|The following article features coverage from the 2019 San Antonio Breast Cancer Symposium. Click here to read more of Cancer Therapy Advisor‘s conference coverage.|
Previously treated patients with HER2-positive metastatic breast cancer — in particular, CD16A-F carriers — who received margetuximab and chemotherapy had improved outcomes compared with those who received trastuzumab and chemotherapy, according to the second interim analysis of the phase 3 SOPHIA trial (ClinicalTrials.gov Identifier: NCT02492711). The latest findings were presented at the 2019 San Antonio Breast Cancer Symposium (SABCS) in San Antonio, Texas.
The intention-to-treat population of the SOPHIA trial had 536 patients with HER2-positive metastatic breast cancer, of whom 266 were randomized to receive margetuximab and chemotherapy and 270 to receive trastuzumab and chemotherapy. Eligible patients received at least 2 prior lines of anti-HER2 therapy and 1 to 3 prior lines in the metastatic setting.
In the primary analysis of the SOPHIA trial, as reported by Cancer Therapy Advisor, a nearly 1-month median progression-free survival (PFS) benefit was seen among patients who received margetuximab compared with trastuzumab (5.8 vs 4.9 months, respectively; hazard ratio [HR], 0.76; 95% CI, 0.59–0.98; P =.033).
The primary analysis also showed that patients with CD16a genotypes containing a 158F allele seemed to benefit more from margetuximab, having a nearly 2-month median PFS benefit compared with trastuzumab (6.9 vs 5.1 months, respectively; HR, 0.68; 95% CI, 0.52-0.90; nominal P =.005).
The second planned interim analysis also showed that that patients who received margetuximab had lower risk of disease progression or death compared with those who received trastuzumab (HR, 0.71; 95% CI, 0.58-0.86; P =.0006), and median PFS benefit of more than 1 month (5.7 vs 4.4 months, respectively). Objective response rate was also significantly higher for the margetuximab arm compared with the trastuzumab arm (25.2% vs 13.7%, respectively; P =.0006)
However, at a median follow-up of 15.6 months, an overall survival (OS) benefit has yet to be seen for the margetuximab arm compared with the trastuzumab arm (21.6 vs 19.8 months; HR, 0.89; 95% CI, 0.69-1.13; P =.326).
An exploratory analysis revealed that for patients with CD16A genotypes containing a 158F allele, a 4.3-month median OS benefit was seen with margetuximab compared with trastuzumab (23.7 vs 19.4 months, respectively; HR, 0.79; 95% CI, 0.61-1.04; P =.087).
“In this exploratory analysis, patients carrying the lower-affinity CD16A-F allele appear to have a better outcome with margetuximab compared with trastuzumab,” said study presenter Hope Rugo, MD, University of California San Francisco Comprehensive Cancer Center.
“A final protocol-specified overall survival analysis is anticipated in late 2020,” Dr Rugo said.
Disclosure: Some of the authors disclosed financial relationships with the pharmaceutical industry. For a full list of disclosures, please refer to the original abstract.
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- Rugo HS, Im S-A, Cardoso F, et al. Phase 3 SOPHIA study of margetuximab + chemotherapy vs trastuzumab + chemotherapy in patients with HER2+ metastatic breast cancer after prior anti-HER2 therapies: second interim overall survival analysis. Oral presentation at: 2019 San Antonio Breast Cancer Symposium; December 10-14, 2019; San Antonio, TX. Abstract GS1-02.