Sacituzumab Govitecan PFS Benefit Holds Across Subgroups in Untreated mTNBC

First-line sacituzumab govitecan-hziy (Trodelvy) improved progression-free survival (PFS) vs chemotherapy across key clinical subgroups of patients with previously untreated metastatic triple-negative breast cancer (TNBC) who were not candidates for PD-1 or PD-L1 inhibitor–based therapy, according to an exploratory subgroup analysis of the phase 3 ASCENT-03 trial presented during a poster session at the European Society for Medical Oncology (ESMO) Congress 2026.¹

The benefit was observed regardless of the chemotherapy selected before randomization, disease status at enrollment, or the presence of brain or visceral metastases at baseline. Fewer patients who received sacituzumab govitecan also developed new visceral lesions at the time of progression.

In the primary PFS analysis of ASCENT-03, the median PFS by blinded independent central review (BICR) was 9.7 months with sacituzumab govitecan vs 6.9 months with chemotherapy (stratified HR, 0.62; 95% CI, 0.50-0.77), and the median PFS by investigator assessment was 9.6 months vs 6.8 months (stratified HR, 0.64; 95% CI, 0.52-0.79). Overall survival data were immature at the time of that analysis, at 37% maturity.

In the trial, 558 patients were randomly assigned 1:1 to sacituzumab govitecan (n = 279) or chemotherapy (n = 279), which consisted of a taxane (paclitaxel or nab-paclitaxel) or gemcitabine plus carboplatin selected before randomization. The primary end point was PFS by BICR. Prespecified subgroups included the preselected chemotherapy, disease status (de novo metastatic disease, recurrence within 6 to 12 months of prior treatment in the curative setting, or recurrence after more than 12 months), and the presence of brain metastases at baseline. A post hoc analysis by the presence of visceral metastases was also conducted. The authors noted that these analyses were not powered to detect statistically significant differences between subgroups.

Baseline characteristics were generally well balanced between the arms, both overall and within each subgroup. The median age ranged from 49 to 58 years across subgroups, and most patients had an ECOG performance status of 0 and lung metastases at baseline. Recurrent disease was more common than de novo metastatic disease, with roughly half of patients experiencing recurrence more than 12 months after curative-setting treatment. Consistent with contemporary practice, patients with recurrent disease were more often preselected for gemcitabine plus carboplatin, whereas those with de novo disease were more often preselected for a taxane.

Across all assessed subgroups, the median PFS by BICR numerically favored sacituzumab govitecan, with unstratified HRs ranging from 0.38 to 0.89; HRs by investigator assessment ranged from 0.39 to 0.84. In the intent-to-treat population, the unstratified HR by BICR was 0.66 (95% CI, 0.53–0.82).

Among patients preselected for a taxane, the median PFS by BICR was 11.1 months (95% CI, 8.1-12.7) with sacituzumab govitecan vs 5.7 months (95% CI, 4.3-8.1) with chemotherapy (HR, 0.51; 95% CI, 0.38-0.68). In those preselected for gemcitabine plus carboplatin, the median PFS was 8.5 months (95% CI, 6.9-9.9) vs 8.1 months (95% CI, 5.7-8.3; HR, 0.89; 95% CI, 0.64-1.22).

By disease status, the median PFS by BICR was 8.3 months vs 5.5 months in patients with de novo metastatic disease (HR, 0.65; 95% CI, 0.45-0.94), 8.3 months vs 5.6 months in those with recurrence within 6 to 12 months (HR, 0.46; 95% CI, 0.29-0.72), and 11.1 months vs 8.4 months in those with recurrence after more than 12 months (HR, 0.72; 95% CI, 0.52-1.00).

In the visceral metastases subgroup, PFS by BICR was 8.5 months vs 5.7 months (HR, 0.66; 95% CI, 0.52-0.84), with a corresponding HR of 0.68 by investigator assessment. Among patients with brain metastases at baseline, the median PFS by BICR was 8.4 months vs 4.4 months (HR, 0.38; 95% CI, 0.15-1.01), and the HR by investigator assessment was 0.39; however, only 29 patients were in this subgroup, and the investigators cautioned that interpretation is limited.

At the time of progression, the incidence of new lesions was similar between the sacituzumab govitecan arm (30%) and the chemotherapy arm (31%), but a smaller proportion of patients developed new visceral lesions with sacituzumab govitecan (15% vs 19%).

The investigators concluded that these findings, consistent with the overall ASCENT-03 results and taken together with data from the ASCENT-04 study of sacituzumab govitecan plus pembrolizumab (Keytruda) in PD-L1–positive metastatic TNBC, support the use of first-line sacituzumab govitecan as the backbone of care for patients with previously untreated, locally advanced unresectable or metastatic TNBC, regardless of PD-L1 status.

Reference

Punie K, Cortes J, Hurvitz S, et al. Subgroup analysis from the ASCENT-03 study of sacituzumab govitecan vs chemotherapy in previously untreated metastatic triple-negative breast cancer: PFS by preselected chemotherapy, disease status, and brain and visceral metastases. Presented at: European Society for Medical Oncology Congress 2026; October 23-27, 2026; Madrid, Spain. Poster 4649