First-line datopotamab deruxtecan (Dato-DXd) vs chemotherapy in patients with locally recurrent inoperable or metastatic triple-negative breast cancer (TNBC) for whom immunotherapy was not an option: Additional efficacy endpoints from the TROPION-Breast02 study.

1002 Background: In the primary analysis of the phase 3 TROPION-Breast02 study (NCT05374512), first-line Dato-DXd demonstrated statistically significant and clinically meaningful improvements in overall survival (OS; hazard ratio [HR]: 0.79 [95% confidence interval [CI]: 0.64–0.98]; p = 0.0291) and progression-free survival (PFS; HR: 0.57 [95% CI: 0.47–0.69]; p < 0.0001) compared with investigator’s choice of chemotherapy (ICC) in patients with locally recurrent inoperable or metastatic TNBC for whom immunotherapy was not an option. Both median OS and PFS by blinded independent central review (BICR) were ≥5 months longer with Dato-DXd compared with ICC. Moreover, with Dato-DXd vs ICC, the confirmed objective response rate was more than double and median duration of response was > 5 months longer. The Dato-DXd safety profile was manageable and generally consistent with the known profile. Here we report additional efficacy endpoints. Methods: Adult patients with previously untreated locally recurrent inoperable or metastatic TNBC, for whom immunotherapy was not an option, were randomized 1:1 to Dato-DXd (6 mg/kg IV every 3 weeks) or ICC ([nab]-paclitaxel/capecitabine/eribulin mesylate/carboplatin). Dual primary endpoints were OS and PFS by BICR per RECIST 1.1; secondary endpoints included time to second progression or death (PFS2), time to first subsequent therapy or death (TFST), and time to second subsequent therapy or death (TSST). The planned sample size was approximately 600 randomized patients. A stratified log-rank test was used to analyze PFS2, TFST, and TSST. HRs and 95% CIs were estimated from a stratified Cox proportional hazards model. Results: A total of 644 patients were randomized (Dato-DXd: 323; ICC: 321). At data cutoff (25 Aug 2025), median study follow-up was 27.5 months and 53 (8.4%) patients remained on treatment (Dato-DXd: 45 [14.1%]; ICC: 8 [2.6%]). PFS2 was longer with Dato-DXd vs ICC: median 15.6 vs 11.8 months (HR: 0.61 [95% CI: 0.50‒0.74]). Both TFST and TSST were prolonged in the Dato-DXd vs ICC arm: median TFST was 10.9 vs 5.6 months with Dato-DXd vs ICC (HR: 0.49 [95% CI: 0.41‒0.59]) and median TSST was 16.7 vs 12.6 months (HR: 0.67 [95% CI: 0.55‒0.81]). Conclusions: In TROPION-Breast02, improvements in the secondary endpoints of PFS2, TFST, and TSST were observed for patients receiving Dato-DXd compared with ICC, consistent with the dual primary endpoints of OS and PFS by BICR. Alongside the manageable safety profile for Dato-DXd, these data further support Dato-DXd as the new first-line standard of care in this setting. Clinical trial information: NCT05374512 .