In a significant showcase of advancements in the treatment of metastatic triple-negative breast cancer (TNBC) during the ongoing 2025 European Society for Medical Oncology (ESMO) Congress in Berlin, AstraZeneca and Daiichi Sankyo’s Datroway has emerged as a strong contender, showing a notable reduction in the risk of death compared to chemotherapy. This conclusion stems from the phase 3 Tropion-Breast02 trial, in which Datroway achieved a 21% decrease in mortality risk for patients not candidates for immunotherapy, a finding that has been deemed statistically significant.
In contrast, Gilead Sciences’ Trodelvy, assessed in the Ascent-03 study under similar conditions, has not yet demonstrated a statistically significant overall survival (OS) benefit in the same patient population. Although the OS outcomes for Trodelvy are still maturing and trending positively, according to Gilead’s Chief Medical Officer, Dietmar Berger, there are notable differences in trial design between the two drugs.
Both clinical studies featured participant pools of over 600 patients and were launched within a couple of months of each other in the summer of 2022. However, Gilead’s trial incorporated a crossover design that allowed patients to receive Trodelvy after first-line progression, complicating the comparison of results. This trial design has implications for OS outcomes, as Berger pointed out that the high crossover rate—over 80%—could significantly influence overall survival data.
Despite some weaknesses in Trodelvy’s dataset, such as an almost negligible advantage over chemotherapy in achieving tumor response rates, the drug still met its primary endpoint of progression-free survival (PFS) in the Ascent-03 trial. Trodelvy reduced the risk of progression or death by 38%, achieving a median PFS of 9.7 months compared to 6.9 months for the control group. However, Datroway outperformed in PFS as well, showing a 43% reduction in risk with a median PFS of 10.8 months.
Trodelvy’s objective response rate (ORR) stood at 48%, closely matching chemotherapy’s 46%, a striking contrast from its earlier results in the Ascent trial where the ORR was significantly better than chemotherapy for previously treated TNBC patients. Datroway distinguished itself with an ORR of 62.5% versus 29.3% for chemotherapy.
Susan Galbraith, AstraZeneca’s oncology R&D chief, credited the efficacy of Datroway to its innovative antibody-drug conjugate structure, which employs a unique linker-payload technology. Meanwhile, Berger acknowledged that Trodelvy’s benefit largely comes from the duration of response, which did not show a substantial difference compared to Datroway across trials.
Looking ahead, Gilead is optimistic that the accumulation of data from Ascent-03 and Ascent-04 could solidify Trodelvy’s role in first-line TNBC treatment, as the company engages with regulators regarding these trial results. Meanwhile, AstraZeneca and Daiichi aim to expand Datroway’s application into earlier treatment stages, conducting studies to explore its potential as an adjuvant treatment in patients with TNBC exhibiting residual invasive disease after neoadjuvant therapy.
The competitive landscape is heating up, with stakeholders closely monitoring how these two TROP2-targeted therapies might coexist in a rapidly evolving treatment protocol. As more data become available, the future positioning of both Datroway and Trodelvy in clinical practice will become clearer, alongside the broader implications for patient care in this challenging subclass of breast cancer.
