Sacituzumab Govitecan-hziy for Locally Advanced or Metastatic Urothelial Cancer
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.
OF NOTE
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.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.
