On December 20, the U.S. Food and Drug Administration (FDA) granted accelerated approval to fam-trastuzumab deruxtecan-nxki (Enhertu) for patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti–HER2-based regimens in the metastatic setting.
DESTINY-Breast01 and Study DS8201-A-J101
Efficacy was investigated in DESTINY-Breast01, a multicenter, single-arm trial enrolling 184 female patients with HER2-positive, unresectable and/or metastatic breast cancer who had received two or more prior anti-HER2 therapies. Patients received 5.4 mg/kg of fam-trastuzumab deruxtecan-nxki by intravenous infusion every 3 weeks until unacceptable toxicity or disease progression.
The main efficacy outcome measures were confirmed objective response rate assessed by independent central review using Response Evaluation Criteria in Solid Tumors, version 1.1, and response duration. Objective response rate was 60.3% (95% confidence interval [CI] = 52.9–67.4), with a 4.3% complete response rate and a 56% partial response rate. Median response duration was 14.8 months (95% CI = 13.8–16.9).
The safety was evaluated in a pooled analysis of 234 patients with unresectable or metastatic HER2-positive breast cancer who received at least one dose of fam-trastuzumab deruxtecan-nxki at 5.4 mg/kg in the DESTINY-Breast01 trial and Study DS8201-A-J101.
The most common adverse reactions (frequency ≥ 20%) to fam-trastuzumab deruxtecan-nxki were nausea, fatigue, vomiting, alopecia, constipation, decreased appetite, anemia, neutropenia, diarrhea, leukopenia, cough, and thrombocytopenia. The prescribing information includes a Boxed Warning to advise health professionals of the risk of interstitial lung disease and embryofetal toxicity. Fatal outcomes due to interstitial lung disease occurred in 2.6% of patients.
The recommended dose of fam-trastuzumab deruxtecan-nxki is 5.4 mg/kg given as an intravenous infusion once every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity.
