The FDA has granted regular approval to sacituzumab govitecan (Trodelvy®, Immunomedics Inc.) for patients with unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who previously have been treated with two or more systemic therapies, at least one of them for metastatic disease. Previously, the FDA had granted accelerated approval to sacituzumab govitecan based on the results of the phase 1/2 IMMU-132-01 study (NCT01631552); the ASCENT study (NCT02574455), on which the regular approval was based, was initiated to confirm those results.
"In patients with pretreated mTNBC, standard of care chemotherapy is associated with low objective response rates and short median progression-free survival," wrote Aditya Bardia, MD, MPH, of Massachusetts General Hospital Cancer Center, and colleagues, in the abstract for the ASCENT study, which was presented at the European Society of Medical Oncology Virtual Congress in September 2020. "Sacituzumab govitecan is a first-in-class antibody-drug conjugate composed of an anti–Trop-2 antibody coupled to the active metabolite of irinotecan, SN-38, via a unique hydrolyzable linker that allows for SN-38 release intracellularly and in the tumor microenvironment (bystander effect)."
The approval was supported by safety and efficacy results from the randomized phase 3 ASCENT study, in which 529 patients with unresectable locally advanced or mTNBC who relapsed after previous treatment with at least two chemotherapy treatments enrolled. Patients were randomized in a one-to-one ratio to be treated with either 10 mg/kg sacituzumab govitecan as an intravenous infusion or a physician's choice of single agent chemotherapy. The primary end point was progression-free survival in patients without brain metastases at baseline. Secondary end points were progression-free survival for the full population and overall survival.
In patients who did not have brain metastases, sacituzumab govitecan significantly improved median progression-free survival (5.6 months vs 1.7 months) and median overall survival (12.1 months vs. 6.7 months). Sacituzumab govitecan also significantly improved progression-free survival for the total population of randomized patients (4.8 months vs 1.7 months), as well as overall survival (11.8 months vs 6.9 months).
Adverse events described in the prescribing information that occurred in more than 25% of patients treated with sacituzumab govitecan included nausea, neutropenia, diarrhea, fatigue, alopecia, anemia, vomiting, constipation, rash, decreased appetite, and abdominal pain.
Dr. Bardia and colleagues concluded, "ASCENT is the first phase 3 study of an antibody-drug conjugate with significant progression-free survival and overall survival improvement over standard of care chemotherapy in pretreated mTNBC, confirming the clinical activity and safety profile of sacituzumab govitecan monotherapy."
The recommended dose of sacituzumab govitecan is 10 mg/kg once weekly on Days 1 and 8 of 21-day treatment cycles until disease progression or unacceptable toxicity.
For More Information
Bardia A, Tolaney SM, Loirat D, et al (2020). ASCENT: A randomized phase III study of sacituzumab govitecan (SG) vs treatment of physician's choice (TPC) in patients (pts) with previously treated metastatic triple-negative breast cancer (mTNBC). Ann Oncol (ESMO Virtual Congress 2020), 31(suppl_4):S1142-S1215. Abstract LBA17. DOI:10.1016/j.annonc.2020.08.2245
US Food & Drug Administration (2021). FDA grants regular approval to sacituzumab govitecan for triple-negative breast cancer. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-regular-approval-sacituzumab-govitecan-triple-negative-breast-cancer
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