Gilead Sciences has announced the voluntary withdrawal of Trodelvy (sacituzumab govitecan-hziy) from the U.S. market as a treatment for advanced urothelial carcinoma. This decision, made in consultation with the FDA, follows the failure of the Phase 3 TROPiCS-04 confirmatory study to meet its primary endpoint of overall survival (OS). The withdrawal does not affect Trodelvy’s approved indications for triple-negative breast cancer (TNBC) and HR-positive/HER2-negative breast cancer.
The accelerated approval for urothelial carcinoma was granted in 2021 based on Phase 2 TROPHY-U-01 study data, which demonstrated promising tumor response rates and duration of response in patients who had previously received platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor. However, continued approval was contingent upon verification of clinical benefit in the confirmatory TROPiCS-04 trial.
The TROPiCS-04 study, a global, open-label, multicenter, phase 3 trial, enrolled 711 patients with metastatic or locally advanced unresectable urothelial carcinoma who had progressed after prior platinum-containing chemotherapy and checkpoint inhibitor therapy. Patients were randomized 1:1 to receive either Trodelvy or single-agent chemotherapy (paclitaxel, docetaxel, or vinflunine). While a numerical improvement in overall survival was observed in the Trodelvy arm, it did not reach statistical significance in the intention-to-treat population.
According to a Gilead press release, more deaths due to adverse events (AEs) were observed in the Trodelvy arm compared to the chemotherapy arm. These AEs leading to death generally occurred early in treatment and were related to neutropenic complications, including infection. Gilead stated it would further investigate these data and reiterate the importance of granulocyte-colony stimulating factor (G-CSF) use for the prevention of neutropenic complications.
Trodelvy is an antibody-drug conjugate (ADC) targeting TROP-2, a protein highly expressed in various tumor types. It combines a targeting antibody with a cytotoxic payload (SN-38, a topoisomerase I inhibitor) designed to selectively deliver potent activity to both TROP-2 expressing cells and the tumor microenvironment.
Despite this setback, Gilead remains committed to Trodelvy, with over 20 ongoing clinical trials evaluating its potential in other solid tumors, including lung and gynecological cancers. The company is also awaiting results from Phase 3 trials that could support moving Trodelvy into earlier lines of treatment for breast cancer. In 2023, Trodelvy generated $1.1 billion in sales, a 56% increase year-over-year, highlighting its importance to Gilead's oncology portfolio. Bladder cancer accounted for approximately 10% of Trodelvy's sales.
Clinicians are advised to notify patients receiving Trodelvy for metastatic urothelial cancer in the U.S. to discuss alternative treatment options. Full data from the TROPiCS-04 trial will be presented at an upcoming medical meeting.
