Based on results from a phase I/II clinical trial, the antibody drug conjugate sacituzumab govitecan was recently granted accelerated approval in the treatment of patients with advanced triple-negative breast cancer, contingent on a larger study confirming its benefit. The confirmatory phase III ASCENT trial has now done so, showing not only a progression-free survival advantage, but also an overall survival benefit in the third line and beyond setting.
In patients without brain metastases who had received two or more lines of prior therapy, treatment with sacituzumab govitecan led to median 5.6 months vs 1.7 months with physician’s choice of single-agent chemotherapy (hazard ratio [HR] = 0.41; P < .0001), which met the study’s primary endpoint. In addition, median overall survival was 12.1 months vs 6.7months (HR = 0.48; P < .0001), Aditya Bardia, MD, MPH, of Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, reported at the European Society for Medical Oncology (ESMO) Virtual Congress 2020.1
Aditya Bardia, MD, MPH
“ASCENT is the first phase III study to demonstrate a significant improvement in efficacy with a first-in-class Trop-2–directed antibody-drug conjugate compared with standard chemotherapy in patients with previously treated metastatic triple-negative breast cancer,” Dr. Bardia noted.
Sacituzumab govitecan is a monoclonal antibody linked to a topoisomerase inhibitor and directed against trophoblast cell-surface antigen 2 (Trop-2), which is highly expressed in breast cancer. The U.S. Food and Drug Administration recently granted accelerated approval to the drug as a third-line treatment for patients with metastatic triple-negative disease, but continued approval was contingent on results from confirmatory trials such as ASCENT.
ASCENT Details
The global ASCENT trial randomly assigned 529 patients with advanced triple-negative breast cancer who had at least two prior lines to either intravenous sacituzumab govitecan (10 mg/kg on days 1 and 8 every 3 weeks) or physician’s choice of chemotherapy (eribulin, vinorelbine, gemcitabine, or capecitabine). Patients with brain metastases could enroll but were limited to 15% of the population to avoid potential confounding. All patients had received prior taxanes, and about one-third had been treated with a checkpoint inhibitor.
Median progression-free survival was 5.6 months with sacituzumab govitecan vs 1.7 months with physician’s choice of single-agent chemotherapy (hazard ratio [HR] = 0.41; P < .0001), which met the study’s primary endpoint of progression-free survival in the 468 patients without brain metastases on blinded review. Median overall survival was 12.1 months vs 6.7months (HR = 0.48; P < .0001). An improvement in progression-free survival for the full population was also significant (HR = 0.43; P < .0001).
KEY POINTS
- In the phase III ASCENT trial, sacituzumab govitecan yielded a median progression-free survival of 5.6 months vs 1.7 months with physician’s choice of single-agent chemotherapy (HR = 0.41; P < .0001) in patients with triple-negative advanced breast cancer who had at least two prior lines of therapy and lacked brain metastases.
- Median overall survival was 12.1 months vs 6.7 (HR = 0.48; P < .0001).
- Sacituzumab govitecan is a first-in-class antibody-drug conjugate for breast cancer. The study results are confirmatory of earlier results that led to its accelerated approval.
Sacituzumab govitecan also induced significantly more responses: 35% vs 5%, including complete responses in 4% and 1%, respectively. The clinical benefit rate was 45% vs 9%, respectively. At data cutoff, 15 patients remained on sacituzumab govitecan vs none in the control arm. “The clinical benefit here confirms the use of sacituzumab govitecan as a standard therapy for patients with pretreated metastatic triple-negative breast cancer,” Dr. Bardia said.
The results were consistent across all prespecified subgroups, including age, race, region, prior chemotherapy, liver involvement, and prior use of checkpoint inhibitors.
The most common adverse events of any grade included neutropenia, diarrhea, nausea, alopecia, fatigue, and anemia. Common grade 3 or 4 toxicities in the experimental vs control arms were neutropenia (51% vs 33%), leukopenia (10% vs 5%), diarrhea (10% vs < 1%), anemia (8% vs 5%), and febrile neutropenia (6% vs 2%). Dose reductions were necessary in about one-quarter of patients in each arm. One treatment-related death was due to sepsis in the chemotherapy arm.
DISCLOSURE: ASCENT was supported by Immunomedics. Dr. Bardia has served as a consultant or advisor to bioTheranostics, Daiichi Sankyo/AstraZeneca, Genentech, Immunomedics, Merck, Novartis, Pfizer, Puma Biotechnology, Radius Pharma, Sanofi, and Spectrum Pharmaceuticals; has received research funding (institution) from Genentech/Roche, Immunomedics, Innocrin Pharma, Novartis, Pfizer, Merck, Radius Health, Daiichi Sankyo/AstraZeneca, and bioTheranostics.
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