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Among patients with muscle-invasive bladder cancer, adjuvant Opdivo showed a continued benefit in survival versus placebo.
Among patients with MIBC, adjuvant Opdivo showed a continued benefit in survival versus placebo.© stock.adobe.com
Among patients with muscle-invasive bladder cancer (MIBC), treatment with adjuvant Opdivo (nivolumab) continued to showcase a benefit in disease-free survival (DFS) versus placebo, irrespective of previous treatment with neoadjuvant chemotherapy, according to data from an analysis of the phase 3 CheckMate-274 trial shared during the 2025 Genitourinary Cancers Symposium.
Adjuvant: any additional cancer treatment given after the primary treatment.
Disease-free survival: the time after treatment when someone is free of signs or symptoms of a disease.
Neoadjuvant: type of cancer treatment that is given before the main treatment.
Overall survival (OS): the average length of time that patients are alive after being diagnosed with or starting treatment for a disease.
Intravenous: means into the vein.
In all randomized patients with MIBC, the median DFS was 25.6 months with Opdivo (353 patients) versus 8.5 months with placebo (356 patients). The 24-month DFS rates in the respective arms were 50.5% and 35.9%; at 36 months, these rates were 46.8% and 32%. The median follow-up in the intention-to-treat (ITT) population was 36.1 months; in the MIBC population, the median follow-up was 34.5 months.
In patients with MIBC who previously received neoadjuvant chemotherapy, the median DFS with Opdivo (279 patients) was 19.6 months versus 8.3 months with placebo (281 patients). In patients with MIBC who had not previously received neoadjuvant chemotherapy, the median DFS was 25.9 months with Opdivo versus 13.7 months with placebo.
Data from the interim overall survival (OS) analysis indicated that in all patients with MIBC, the median OS was not reached versus 39.9 months with placebo. The 24- and 36-month OS rates in the Opdivo arm were 75.3% and 64.2%, respectively; in the placebo arm, these rates were 66.2% and 53.7%, respectively.
In all randomized patients with MIBC and a tumor PD-L1 expression of at least 1%, the median OS with Opdivo was again not reached versus 37.6 months with placebo. Those with MIBC who received prior neoadjuvant chemotherapy adjuvant Opdivo experienced a median OS of 55.2 months versus 40.2 months with placebo. Those with MIBC without prior neoadjuvant chemotherapy experienced a median OS that was not reached with Opdivo versus 37.7 months with placebo.
“The improvements demonstrated in patients with MIBC provide additional support for adjuvant Opdivo as a standard of care for high-risk muscle-invasive urothelial carcinoma [MIUC,] including MIBC after radical surgery, and regardless of prior neoadjuvant chemotherapy,” Dr. Matthew I. Milowsky said in a presentation of the data. “Of note, subcutaneous Opdivo was approved for multiple indications, including as adjuvant therapy for MIUC by the FDA late last year, and might provide an alternative for patients across tumors.”
Milowsky is the George Gabriel and Frances Gable Villere Distinguished Professor of Bladder and Genitourinary Cancer Research, co-leader of the University of North Carolina (UNC) Lineberger Clinical Research Program, section chief of Genitourinary Oncology and co-director of the Urologic Oncology Program at UNC School of Medicine in Chapel Hill.
The randomized, double-blind, multicenter, phase 3 CheckMate-274 trial enrolled patients with ypT2 to ypT4a or ypN-positive MIUC who had neoadjuvant chemotherapy. Those with pT3a to pT4a or pN-positive MIUC without previously neoadjuvant chemotherapy who were not eligible for or refused adjuvant cisplatin chemotherapy were also included. Patients underwent radical surgery within the past 120 days and had to be free of disease within four weeks of undergoing randomization.
Participants were randomized to receive intravenous (IV) Opdivo or placebo at 240 mg every two weeks. They received adjuvant treatment for up to 1 year. Stratification factors included tumor PD-L1 status (at least 1% versus less than 1% or indeterminate), prior receipt of neoadjuvant chemotherapy (yes versus no) or nodal status.
The primary end points of the trial were DFS in all randomized patients and in the subset of patients with a tumor PD-L1 expression of at least 1%. Data showed that adjuvant Opdivo significantly improved DFS versus placebo in patients with high-risk MIUC post–radical surgery with or without cisplatin-based neoadjuvant chemotherapy. Extended follow-up data with a median of three years indicated that Opdivo continued to improve DFS versus placebo in all randomized patients, those with PD-L1 expression of at least 1% and those with MIBC. The first report of OS outcomes showed that survival favored Opdivo versus placebo in all randomized patients and the subset of patients with a PD-L1 expression of at least 1%.
For the post-hoc analysis shared at conference, the key end points were DFS in all randomized patients with MIBC and in those with MIBC according to previous neoadjuvant chemotherapy, and OS in all randomized patients with MIBC, those with MIBC and a tumor PD-L1 expression of 1% or higher and those with MIBC according to prior neoadjuvant chemotherapy.
Milowsky said that baseline clinical and demographic characteristics were generally well-balanced between the arms. “[They] were largely consistent between the ITT and MIBC populations. About 80% of patients in CheckMate-274 had bladder tumor origin. Of those patients with MIBC, about 50% received prior neoadjuvant chemotherapy and about 40% had tumor PD-L1 positivity,” he said.
Additional efficacy data indicated that in patients with MIBC who received prior neoadjuvant chemotherapy, the 24-month DFS rates with Opdivo and placebo were 48.9% versus 33.2%, respectively; the 36-month rates were 46.5% versus 28.9%, respectively. In patients with MIBC who had not received prior neoadjuvant chemotherapy, the 24-month DFS rates in the Opdivo and placebo arms were 52.1% versus 38.8%, respectively; the 36-month DFS rates were 46.9% versus 35.4%, respectively.
In all patients with MIBC and a tumor PD-L1 expression of at least 1%, the 24-month OS rate with Opdivo was 82.6% versus 67.4% with placebo; the respective 36-month rates were 71.8% and 52.0%. In those with MIBC and prior neoadjuvant chemotherapy, the 24-month OS rates with Opdivo and placebo were 73.6% versus 63.2%, respectively; the 36-month rates were 64.5% and 53.4%, respectively. In those with MIBC without prior neoadjuvant chemotherapy, the 24-month OS rate with Opdivo was 77.1% versus 69.4% with placebo; the respective OS rates at 36 months were 63.8% versus 53.9%.
“Safety in patients with MIBC was consistent with previous data in ITT patients, and no new safety signals were identified,” Milowsky concluded.
