Gilead Sciences will withdraw the accelerated approval status for sacituzumab govitecan (Trodelvy) as a treatment for adults with locally advanced or metastatic urothelial cancer who have previously received platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor. The decision, made in consultation with the FDA, follows the failure of the phase 3 TROPiCS-04 trial to confirm the clinical benefit observed in earlier studies. The withdrawal will not impact other approved indications for sacituzumab govitecan.
The accelerated approval, granted in April 2021, was based on data from the phase 2 TROPHY-U-01 trial (NCT03547973). That trial showed a confirmed objective response rate (ORR) of 27.7% (95% CI, 19.6%-36.9%) in 112 evaluable patients. This included complete responses (CRs) in 5.4% of patients and partial responses (PRs) in 22.3%. The median duration of response (DOR) was 7.2 months (95% CI, 4.7-8.6).
TROPiCS-04 Trial Results
The phase 3 TROPiCS-04 trial (NCT04527991) was designed to confirm the clinical benefits of sacituzumab govitecan in this patient population. However, the trial failed to meet its primary endpoint of overall survival (OS) compared to physician's choice of chemotherapy. While a numerical OS improvement favoring the sacituzumab govitecan arm was observed, it was not statistically significant. There were also trends in improved outcomes across select prespecified subgroups as well secondary end points such as progression-free survival (PFS) and ORR.
The open-label, international, multicenter trial randomized 711 patients 1:1 to receive either sacituzumab govitecan (10 mg/kg intravenously on days 1 and 8 of every 21-day cycle) or investigator’s choice of paclitaxel, docetaxel, or vinflunine. Eligible patients had metastatic or locally advanced unresectable urothelial cancer, had an ECOG performance status of 0 or 1, and had progressed or recurred following platinum-containing chemotherapy and anti–PD-1 or anti–PD-L1 therapy.
Safety Concerns
Notably, a higher proportion of patients in the sacituzumab govitecan arm died due to adverse effects compared with those who received chemotherapy. These deaths primarily occurred early in treatment and were often associated with neutropenic complications such as infection. The safety profile observed in TROPiCS-04 was consistent with the known safety profile of sacituzumab govitecan in its approved breast cancer indications.
Impact on Patients
Gilead recommends that patients in the United States currently receiving sacituzumab govitecan for metastatic urothelial cancer discuss their treatment plan with their healthcare provider. The withdrawal does not affect other approved indications for sacituzumab govitecan, both in and outside of the United States.
