Final overall survival results from the phase 3 SOPHIA trial revealed that the progression-free survival advantage seen with margetuximab over trastuzumab in an earlier analysis did not translate into a significant OS benefit in patients with previously treated HER2-positive metastatic breast cancer.  

The earlier PFS analysis of the study led to FDA approval of margetuximab with chemotherapy in patients with HER2-positive metastatic breast cancer who have received at least 2 prior anti-HER2 regimens—at least one of which was for metastatic disease. 

A total of 536 patients in the intention-to-treat population were randomly assigned to treatment with either IV margetuximab (15 mg/kg once every 3 weeks; n = 266) plus chemotherapy or IV trastuzumab (6 mg/kg once every 3 weeks after a loading dose of 8 mg/kg; n = 270) plus chemotherapy.  

The final OS analysis was triggered by a total of 385 deaths, which had occurred at a median follow-up of 20.2 months. At that point, it was found that median OS was 21.6 months among patients treated with margetuximab, compared with 21.9 months among their counterparts treated with trastuzumab.  

The researchers also performed a pre-planned subgroup analyses of OS by type of chemotherapy and HER2 status, which showed no difference in survival between margetuximab and trastuzumab.  
 
On the other hand, an exploratory analysis of CD16A genotyping suggested a possible OS improvement among CD16A-158FF patients treated with margetuximab (median 23.6 months) relative to trastuzumab (median 19.2 months; HR = 0.72; 95% CI, 0.5-1).  

Similar analyses revealed a possible OS benefit for trastuzumab in CD16A-158VV patients relative to margetuximab (median OS 31.1 vs 22 months; HR = 1.77; 95% CI, 1-3.1). 

Safety analyses found that margetuximab was comparable with trastuzumab. Treatment discontinuation due to adverse events were observed in 4% of patients in each treatment group.  

In light of these findings, the investigators wrote that the PFS advantage previously observed with margetuximab-chemotherapy did not translate into a significant difference in OS in the intention-to-treat population of the SOPHIA trial.  

They added that further studies of margetuximab in patients with HER2+ breast cancer with different CD16A allelic variants are warranted. 

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Reference:  
ascopubs.org/doi/full/10.1200/JCO.21.02937 

Disclosures: Authors declared financial ties to drugmakers. See full study for details. SOPHIA was supported by MacroGenics. 

Photo Credit: Getty Images. 

By Michael Vlessides, MD /alert Contributor