FDA Approves HER2+ Breast Cancer Treatment

The U.S. Food and Drug Administration granted accelerated approval to Enhertu® (fam-trastuzumab deruxtecan-nxki) for adults with unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting.

The approval was based on results from the open-label, multicenter, phase II DESTINY-Breast01 study that included 184 female patients (median age, 55 years; range, 28-96 years) with HER2+ unresectable and/or metastatic breast cancer who were heavily pretreated in the metastatic setting, with number of prior regimens ranging from two and 17. Patients received fam-trastuzumab deruxtecan-nxki 5.4 mg/kg intravenously every three weeks and underwent tumor imagining every six weeks.

Response rate with fam-trastuzumab deruxtecan-nxki

The overall response rate (primary endpoint) was 60.3%, with a median duration of response of 14.8 months and a median time to response of 1.6 months. Among responders, 67 (36.4%) had stable disease and three (1.6%) had progressive disease, translating to a disease control rate of 97.3% and a clinical benefit rate at six months of 76.1%.

Median progression-free survival was 16.4 months in the entire treated cohort and 18.1 months among patients with prior brain metastases. Median overall survival was not yet reached.

Fam-trastuzumab deruxtecan-nxki carries a Boxed Warning for the risk of interstitial lung disease and embryo-fetal toxicity, both of which have been reported with use and have resulted in death.

The most common adverse events (AEs) associated with fam-trastuzumab deruxtecan-nxki include nausea, fatigue, vomiting, alopecia, constipation, decreased appetite, anemia, decreased neutrophil count, diarrhea, leukopenia, cough, and decreased platelet count. Decreased neutrophil count is a potentially serious and common AE. Patients treated with fam-trastuzumab deruxtecan-nxki may be at increased risk of developing left ventricular dysfunction, which is common with other HER2-directed breast cancer treatments.