Final Overall Survival Results of Datopotamab Deruxtecan in Metastatic HR-Positive, HER2-Low/Negative Breast Cancer (TROPION-Breast01)

High-level findings from the TROPION-Breast01 Phase III trial involving datopotamab deruxtecan (Dato-DXd) showed that while the drug met its key endpoint of progression-free survival (PFS), it did not achieve statistical significance in overall survival (OS) for patients with inoperable or metastatic hormone receptor (HR)-positive, HER2-low or negative breast cancer. These patients had previously undergone endocrine-based therapy and at least one other systemic therapy.

The analysis comes after positive PFS results were shared at the 2023 European Society for Medical Oncology Congress, highlighting the significant and meaningful improvement in PFS provided by datopotamab deruxtecan. Additionally, the trial showed improvements in patient-reported outcomes. This data, along with other secondary endpoint results, has been published in the Journal of Clinical Oncology.

The safety profile of datopotamab deruxtecan remains consistent with earlier findings. The drug demonstrated fewer Grade 3 or higher treatment-related adverse events compared to standard chemotherapy, and no new safety concerns were identified. Rates of interstitial lung disease (ILD) incidents were low, with no new Grade 3 or higher ILD events reported.

The survival outcomes observed in the final OS analysis might have been impacted by the availability of multiple antibody drug conjugates (ADCs) approved during the trial, including ENHERTU® (fam-trastuzumab deruxtecan-nxki), which patients might have transitioned to after disease progression or discontinuation of their initial treatment.

Susan Galbraith, Executive Vice President of Oncology R&D at AstraZeneca, commented on the evolving landscape of metastatic HR-positive breast cancer treatment, noting the clinical value of datopotamab deruxtecan evidenced by the TROPION-Breast01 results. She emphasized the company's commitment to continuing discussions with regulatory authorities and utilizing insights from the trial to further their clinical development program for this promising drug.

Ken Takeshita, MD, Global Head of R&D at Daiichi Sankyo, echoed this sentiment, highlighting the significant PFS benefit shown in the TROPION-Breast01 trial and the additional positive outcomes reported by patients. He reiterated the company’s dedication to introducing new treatment options like datopotamab deruxtecan for patients with metastatic breast cancer, building on their previous success with ENHERTU.

Datopotamab deruxtecan, a TROP2-directed DXd ADC, was discovered by Daiichi Sankyo and is being developed in collaboration with AstraZeneca. Upcoming medical meetings will feature further presentations of the trial data, and regulatory authorities are currently reviewing applications for its use in this indication.

Beyond TROPION-Breast01, AstraZeneca and Daiichi Sankyo are testing datopotamab deruxtecan, both alone and in combination with immunotherapy, in various Phase III trials targeting triple-negative breast cancer and HR-low, HER2-negative breast cancers. These trials include TROPION-Breast02, TROPION-Breast03, TROPION-Breast04, and TROPION-Breast05.

The collaboration between AstraZeneca and Daiichi Sankyo extends beyond breast cancer. They have a robust portfolio of ADCs and other targeted therapies in development, with the aim of bringing more effective treatments to patients with different types of cancer. This partnership also includes the global development and commercialization of fam-trastuzumab deruxtecan-nxki and datopotamab deruxtecan, except in Japan, where Daiichi Sankyo retains exclusive rights. The ultimate objective is to redefine treatment paradigms and improve patient outcomes across various cancer types, leveraging the unique properties of these advanced antibody-drug conjugates.