Margetuximab does not provide an overall survival (OS) benefit over trastuzumab in patients with previously treated, HER2-positive breast cancer, according to final results from the phase 3 SOPHIA trial.1

The updated data confirmed that margetuximab plus chemotherapy can improve progression-free survival (PFS), when compared with trastuzumab plus chemotherapy. However, there was no significant difference in OS between the treatment arms. These results were published in the Journal of Clinical Oncology.

The phase 3 SOPHIA trial ( Identifier: NCT02492711) included 536 patients with HER2-positive, advanced breast cancer. They were randomly assigned to receive margetuximab plus chemotherapy (n=266) or trastuzumab plus chemotherapy (n=270). 

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At baseline, the median age was 55 years in the margetuximab arm and 56 years in the trastuzumab arm (overall range, 27-86 years). Most patients in both arms were women (100% and 98.9%, respectively), were White (77.1% vs 82.2%), had metastatic disease (97.7% vs 97.8%), and had 2 or fewer prior lines of therapy in the metastatic setting (65.8% vs 66.7%). All patients had received prior treatment with trastuzumab. Most had received prior pertuzumab (100% vs 99.6%) and ado-trastuzumab emtansine (91.0% vs 91.5%).

In a prior analysis from this trial, margetuximab was associated with improved PFS, but not OS, compared with trastuzumab.2 According to a blinded review committee, the median PFS was 5.8 months with margetuximab and 4.9 months with trastuzumab (hazard ratio [HR], 0.76; 95% CI, 0.59-0.98; P =.03). The median OS was 21.6 months and 19.8 months, respectively (HR, 0.89; 95% CI, 0.69-1.13; P =.33).

In the current analysis, with a median follow-up of 20.2 months, there was still no OS benefit with margetuximab.1 The median OS was 21.6 months with margetuximab and 21.9 months with trastuzumab (HR, 0.95; 95% CI, 0.77-1.17; P =.620). 

The 12-month OS rate was 75% with margetuximab and 76% with trastuzumab. The 24-month OS rate was 46% and 44%, respectively.

The median PFS, per investigator assessment, was 5.7 months with margetuximab and 4.4 months with trastuzumab (HR, 0.73; 95% CI, 0.60-0.88; P =.001).

In a preplanned, exploratory analysis, researchers found that OS results differed according to the presence of CD16A variants. The researchers found a possible improvement in OS with margetuximab in patients with CD16A-158FF and a possible improvement in OS with trastuzumab in patients with CD16A-158VV. 

Among patients with CD16A-158FF, the median OS was 23.6 months with margetuximab and 19.2 months with trastuzumab (HR, 0.72; 95% CI, 0.52-1.00). Among patients with CD16A-158VV, the median OS was 22.0 months with margetuximab and 31.1 months with trastuzumab (HR, 1.77; 95% CI, 1.01-3.12).

The safety profile of margetuximab was similar to that of trastuzumab. However, fatigue was more common with margetuximab (5.3% vs 3.0%), and febrile neutropenia was more common with trastuzumab (4.9% vs 3.0%).

Disclosures: This research was supported by MacroGenics. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


1. Rugo HS, Im S-A, Cardoso F, et al. Margetuximab versus trastuzumab in patients with previously treated HER2-positive advanced breast cancer (SOPHIA): Final overall survival results from a randomized phase 3 trial. J Clin Oncol. Published online November 4, 2022. doi:10.1200/JCO.21.02937

2. 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. 2021;7(4):573–584. doi:10.1001/jamaoncol.2020.7932