Sacituzumab Govitecan Delivers Rapid Responses in Cisplatin-Ineligible Bladder Cancer

Illustration of bladder cancer

Monotherapy with the antibody-drug conjugate (ADC) sacituzumab govitecan-hziy (SG; Trodelvy) delivered rapid responses with a manageable toxicity profile for the treatment of cisplatin-ineligible patients with locally advanced or metastatic urothelial carcinoma who had disease progression following checkpoint inhibitor immunotherapy.^1,2 These results signal a greater need for research of SG monotherapy in this patient population.

Findings from cohort 2 of the phase 2 TROPHY-U-01 clinical trial (NCT03547973) showed that at a median follow-up of 9.3 months, the overall response rate (ORR) was 32% (12/38; 95% CI, 17.5%-48.7%). All responders achieved a partial response.

The median duration of response 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 progression-free survival was 5.6 months (95% CI, 4.1-8.3), and the median overall survival was 13.5 months (95% CI, 7.6-15.6).

“This clinically meaningful antitumor activity is consistent with results from TROPHY-U-01 cohort 1, which involved patients progressing on previous [platinum]-based chemotherapy (in the metastatic or [neo]adjuvant setting) and a [checkpoint inhibitor]. Cohort 2 results compare favorably with single-agent chemotherapy (ORR approximately 11%- 14%), although differences in patient populations, baseline factors, and study designs significantly limit such a comparison,” authors wrote in the study published in the Journal of Clinical Oncology.¹

“Antitumor activity was observed across multiple subgroups, including those with >2 previous therapies and those with an ECOG [performance status] of 1, although sample sizes were small in a few subgroups. Further analysis in larger trials is needed to determine [sacituzumab govitecan] activity in specific subgroups,” authors continued.

All patients experienced at least 1 treatment-emergent adverse effect (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.

“[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 Daniel P. Petrylak, MD, professor of medicine and urology at Yale School of Medicine and study investigator, said in an interview with Targeted Oncology^TM.

REFERENCES:

1. 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.

2. Sacituzumab govitecan demonstrates a relatively high ORR with rapid responses in cisplatin-ineligible patients with mUC progressing to previous treatment with ICI. News release. ESMO. September 16, 2024. Accessed September 24, 2024. https://tinyurl.com/5xtr7964