Sacituzumab Govitecan Shows Promise for HR+/HER2− Breast Cancer

Sacituzumab govitecan (SG), marketed as Trodelvy by Gilead Sciences, has demonstrated early signs of benefit for patients with hormone receptor-positive, HER2-negative (HR+/HER2−) metastatic breast cancer, according to findings from the phase 3 ASCENT-07 trial (NCT05840211). These results were presented at the 2025 San Antonio Breast Cancer Symposium, highlighting SG’s potential impact on overall survival.

Study Design and Methodology

The ASCENT-07 trial involved 690 adults with HR+/HER2− locally advanced unresectable or metastatic breast cancer. Participants were randomly assigned to receive SG at a dose of 10 mg/kg intravenously or a chemotherapy regimen of the physician’s choice, which included capecitabine, nab-paclitaxel, or paclitaxel. Randomization was stratified based on prior use of CDK4/6 inhibitors, HER2 immunohistochemistry status, and geographic region.

The primary endpoint was progression-free survival (PFS), assessed by blinded independent central review (BICR) according to RECIST v1.1 criteria. Key secondary endpoints included overall survival (OS), objective response rate (ORR), and quality of life, along with other safety and duration of response assessments.

Primary Results from ASCENT-07

Of the 690 participants, 456 received SG and 234 received the chemotherapy regimen. The median age of participants was approximately 57 years, with a significant proportion having previously received CDK4/6 inhibitors (SG: 93%; TPC: 92%).

At a median follow-up of 15.4 months, SG did not show a statistically significant improvement in PFS compared to the chemotherapy regimen (hazard ratio [HR] of 0.85; 95% confidence interval [CI], 0.69–1.05; P = 0.130). However, investigator assessments indicated a numerical improvement in PFS for SG (HR of 0.78; 95% CI, 0.64–0.93; nominal P = 0.008).

While OS data were still immature at the primary analysis (27% maturity), an early trend favored SG with a HR of 0.72 (95% CI, 0.54–0.97; nominal P = 0.029). The ORR by BICR was similar for both groups (SG: 37%; TPC: 33%), while the median duration of response was longer with SG (12.1 months versus 9.3 months for TPC).

The most common grade 3 or higher treatment-emergent adverse event was neutropenia, affecting 56% of SG recipients compared to 21% for the chemotherapy group. Despite the higher incidence of severe adverse events with SG, the rates of dose reductions were comparable between the two groups, and fewer participants discontinued treatment with SG compared to TPC.

In conclusion, while the ASCENT-07 trial did not meet its primary endpoint of PFS as assessed by BICR, it revealed promising trends towards improved OS with SG. No new safety concerns were identified during the trial. These findings indicate that although SG may not significantly extend PFS for patients in this setting, its tolerability and potential OS benefits warrant further investigation.