FDA Grants Breakthrough Therapy Designation to Trastuzumab Deruxtecan in HER2-Low Metastatic Breast Cancer

Trastuzumab deruxtecan has received FDA Breakthrough Therapy designation for the treatment of HER2-low metastatic breast cancer.

According to a press release from AstraZeneca.1

The Breakthrough Therapy designation was based on results from the Phase 3 DESTINY-Breast04 trial (NCT03734029). Previously reported results indicated that patients saw a statistically significant and clinically meaningful increase improvement in progression-free survival (PFS) and overall survival (OS) after treatment with trastuzumab deruxtecan.2

“Today’s news is significant validation of the potential we see for the landmark DESTINY-Breast04 trial to enable a paradigm shift in how breast cancer is classified by targeting the full spectrum of expression. of HER2. [Trastuzumab deruxtecan] continues to show transformative potential, and this milestone represents an important step forward for patients with low HER2 metastatic breast cancer who urgently need new treatment options and better outcomes,” said Susan Galbraith, Executive Vice President of Oncology R&D at AstraZeneca. the press release.

About 540 patients participated in the trial in Asia, Europe and North America. Patients were randomized 2:1 to receive either trastuzumab deruxtecan 5.4 mg/kg or chemotherapy of physician’s choice. A total of 480 patients were hormone receptor (HR) positive and 60 were hormone receptor negative.

The primary endpoint was PFS and secondary endpoints included PFS via investigator assessment, OS, objective response rate and duration of response.

Patients were eligible for treatment if they had pathologically documented breast cancer. This included those who had unresectable or metastatic disease, low HER2 expression, HR-positive or HR-negative disease, and who had progressed and would no longer benefit from hormone therapy. In addition, patients were required to have 1 measurable lesion and had adequate heart, bone marrow, kidney, liver, and blood clotting function.

Exclusion criteria included being ineligible for the doctor’s treatment choice, having an elevated expression of HER2 and having previously been treated with anti-HER2 therapy.

Trastuzumab deruxtecan previously received priority review from the FDAin January 2022.3 This was based on results from the DESTINY-Breast03 trial (NCT03529110) for patients with unresectable or metastatic HER2-positive breast cancer.

“Historically, only patients with HER2-positive metastatic breast cancer have benefited from HER2-directed therapy. DESTINY-Breast04, in which Enhertu showed a clinically significant survival benefit in patients with metastatic low HER2 breast cancer, is the first trial to demonstrate that selecting patients for treatment based on low expression of HER2 has the potential to change diagnostic and treatment paradigms for these patients. This

Breakthrough Therapy designation recognizes the potential of [trastuzumab deruxtecan] to address an unmet medical need and we look forward to working closely with the FDA to bring the first HER2-directed therapy to patients with metastatic breast cancer whose tumors have higher levels of HER2 expression. weak,” Ken Takeshita, global head of R&D at Daiichi Sankyo, concluded.


  1. Enhertu has been granted Breakthrough Therapy designation in the United States for patients with HER2-low metastatic breast cancer. Press release. AstraZeneca. April 27, 2022. Accessed April 27, 2022. https://bit.ly/3KkJjts
  2. Enhertu significantly improved both progression-free survival and overall survival in the DESTINY-Breast04 trial in patients with HER2 low metastatic breast cancer. Press release. Daiichi Sankyo. February 21, 2022. Accessed April 27, 2022. https://bwnews.pr/3KqNVhn
  3. Correction and replacement of Enhertu has received priority review in the United States for patients with HER2-positive metastatic breast cancer treated with prior anti-HER2 therapy. Press release. AstraZeneca and Daiichi Sankyo. January 17, 2022. Accessed April 27, 2022. https://bwnews.pr/3y19dzJ

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