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

• Published in: Journal of clinical oncology Vol. 41; no. 2; pp. 198 - 205
• Main Authors: Rugo, Hope S, Im, Seock-Ah, Cardoso, Fatima, Cortes, Javier, Curigliano, Giuseppe, Musolino, Antonino, Pegram, Mark D, Bachelot, Thomas, Wright, Gail S, Saura, Cristina, Escrivá-de-Romaní, Santiago, De Laurentiis, Michelino, Schwartz, Gary N, Pluard, Timothy J, Ricci, Francesco, Gwin, 3rd, William R, Levy, Christelle, Brown-Glaberman, Ursa, Ferrero, Jean-Marc, de Boer, Maaike, Kim, Sung-Bae, Petráková, Katarína, Yardley, Denise A, Freedman, Orit, Jakobsen, Erik H, Gal-Yam, Einav Nili, Yerushalmi, Rinat, Fasching, Peter A, Kaufman, Peter A, Ashley, Emily J, Perez-Olle, Raul, Hong, Shengyan, Rosales, Minori Koshiji, Gradishar, William J
• Format: Journal Article
• Language: English
• Published: United States Wolters Kluwer Health 10.01.2023
• Subjects: Antibodies, Monoclonal, Humanized - adverse effects; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; CLINICAL TRIAL UPDATES; Female; Humans; Receptor, ErbB-2; Trastuzumab - adverse effects
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.21.02937

JCO 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; = .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 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 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.