The Food and Drug Administration (FDA) has accepted for Priority Review the supplemental Biologics License Application (sBLA) for Enhertu® (fam-trastuzumab deruxtecan-nxki), a HER2-directed antibody and topoisomerase inhibitor conjugate, for the treatment of adults with unresectable or metastatic HER2-low (immunohistochemistry [IHC] 1+ or IHC 2+/in-situ hybridization [ISH]-negative) breast cancer who have received a prior therapy in the metastatic setting.
The sBLA is supported by data from the open-label, phase 3 DESTINY-Breast04 trial (ClinicalTrials.gov Identifier: NCT03734029), which evaluated the safety and efficacy of Enhertu in 557 adults with unresectable or metastatic HER2-low breast cancer who had received 1 or 2 previous lines of chemotherapy.
HER2-low status was defined as an IHC score of 1+ or IHC 2+ with a negative ISH score. Patients were randomly assigned 2:1 to receive either Enhertu or physician’s choice of treatment (capecitabine, eribulin, gemcitabine, paclitaxel, nab-paclitaxel).
Results showed that among patients with hormone receptor-positive disease (n=494), median progression-free survival (PFS; primary endpoint) was 10.1 months in the Enhertu arm and 5.4 months in the physician’s choice of chemotherapy arm (hazard ratio [HR], 0.51; P <.001); overall survival (OS) was 23.9 months and 17.5 months, respectively (HR, 0.64; P =.003).
Among all patients, median PFS was 9.9 months in the Enhertu arm and 5.1 months in the physician’s choice of chemotherapy arm (HR, 0.50; P <.001), and OS was 23.4 months and 16.8 months, respectively (HR, 0.64; P =.001).
“The data from DESTINY-Breast04 represent the first time a HER2-targeted therapy has shown a survival benefit in patients with HER2-low metastatic breast cancer,” said Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca. “If approved, Enhertu will redefine how we classify and treat metastatic breast cancer, enabling patients whose tumors have lower levels of HER2 expression the opportunity to benefit from a HER2-directed therapy.”
The FDA previously granted Breakthrough Therapy designation to Enhertu for this indication. The safety profile of Enhertu was consistent with previous clinical trials; no new safety concerns were identified.
Enhertu is currently approved for the treatment of unresectable or metastatic HER2-positive breast cancer in patients who have received 2 or more prior anti-HER2-based regimens in the metastatic setting. It is also indicated for locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma in patients who have received a prior trastuzumab-based regimen.
- Enhertu® (fam-trastuzumab deruxtecan-nxki) granted Priority Review in the US for patients with HER2-low metastatic breast cancer. News release. AstraZeneca. Accessed July 25, 2022. https://www.businesswire.com/news/home/20220725005244/en/ENHERTU%C2%AE-fam-trastuzumab-deruxtecan-nxki-granted-Priority-Review-in-the-US-for-patients-with-HER2-low-metastatic-breast-cancer
- Modi S, Jacot W, Yamashita T, et al. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med. Published online July 7, 2022. doi: 10.1056/NEJMoa2203690