Dr Cortés on Secondary End Points Supporting First-Line Dato-DXd Use in Metastatic TNBC

“When patients receive 2 lines of therapy, the benefit continues to be there. That’s why it’s important to optimize this first line of therapy with Dato-DXd.”

Javier Cortés, MD, PhD, head of the International Breast Cancer Centre, discussed additional efficacy end points from the phase 3 TROPION-Breast02 trial (NCT05374512) evaluating first-line datopotamab deruxtecan-dlnk (Dato-DXd; Datroway) vs investigator’s choice of chemotherapy in patients with locally recurrent inoperable or metastatic triple-negative breast cancer (TNBC) for whom immunotherapy was not an option.

The analyses, presented at the 2026 ASCO Annual Meeting, examined the prespecified secondary end points of time to first subsequent therapy or death (TFST), time to second progression or death (PFS2), and time to second subsequent therapy or death (TSST) to assess the durability of benefit beyond first progression. At a data cutoff of August 25, 2025, the median study follow-up was 27.5 months (range, 13.3-38.7), and in the primary analysis, first-line Dato-DXd had improved both dual primary endpoints vs investigator’s choice of chemotherapy, with a median progression-free survival (PFS) by blinded independent central review of 10.8 months vs 5.6 months, respectively (HR, 0.57; 99% CI, 0.44-0.73; P < .0001) and a median overall survival (OS) of 23.7 months vs 18.7 months, respectively (HR, 0.79; 95.01% CI, 0.64-0.98; P = .029). The overall response rate was more than doubled in the Dato-DXd arm (63% vs 29%), and the median respective durations of response were 12.3 months vs 7.1 months.

The hazard ratio for TFST clearly favored Dato-DXd, Cortés said. The median TFST was 10.9 months (95% CI, 9.5-12.1) with Dato-DXd vs 5.6 months (95% CI, 4.9-6.3) with investigator’s choice of chemotherapy (HR, 0.49; 95% CI, 0.41-0.59).

The PFS2 outcomes also favored Dato-DXd, Cortés noted, with a median of 15.6 months (95% CI, 13.3-17.4) vs 11.8 months (95% CI, 10.9-12.8) in the control arm (HR, 0.61; 95% CI, 0.50-0.74). The TSST data were consistent with these results, showing a median of 16.7 months (95% CI, 15.2-19.5) with Dato-DXd vs 12.6 months (95% CI, 11.3-13.6) with control (HR, 0.67; 95% CI, 0.55-0.81). Notably, the TSST sustained advantage was seen even though more patients in the control arm went on to receive a subsequent antibody-drug conjugate.

These data reinforce what was observed in the primary analysis and underscore the importance of optimizing first-line treatment with Dato-DXd, Cortés said. In a patient population with a poor prognosis, such as metastatic TNBC, improving the first-line setting tends to carry over into later outcomes, he added.

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