FDA accelerates approval for sacituzumab govitecan in advanced urothelial cancer

On November 22, 2024, the FDA officially revoked the approval of sacituzumab govitecan-hziy (Trodelvy) for adult patients with locally advanced or metastatic urothelial cancer (mUC) who had previously undergone treatment with a platinum-containing chemotherapy as well as either a programmed death receptor-1 (PD-1) or a programmed death-ligand 1 (PD-L1) inhibitor. This decision followed the earlier accelerated approval granted on April 13, 2021, by the Food and Drug Administration for the same drug and patient group.

Sacituzumab govitecan, marketed as Trodelvy by Immunomedics Inc., had shown promise for patients with advanced or metastatic urothelial cancer who had already received specific prior treatments. This approval was based on the results from the TROPHY (IMMU-132-06) trial (NCT03547973), which was a single-arm, multicenter study enrolling 112 participants with advanced urothelial cancer. These participants had previously been treated with a platinum-based chemotherapy and either a PD-1 or PD-L1 inhibitor. During the trial, patients were administered sacituzumab govitecan at a dose of 10 mg/kg intravenously on the first and eighth days of a 21-day treatment cycle.

The main metrics for effectiveness in this trial were the objective response rate (ORR) and the duration of response (DOR), both assessed by independent reviewers according to RECIST 1.1 criteria. The study found a confirmed ORR of 27.7% with a 95% confidence interval (CI) ranging from 19.6% to 36.9%. This comprised 5.4% complete responses and 22.3% partial responses. The median duration of response was recorded at 7.2 months (with a 95% CI of 4.7 to 8.6 months, and a range from 1.4+ to 13.7 months).

Several adverse reactions were observed in over 25% of patients treated with sacituzumab govitecan. These included neutropenia, nausea, diarrhea, fatigue, alopecia, anemia, vomiting, constipation, decreased appetite, rash, and abdominal pain. The prescribed dosage for sacituzumab govitecan was 10 mg/kg administered weekly on days 1 and 8 within 21-day cycles, continuing until disease progression or unacceptable toxicity levels were reached.

This indication had initially been approved based on the observed tumor response rate and response duration. However, continued approval was dependent on further verification and description of clinical benefits in a confirmatory trial. The review process benefitted from the Real-Time Oncology Review (RTOR) pilot program, which expedited data submission before the complete clinical application, as well as the Assessment Aid, a voluntary submission by the applicant to aid the FDA's assessment. This application was approved six weeks ahead of the FDA's goal date and had been granted priority review and fast track designation.

Despite the initial promise, the withdrawal of Trodelvy's approval signifies a step back for patients with advanced urothelial cancer, underscoring the necessity for ongoing research and validation in the field of oncology treatments.