Contrasting Adjuvant and Perioperative Trial Designs Help Refine MIBC Management

Petros Grivas, MD, PhD

Evolving insights and maturing data from bladder cancer clinical trials, such as the phase 3 CheckMate 274 trial (NCT02632409) evaluating adjuvant nivolumab (Opdivo) in patients with muscle-invasive bladder cancer (MIBC), are prompting further considerations for adjuvant treatment strategies that may better personalize care and enable bladder preservation, according to Petros Grivas, MD, PhD.

In an interview with OncLive®, Grivas highlighted differences in trial design and patient populations between the CheckMate 274 and phase 3 NIAGARA (NCT03732677) trials; practice-changing data from CheckMate 274; the potential overall survival (OS) benefit observed with nivolumab vs placebo in this trial; and how emerging findings from bladder cancer trials are shaping future treatment strategies and strengthening efforts toward bladder preservation in this disease.

Grivas, who is a professor in the Clinical Research Division and clinical director of the Genitourinary Cancers Program at Fred Hutchinson Cancer Center, further expanded on the findings and key implications of the NIAGARA trial in another article.

Grivas is also a professor in the Division of Hematology and Oncology at the University of Washington School of Medicine in Seattle, Washington.

OncLive: What were some of the key differences in trial design between CheckMate 274 and NIAGARA?

Grivas: We were interested to see updates from the CheckMate 274 trial [presented] by Matthew Milowsky, MD, FASCO, [of the University of North Carolina Lineberger Comprehensive Cancer Center in Chapel Hill], at the 2025 Genitourinary Cancers Symposium (ASCO GU). CheckMate 274 is a practice-changing…and purely adjuvant therapy trial.

It's important to point out the differences between the designs of the NIAGARA and CheckMate 274 trials, because the patient populations are different. [Additionally], NIAGARA started in the neoadjuvant setting, [whereas] CheckMate 274—as well as the [phase 3] AMBASSADOR trial [NCT03244384]—was purely in the adjuvant setting. [NIAGARA and CheckMate 274 enrolled] different patient populations [that may have had] different risks of recurrence. There is probably enrichment for higher-risk [patients] and more [recurrence] events in the purely adjuvant trials because patients must have certain pathologic states and risks of recurrence to [enroll] in a purely adjuvant trial.

What key findings from CheckMate 274 have been reported to date?

CheckMate 274 was positive for disease-free survival. That HR was 0.70 favoring adjuvant nivolumab vs placebo.1 There is an FDA approval [for adjuvant nivolumab for the treatment of patients with high-risk urothelial carcinoma] as of August 2021 based on [early] results of the CheckMate 274 trial.

We [also] saw interesting data [from this trial reported] in a [January 2025 Journal of Clinical Oncology] publication by Matthew Galsky, MD, [of The Tisch Cancer Institute of Mount Sinai in New York, New York], Dean F. Bajorin, MD, [of Memorial Sloan Kettering Cancer Center in New York], and colleagues investigating the potential OS difference between the 2.2 This OS analysis was not final, [as fully mature OS data will] depend on the number of [OS] events, but there seemed to be a trend toward an OS benefit with adjuvant nivolumab vs placebo. We're waiting for the final analysis, but [this] at least gives us a hint.

OS can be affected by access to and the effectiveness of salvage therapies at the time of disease recurrence. However, the data from CheckMate 274 are interesting. We saw updates at the 2025 ASCO GU meeting in the subset of patients with MIBC—the trial also included [patients with] upper tract [disease]—and these data are helpful. [The investigators] partitioned patients [based on whether they had received] neoadjuvant chemotherapy and the data in those subsets [can] inform our dialogue with patients.

Now that CheckMate 274 and other bladder cancer immunotherapy trials have begun to read out, how might these data further clarify MIBC treatment decision-making?

Our job in the clinic is to synthesize these datasets— [including those from the phase 3] NIAGARA, AMBASSADOR, and CheckMate 274 [trials— alongside] interesting data with circulating tumor DNA that are also coming out from different trials. We're also waiting on [data readouts from] several trials [in the MIBC setting, including] perioperative trials, as well as adjuvant trials like the phase 3 IMvigor011 [NCT04660344] and the phase 2/3 MODERN trial [NCT05987241]. All the above—including the perioperative trials with enfortumab vedotin-ejfv [Padcev] plus checkpoint inhibition, and gemcitabine/cisplatin plus or minus nivolumab or pembrolizumab [Keytruda]—will inform the future therapeutic paradigm for localized MIBC. We're always looking forward to a future with more bladder preservation for our patients [and are searching for ways to] achieve that.

References

1. U.S. Food and Drug Administration approves Opdivo (nivolumab) for the adjuvant treatment of patients with high-risk urothelial carcinoma. News release. Bristol Myers Squibb. August 20, 2021. Accessed May 6, 2025. https://news.bms.com/news/details/2021/U.S.-Food-and-Drug-Administration-Approves-Opdivo-nivolumab-for-the-Adjuvant-Treatment-of-Patients-with-High-Risk-Urothelial-Carcinoma/default.aspx
2. 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;43(1):15-21. doi:10.1200/JCO.24.00340