On April 7, 2021, sacituzumab govitecan-hziy was granted regular approval 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.1
Sacituzumab govitecan was developed as a conjugation of the irinotecan active metabolite, SN-38, to a humanized monoclonal antibody against trophoblastic cell-surface antigen-2.
Supporting Efficacy Data
Regular approval was based on findings from the phase III ASCENT trial (ClinicalTrials.gov identifier NCT02574455). In the trial, 529 patients were randomly assigned to receive sacituzumab govitecan at 10 mg/kg via intravenous infusion on days 1 and 8 of 21-day cycles (n = 267) or physician’s choice of single-agent chemotherapy (n = 262).
On blinded independent centralized review, 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] = 0.43, 95% CI = 0.35–0.54, P < .0001). Median overall survival was 11.8 months (95% CI = 10.5–13.8 months) vs 6.9 months (95% CI = 5.9–7.6 months), with a hazard ratio of 0.51 (95% CI = 0.41–0.62, P < .0001).
How It Is Used
The recommended dose is 10 mg/kg via intravenous infusion once weekly on days 1 and 8 of 21-day cycles, with treatment continuing until disease progression or unacceptable toxicity. Premedication for prevention of infusion reactions and chemotherapy-induced nausea and vomiting is recommended prior to each dose.
Prescribing information provides instructions for dose modification, including dose reduction, for adverse events including severe neutropenia and severe non-neutropenic toxicity. Concomitant use with UGT1A1 inhibitors or inducers should be avoided.
In the ASCENT trial, the most common adverse events of any grade in the sacituzumab govitecan group were fatigue (65% vs 50% in chemotherapy group), neutropenia (64% vs 44%), diarrhea (59% vs 17%), and nausea (57% vs 26%). The most common grade 3 to 4 adverse events included neutropenia (52% vs 34%) and leukopenia (11% vs 6%). The most common grade 3 or 4 laboratory abnormalities included decreased neutrophils (49% vs 36%) and decreased leukocytes (41% vs 25%).
Serious adverse events occurred in 27% of the sacituzumab govitecan group, with the most common being neutropenia (7%). Treatment was permanently discontinued in 5% of patients. Fatal adverse events occurred in 1.2% of patients, including respiratory failure (0.8%) and pneumonia (0.4%).
Sacituzumab govitecan has a boxed warning for neutropenia and diarrhea, as well as warnings/precautions for hypersensitivity reactions, nausea/vomiting, patients with reduced UGT1A1 activity, and embryofetal toxicity. Individuals homozygous for the UGT1A1*28 allele and those with Gilbert’s syndrome are at increased risk for hematologic toxicity. Sacituzumab govitecan is contraindicated in patients with a severe hypersensitivity reaction to the agent.
1. Trodelvy (sacituzumab govitecan-hziy) for injection prescribing information, Immunomedics, Inc, April 2021. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761115s005s013lbl.pdf. Accessed May 4, 2021.