On April 13, 2021, sacituzumab govitecan-hziy was granted accelerated approval to treat patients with locally advanced or metastatic urothelial cancer who had received platinum-containing chemotherapy and either a PD-1 or a PD-L1 inhibitor.¹

Supporting Efficacy Data

Approval was based on findings from the multicenter, phase II TROPHY trial (ClinicalTrials.gov identifier NCT03547973), in which 112 patients received sacituzumab govitecan at 10 mg/kg via intravenous infusion on days 1 and 8 of 21-day cycles until disease progression or unacceptable toxicity. 

On independent review, objective response was observed in 31 patients (27.7%, 95% confidence interval [CI] = 19.6%–36.9%), with complete response in 5.4%. The median duration of response was 7.2 months (95% CI = 4.7–8.6 months; range = 1.4+ to 13.7 months).

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. 

Treatment should be permanently discontinued for life-threatening infusion reactions. Premedication for prevention of infusion reactions and prevention of chemotherapy-induced nausea and vomiting is recommended prior to each dose.

Prescribing information provides instructions for dose modification, including dose reductions, for adverse events including severe neutropenia and severe non-neutropenic toxicity. Concomitant use with UGT1A1 inhibitors or inducers, as well as use in patient’s with Gilbert’s syndrome, should be avoided.

Safety Profile

In the TROPHY trial, the most common adverse events of any grade were diarrhea (72%), fatigue (68%), nausea (66%), and any infection (50%). The most common grade 3 or 4 adverse events included any infection (25%), urinary tract infection (12%), and diarrhea (12%).  The most common grade 3 to 4 laboratory abnormalities were decreased neutrophils (43%), decreased leukocytes (38%), and decreased lymphocytes (35%). 

Serious adverse events occurred in 44% of the patients, with the most common being infection (18%) and neutropenia (12%, including febrile neutropenia in 10%). Treatment was permanently discontinued due to adverse events in 10% of patients, most commonly due to neutropenia (4%, including febrile neutropenia in 2%). Fatal adverse events occurred in 3.6% of patients, including sepsis, respiratory failure, epistaxis, and suicide.

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 who are homozygous for the UGT1A1*28 allele and patients 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. 

REFERENCE

1. Trodelvy (sacituzumab govitecan-hziy) for injection prescribing information, Immunomedics, Inc., April 2021. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761115s009lbl.pdf. Accessed on April 20, 2021.