de Boer M, Kim SB, Petráková K, Yardley DA, Freedman O, Jakobsen EH, Gal-Yam EN, Yerushalmi R, Fasching P, Kaufman PA, Ashley EJ, Perez-Olle R, Hong S, Rosales MK, Gradishar WJ (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Book Volume: 41

Pages Range: 198-205

Journal Issue: 2

DOI: 10.1200/JCO.21.02937

Abstract

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.Final overall survival (OS) in SOPHIA (ClinicalTrials.gov identifier: NCT02492711), a study of margetuximab versus trastuzumab, both with chemotherapy, in patients with previously treated human epidermal growth factor receptor 2-positive advanced breast cancer, is reported with updated safety. Overall, 536 patients in the intention-to-treat population were randomly assigned to margetuximab (15 mg/kg intravenously once every 3 weeks; n = 266) plus chemotherapy or trastuzumab (6 mg/kg intravenously once every 3 weeks after a loading dose of 8 mg/kg; n = 270) plus chemotherapy. Primary end points were progression-free survival, previously reported, and OS. Final OS analysis was triggered by 385 prespecified events. The median OS was 21.6 months (95% CI, 18.89 to 25.07) with margetuximab versus 21.9 months (95% CI, 18.69 to 24.18) with trastuzumab (hazard ratio [HR], 0.95; 95% CI, 0.77 to 1.17; P = .620). Preplanned, exploratory analysis of CD16A genotyping suggested a possible improvement in OS for margetuximab in CD16A-158FF patients versus trastuzumab (median OS, 23.6 v 19.2 months; HR, 0.72; 95% CI, 0.52 to 1.00) and a possible improvement in OS for trastuzumab in CD16A-158VV patients versus margetuximab (median OS, 31.1 v 22.0 months; HR, 1.77; 95% CI, 1.01 to 3.12). Margetuximab safety was comparable with trastuzumab. Final overall OS analysis did not demonstrate margetuximab advantage over trastuzumab. Margetuximab studies in patients with human epidermal growth factor receptor 2-positive breast cancer with different CD16A allelic variants are warranted.

Authors with CRIS profile

Involved external institutions

UCSF Helen Diller Family Comprehensive Cancer Center United States (USA) (US) Seoul National University (SNU) / 서울대학교 Korea, Republic of (KR) Champalimaud Foundation / Fundação Champalimaud Portugal (PT) International Breast Cancer Centre (IBCC) Spain (ES) Università degli studi di Milano Italy (IT) University of Parma / Università degli Studi di Parma Italy (IT) Stanford University United States (USA) (US) Centre Léon-Bérard (UNICANCER) France (FR) Florida Cancer Specialists & Research Institute (FCS) United States (USA) (US) Vall d'Hebron University Hospital / Hospital Universitari Vall d'Hebron Spain (ES) Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale" Italy (IT) Dartmouth-Hitchcock Medical Center (DHMC) United States (USA) (US) Saint Luke's Health System United States (USA) (US) Institut Curie France (FR) University of Washington United States (USA) (US) Center François Baclesse France (FR) University of New Mexico (UNM) / Universidad de Nuevo México United States (USA) (US) University of Côte d'Azur / Université Côte d'Azur France (FR) Maastricht University Netherlands (NL) University of Ulsan / 울산대학교 Korea, Republic of (KR) Masaryk Memorial Cancer Institute (MMCI) / Masarykův onkologický ústav (MOÚ) Czech Republic (CZ) Sarah Cannon Research Institute (SCRI) United States (USA) (US) Lakeridge Health Oshawa Canada (CA) Vejle Sygehus Denmark (DK) Chaim Sheba Medical Center at Tel HaShomer / המרכז הרפואי עש חיים שיבא – תל השומר‎‎ Israel (IL) Rabin Medical Center / מרכז רפואי רבין‎‎ Israel (IL) University of Vermont United States (USA) (US) MacroGenics, Inc. United States (USA) (US) Northwestern University United States (USA) (US)

How to cite

APA:

Rugo, H.S., Im, S.A., Cardoso, F., Cortes, J., Curigliano, G., Musolino, A.,... Gradishar, W.J. (2023). Margetuximab Versus Trastuzumab in Patients With Previously Treated HER2-Positive Advanced Breast Cancer (SOPHIA): Final Overall Survival Results From a Randomized Phase 3 Trial. Journal of Clinical Oncology, 41(2), 198-205. https://doi.org/10.1200/JCO.21.02937

MLA:

Rugo, Hope S., et al. "Margetuximab Versus Trastuzumab in Patients With Previously Treated HER2-Positive Advanced Breast Cancer (SOPHIA): Final Overall Survival Results From a Randomized Phase 3 Trial." Journal of Clinical Oncology 41.2 (2023): 198-205.

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