San Antonio, Texas—Second interim analysis data being presented at the 2019 San Antonio Breast Cancer Symposium show that combining margetuximab with chemo improves progression-free survival (PFS) over trastuzumab in patients with treated HER2-positive metastatic breast cancer.

“[HER2]-targeting monoclonal antibodies (mAb) are the standard of care in early-to-advanced HER2-positive breast cancer. However, for relapsed/refractory disease, limited options exist after progression on trastuzumab, pertuzumab, and ado-trastuzumab emtansine,” explained Hope S. Rugo, MD, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, and colleagues.

“Margetuximab targets the same epitope as trastuzumab and exerts similar antiproliferative effects. Compared with trastuzumab, margetuximab has higher affinity for both 158V (high binding) and 158F (low binding) alleles of the activating Fc receptor, CD16A. Margetuximab enhances innate immunity more effectively than trastuzumab, and potentiates adaptive immunity in treated patients,” they continued.

In the phase 3 SOPHIA trial, patients with metastatic breast cancer that progressed after prior therapy were randomized in a 1:1 ratio to receive chemotherapy plus margetuximab 15 mg/kg intravenously every 3 weeks or trastuzumab. The primary end points of the study were PFS and overall survival (OS); at the time of PFS analysis (October 2018), the first interim OS analysis was immature, with 158 (41%) of 385 deaths required for final OS analysis. Findings from the second interim OS analysis are reported here. In the intent-to-treat (ITT) population (n = 536), margetuximab plus chemotherapy was shown to prolong PFS compared with trastuzumab plus chemotherapy (median PFS, 5.8 vs 4.9 months; hazard ratio [HR], 0.76; 95% CI, 0.59-0.98; P = .033).

According to Dr Rugo and her co-investigators, these findings were more pronounced in patients with versus without CD16A genotypes containing a 158F allele (median PFS, 6.9 vs 5.1 months; HR, 0.68; 95% CI, 0.52-0.90; nominal P = .005).

At the first interim analysis, the OS had an HR of 0.95 (95% CI, 0.69-1.31) in the ITT population and 0.82 (95% CI: 0.58-1.17) for the CD16A/FF or FV genotype population (n = 457). Among patients receiving margetuximab versus trastuzumab, grade ≥3 adverse events occurred in 138 (52%) and 128 (48%), respectively. Serious adverse events were reported in 39 (15%) and 46 (17%) patients in either arm, respectively.

“Margetuximab plus chemotherapy in patients with treated HER2-positive metastatic breast cancer improves PFS versus trastuzumab. Safety was comparable. CD16A genotyping suggests a greater benefit in patients with a 158F allele,” concluded Dr Rugo and colleagues.

“Maturing data comparing the OS of patients treated with margetuximab versus trastuzumab with chemotherapy will provide important new insights in characterizing clinical activity of this regimen in patients with metastatic breast cancer,” they added.—Hina Porcelli

Rugo HS, Im SA, 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. Presented at: the 2019 San Antonio Breast Cancer Symposium; December 10-14, 2019; San Antonio, TX. Abstract GS1-02.