SOPHIA
In pretreated HER2-positive advanced breast cancer, does margetuximab plus chemotherapy improve outcomes versus trastuzumab plus chemotherapy?
Trial design and population
536 patients with HER2-positive advanced breast cancer previously treated with ≥2 anti-HER2 regimens in metastatic setting, including pertuzumab and T-DM1.
Margetuximab 15 mg/kg IV every 3 weeks plus investigator-selected chemotherapy vs trastuzumab plus the same chemotherapy.
536
PFS; OS key secondary endpoint
Key results
Median PFS was 5.8 vs 4.9 months (HR 0.76, 95% CI 0.59–0.98; P=.03). Final median OS was 21.6 vs 21.9 months (HR 0.95, 95% CI 0.77–1.17); no OS improvement was demonstrated.
Source-reported outcome visualization
Median progression-free survival · Median
Source-reported endpoint and unit; median survival is not converted into an NNT.
Absolute Effect
Median PFS difference 0.9 months is not an NNT. OS was not improved.
NNT: Not calculated; median PFS difference is not a valid NNT. Endpoint/time horizon are stated above; do not convert median survival differences into NNT.
NNH: Not quantifiable. Infusion-related reactions were more common with margetuximab; grade ≥3 AEs largely reflected chemotherapy and advanced disease. Modest PFS gain must be weighed against infusion burden and absence of OS benefit.
Safety and treatment burden
Infusion-related reactions were more common with margetuximab; grade ≥3 AEs largely reflected chemotherapy and advanced disease. Modest PFS gain must be weighed against infusion burden and absence of OS benefit.
Follow-up, maturity and limitations
Final OS analysis with approximately 30 months follow-up.
Compared with trastuzumab plus chemotherapy, not newer ADCs. Treatment landscape has changed with trastuzumab deruxtecan and tucatinib-based regimens.
Clinical interpretation
Current-practice context · reviewed 20 October 2026
Historical evidence is separated from current sequencing. Confirm local regulatory status, current guidelines, biomarkers, prior therapies and patient-specific contraindications before applying these results. Newer treatments may have changed the preferred sequence; where NNT/NNH cannot be defensibly quantified, no surrogate calculation is made.