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

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.

Cardiac Safety and Efficacy of SB3 Trastuzumab Biosimilar for ERBB2-Positive Early Breast Cancer

“…26 The SOPHIA study suggested clinical benefit of margetuximab over trastuzumab in patients with ERBB2-positive metastatic breast cancer with CD16A-158F polymorphism. 27 Findings in the present study and the SOPHIA study support the hypothesis of ADCC activity being one of the anticancer mechanisms of trastuzumab and show how the shift in trastuzumab's ADCC activity may affect clinical outcomes. Biologic drugs are produced in living cells through complex multistep processes, and their inherent nature prevents any manufacturer from replicating the exact molecule.…”

Update Breast Cancer 2022 Part 5 – Early Stage Breast Cancer

“…The hazard ratio for overall survival was 0.95 (95% CI: 0.77 – 1.17). However, for the subcohort who were carriers of the homozygous gene CD16A-158FF, overall survival was better with margetuximab (HR = 0.72; 95% CI: 0.52 – 1.00), while conversely for the rarer genotype CD16-158VV, overall survival results were better with trastuzumab (HR = 1.77 95% CI: 1.01 – 3.12 43 .…”

“…Die Hazard Ratio für das Gesamtüberleben lag bei 0,95 (95%-KI: 0,77 – 1,17). Jedoch konnte in der Population der homozytogen CD16A-158FF-Träger gezeigt werden, dass das Gesamtüberleben mit Margetuximab besser war (HR = 0,72; 95%-KI: 0,52 – 1,00), während beim selteneren CD16-158VV-Genotyp umgekehrt das Trastuzumab in einem besseren Gesamtüberleben resultierte (HR = 1,77 95%-KI: 1,01 – 3,12) 43 .…”

“…Based on the Fc gamma receptor data from the SOPHIA study [43] as well as data from the study by Pivot et al [37], these biomarkers are a very interesting topic for future research. Consequently, in the NeoOn study, AGO-B is investigating whether a real-time ADCC test is able to predict the efficacy of ontruzant [44].…”

“…Die Daten zum Fc-Gamma-Rezeptor aus der SOPHIA-Studie [43] und die Daten der Studie von Pivot et al [37] machen diesen Biomarker für künftige Studien sehr interessant. So untersucht die AGO-B in der NeoOn-Studie, ob mit einem Real-Time-ADCC-Test die Wirksamkeit von Ontruzant vorhergesagt werden kann [44].…”