In a cohort of the phase II TROPHY-U-01 trial (cohort 3) reported in the Journal of Clinical Oncology, Petros Grivas, MD, PhD, and colleagues found that the combination of sacituzumab govitecan-hziy and pembrolizumab showed activity in patients with metastatic urothelial cancer and disease progression after platinum-based chemotherapy.

Petros Grivas, MD, PhD

Study Details

Cohort 3 of the international multicohort study included 41 patients who had received no prior immune checkpoint inhibitor therapy and had disease progression after platinum-based chemotherapy in the metastatic setting or within 12 months after (neo)adjuvant treatment. Patients received sacituzumab govitecan at 10 mg/kg on days 1 and 8 and pembrolizumab at 200 mg on day 1 of 21-day cycles. The primary endpoint was objective response rate on central review, with the objective of achieving objective response in at least 13 of 41 patients.

Responses

Median follow-up was 14.8 months (95% confidence interval [CI] = 12.6–16.8 months). Objective response was achieved in 17 patients (41%, 95% CI = 26.3%–57.9%; thus meeting the primary endpoint), including a complete response in 8 (20%). Median duration of response was 11.1 months (95% CI = 4.8 months to not estimable). The clinical benefit rate was 46% (95% CI = 30.7%–62.6%).

Median progression-free survival was 5.3 months (95% CI = 3.4–10.2 months). Median overall survival was 12.7 months (95% CI = 10.7 months to not estimable).

Adverse Events

Grade ≥ 3 treatment-related adverse events occurred in 61% of patients, most commonly neutropenia (37%), leukopenia (20%), and diarrhea (20%). Grade ≥ 3 serious treatment-related adverse events included diarrhea in four patients, febrile neutropenia in three, and pneumonitis in two. No treatment-related deaths were reported.

The investigators concluded: “Sacituzumab govitecan plus pembrolizumab demonstrated a high response rate with an overall manageable toxicity profile in patients with metastatic urothelial cancer who progressed after platinum-based chemotherapy. No new safety signals were detected. These data support further evaluation of sacituzumab govitecan plus checkpoint inhibitors in metastatic urothelial cancer.”

Dr. Grivas, of the Fred Hutchinson Cancer Center, University of Washington, Seattle, is the corresponding author of the Journal of Clinical Oncology article.

Disclosure: The study was supported by Gilead Sciences, Inc. For full disclosures of the study authors, visit ascopubs.org.