AstraZeneca and Daiichi Sankyo’s Datopotamab Deruxtecan Falls Short in Breast Cancer Survival Study

AstraZeneca and Daiichi Sankyo’s Phase III TROPION-Breast01 trial of datopotamab deruxtecan (Dato-DXd) in patients with metastatic hormone receptor (HR)-positive, HER2-low or negative breast cancer did not meet its overall survival (OS) target. Despite achieving the primary endpoint of progression-free survival (PFS), the final OS analysis showed no statistically significant improvement compared to chemotherapy.

Earlier findings presented at the 2023 European Society for Medical Oncology (ESMO) Congress highlighted datopotamab deruxtecan’s ability to improve PFS and patient-reported outcomes. These results were published in the Journal of Clinical Oncology. The safety profile remained consistent, with fewer serious side effects than chemotherapy, and no new concerns, including a low incidence of interstitial lung disease.

The trial’s survival results may have been impacted by the approval of other antibody drug conjugates (ADCs) during the study, including Enhertu, which patients received after disease progression.

Susan Galbraith, AstraZeneca’s Executive Vice President of Oncology R&D, acknowledged the progress in the HR-positive breast cancer treatment landscape and reiterated the company’s commitment to further exploring datopotamab deruxtecan’s potential in this setting. Daiichi Sankyo’s Global Head of R&D, Ken Takeshita, noted the drug’s significant PFS benefit and expressed confidence in its clinical value.

Datopotamab deruxtecan, a TROP2-directed ADC developed by Daiichi Sankyo, will be evaluated in further clinical trials, including TROPION-Breast02, Breast03, Breast04, and Breast05, aimed at treating various types of breast cancer. Results will be shared at future medical meetings and with regulatory authorities currently reviewing the drug’s application.

Breast cancer remains the second most common cancer globally, with HR-positive, HER2-negative types accounting for roughly 70% of cases. While early-stage breast cancer has high survival rates, metastatic HR-positive breast cancer is much harder to treat, with fewer than 35% of patients surviving five years post-diagnosis. Current treatments beyond endocrine therapy often show limited efficacy, making new therapies essential for improving patient outcomes.