Sacituzumab govitecan (Trodelvy) has shown promising activity in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer who have progressed after immune checkpoint inhibitor (ICI) therapy. The phase II TROPHY-U-01 study, published in the Journal of Clinical Oncology, demonstrated a clinically significant objective response rate and manageable toxicity profile with sacituzumab govitecan monotherapy in this challenging patient population.
Study Details and Patient Population
The multicenter study enrolled 38 patients in the U.S. who had experienced disease progression after ICI therapy. Patients received sacituzumab govitecan at 10 mg/kg on days 1 and 8 of 21-day cycles. Half of the patients had also received prior platinum-based chemotherapy as (neo)adjuvant therapy. The median number of prior regimens was two (range = 1–5). The primary outcome measure was objective response rate (ORR) on central review.
Efficacy Results
After a median follow-up of 9.3 months (range = 0.5–30.6 months), the study reported an ORR of 32% (95% CI = 17.5%–48.7%), with all responses being partial responses. The median time to response was 1.4 months (95% CI = 1.3–1.5 months). The median duration of response was 5.6 months (95% CI = 2.8–13.3 months), and the clinical benefit rate was 42% (95% CI = 26.3%–59.2%). Median progression-free survival (PFS) was 5.6 months (95% CI = 4.1–8.3 months), and median overall survival (OS) was 13.5 months (95% CI = 7.6–15.6 months).
Notably, in a subgroup of 13 patients with no previous enfortumab vedotin treatment or platinum-based chemotherapy, the ORR was 54% (95% CI = 25.1%–80.8%), and the clinical benefit rate was 69% (95% CI = 38.6%–90.9%). Median PFS was 8.3 months (95% CI = 1.8 months to not estimable), and median OS was 14.8 months (95% CI = 6.6–20.3 months) in this subgroup.
Safety Profile
The most common adverse events of any grade were diarrhea (66%), nausea (53%), fatigue (50%), alopecia (50%), neutropenia (45%), constipation (40%), and anemia (40%). Grade ≥ 3 adverse events occurred in 87% of patients, most commonly neutropenia (34%), anemia (24%), leukopenia (19%), fatigue (18%), and diarrhea (16%). No adverse events leading to death were reported.
Expert Commentary
Daniel P. Petrylak, MD, of Yale School of Medicine, the corresponding author of the Journal of Clinical Oncology article, noted that sacituzumab govitecan monotherapy demonstrated a relatively high ORR with rapid responses and a manageable toxicity profile in cisplatin-ineligible patients who had progression after ICI therapy. He also acknowledged the limitations of the study, including a moderate sample size and lack of random assignment, and suggested further evaluation of sacituzumab govitecan alone and in combinations in patients with locally advanced or metastatic urothelial cancer.
"Metastatic bladder cancer previously was a disease that once a patient progressed after primary chemotherapy, there was little that could be done. Now, with the checkpoints, with the ADCs, we have active drugs that can be administered to patients that can significantly improve their survival, as well as their quality of life," said Dr. Petrylak in an interview with Targeted Oncology™.
