Margetuximab

The primary PFS analysis from the phase III SOPHIA study (NCT02492711) led to the FDA approval of margetuximab with chemotherapy in patients with HER2-positive metastatic breast cancer who have received as least two previous anti-HER2 regimens, at least one of which was for metastatic disease. The open-label SOPHIA trial randomly assigned 536 patients in the ITT population to receive either margetuximab or trastuzumab. Both groups received investigator's choice of chemotherapy (capecitabine, eribulin, gemcitabine, or vinorelbine). Eligible patients had disease progression after two or more previous anti-HER2 therapies and one to three lines of therapy for metastatic disease. All patients had received previous trastuzumab, all but one had received previous pertuzumab, and 91.2% had received prior ado-trastuzumab emtansine. The sequential primary end points were PFS by central review followed by OS.[80,81][Level of evidence B1]

The primary PFS analysis from the phase III SOPHIA study (NCT02492711) led to the FDA approval of margetuximab with chemotherapy in patients with HER2-positive metastatic breast cancer who have received as least two previous anti-HER2 regimens, at least one of which was for metastatic disease. The open-label SOPHIA trial randomly assigned 536 patients in the ITT population to receive either margetuximab or trastuzumab. Both groups received investigator's choice of chemotherapy (capecitabine, eribulin, gemcitabine, or vinorelbine). Eligible patients had disease progression after two or more previous anti-HER2 therapies and one to three lines of therapy for metastatic disease. All patients had received previous trastuzumab, all but one had received previous pertuzumab, and 91.2% had received prior ado-trastuzumab emtansine. The sequential primary end points were PFS by central review followed by OS.[80,81][Level of evidence B1]

Margetuximab improved primary PFS over trastuzumab with a 24% relative risk reduction (HR, 0.76; 95% CI, 0.59–0.98; P = .03) (median PFS, 5.8 months vs. 4.9 months, favoring margetuximab).

The primary PFS analysis from the phase III SOPHIA study (NCT02492711) led to the FDA approval of margetuximab with chemotherapy in patients with HER2-positive metastatic breast cancer who have received as least two previous anti-HER2 regimens, at least one of which was for metastatic disease. The open-label SOPHIA trial randomly assigned 536 patients in the ITT population to receive either margetuximab or trastuzumab. Both groups received investigator's choice of chemotherapy (capecitabine, eribulin, gemcitabine, or vinorelbine). Eligible patients had disease progression after two or more previous anti-HER2 therapies and one to three lines of therapy for metastatic disease. All patients had received previous trastuzumab, all but one had received previous pertuzumab, and 91.2% had received prior ado-trastuzumab emtansine. The sequential primary end points were PFS by central review followed by OS.[80,81][Level of evidence B1]

The median follow-up was 20.2 months. The median OS in the ITT population was not statistically different between the two treatment groups: 21.6 months in the margetuximab group and 21.9 months in the trastuzumab group (HR, 0.95; 95% CI, 0.77–1.17; P = .620).

The primary PFS analysis from the phase III SOPHIA study (NCT02492711) led to the FDA approval of margetuximab with chemotherapy in patients with HER2-positive metastatic breast cancer who have received as least two previous anti-HER2 regimens, at least one of which was for metastatic disease. The open-label SOPHIA trial randomly assigned 536 patients in the ITT population to receive either margetuximab or trastuzumab. Both groups received investigator's choice of chemotherapy (capecitabine, eribulin, gemcitabine, or vinorelbine). Eligible patients had disease progression after two or more previous anti-HER2 therapies and one to three lines of therapy for metastatic disease. All patients had received previous trastuzumab, all but one had received previous pertuzumab, and 91.2% had received prior ado-trastuzumab emtansine. The sequential primary end points were PFS by central review followed by OS.[80,81][Level of evidence B1]

Grade 3 or higher adverse events that occurred in at least 5% of patients included decreased neutrophil count and anemia in both groups, fatigue in the margetuximab group, and febrile neutropenia in the trastuzumab group.