Exploratory TROPION-Breast02 analysis shows improved CNS progression-free survival and intracranial response versus chemotherapy in patients with asymptomatic, stable brain metastases.

First-line datopotamab deruxtecan (Dato-DXd; Datroway) demonstrated systemic and intracranial activity compared with investigator’s choice chemotherapy in patients with metastatic triple-negative breast cancer (TNBC) and baseline brain metastases who were ineligible for immunotherapy, according to an exploratory analysis of the phase 3 TROPION-Breast02 trial presented at the 2026 ESMO Congress.

Among 61 patients with baseline brain metastases, median CNS progression-free survival (PFS) was 9.5 months with Dato-DXd versus 2.6 months with chemotherapy (HR, 0.27; 95% CI, 0.13–0.56). Median systemic PFS was 7.7 versus 3.5 months, respectively (HR, 0.37; 95% CI, 0.20–0.72).

Intracranial response and disease control

Among patients with measurable intracranial disease, the confirmed intracranial objective response rate (ORR) was 62.5% with Dato-DXd versus 37.5% with chemotherapy. The corresponding 12-week intracranial disease control rates were 75.0% and 50.0%. These response analyses included 16 patients in the Dato-DXd arm and eight in the chemotherapy arm, underscoring the limited sample size.

Activity was observed in patients with and without prior CNS-directed therapy. Of the 61 patients with baseline brain metastases, 30 had not received prior CNS-directed treatment: 19 assigned to Dato-DXd and 11 assigned to chemotherapy. The remaining 31 patients had previously treated brain metastases.

Systemic efficacy and overall survival

Systemic ORR was 62.9% with Dato-DXd compared with 19.2% with chemotherapy. Median overall survival (OS) was 13.5 versus 10.7 months (HR, 0.55; 95% CI, 0.29–1.05). Although the OS estimate favored Dato-DXd, the confidence interval crossed 1, and an OS benefit was not established in this subgroup.

Study population and interpretation

TROPION-Breast02 enrolled 644 patients with previously untreated, inoperable locally recurrent or metastatic TNBC for whom immunotherapy was not an option. Patients received Dato-DXd at 6 mg/kg every three weeks or investigator’s choice of paclitaxel, nab-paclitaxel, capecitabine, carboplatin, or eribulin. PFS and OS were the primary end points in the overall trial; the brain metastases analysis was exploratory.

The baseline brain metastases subgroup comprised 35 patients receiving Dato-DXd and 26 receiving chemotherapy. All had asymptomatic, stable brain metastases. Baseline imbalances included older median age in the Dato-DXd arm—62 versus 55 years—and differences in prior CNS-directed treatment. No safety analysis specific to the brain metastases subgroup was reported in the supplied meeting summary.

The findings support a signal of intracranial activity for Dato-DXd in immunotherapy-ineligible TNBC, including in patients without prior CNS-directed therapy. However, the small subgroup, baseline imbalances, and exploratory design limit definitive conclusions. The results should not be extrapolated to symptomatic or progressing brain metastases, interpreted as establishing superiority over other antibody–drug conjugates, or used to support omission of indicated local CNS therapy.

Reference

Dent R, Cescon DW, Jung KH, et al. 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: exploratory analysis of patients with brain metastasis in TROPION-Breast02. Presented at: 2026 ESMO Congress; October 23-27, 2026; Madrid, Spain. Abstract LBA96.