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.

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Last modified: November 2, 2022
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