Matthew Milowsky, MD, University of North Carolina, Chapel Hill, North Carolina, discusses additional efficacy results from the CheckMate 274 trial presented at the 2025 American Society for Clinical Oncology (ASCO) Genitourinary Cancers Symposium. Results demonstrated that adjuvant nivolumab continued to show survival benefit compared to placebo among patients with high-risk muscle-invasive urothelial carcinoma. 

Transcript: 

I am Matt Milowski, a GU Medical Oncologist from the University of North Carolina at Chapel Hill, and I'm here to talk about the recently presented updated data from the Checkmate 274 trial presented at the genitourinary ASCO meeting in San Francisco. 

Checkmate 274 is a randomized clinical trial that investigated the role for adjuvant nivolumab in patients with high-risk urothelial carcinoma. Patients were randomized 1-to-1 to nivolumab for up to 1 year versus placebo. The primary end points of the study were [disease-free survival] DFS in all randomized patients, that is in the [intention-to-treat] ITT, and DFS in all randomized patients with tumor PD-L1 ≥ 1%. Data have previously been presented and published demonstrating a significant DFS benefit seen both in the ITT population and in those patients with PD-L1 positivity. 

The purpose of the presentation at the recent ASCO meeting was to provide additional efficacy outcomes, specific to the high-risk muscle-invasive population that is of patients with bladder cancer in Checkmate 274 and that comprised 80% of the patients treated on Checkmate 274. Consistent with the initial findings, the benefit for disease-free survival was seen in patients with muscle-invasive bladder cancer [MIBC] as compared to placebo, and this was seen regardless of whether or not patients had received prior treatment with neoadjuvant chemotherapy. 

In addition, overall survival [OS] data were presented, this was all from a pre-planned interim analysis at 36 months, and this was evaluated in the subgroup of patients with muscle-invasive bladder cancer. This was a post hoc analysis in this patient population at this interim analysis, and although the overall survival data did not meet the pre-specified boundary for significance, the data was very promising with regard to overall survival in patients with muscle-invasive bladder cancer with a hazard ratio of 0.70 in all randomized patients with MIBC and a hazard ratio of 0.48 in all randomized patients with MIBC and tumor PD-L1 ≥ 1%. The OS data was also promising in patients whether or not they received prior neoadjuvant chemotherapy. With regard to safety, the safety in patients with MIBC was really quite consistent with previous data that had been presented in the ITT population with no safety signals identified. 

In summary, with extended follow-up of Checkmate 274, adjuvant nivolumab continued to show a DFS benefit versus placebo in patients with MIBC and this again was regardless of prior treatment with neoadjuvant chemotherapy and the overall survival data from this pre-planned interim analysis, the MIBC population favored adjuvant nivolumab over placebo regardless of prior neoadjuvant chemotherapy, as well as in patients with MIBC and tumor PD-L1  positivity. Again, no new safety signals were identified and I think this just provides additional support that improvements in outcome are demonstrated with the use of adjuvant nivolumab in patients with MIBC, and there are now potential options with regard to subcutaneous nivolumab, which appears to have clinical equipoise to standard IV dosing and may provide an alternative for patients not only in MIBC but across other tumor types as well. Thank you.

Source:  

Milowsky M, Galsky M, Witjes J, et al. Adjuvant nivolumab (NIVO) vs placebo (PBO) for high-risk muscle-invasive urothelial carcinoma (MIUC): Additional efficacy outcomes including overall survival (OS) in patients (pts) with muscle-invasive bladder cancer (MIBC) from CheckMate 274. Presented at 2025 ASCO Genitourinary Cancers Symposium. February 13-15, 2025; San Francisco, CA. Abstract 658