Bladder Cancer Indication of Sacituzumab Govitecan Withdrawn in US

The accelerated approval of sacituzumab govitecan-hziy (Trodelvy) is being voluntarily withdrawn from the US market for the treatment of patients with locally advanced or metastatic urothelial cancer who previously received platinum-containing chemotherapy and a PD-1 or PD-L1 inhibitor.¹

Gilead, sacituzumab govitecan’s manufacturer, made the decision in consultation with the FDA. This decision does not affect other indications or approvals of the agent.

The decision was made after the confirmatory phase 3 TROPiCS-04 study (NCT04527991) failed to meet its primary end point of overall survival (OS) in the intention-to-treat population.² There was a numerical, but not statistically significant, improvement in OS, and improvement was also observed in prespecified subgroup analyses. However, the subgroup analyses were not controlled for formal statistical testing. Further, secondary end points of objective response rate (ORR) and progression-free survival (PFS) showed improvement.

There were also a higher number of deaths due to adverse events (AEs) with sacituzumab govitecan vs investigator’s choice of therapy. These were primarily seen early in treatment and related to neutropenic complications. Gilead is further investigating these data.

About the Accelerated Approval of Sacituzumab Govitecan

In 2021, the FDA granted sacituzumab govitecan accelerated approval in this patient population, as supported by data from the phase 2 TROPHY-U-01 study (NCT03547973).³ Here, the confirmed ORR was 27.7% (95% CI, 19.6%-36.9%), with 22.3% of patients achieving a partial response (PR) and 5.4% achieving a complete response. The median duration of response (DOR) was 7.2 months (95% CI, 4.7-8.6).

Findings from a cohort analysis TROPHY-U-01 of patients who were ineligible for cisplatin showed that at a median follow-up of 9.3 months, the ORR with sacituzumab govitecan was 32% (12/38; 95% CI, 17.5%-48.7%). All responders achieved a PR. The median DOR was 5.6 months (95% CI, 2.8-13.3) and the clinical benefit rate was 42% (95% CI, 26.3%-59.2%). The median PFS was 5.6 months (95% CI, 4.1-8.3), and the median OS was 13.5 months (95% CI, 7.6-15.6).⁴

All patients experienced at least 1 treatment-emergent AE (TEAE), and 87% (n = 33) experienced a grade 3 or higher TEAE. The most common grade 3 or higher TEAEs were neutropenia (34%), anemia (24%), leukopenia (19%), fatigue (18%), and diarrhea (16%). There were no TEAEs that led to patient death.

REFERENCES:

1. Gilead provides update on U.S. indication for Trodelvy® in metastatic urothelial cancer. News release. Gilead. October 18, 2024. Accessed October 21, 2024. https://tinyurl.com/2rs4r3zb

2. Gilead provides update on phase 3 TROPiCS-04 study. News release. Gilead. May 30, 2024. Accessed October 21, 2024. https://tinyurl.com/2vmakum2

3. FDA grants accelerated approval to sacituzumab govitecan for advanced urothelial cancer. News release. FDA. April 13, 2021. Accessed October 21, 2024. https://bit.ly/2QoWumx

4. Petrylak D, Tagawa ST, Jain RK, et al. TROPHY-U-01 cohort 2: a phase II study of sacituzumab govitecan in cisplatin-ineligible patients with metastatic urothelial cancer progressing after previous checkpoint inhibitor therapy. J Clin Oncol. Published online August 26, 2024. doi:10.1200/JCO.23.01720.