As reported in the Journal of Clinical Oncology by Hope S. Rugo, MD, FASCO, and colleagues, the final overall survival results of the pivotal phase III SOPHIA trial have shown no significant difference between margetuximab-cmkb plus chemotherapy vs trastuzumab plus chemotherapy in previously treated patients with advanced HER2-positive breast cancer. Potential differences between treatment groups were observed according to CD16A genotype.
The trial supported the December 2020 approval of margetuximab combined with chemotherapy in patients with metastatic disease who had received two or more prior anti-HER2 regimens, at least one of which was for metastatic disease, on the basis of a progression-free survival benefit with margetuximab; at primary analysis, median progression-free survival was 5.8 vs 4.9 months (hazard ratio [HR] = 0.76, 95% confidence interval [CI] = 0.59–0.98, P = .033).
Hope S. Rugo, MD, FASCO
Study Details
In the trial, 536 patients in the intention-to-treat population were randomly assigned to receive margetuximab at 15 mg/kg every 3 weeks plus chemotherapy (n = 266) or trastuzumab at 6 mg/kg every 3 weeks following a loading dose of 8 mg/kg plus chemotherapy (n = 270). Metastatic disease was present in 98% of patients in each group. The primary endpoints were progression-free survival (reported previously) and overall survival. The final overall survival analysis was triggered by occurrence of 385 events.
Key Findings
At data cutoff (in June 2021), with a median follow-up of 20.2 months (range = 0.1–64.5 months), death had occurred in 194 patients (73%) in the margetuximab group and 191 patients (71%) in the trastuzumab group.
Median overall survival was 21.6 months (95% CI = 18.89–25.07 months) in the margetuximab group vs 21.9 months (95% CI = 18.69–24.18 months) in the trastuzumab group (HR = 0.95, 95% CI = 0.77–1.17, P = .620).
Genotyping was available for 506 patients (94%). In preplanned exploratory analyses, no relationships between CD32A or CD32B genotypes and survival were observed, but potential associations with CD16A genotype were identified. Among 102 vs 90 CD16A-158FF carriers, median overall survival was 23.6 months in the margetuximab group vs 19.2 months in the trastuzumab group (HR = 0.72, 95% CI = 0.52–1.00). Among 37 vs 32 CD16A-158VV carriers, median overall survival was 22.0 months in the margetuximab group vs 31.1 months in the trastuzumab group (HR = 1.77, 95% CI = 1.01–3.12).
The investigators concluded, “Final overall overall survival analysis did not demonstrate [a] margetuximab advantage over trastuzumab. Margetuximab studies in patients with HER2-positive breast cancer with different CD16A allelic variants are warranted.”
Dr. Rugo, of the University of California San Francisco, Helen Diller Family Comprehensive Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by MacroGenics, Inc. For full disclosures of the study authors, visit ascopubs.org.
