In cohort 2 of the phase II TROPHY-U-01 study, reported in the Journal of Clinical Oncology, Petrylak et al found that sacituzumab govitecan-hziy was active in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer progressing after immune checkpoint inhibitor (ICI) therapy.
Study Details
In the U.S. multicenter study, 38 patients who experienced disease progression after ICI therapy received sacituzumab govitecan at 10 mg/kg on days 1 and 28 of 21-day cycles. Overall, 50% 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 on central review.
Responses
After a median follow-up of 9.3 months (range = 0.5–30.6 months), objective responses (all partial) were observed in 12 patients (32%, 95% confidence interval [CI] = 17.5%–48.7%). Median time to response was 1.4 months (95% CI = 1.3–1.5 months). 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 was 5.6 months (95% CI = 4.1–8.3 months). Median overall survival was 13.5 months (95% CI = 7.6–15.6 months).
Among 13 patients with no previous enfortumab vedotin treatment or platinum-based chemotherapy, an objective response was observed in 7 patients (54%, 95% CI = 25.1%–80.8%), and the clinical benefit rate was 69% (95% CI = 38.6%–90.9%), Median progression-free survival was 8.3 months (95% CI = 1.8 months to not estimable), and median overall survival was 14.8 months (95% CI = 6.6–20.3 months).
Adverse Events
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.
The investigators concluded: “[Sacituzumab govitecan] monotherapy demonstrated a relatively high [objective response rate] with rapid responses; this was feasible with a manageable toxicity profile in cisplatin-ineligible patients who had progression after [ICI] therapy. Limitations include a moderate sample size and lack of random assignment. These results warrant further evaluation of [sacituzumab govitecan] alone and in combinations in patients with [locally advanced or metastatic urothelial cancer].”
Daniel P. Petrylak, MD, of Yale School of Medicine, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by Gilead Sciences. For full disclosures of the study authors, visit ascopubs.org.
