The Food and Drug Administration (FDA) has approved 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 chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy.

The approval was based on 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. Findings from the trial showed that treatment with Enhertu improved both progression free survival and overall survival compared with physician’s choice of chemotherapy (capecitabine, eribulin, gemcitabine, paclitaxel, nab-paclitaxel).

As for safety, the most common adverse reactions reported with Enhertu in DESTINY-Breast04 were nausea, fatigue, alopecia, vomiting, constipation, decreased appetite, musculoskeletal pain and diarrhea. Enhertu carries a Boxed Warning regarding the risk of interstitial lung disease and embryo-fetal toxicity.

“Today’s FDA approval marks a monumental moment in breast cancer treatment as Enhertu is the first-ever HER2-directed medicine to be approved for the treatment of patients with HER2-low metastatic breast cancer,” said Ken Keller, Global Head of Oncology Business and President and CEO, Daiichi Sankyo, Inc. “With the ground-breaking survival benefit seen in the DESTINY-Breast04 trial, this milestone confirms the importance of targeting lower levels of HER2 expression in the treatment of metastatic breast cancer and we are thrilled that we can now offer Enhertu to even more patients.”

Enhertu is also 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. Additionally, it is indicated for locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma in patients who have received a prior trastuzumab-based regimen.

References

  1. FDA approves first targeted therapy for HER2-low breast cancer. News release. US Food and Drug Administration. Accessed August 8, 2022. https://www.fda.gov/news-events/press-announcements/fda-approves-first-targeted-therapy-her2-low-breast-cancer
  2. Enhertu approved in the US as the first HER2-directed therapy for patients with HER2-low metastatic breast cancer. News release. AstraZeneca and Daiichi Sankyo. Accessed August 8, 2022. https://www.astrazeneca.com/media-centre/press-releases/2022/enhertu-approved-in-the-us-for-her2-low-mbc.html
  3. Enhertu. Package insert. Daiichi Sankyo, Inc.; 2022. Accessed August 8, 2022. https://daiichisankyo.us/prescribing-information-portlet/getPIContent?productName=Enhertu&inline=true