FDA Grants Priority Review of DS-8201 for HER2+ Metastatic Breast Cancer

The FDA has accepted and granted a priority review to a biologics license application for [fam-] trastuzumab deruxtecan (DS-8201) for the treatment of patients with HER2-positive metastatic breast cancer.

Antoine Yver, MD, MSc

The FDA has accepted and granted a priority review to a biologics license application (BLA) for [fam-] trastuzumab deruxtecan (DS-8201) for the treatment of patients with HER2-positive metastatic breast cancer.1

Under the Prescription Drug User Fee Act, the agency has determined that a decision will be made on the BLA by the first quarter of fiscal year 2020.

Regulatory submission for the HER2-targeted antibody—drug conjugate (ADC) was also recently completed with Japan’s Ministry of Health, Labour and Welfare (MHLW).

“We are pleased that the FDA has accepted the application and granted Priority Review as we believe [fam-] trastuzumab deruxtecan has the potential to redefine the treatment of patients with HER2 positive metastatic breast cancer,” Antoine Yver, MD, MSc, executive vice president and global head, Oncology Research and Development, Daiichi Sankyo, said in a statement. Daiichi Sankyo is jointly manufacturing [fam-] trastuzumab deruxtecan with AstraZeneca. “Following the recent regulatory submission in Japan, we look forward to working closely with regulatory authorities to bring [fam-] trastuzumab deruxtecan to patients in the United States and Japan as soon as possible.”

The BLA is based off of findings from the pivotal phase II DESTINY-Breast01 trial and the phase I dose-expansion trial of the agent.

“[Fam-] trastuzumab deruxtecan has the potential to transform the treatment landscape for patients with HER2 positive metastatic breast cancer who have limited treatment options,” José Baselga, MD, PhD, executive vice president, Research & Development Oncology, AstraZeneca, said in a statement. “The priority review draws on the strength and consistency of results seen in phase 1 and phase 2 trials and is an important step on the journey to deliver this potential new medicine to patients.”

Early findings from the DESTINY-Breast01 study (NCT03248492) released by the manufacturing companies revealed that the ADC induced clinically meaningful responses in patients with HER2-positive, unresectable and/or metastatic breast cancer who had previously been treated with trastuzumab emtansine (T-DM1; Kadcyla).2

The open-label, international, multicenter consists of 2 parts, one of which confirmed the recommended dose of [fam-] trastuzumab deruxtecan as 5.4 mg/kg. Part 2, which is ongoing, is exploring the safety and efficacy of the recommended dose. A small group of patients who were intolerant of T-DM1 are also being treated in an exploratory-only arm of the trial.

Further findings from the trial will be presented at the 2019 San Antonio Breast Cancer Symposium.

The response rate already seen in the DESTINY-Breast01 study confirms the benefit of [fam-] trastuzumab deruxtecan seen in the phase I trial.

The ADC was explored in an open-label dose-escalation and dose-expansion phase I trial in patients with advanced solid tumors regardless of HER2 expression.3

Among patients with HER2-positive breast cancer (n = 115) who were previously treated with trastuzumab emtansine who received [fam-] trastuzumab deruxtecan, the response rate was 59.5% among 111 evaluable patients. Three of these patients achieved a complete response and an additional 34% of patients had stable disease.

The median progression-free survival was 22.1 months and the median overall survival was not reached. The median duration of response was 20.7 months.

Additionally, a post-hoc analysis of patients who had previously received treatment with pertuzumab (Perjeta) showed an objective response rate of 62.5% and a disease control rate of 93.8%. The median progression-free survival in this subgroup was 16.4 months.

Treatment-emergent adverse events (TEAE) were observed in all 115 patients, with 50% having a grade ≥3 and 19% had a serious TEAE. Drug-related TEAEs led to treatment discontinuation in 11% of patients.

The most common grade ≥3 TEAEs were anemia in 17% of patients, decreased neutrophil counts in 14%, decreased white blood cell counts in 9%, and decreased platelet counts in 8%.

Twenty cases of interstitial lung disease, pneumonitis, or organizing pneumonia were reported, and 2 cases of pneumonitis led to treatment-related death.

An independent adjudication committee was established to review cases of interstitial lung disease, pneumonitis, or organizing pneumonia, and a formal monitoring and management program is also in place to help determine the risk of these toxicities.

[Fam-] trastuzumab deruxtecan previously received both a breakthrough designation and a fast track designation from the FDA for the treatment of patients with HER2-positive breast cancer.


  1. [Fam-] Trastuzumab Deruxtecan (DS-8201) Granted FDA Priority Review for Treatment of Patients with HER2 Positive Metastatic Breast Cancer [press release]. Tokyo, Munich, and Basking Ridge: Daiichi Sankyo Company, Limited and AstraZeneca; October 17, 2019. https://bit.ly/2BgzPOL. Accessed October 17, 2019.
  2. Trastuzumab Deruxtecan Demonstrated Clinically-Meaningful Response in Patients With Refractory HER2-Positive Metastatic Breast Cancer, a Population With High Unmet Need. AstraZeneca. Published May 8, 2019. https://bit.ly/2Q1SuEF. Accessed October 17, 2019.
  3. Tamura K, Tsurutani J, Takahashi S, et al. Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive breast cancer previously treated with trastuzumab emtansine: a dose-expansion, phase 1 study.Lancet Oncol.2019;20(6):816-826. doi: 10.1016/S1470-2045(19)30097-X.