On December 23, 2019, the FDA accelerated the approval of fam-trastuzumab deruxtecan-nxki (Enhertu; Daiichi Sankyo), a HER2-directed antibody and topoisomerase inhibitor conjugate, for the treatment of adults with unresectable or metastatic HER2-positive breast cancer after ≥2 previous anti-HER2–based regimens in the metastatic setting. The FDA granted fam-trastuzumab deruxtecan-nxki a breakthrough therapy designation.
“There have been many advances in the development of drugs for HER2-positive breast cancer since the introduction of Herceptin (trastuzumab) in 1998. The approval of Enhertu represents the newest treatment option for patients who have progressed on available HER2-directed therapies,” said Richard Pazdur, MD, Director of the FDA’s Oncology Center of Excellence. “Drug development in the area of targeted therapies builds on our scientific understanding of malignant diseases not only in breast cancer, but in multiple other diseases.”
Approximately 1 of 5 breast cancers is associated with the HER2 gene mutation, an aggressive type of breast cancer.
Enhertu’s approval was based on the results of a clinical trial of 184 female patients with HER2-positive, unresectable and/or metastatic breast cancer who had received ≥2 previous anti-HER2 therapies in the metastatic setting. Patients were heavily pretreated in the metastatic setting, receiving from 2 to 17 previous therapies. In the study, patients received fam-trastuzumab deruxtecan-nxki every 3 weeks, and tumor imaging was obtained every 6 weeks. The overall response rate was 60.3%, with a median duration of response of 14.8 months.
The most common adverse events with fam-trastuzumab deruxtecan-nxki were nausea, fatigue, vomiting, alopecia, constipation, decreased appetite, anemia, decreased neutrophil count, diarrhea, leukopenia, cough, and decreased platelet count. This drug may increase the risk for ventricular dysfunction.
Fam-trastuzumab deruxtecan-nxki is associated with a risk for interstitial lung disease and embryo-fetal toxicity. Pregnant women should not take this medication.