As reported in The New England Journal of Medicine by Aditya Bardia, MD, and colleagues, the phase III ASCENT trial has shown prolonged progression-free and overall survival with the antibody-drug conjugate sacituzumab govitecan-hziy vs single-agent chemotherapy in patients with relapsed or refractory metastatic triple-negative breast cancer without brain metastases. A progression-free and overall survival benefit was also observed in the total population including patients with baseline brain metastases.
The trial supported the April 2021 regular approval of sacituzumab govitecan for treatment of patients with unresectable locally advanced or metastatic triple-negative breast cancer who have received two or more prior systemic therapies, at least one of them for metastatic disease.
Aditya Bardia, MD
The open-label trial included 529 patients from sites in seven countries who had received two or more previous standard chemotherapies for unresectable locally advanced or metastatic disease and a taxane for any indication. They were randomly assigned to receive sacituzumab govitecan at 10 mg/kg intravenously on days 1 and 8 of each 21-day cycle (n = 267) or investigator’s choice of single-agent chemotherapy determined prior to random assignment (n = 262); chemotherapy options consisted of eribulin, vinorelbine, capecitabine, and gemcitabine. Treatment continued until disease progression or unacceptable toxicity.
The primary trial population consisted of 468 patients with no evidence of brain metastases, including 235 in the sacituzumab govitecan group vs 233 in the chemotherapy group (54% received eribulin; 20%, vinorelbine; 13%, capecitabine; and 12%, gemcitabine). The primary endpoint was progression-free survival on blinded independent central review among patients without brain metastases. Efficacy analyses involved the patients without brain metastases at baseline, as well as the full trial population.
A total of 32 patients assigned to receive chemotherapy in the primary population received no trial drug (n = 26) or withdrew consent (n = 6) before treatment; these patients are included in the efficacy analysis, but not in the safety analyses.
Median follow-up was 17.7 months (range = 5.8–28.1 months). In the primary trial population, median progression-free survival was 5.6 months (95% confidence interval [CI] = 4.3–6.3 months) in the sacituzumab govitecan group vs 1.7 months (95% CI = 1.5–2.6 months) in the chemotherapy group (hazard ratio [HR] = 0.41, 95% CI = 0.32–0.52, P < .001). Median overall survival was 12.1 months (95% CI = 10.7–14.0 months) in the sacituzumab govitecan group vs 6.7 months (95% CI = 5.8–7.7 months) in the chemotherapy group (HR = 0.48, 95% CI = 0.38–0.59, P < .001). Objective response was observed in 35% vs 5% of patients; median duration of response was 6.3 months vs 3.6 months (HR = 0.39, 95% CI = 0.14–1.07).
In the total population (including 61 patients with baseline brain metastases), median progression-free survival was 4.8 months (95% 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 (HR = 0.43, 95% CI = 0.35–0.54, P < .001). Median overall survival was 11.8 months (95% CI = 10.5–13.8 months) vs 6.9 months (95% CI = 5.9–7.7 months; HR = 0.51, 95% CI = 0.41–0.62).
The safety population consisted of 258 patients in the sacituzumab govitecan group and 224 in the chemotherapy group who received at least one dose of the study drug. Treatment-related grade 3 to 4 adverse events were observed in 64% of the sacituzumab govitecan group vs 47% of the chemotherapy group, with the most common in the sacituzumab group being neutropenia (51% vs 33% with chemotherapy), leukopenia (10% vs 5%), diarrhea (10% vs < 1%), anemia (8% vs 5%), and febrile neutropenia (6% vs 2%).
Serious treatment-related adverse events occurred in 15% vs 8% of patients. Adverse events led to permanent treatment discontinuation in 5% vs 5%. Fatal adverse events occurred in three patients in each group, with none in the sacituzumab group considered treatment-related and one in the chemotherapy group (neutropenic sepsis) considered treatment-related.
The investigators concluded, “Progression-free and overall survival were significantly longer with sacituzumab govitecan than with single-agent chemotherapy among patients with metastatic triple-negative breast cancer. Myelosuppression and diarrhea were more frequent with sacituzumab govitecan.”
Disclosure: The study was funded by Immunomedics. For full disclosures of the study authors, visit nejm.org.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.