Benefit greatest in CD16A-158F carriers

By Peggy Peck, Editor-in-Chief, BreakingMED


CHICAGO — The possibility of a new treatment option for patients who fail standard first-line therapy always raises the interest level when oncologists are gathered, and that holds true for a report from the SOPHIA investigators that the investigational immune-enhancing monoclonal antibody margetuximab improved progression free survival in women with HER2+ metastatic breast cancer who were previously treated with at least two anti-HER2 regimens.

The median progression-free survival was 5.8 months in the margetuximab arm versus 4.9 months in the control arm (trastuzumab plus chemotherapy), said Hope S. Rugo, MD, director of Breast Oncology and Clinical Trials Education at the University of California San Francisco Comprehensive Cancer Center. Rugo reported results of the SOPHIA trial here at the American Society of Clinical Oncology. The objective response rate was 22% in the margetuximab arm (95% CI: 17.3-27.7%) compared to 16% in the trastuzumab arm (95% CI: 11.8-21.0%).

In addition to the PFS benefit, SOPHIA also confirmed the potential of CD16A genotyping as a predictor of efficacy for anti-HER2 treatments. In the study, margetuximab demonstrated the greatest benefit in low-affinity CD16A-158F carriers (HR = 0.68, P=0.005).

But Carlos H. Barrios, MD, of the Latin American Cooperative Oncology Group, who served as discussant for the SOPHIA results, questioned “a one-month benefit in PFS — is it clinically relevant?” Barrios, who lauded the trial’s use of an appropriate third-line regimen for a comparator, noted that the study’s open label design was a limitation. Still needed, he said, was the overall survival follow-up. Rugo noted that data were expected late this year — as well as evidence of activity of the agent in the central nervous system. “As survival is extended in metastatic disease, evidence of CNS activity becomes more important,” Barrios explained.

SOPHIA recruited 536 patients who were evenly randomized to margetuximab (n=266) given intravenously at 15 mg/kg every three weeks or trastuzumab (n=270) given intravenously at 6 mg/kg (or 8 mg/kg for loading dose) every three weeks in combination with one of four chemotherapy agents (capecitabine, eribulin, gemcitabine or vinorelbine) given at the standard dose.


SOPHIA was funded by MacroGenics.

Rugo disclosed honoraria and speakers bureau fees from Genomic Health; research funding from Celsion (Inst); Eisai (Inst); Genentech (Inst); GlaxoSmithKline (Inst); Lilly (Inst); Macrogenics (Inst); Merck (Inst); Nektar (Inst); Novartis (Inst); OBI Pharma (Inst); Pfizer (Inst); Plexxikon (Inst); and travel grants from Mylan; Nektar; Novartis; OBI Pharma; and Roche/Genentech.


Rugo H “SOPHIA primary PFS analysis: A phase 3 study of margetuximab + chemotherapy vs trastuzumab + chemotherapy patients with HER2+ metastatic breast cancer after prior anti-HER2 therapies” ASCO 2019; Oral Abstract Session Breast Cancer-Metastatic, June 4: Abstract 1000.


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