Sacituzumab Govitecan Fails to Improve PFS in HR-Positive, HER2-Negative Metastatic Breast Cancer
Key Clinical Takeaways
- Design/Population: This phase 3 trial randomized 690 patients with HR-positive, HER-negative locally advanced unresectable or metastatic breast cancer previously treated with endocrine therapy to receive sacituzumab govitecan or physician’s choice chemotherapy. Randomization was stratified by duration of prior CDK4/6 inhibitor use, HER2 immunohistochemistry status, and geographic region.
- Key Outcomes: Sacituzumab govitecan did not significantly improve PFS by blinded central review, though investigator-assessed PFS and early OS trends numerically favored the drug. Objective response rates were similar between groups, and duration of response was longer with sacituzumab govitecan.
- Clinical Relevance: Despite not meeting the primary PFS end point, sacituzumab govitecan demonstrated early signals of clinical activity and maintained a manageable safety profile. Ongoing follow-up will clarify its potential role for patients with HR-positive, HER2-negative metastatic breast cancer progressing after endocrine therapy.
According to results from the phase 3 ASCENT-07 trial, sacituzumab govitecan did not significantly improve progression-free survival (PFS) compared with physician’s choice chemotherapy among patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced unresectable or metastatic breast cancer previously treated with endocrine therapy
These findings were presented by Komal Jhaveri, MD, Memorial Sloan Kettering Cancer Center, New York, New York, at the 2025 San Antonio Breast Cancer Symposium in San Antonio, Texas.
In this study, 690 patients were randomized 2:1 to receive either 10 mg/kg of sacituzumab govitecan on days 1 and 8 of each 21-day cycle (n = 456) or physician’s choice of capecitabine, paclitaxel, or nab-paclitaxel (n = 234). Patients were stratified according to duration of prior CDK4/6 inhibitor therapy, HER2 immunohistochemistry status, and geographic region. The primary end point was PFS as assessed by blinded independent central review. Key secondary end points included investigator-assessed PFS, overall survival (OS), objective response rate (ORR), duration of response, and safety.
At a median follow-up of 15.4 months, median PFS was 8.3 months in both treatment arms (hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.69 to 1.05; P = .130) per blinded independent central review. By investigator assessment, median PFS was 8.4 months with sacituzumab govitecan and 6.4 months with chemotherapy (P = .008). OS data were immature; however, an early trend favoring sacituzumab govitecan was observed (HR, 0.72; 95% CI, 0.54 to 0.97; P = .029). The ORR was 37% in the sacituzumab govitecan arm and 33% in the chemotherapy arm, and the median duration of response was 12.1 months and 9.3 months, respectively.
Grade ≥3 treatment-emergent adverse events occurred in 72% of patients receiving sacituzumab govitecan and 48% receiving chemotherapy. Adverse events led to dose reductions in 39% of patients receiving sacituzumab govitecan and 38% of patients receiving chemotherapy, and treatment discontinuations in 3% and 7% of patients, respectively.
“The study did not meet the primary endpoint of PFS by [blinded independent central review] in participants with HR[-positive]/HER2[-negative], locally advanced unresectable or [metastatic breast cancer] who have received prior [endocrine therapy] and are candidates for first chemotherapy,” concluded Dr Jhaveri. “An early trend in improvement of OS was observed, and the study will continue to further assess OS.”
Source:
Jhaveri K, Park Y, Barrios C, et al. Sacituzumab govitecan vs chemotherapy as first therapy after endocrine therapy in HR+/HER2− (IHC 0, 1+, 2+/ISH−) metastatic breast cancer: Primary results from ASCENT-07. Presented at SABCS 2025. December 9 - 12, 2025. San Antonio, Texas. Abstract GS1-09
