As reported in the Journal of Clinical Oncology by Aditya Bardia, MD, MPH, and colleagues, final results of the phase III ASCENT trial showed continued superior progression-free and overall survival with sacituzumab govitecan-hziy, an anti–trophoblast cell surface antigen 2 (Trop-2) antibody-drug conjugate, vs physician’s choice of single-agent chemotherapy in previously treated patients with metastatic triple-negative breast cancer.
The primary analysis of the trial supported the April 2021 approval of sacituzumab govitecan in this setting, showing improved progression-free and overall survival with the agent.
Aditya Bardia, MD, MPH
Study Details
In the trial, patients who had received two or more prior systemic therapies, including at least one for metastatic disease, were randomly assigned to receive sacituzumab govitecan (n = 267) or physician’s choice of single-agent chemotherapy (n = 262) until disease progression or unacceptable toxicity.
Key Findings
In the preplanned final analysis in the intention-to-treat population, median progression-free survival was 4.8 months (95% confidence interval [CI] = 4.1–5.8 months) in the sacituzumab govitecan group vs 1.7 months (95% CI = 1.5–2.5 months) in the chemotherapy group (hazard ratio [HR] = 0.41, 95% CI = 0.33–0.52). Median overall survival was 11.8 months (95% CI = 10.5–13.8 months) in the sacituzumab govitecan group vs 6.9 months (95% CI = 5.9–7.7 months) in the chemotherapy group (HR = 0.51, 95% CI = 0.42–0.63).
In analyses according to Trop-2 expression, staining for expression was available for 60% of the total population. Sacituzumab govitecan significantly improved progression-free survival over chemotherapy in each Trop-2 expression quartile (4th quartile = highest expression), with significant hazard ratios of 0.583, 0.517, 0.196, and 0.314 in the 1st through 4th quartiles, respectively. A trend in improvement in overall survival was observed for sacituzumab govitecan across quartiles; hazard ratios were 0.739, 0.690, 0.344 (significant), and 0.358 (significant) across the respective quartiles.
In analysis according to HER2 immunohistochemistry (IHC) status, results were available for 78% of the total population; among these, 71% had IHC0 and 29% had HER2-low status. Sacituzumab govitecan improved progression-free and overall survival over chemotherapy in both categories.
Overall, sacituzumab govitecan was considered to have a manageable safety profile, with discontinuation due to treatment-related adverse events in ≤ 5% of patients. No treatment-related deaths were observed.
The investigators concluded, “These data confirm the clinical benefit of sacituzumab govitecan over chemotherapy, reinforcing sacituzumab govitecan as an effective treatment option in patients with metastatic triple-negative breast cancer in the second line or later.”
Aditya Bardia, MD, MPH, of the David Geffen School of Medicine and UCLA Health Jonsson Comprehensive Cancer Center, Los Angeles, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Gilead Sciences, Inc. For full disclosures of the study authors, visit ascopubs.org.
