The Food and Drug Administration has granted Breakthrough Therapy designation to Enhertu® (fam-trastuzumab deruxtecan-nxki), a HER2-directed antibody and topoisomerase inhibitor conjugate, for the treatment of unresectable or metastatic HER2-low (immunohistochemistry [IHC] 1+ or IHC 2+/ in-situ hybridization [ISH]-negative) breast cancer in patients who have received a prior systemic therapy in the metastatic setting, or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy. Patients with hormone receptor (HR) positive breast cancer should also have received or be ineligible for endocrine therapy.

The designation was based on data from the DESTINY-Breast04 trial (ClinicalTrials.gov Identifier: NCT03734029), a phase 3, open-label study that compared the safety and efficacy of fam-trastuzumab deruxtecan to physician’s choice of treatment (capecitabine, eribulin, gemcitabine, paclitaxel, nab-paclitaxel) in HER2-low, unresectable and/or metastatic breast cancer patients with HR-positive or HR-negative disease (N=557). HER2-low status was defined as an IHC score of 1+ or IHC 2+ with a negative ISH score.

Results showed a statistically significant and clinically meaningful improvement in both progression-free survival (PFS; primary endpoint) and overall survival (OS; secondary endpoint) in patients treated with fam-trastuzumab deruxtecan compared with physician’s choice of chemotherapy.

“Historically, only patients with HER2-positive metastatic breast cancer were shown to benefit from HER2-directed therapy,” said Ken Takeshita, Global Head, R&D, Daiichi Sankyo. “DESTINY-Breast04, in which Enhertu showed a clinically meaningful survival benefit in patients with HER2-low metastatic breast cancer, is the first trial to demonstrate that selecting patients for treatment based on low expression of HER2 has the potential to change the diagnostic and treatment paradigms for these patients.”

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.

References

  1. ENHERTU® (fam-trastuzumab deruxtecan-nxki) granted Breakthrough Therapy designation in the US for patients with HER2-low metastatic breast cancer. News release. April 27, 2022. https://www.businesswire.com/news/home/20220427005187/en/ENHERTU%C2%AE-fam-trastuzumab-deruxtecan-nxki-granted-Breakthrough-Therapy-Designation-in-the-US-for-patients-with-HER2-low-metastatic-breast-cancer
  2. ENHERTU® (fam-trastuzumab deruxtecan-nxki) significantly improved both progression-free and overall survival in DESTINY-Breast04 trial in patients with HER2-low metastatic breast cancer. News release. February 21, 2022. https://www.astrazeneca-us.com/content/az-us/media/press-releases/2022/enhertu-fam-trastuzumab-deruxtecan-nxki-significantly-improved-both-progression-free-and-overall-survival-in-destiny-breast04-trial-in-patients-with-her2-low-metastatic-breast-cancer-02212022.html