Sacituzumab govitecan received FDA approval for urothelial (bladder–urinary tract) cancer

On April 13, 2021, FDA (the US Food and Drug Administration), for people previously treated with platinum containing chemotherapy and immunotherapy whose cancer had worsened, with locally advanced or metastatic stage urothelial (bladder and urinary tract) cancer, granted accelerated approval to sacituzumab govitecan (Trodelvy, Immunomedics Inc.).

How does sacituzumab govitecan work?

Cancer cells contain a protein called Trop-2 that activates a calcium-dependent signaling pathway. Activation of Trop-2 causes growth signals to be sent into the cell. Sacituzumab govitecan is a treatment directed at a "new target" in cancer therapy, and is an antibody–drug conjugate developed against this protein.

Sacituzumab, one of two conjugated drugs being investigated in this field and an inhibitor of the Trop2 pathway, first received FDA approval for the treatment of triple-negative breast cancer in April 2020 for this indication.

The TROPHY clinical study that led to FDA approval

The efficacy and safety of sacituzumab in bladder–urinary tract cancer were evaluated in the single-arm, multicenter TROPHY clinical trial, which included 112 patients with locally advanced or metastatic cancer. The patients had previously received platinum-containing chemotherapy and immunotherapy from the PD-1 or PD-L1 inhibitor class. Patients received sacituzumab govitecan at a dose of 10 mg/kg on days 1 and 8 of each 21-day treatment cycle.

The study’s main efficacy endpoints were objective response rate and duration of response, assessed by independent review using RECIST 1.1 criteria.

Results

• The confirmed objective response rate was 27.7%;
  • the complete response rate was 5.4% and
  • the partial response rate was 22.3% (95% CI: 19.6, 36.9).
• For the 31 patients who responded to treatment, the median duration of response was 7.2 months.

Side effects

The most common (> % 25) side effects in patients receiving sacituzumab govitecan are neutropenia, nausea, diarrhea, fatigue, alopecia, anemia, vomiting, constipation, decreased appetite, rash and abdominal pain.

Dose

The recommended sacituzumab govitecan dose is 10 mg / kg once a week on days 1 and 8 of a 21-day treatment cycle, until disease progression or unacceptable toxicity.