FDA Approves Trastuzumab Deruxtecan for HER2-Positive Breast Cancer


The FDA granted accelerated approval to trastuzumab deruxtecan for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer.

The FDA granted accelerated approval to fam-trastuzumab deruxtecan-nxki (Enhertu; DS-8201) for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received 2 or more prior anti-HER2-based regimens in the metastatic setting.1

“There have been many advances in the development of drugs for HER2-positive breast cancer since the introduction of [Herceptin (trastuzumab)] in 1998. The approval of Enhertu represents the newest treatment option for patients who have progressed on available HER2-directed therapies,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, said in a press release issued by the agency. “Drug development in the area of targeted therapies builds on our scientific understanding of malignant diseases not only in breast cancer, but in multiple other diseases.”

The agency based its decision on findings from the global pivotal phase II single-arm DESTINY-Breast01 trial, designed to evaluate the HER2-targeting antibody drug conjugate in 194 patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab emtansine.2

“These patients were heavily pretreated in the metastatic setting, receiving between two and 17 therapies prior to receiving Enhertu,” the FDA wrote in a release.

The trial consisted of part 1 to evaluate pharmacokinetics (n = 65) and to determine recommended dose (RP2D; n = 54) for part 2 (n = 134), which was 5.4 mg/kg trastuzumab deruxtecan. Patients received trastuzumab deruxtecan every 3 weeks in the trial, and tumor shrinkage was obtained every 6 weeks. 

Confirmed objective response rate (ORR) per independent central review (ICR) served as the primary endpoint, while secondary endpoints included disease control rate (DCR), duration of response (DOR), and progression-free survival (PFS).

Trastuzumab deruxtecan induced an ORR of 60.3% per ICR (95% CI, 53.4-68.0), including 11 complete responses (CRs; 6.0%), 101 partial responses (PRs; 54.9%), 67 with stable disease (SD; 36.4%), and 3 with progressive disease (PD; 1.6%). Two patients were not evaluable.

Patients achieved a DCR of 97.3% with a median duration of response of 14.8 months and median PFS of 16.4 months. 

Moreover, mxedian overall survival (OS) has not yet been reached, with an estimated survival rate of 86% at 1 year.

The safety and tolerability profile was consistent with that observed in the phase I trial. The most common grade 3 or higher treatment-emergent adverse events (TEAEs) were decreased neutrophil count (20.7%), anemia (8.7%), nausea (7.6%), decreased white cell count (6.5%), decreased lymphocyte count (6.5%) and fatigue (6.0%). 

Overall, 13.6% of patients had confirmed interstitial lung disease (ILD) related to treatment; however, ILD was primarily grade 1 or 2 (10.9%) in severity, with 1 grade 3 (0.5%) and no grade 4 events. Four deaths (2.2%) were determined to be due to ILD.

“Trastuzumab deruxtecan has several distinct features,” Ian Krop MD, PhD, associate chief of the Division of Breast Oncology at Dana-Farber Cancer Institute, said during a press briefing held at the San Antonio Breast Cancer Symposium, where these study results were recently presented. 

“One is the payload is a potent topoisomerase I inhibitor. This is a kind of chemotherapy that is not typically used in HER2-positive breast cancer so it is less likely that cancers will develop resistance to this agent. There are about 8 of these payload molecules per antibody, and this is a higher drug-antibody ratio than is typically seen in current antibody conjugates. Lastly, the payload is membrane permeable so in preclinical studies it allows it to diffuse out of the cell and kill neighboring tumor cells regardless of their HER2 expression.”


1. FDA approves new treatment option for patients with HER2-positive breast cancer who have progressed on available therapies. FDA. Published December 20, 2019. https://bit.ly/2tzcabv. Accessed December 20, 2019.


2. AstraZeneca and Daiichi Sankyo’s trastuzumab deruxtecan demonstrated an impressive 14.8-month median duration of response and 16.4-month median progression-free survival. Published December 11, 2019. https://bit.ly/35L5RQr. Accessed December 20, 2019.

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