The Food and Drug Administration (FDA) has approved Enhertu® (fam-trastuzumab deruxtecan-nxki) for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received a prior anti-HER2-based regimen either in the metastatic setting, or in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within 6 months of completing therapy.
The approval was based on data from the phase 3 DESTINY-Breast03 trial (ClinicalTrials.gov Identifier: NCT03529110), which included 524 patients with HER2-positive, unresectable and/or metastatic breast cancer who received prior trastuzumab and taxane therapy for metastatic disease or developed disease recurrence during or within 6 months of completing adjuvant therapy.
Patients were randomly assigned to receive Enhertu (n=261) or ado-trastuzumab emtansine (n=263) by intravenous infusion every 3 weeks until unacceptable toxicity or disease progression.
The primary efficacy outcome was progression free survival (PFS). Overall survival (OS) and objective response rate (ORR) were also assessed as secondary outcome measures.
Results showed that Enhertu reduce the risk of disease progression or death by 72% when compared with ado-trastuzumab emtansine (hazard ratio, 0.28; 95% CI, 0.22-0.37; P <.0001). Median PFS was not reached in the Enhertu arm (95% CI, 18.5 months, not estimable) and was 6.8 months (95% CI, 5.6-8.2) in the ado-trastuzumab emtansine arm.
At the time of the PFS analysis, 16% of patients had died and OS was immature. The confirmed ORR based on patients with measurable disease was 82.7% (95% CI, 77.4-87.2) for Enhertu and 36.1% (95% CI, 30-42.5) for ado-trastuzumab emtansine.
“Today’s FDA approval, which converts the accelerated approval of Enhertu to regular approval, highlights the importance of the FDA’s accelerated pathway that allows for earlier approval of medicines to treat serious medical conditions such as breast cancer,” said Ken Keller, Global Head, Oncology Business and President and CEO, Daiichi Sankyo, Inc. “Data from DESTINY-Breast03 not only confirmed the results of DESTINY-Breast01, but also demonstrated the superiority of Enhertu in prolonging progression-free survival compared to [ado-trastuzumab emtansine] in an earlier setting of HER2-positive metastatic breast cancer.”
- Enhertu approved in the US for patients with HER2-positive metastatic breast cancer treated with a prior anti-HER2-based regimen. News release. May 5, 2022. https://www.astrazeneca.com/media-centre/press-releases/2022/enhertu-approved-in-us-for-2l-her2-positive-breast-cancer.html.
- Enhertu. Package insert. AstraZeneca and Daiichi Sankyo. Accessed May 5, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761139s017s020lbl.pdf