Breast Cancer: DATROWAY® Approved in U.S. for Metastatic HR Positive, HER2 Negative Type
DATROWAY® (datopotamab deruxtecan-dlnk), an innovative TROP2-directed antibody-drug conjugate (ADC), has been approved by the U.S. Food and Drug Administration (FDA) for treating adult patients with unresectable or metastatic hormone receptor (HR) positive, HER2 negative (IHC 0, IHC 1+, or IHC 2+/ISH-) breast cancer. This approval is for patients who have already received prior endocrine-based therapy and chemotherapy for their unresectable or metastatic disease.
Developed by Daiichi Sankyo and AstraZeneca, DATROWAY is the second ADC approved in the U.S. based on Daiichi Sankyo’s proprietary DXd ADC technology. This marks a significant milestone in the treatment of breast cancer, as DATROWAY provides a new option for patients who have progressed after conventional therapies.
The FDA’s decision was based on data from the TROPION-Breast01 Phase 3 trial. This trial demonstrated that DATROWAY significantly reduced the risk of disease progression or death by 37% compared to the investigator’s choice of chemotherapy (hazard ratio [HR] = 0.63; 95% confidence interval [CI]: 0.52-0.76; p<0.0001). Patients treated with DATROWAY showed a median progression-free survival (PFS) of 6.9 months, compared to 4.9 months in the chemotherapy arm. Additionally, the confirmed objective response rate (ORR) was 36% for DATROWAY, compared to 23% for chemotherapy. The median duration of response (DoR) was 6.7 months for DATROWAY, compared to 5.7 months for chemotherapy.
Dr. Aditya Bardia, Program Director of Breast Oncology at UCLA Health, and Global Principal Investigator for TROPION-Breast01, commented on the approval, emphasizing that, despite advancements in HR positive, HER2 negative metastatic breast cancer treatment, there is still a pressing need for therapies that address disease progression following endocrine and initial chemotherapy treatments. “The approval of datopotamab deruxtecan marks a major therapeutic milestone, providing patients with a new treatment option beyond conventional chemotherapy,” Dr. Bardia said.
Caitlin Lewis, Senior Vice President of Strategy & Mission at Living Beyond Breast Cancer, also welcomed the approval, pointing out the urgent need for effective therapies. “With only one in three patients with metastatic HR positive, HER2 negative breast cancer surviving more than five years, DATROWAY provides a crucial new treatment alternative,” she noted.
In the TROPION-Breast01 trial, DATROWAY (administered at 6 mg/kg) was generally well-tolerated. Common adverse reactions included stomatitis, nausea, fatigue, decreased leukocytes, alopecia, and abdominal pain. Serious adverse reactions included urinary tract infections, COVID-19 infections, interstitial lung disease (ILD), and pulmonary embolism. Notably, one fatality was linked to ILD/pneumonitis. These adverse reactions were primarily reflective of the underlying comorbidities of the patient population.
Ken Keller, Global Head of Oncology Business at Daiichi Sankyo, highlighted the importance of DATROWAY in offering a novel treatment option for patients with metastatic HR positive, HER2 negative breast cancer. “DATROWAY provides a new ADC approach to patients who have already been treated with endocrine-based therapy and chemotherapy,” Keller said. “This approval is a significant addition to our portfolio of innovative cancer treatments.”
Dave Fredrickson, Executive Vice President at AstraZeneca, also shared his excitement, noting that DATROWAY is an example of how antibody-drug conjugates are transforming cancer treatment. “The approval of DATROWAY represents a significant achievement for AstraZeneca and Daiichi Sankyo in the fight against metastatic breast cancer,” Fredrickson stated.
DATROWAY is expected to be available by prescription in the U.S. within two weeks, and the companies are committed to ensuring patients can access the treatment. To assist with access, financial support, and reimbursement, Daiichi Sankyo and AstraZeneca have established resources such as Datroway4u.com and a dedicated helpline.
In addition to the U.S. approval, regulatory submissions for DATROWAY in breast cancer are currently under review in the European Union, China, and other regions.
TROPION-Breast01, the pivotal Phase 3 trial, involved 732 patients from diverse global regions. The trial was designed to evaluate the efficacy of DATROWAY compared to investigator’s choice of chemotherapy (eribulin, capecitabine, vinorelbine, or gemcitabine). The study’s dual primary endpoints included progression-free survival (PFS) as assessed by blinded independent central review (BICR) and overall survival (OS). Secondary endpoints included objective response rate (ORR), duration of response (DoR), and safety.
DATROWAY (6 mg/kg) is now approved in both the U.S. and Japan for the treatment of HR positive, HER2 negative metastatic breast cancer, based on the encouraging results from the TROPION-Breast01 trial. Daiichi Sankyo and AstraZeneca are also conducting a comprehensive global clinical development program with more than 20 ongoing trials investigating DATROWAY for various cancers, including non-small cell lung cancer and triple-negative breast cancer.
The collaboration between Daiichi Sankyo and AstraZeneca, which began in 2020 for DATROWAY and 2019 for ENHERTU®, has resulted in the development of several ADCs. These therapies are considered promising in providing better treatment options for cancer patients.
As DATROWAY moves forward in its clinical program, it represents a pivotal step in improving the treatment landscape for patients with metastatic HR positive, HER2 negative breast cancer.
