(UroToday.com) The 2025 GU ASCO annual meeting featured a urothelial carcinoma session and a presentation by Dr. Matthew Milowsky discussing additional efficacy outcomes in patients with muscle-invasive bladder cancer from CheckMate 274 assessing adjuvant nivolumab versus placebo.
In the phase 3, randomized, double-blind CheckMate 274 trial,1 adjuvant nivolumab demonstrated statistically significant and clinically meaningful disease free survival benefit versus placebo in patients with high-risk muscle-invasive urothelial carcinoma after radical surgery ± prior neoadjuvant cisplatin-based chemotherapy. With extended 3 year median follow-up, continued improvements in disease free survival were seen with nivolumab versus placebo in the primary efficacy populations (intent-to-treat [ITT], tumor PD-L1 expression ≥ 1%) and in patients with muscle invasive bladder cancer.2 Moreover, early trends in interim overall survival favored nivolumab versus placebo in ITT and tumor PD-L1 ≥ 1% patients. In patients with bladder tumors, especially those who refuse or are ineligible for neoadjuvant chemotherapy, addressing the unmet need for effective systemic therapies is critical. At the GU ASCO 2025 annual meeting Dr. Milowsky and colleagues reported additional efficacy outcomes for patients with muscle invasive bladder cancer.
Patients were randomized 1:1 to nivolumab 240 mg every 2 week or placebo for ≤ 1 year of adjuvant treatment, stratified by tumor PD-L1 expression, nodal status, and prior neoadjuvant chemotherapy:
The primary endpoints were disease free survival in ITT and tumor PD-L1 expression ≥ 1% patients. Overall survival in ITT and PD-L1 ≥ 1% patients was a secondary endpoint, and analysis of muscle invasive bladder cancer patients was exploratory. Muscle invasive bladder cancer overall survival data are from preplanned interim analyses of ITT and PD-L1 ≥ 1% patients. Overall survival follow-up is ongoing as the prespecified statistical boundaries for significance in ITT and PD-L1 ≥ 1% patients were not crossed at the time of these analyses.
Of 709 randomized patients (ITT), 560 (79%) had muscle invasive bladder cancer (nivolumab, n = 279; placebo, n = 281) and 284 (51%) of muscle invasive bladder cancer patients had prior neoadjuvant chemotherapy:
With a median follow-up of 36.1 months (ITT), disease free survival improvement with nivolumab versus placebo was consistent between all patients with muscle invasive bladder cancer (HR 0.63, 95% CI 0.51-0.78):
Additionally, there was disease free survival benefit for adjuvant nivolumab in patients with muscle invasive bladder cancer who had received neoadjuvant chemotherapy (HR 0.58, 95% CI 0.43-0.79) and patients without prior neoadjuvant chemotherapy (HR 0.69, 95% CI 0.50-0.94):
For overall survival, nivolumab versus placebo resulted in improved outcomes among all patients with muscle invasive bladder cancer (HR 0.70, 95% CI 0.55-0.90):
Additionally, adjuvant nivolumab improved survival for patients with muscle invasive bladder cancer and had tumor PD-L1 ≥ 1% (HR 0.48, 95% CI 0.29-0.77), as well as in patients with muscle invasive bladder cancer with (HR 0.74, 95% CI 0.53-1.03) and without prior neoadjuvant chemotherapy (HR 0.67, 95% CI 0.47-0.95):
Safety was consistent with previous data in ITT patients, and there were no new safety signals identified:
Dr. Milowsky concluded his presentation discussing additional efficacy outcomes in patients with muscle-invasive bladder cancer from CheckMate 274 assessing adjuvant nivolumab versus placebo with the following take-home points:
- With a 3 year median follow-up, consistent benefit in disease free survival was observed with nivolumab versus placebo in all muscle invasive bladder cancer patients and across prior neoadjuvant chemotherapy subgroups
- The hazard ratio for overall survival favored nivolumab in all muscle invasive bladder cancer patients, in those with PD-L1 ≥ 1%, and regardless of prior neoadjuvant chemotherapy status.
- These results continue to support adjuvant nivolumab as a standard of care for high-risk muscle-invasive urothelial carcinoma and muscle invasive bladder cancer, potentially providing an opportunity for a curative outcome
- Subcutaneous nivolumab has been shown to provide clinical equipoise to standard IV dosing and may provide an alternative for patients across various tumors
Presented by: Matthew I. Milowsky, MD, FASCO, University of North Carolina School of Medicine, Chapel Hill, NC
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2025 Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, CA, Thurs, Feb 13 – Sat, Feb 15, 2025.
Related content: CheckMate 274 Analysis Shows Improved Outcomes for Bladder Cancer Patients with Adjuvant Nivolumab - Matthew Galsky
References:
- Bajorin DF, Witjes JA, Gschwend JE, et al. Adjuvant nivolumab versus placebo in muscle-invasive urothelial carcinoma. N Engl J Med. 2021 Jun 3;384(22):2102-2114.
- Galsky MD, Witjes JA, Gschwend JE, et al. Adjuvant nivolumab in high-risk muscle-invasive urothelial carcinoma: Expanded efficacy from CheckMate 274. J Clin Oncol. 2025 Jan;43(1):15-21.