Compared with chemotherapy, datopotamab deruxtecan (Dato-DXd) did not achieve a statistically significant overall survival (OS) in patients with inoperable or metastatic HR+/HER2-low or negative breast cancer.
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Trial Name: A Phase-3, Open-Label, Randomized Study of Dato-DXd Versus Investigator's Choice of Chemotherapy (ICC) in Participants With Inoperable or Metastatic HR-Positive, HER2-Negative Breast Cancer Who Have Been Treated With One or Two Prior Lines of Systemic Chemotherapy (TROPION-Breast01)
ClinicalTrials.gov ID: NCT05104866
Sponsor: AstraZeneca
Completion Date (Estimated): August 15, 2025
According to analysis results from the phase 3 clinical trial TROPION-Breast01 (NCT05104866), datopotamab deruxtecan (Dato-DXd; AstraZeneca, Daiichi Sankyo) did not achieve statistical significance in final overall survival (OS) results in patients with inoperable or metastatic hormone receptor-positive (HR+), HER2-low, or HER2-negative (HER2–; IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who were previously treated with endocrine-based therapy and at least 1 systemic therapy. Compared with investigator’s choice of chemotherapy, Dato-DXd had previously met the dual primary end point of progression-free survival (PFS).1
Dato-DXd is an investigational TROP2-directed antibody drug conjugate, and it is comprised of a humanized anti-TROP2 immunoglobulin G-1 monoclonal antibody. Currently, the agent is being investigated in multiple cancers, such as non-small cell lung cancer, triple-negative breast cancer, and HR+/HER2- breast cancer. Specifically, 7 phase 3 trials are being conducted in lung cancer and 5 phase 3 trials in breast cancer; these trials are evaluating Dato-DXd as a monotherapy and in combination with other anticancer treatments.1
For this global, randomized, multicenter, open-label, phase 3 clinical trial, investigators assessed the efficacy and safety of Dato-DXd compared with single-agent chemotherapy in adult patients who have unresectable or metastatic HR+, HER2-low, or HER2– (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer. The enrolled patients had all progressed on and are not considered suitable for further endocrine therapy—determined by an investigator assessment—and have received at least 1 additional systemic therapy for unresectable or metastatic disease.1,2
Patients were randomly assigned to receive either Dato-DXd (n=365) administered intravenously (IV), or investigator’s choice of chemotherapy (n=367) which consisted of either oral capecitabine (Xeloda; Genentech), IV gemcitabine (Gemzar; Eli Lilly & Co.), IV eribulin (Halaven; Eisai), or IV vinorelbine (Navelbine; Pierre Fabre Pharmaceuticals). Following disease progression or discontinuation of Dato-DXd or chemotherapy, patients were given the option to receive subsequent treatment if advised by their providers, but crossover between treatment groups was not permitted. The trial’s primary end points were PFS and OS, and secondary end points included objective response rate, duration of response, disease control rate, time to first subsequent and second subsequent therapy, among others.2,3
Positive PFS results were published in the Journal of Clinical Oncology and showed that Dato-DXd had significantly reduced the risk of progression or death compared with chemotherapy (PFS by BICR hazard ratio, 0.63 [95% CI, 0.52 to 0.76]; P < .0001), with consistent benefits observed across all subgroups. Additionally, OS data at the time of this analysis were not mature, but demonstrated favorable trends for Dato-DXd (hazard ratio, 0.84 [95% CI, 0.62 to 1.14]). The current OS analysis results show that patients who received Dato-DXd did not achieve an OS of statistical significance.1,3
“The metastatic HR+ breast cancer treatment landscape has advanced remarkably in the last several years to the benefit of patients. Based on the TROPION-Breast01 results, there is evidence of the clinical value of Dato-DXd in this setting,” said Susan Galbraith, executive vice president, oncology R&D, AstraZeneca, in a news release. “We will continue discussions with regulatory authorities and apply insights from these results to our clinical development program for Dato-DXd in breast cancer.”1
In the PFS analysis, the most common treatment-related adverse events were any grade nausea (51.1%) and stomatitis (50%) in the Dato-DXd group, and neutropenia (42.5%) in the chemotherapy group. Additionally, there were occurrences of grade 3 or higher nausea (1.4%), stomatitis (6.4%), and neutropenia (30.8%) in the respective groups.3
“Dato-DXd has previously shown a statistically significant PFS benefit in TROPION-Breast01, a result supported by multiple meaningful secondary measures including patient-reported outcomes,” said Ken Takeshita, MD, global head, R&D, Daiichi Sankyo, in the news release. “We are proud to have brought forth a new standard of care for patients with metastatic breast cancer with [trastuzumab deruxtecan (Enhertu; AstraZeneca, Daiichi Sankyo)] and we remain committed to making Dato-DXd another potential option for patients who can benefit.”1
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