On February 3, 2023, sacituzumab govitecan-hziy was approved for unresectable locally advanced or metastatic hormone receptor (HR)-positive, HER2-negative (immunohistochemistry [IHC] 0, IHC 1+, or IHC 2+/in situ hybridization–negative) breast cancer who have received endocrine-based therapy and at least two additional systemic therapies in the metastatic setting.1
Supporting Efficacy Data
Approval was based on findings in the open-label TROPiCS-02 trial (ClinicalTrials.gov identifier NCT03901339). In this study, 543 patients were randomly assigned to receive sacituzumab govitecan at 10 mg/kg on days 1 and 8 of 21-day cycles (n = 272) or single-agent chemotherapy selected by investigators prior to randomization (n = 271); options were eribulin (n = 130), vinorelbine (n = 63), gemcitabine (n = 56), or capecitabine (n = 22). Treatment continued until disease progression or unacceptable toxicity.
Median progression-free survival on blinded independent central review (primary endpoint) was 5.5 months (95% confidence interval [CI] = 4.2–7.0 months) with sacituzumab govitecan vs 4 months (95% CI = 3.1–4.4 months) with single-agent chemotherapy (hazard ratio [HR] = 0.661, 95% CI = 0.529–0.826, P = .0003). Median overall survival was 14.4 months (95% CI = 13.0–15.7 months) vs 11.2 months (95% CI = 10.1–12.7 months; HR = 0.789, 95% CI = 0.646–0.964, P = .0200).
How It Is Used
The recommended dose of sacituzumab govitecan is 10 mg/kg on days 1 and 8 of 21-day cycles until disease progression or unacceptable toxicity.
Prescribing information provides information on premedication for infusion reactions and nausea/vomiting and instructions on dosage modification, including dose reduction, for adverse reactions such as infusion reactions, neutropenia, and non-neutropenic toxicity. Concomitant use of sacituzumab govitecan with UGT1A1 inhibitors or inducers should be avoided.
In TROPiCS-02, the most common adverse events of any grade in the sacituzumab govitecan group were diarrhea (62% vs 23% in single-agent chemotherapy group), fatigue (60% vs 51%), nausea (59% vs 35%), alopecia (48% vs 19%), and constipation (34% vs 25%). The most common grade 3 or 4 adverse events were diarrhea (10%) and fatigue (8%). The most common grade 3 or 4 laboratory abnormalities were decreased neutrophils (53%), leukocytes (38%), and lymphocytes (21%).
Serious adverse events occurred in 28% of patients receiving sacituzumab govitecan, most commonly diarrhea (5%), febrile neutropenia (4%), and neutropenia (3%). Treatment was discontinued because of adverse events in 6%; causes included asthenia, general physical health deterioration, and neutropenia. Fatal adverse events occurred in 2% of patients, including arrhythmia, COVID-19, nervous system disorder, pulmonary embolism, and septic shock.
Sacituzumab govitecan has a boxed warning for neutropenia and diarrhea. The agent also has warnings/precautions for hypersensitivity and infusion-related reactions; nausea/vomiting; patients with reduced UGT1A1 activity; and embryofetal toxicity. Sacituzumab govitecan is contraindicated in patients with severe hypersensitivity reaction to the agent. Patients should be advised not to breastfeed while receiving sacituzumab govitecan.
1. Trodelvy (sacituzumab govitecan-hziy) for injection prescribing information, Gilead Sciences, February 2023. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761115s035lbl.pdf. Accessed February 15, 2023.