Sacituzumab Govitecan Shows Potential Among Patients With Locally Advanced or Metastatic Urothelial Cancer

According to results from Cohort 2 of the phase 2 TROPHY-U-01 trial, sacituzumab govitecan demonstrated clinically meaningful antitumor activityamong patients with locally advanced or metastatic urothelial cancer who are cisplatin-ineligible and experienced disease progression or recurrence after checkpoint inhibitor therapy. 

“Preferred first-line therapy for locally advanced, unresectable, or metastatic urothelial cancer is cisplatin-based chemotherapy; however, factors like compromised performance status and impaired kidney function render 30%-50% of patients ineligible,” stated Daniel P. Petrylak, MD, Yale School of Medicine, New Haven, Connecticut, and coauthors. As previously reported in Cohort 1 (patients progression on previous platinum-based chemotherapy in the metastatic or neo/adjuvant setting and a checkpoint inhibitor), sacituzumab govitecan “monotherapy produced 28% ORR and a manageable safety profile in 113 patients.” 

In cohort 2 of this open-label study, 38 patients with locally advanced or metastatic urothelial cancer who are cisplatin-ineligible and had experienced disease progression or recurrence after checkpoint inhibitor therapy were assigned to receive 10 mg/kg of sacituzumab govitecan on days 1 and 8 of a 21-day cycle until disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR). Key secondary end points included duration of response (DOR), clinical benefit rate, progression-free survival (PFS), overall survival (OS), and safety. 

At a median follow-up of 9.3 months, ORR was 32%, clinical benefit rate was 42%, and median DOR was 5.6 months. The median PFS was 5.6 months and the median OS was 13.5 months. Grade ≥3 treatment-emergent adverse events were experienced by 87% of patients and most frequently included diarrhea (66%), nausea (53%), fatigue (50%), alopecia (50%), neutropenia (45%), constipation (40%), anemia (40%), leukopenia (34%), and decreased appetite (32%). Treatment-emergent adverse events led to dose interruptions in 61% of patients, dose reductions in 37% of patients, and treatment discontinuation in 21% of patients. 

The most common grade ≥3 treatment-related adverse events, occurring in ≥ 5% of patients, included neutropenia (34%), anemia (24%), leukopenia (19%), fatigue (18%), diarrhea (16%), febrile neutropenia (8%), and colitis (8%). Eleven patients experienced grade ≥3 serious treatment-emergent adverse events of sepsis (n = 2), febrile neutropenia (n = 2), colitis ( n= 3), and diarrhea (n = 4). No treatment-emergent adverse events led to death. 

“[Sacituzumab govitecan] monotherapy demonstrated a relatively high ORR with rapid responses; this was feasible with a manageable toxicity profile in cisplatin-ineligible patients who had progression after [checkpoint inhibitor] therapy,” concluded Dr Petrylak et al. “These results warrant further evaluation of [sacituzumab govitecan] alone and in combinations.” 

 Journal of Clinical Oncology Associate Editor Michael A. Carducci, MD, Johns Hopkins Medicine, Baltimore, Maryland, added, “Cohort 2 of TROPHY-U-01 exploring [sacituzumab govitecan] as a single agent in patients with metastatic urothelial cancer suggests significant activity and provides a potential option for patients progressing after prior [checkpoint inhibitor therapy].”. 

Source: 

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