Datopotamab deruxtecan improves survival in breast cancer patients not eligible for immunotherapy

First-line treatment with datopotamab deruxtecan (Dato-DXd) results in statistically significant and clinically meaningful improvements in overall survival (OS) and progression-free survival (PFS) compared with chemotherapy in patients with locally recurrent inoperable or metastatic triple-negative breast cancer (TNBC), as shown by the results of the phase III TROPION-Breast02 trial.

In addition, the safety profile of Dato-DXd was manageable, and the results support this regimen as the new first-line standard of care.

“TROPION-Breast02 met both the dual primary endpoints [of OS and PFS by BICR per RECIST 1.1],” said lead author Dr Rebecca A Dent, professor and chief executive officer, National Cancer Centre Singapore.

“Treatment options are limited and prognosis is poor for the 70 percent of patients with locally recurrent inoperable or metastatic TNBC for whom immunotherapy is not an option; moreover, approximately half of patients with metastatic TNBC do not receive treatment beyond the first line,” she added.

To address this gap, Dent and her team randomized 644 adult patients with previously untreated locally recurrent inoperable or metastatic TNBC, for whom immunotherapy was not feasible, to receive Dato-DXd 6 mg/kg IV Q3W (n=323) or investigator’s choice of chemotherapy (ICC; [nab]-paclitaxel, capecitabine, eribulin mesylate, carboplatin; n=321).

The research team stratified randomization by geographic location, PD-L1 status, and disease-free interval (DFI) history (de novo vs DFI 0‒12 vs >12 months). DFI was defined as time from completion of treatment with curative intent to first documented local or distant disease recurrence. Data cutoff was on 25 August 2025, and the median follow-up was 27.5 months.

Survival benefits

The median PFS was 10.8 months (95 percent confidence interval [CI], 8.6‒13.0) with Dato-DXd vs 5.6 months (95 percent CI, 5.0‒7.0) with ICC, representing a 43-percent decrease in the risk of disease progression of death (hazard ratio [HR], 0.57, 95 percent CI, 0.47‒0.69; p<0.0001).

The PFS rates in the respective arms were 45.6 percent and 25.6 percent at 12 months and 32.7 percent and 16.8 percent at 18 months. [ESMO 2025, abstract LBA21]

For OS, the median values were 23.7 months (95 percent CI, 19.8‒25.6) with Dato-DXd vs 18.7 months (95 percent CI, 16.0‒21.8) with ICC, corresponding to a 21-percent decrease in the risk of death (HR, 0.79, 95 percent CI, 0.64‒0.98; p=0.0291). The respective OS rates at 12 and 18 months were 75.2 percent and 61.2 percent with Dato-DXd and 67.8 percent and 51.3 percent with ICC.

Safety profile

The median treatment duration was 8.5 months with Dato-DXd vs 4.1 months with ICC. More patients in the Dato-DXd arm experienced any-grade treatment-related adverse events (TRAEs; 93 percent vs 83 percent; grade ≥3 TRAEs: 33 percent vs 29 percent). Serious TRAEs did not significantly differ between the two groups (9 percent vs 8 percent)

TRAEs leading to dose interruption or reduction occurred in 24 percent and 27 percent of patients in the Dato-DXd arm, respectively, while treatment discontinuation occurred in 4 percent of patients. In the ICC arm, TRAEs resulting in dose interruption, reduction, or discontinuation occurred in 19 percent, 18 percent, and 7 percent of patients, respectively.

“In TROPION-Breast02, Dato-DXd meaningfully extended patients’ lives and nearly doubled their time without disease progression,” Dent said in a press release. [https://tinyurl.com/46492t3t]

“These are significant outcomes for patients with metastatic triple-negative breast cancer who are not suitable candidates for immunotherapy, and remarkable results considering the trial included a subset of patients with highly aggressive disease who are often excluded from research in this setting,” she added.