Trastuzumab Deruxtecan Granted Breakthrough Therapy Designation in United States for Patients with HER2-Positive Metastatic Breast Cancer Treated with ≥1 Previous Anti-HER2–Based Regimens

Based on data from the DESTINY-Breast03 phase 3 trial reported at the European Society for Medical Oncology Congress 2021, the US Food and Drug Administration (FDA) awarded trastuzumab deruxtecan a Breakthrough Therapy Designation (BTD). This is trastuzumab deruxtecan’s second BTD in breast cancer, bringing the total number of BTDs for this drug to 4. The BTD is a program created by the FDA to expedite the development and review of prospective new medications that are intended to treat a serious ailment and fill a major unmet medical need. The new treatment must have shown promising preliminary clinical outcomes that exhibit a significant improvement over existing medicines on a clinically important end point.¹

Trastuzumab deruxtecan is an antibody–drug conjugate that targets HER2 that was developed by Daiichi Sankyo (currently co-produced with AstraZeneca). In December 2019, the FDA approved trastuzumab deruxtecan for the treatment of patients with unresectable or metastatic HER2-positive breast cancer following ≥2 lines of anti-HER2 therapy. The median duration of response to trastuzumab deruxtecan in patients with HER2-positive metastatic breast cancer who had previously received trastuzumab emtansine was 14.8 months, and the median duration of progression-free survival was 16.4 months in a phase 2 trial evaluating trastuzumab deruxtecan in patients with HER2-positive metastatic breast cancer who had previously received trastuzumab emtansine.

Based on the results of DESTINY-Gastric01, the FDA approved fam-trastuzumab deruxtecan-nxki in January 2021 for patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction cancer. Fam-trastuzumab deruxtecan was found to be superior to single-agent chemotherapy (irinotecan or paclitaxel) as a third-line (or later) treatment for HER2-positive gastric and gastroesophageal junction adenocarcinoma in this trial, with a median overall survival of 12.5 months in the fam-trastuzumab deruxtecan arm compared with 8.4 months in the chemotherapy arm.²

References

1. AstraZeneca. Enhertu granted Breakthrough Therapy Designation in US for patients with HER2-positive metastatic breast cancer treated with one or more prior anti-HER2-based regimens. October 4, 2021. www.astrazeneca.com/media-centre/press-releases/2021/enhertu-granted-btd-for-breast-cancer.html. Accessed December 12, 2021.
2. Azar I, Alkassis S, Fukui J, et al. Spotlight on trastuzumab deruxtecan (DS-8201, T-DXd) for HER2 mutation positive non-small cell lung cancer. Lung Cancer (Auckl). 2021;12:103-114.