Skip to main content

Enhertu First FDA-Approved Treatment for HER2-Low Breast Cancer

Web Exclusives - FDA Approvals

On August 5, 2022, the FDA accelerated the approval of fam-trastuzumab deruxtecan-nxki (Enhertu; Daiichi Sankyo), an HER2-directed antibody and topoisomerase inhibitor conjugate, for unresectable or metastatic HER2-low breast cancer in adults after receiving chemotherapy in the metastatic setting or when the disease recurred during or within 6 months of completing adjuvant chemotherapy. Fam-trastuzumab deruxtecan received a breakthrough therapy designation for this indication.

And on October 4, 2022, the FDA approved the anti-HER2/neu (4B5) Rabbit Monoclonal Primary Antibody pathway to identify HER2-low expression in patients with metastatic breast cancer.

Fam-trastuzumab deruxtecan was previously approved for several solid tumors associated with the HER2 biomarker.

“Approximately half of all patients with breast cancer have tumors that are HER2-low, which have previously been classified as HER2-negative and have not had effective treatment options with HER2-targeted medicines,” said Shanu Modi, MD, Medical Oncologist, Memorial Sloan Kettering Cancer Center, adding that these results will “redefine how metastatic breast cancer is classified with a distinct HER2-low patient population.”

This approval was based on results of the randomized, multicenter, open-label DESTINY-Breast04 clinical trial of 557 patients with unresectable or metastatic HER2-low breast cancer, including 494 with hormone receptor (HR)-positive and 63 with HR-negative disease. The primary end point was progression-free survival (PFS) in HR-positive patients. The secondary end points were PFS and overall survival (OS) in the overall population and OS in HR-positive patients. Overall, 373 patients received 5.4 mg of fam-trastuzumab deruxtecan intravenously every 3 weeks and 184 patients received the physician’s choice of chemotherapy.

The median PFS for HR-positive patients was 10.1 months with fam-trastuzumab deruxtecan (95% confidence interval [CI], 9.5-11.5 months) versus 5.4 months with chemotherapy (95% CI, 4.4-7.1 months). The median PFS in the overall population was 9.9 months (95% CI, 9-11.3 months) versus 5.1 months, respectively (95% CI, 4.2-6.8 months; hazard ratio, 0.5).

In the HR-positive patients, the median OS was 23.9 months with fam-trastuzumab deruxtecan and 17.5 months with chemotherapy (95% CI, 20.8-24.8 months vs 15.2-22.4 months, respectively; hazard ratio, 0.64). In the overall patient population, the median OS was 23.4 months versus 16.8 months, respectively (95% CI, 20-24.8 months vs 14.5-20 months, respectively; hazard ratio, 0.64).

The most common (≥20%) adverse events with fam-trastuzumab deruxtecan in this study were nausea, fatigue, alopecia, vomiting, anemia, constipation, decreased appetite, diarrhea, and musculoskeletal pain.

Related Items
FDA Authorizes Updated COVID-19 Vaccine Formulations for Better Protection Against Current Variants
Web Exclusives published on November 16, 2023 in FDA Approvals
Bosulif Now FDA Approved for Pediatric Patients With Chronic Myelogenous Leukemia
Web Exclusives published on November 1, 2023 in FDA Approvals
FDA Approved Abrysvo, First RSV Vaccine for Immunizing Pregnant Women, as Prophylaxis Against RSV Infection in Infants
Web Exclusives published on October 30, 2023 in FDA Approvals
Tyruko First Biosimilar for the Treatment of Relapsing Forms of Multiple Sclerosis
Web Exclusives published on October 30, 2023 in FDA Approvals
FDA Approved Aphexda, in Combination With Filgrastim, to Mobilize Stem Cells for Transplant in Patients With Multiple Myeloma
Web Exclusives published on October 30, 2023 in FDA Approvals
Last modified: November 2, 2022