Margetuximab plus chemotherapy afforded a statistically significant progression-free survival (PFS) benefit to patients with ERRB2-positive advanced breast cancer compared with trastuzumab and chemotherapy, according to data from the phase 3 SOPHIA trial. Though the field awaits the trial’s ( Identifier: NCT02492711) final overall survival (OS) analysis, SOPHIA data were recently published in JAMA Oncology.

A total of 536 patients with previously treated ERRB2-positive advanced breast cancer were randomly assigned to receive chemotherapy with either margetuximab or trastuzumab. Capecitabine, eribulin, gemcitabine, or vinorelbine were among the list of physician’s choice systemic therapies.

The SOPHIA trial met its primary end point, with margetuximab/chemotherapy demonstrating a 24% PFS relative risk reduction over trastuzumab/chemotherapy. Margetuximab bested trastuzumab in centrally assessed PFS analysis (HR. 0.76; 95% CI, 0.59-0.98; P =0.03) with a median PFS of 5.8 months vs 4.9 months with trastuzumab.

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The investigator-assessed PFS also favored the margetuximab arm (HR, 0.70; 95% CI, 0.56-0.87; P =0.001). This trend continued in the first objective response rate analysis (October 10, 2018; 22% vs 16%; P =0.06) and the second evaluation (September 10, 2019; 25% vs 14%; P <.001). The clinical benefit rate also indicated a greater advantage with margetuximab (37% vs 25%; P =0.003).

After the second planned interim analysis of 270 deaths, the median OS showed no statistical difference between arms (HR, 0.89; 95% CI, 0.69-1.13; P =0.33), but these data are not yet mature. A final OS analysis is anticipated in 2021.

All-grade infusion-related reactions (IRRs) were seen more frequently in the margetuximab arm compared with the trastuzumab arm (13.3% vs 3.4%). Left ventricular dysfunction was seen at similar rates (3.0% in both groups).

“Although IRRs were increased with margetuximab, almost all occurred during the first infusion only, and the observed margetuximab IRR rate aligns with that in published literature on trastuzumab first exposure (16%),” the study authors wrote.

Disclosures: Some of the study authors disclosed financial relationships with the pharmaceutical industry and/or the medical device industry. For a full list of disclosures, please refer to the original study.


Rugo HS, Im S-A, Cardoso F, et al. Efficacy of margetuximab vs trastuzumab in patients with pretreated ERBB2-positive advanced breast cancer: a phase 3 randomized clinical trial. JAMA Oncol. Published online January 22, 2021. doi:10.1001/jamaoncol.2020.7932