The positive findings could make nivolumab the new standard of care in the adjuvant setting for patients with muscle-invasive urothelial cancer.
Nivolumab (Opdivo) improved disease-free survival (DFS) when used after surgery in patients with high-risk, muscle-invasive urothelial carcinoma, according to findings from the pivotal phase 3 CheckMate-274 trial.1
Bristol Myers Squibb (BMS), the developer of the PD-1 inhibitor, reported in a press release that the study met its coprimary end points of improved DFS in both the overall randomized population and in the subgroup of patients with a tumor PD-L1 expression level of ≥1%. No new safety signals emerged with nivolumab compared with the safety data reported in prior studies of the agent.
BMS plans to present the data at a future scientific meeting and submit the results for regulatory review. In order to continue the evaluation of key secondary end points, including overall survival and disease-specific survival, the investigators are continuing the CheckMate-274 trial.
“With currently available therapies, more than 50% of patients with bladder cancer will experience recurrence after surgery, and each year, the disease takes the lives of nearly 200,000 patients,” Matthew Galsky, MD, professor of Medicine, director of Genitourinary Medical Oncology, director of the Novel Therapeutics Unit, and co-director of the Center of Excellence for Bladder Cancer at The Tisch Cancer Institute and the Icahn School of Medicine at Mount Sinai, stated in the press release.
“Advances like immunotherapy have helped bring hope to patients across a growing number of cancer types, including previously treated advanced urothelial carcinoma. The positive results from CheckMate-274 point to the potential for nivolumab to become a new standard of care in the adjuvant setting, extending disease-free survival for post-surgery patients with muscle-invasive urothelial cancer without the use of chemotherapy,” continued Galsky.
The multicenter, double-blind phase 3 CheckMate-274 trial (NCT02632409) included 709 patients with muscle-invasive urothelial cancer at a high risk of recurrence after radical surgery. Investigators randomized patients in a 1:1 ratio to nivolumab or placebo for a maximum treatment time of 1 year. Prior neoadjuvant chemotherapy was allowed.
In urothelial carcinoma, nivolumab currently has an FDA-approved indication for the treatment of patients with locally advanced or metastatic disease that has progressed during or following platinum-containing chemotherapy or those who have disease progression within 12 months of neoadjuvant or adjuvant treatment with a platinum-containing chemotherapy.2
The approval was supported by data from the phase 2 CheckMate-275 trial (NCT02387996), a single-arm study that included 270 patients with locally advanced or metastatic urothelial carcinoma who progressed during or following platinum-containing chemotherapy, or progressed within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. The objective response rate was 19.6% (53 of 270 patients), comprising a 2.6% complete response rate and a 17% partial response rate. The median duration of response was 10.3 months and the median time to response was 1.9 months.
1. Opdivo (nivolumab) Significantly Improves Disease Free-Survival vs. Placebo as Adjuvant Therapy for Patients with High-Risk, Muscle-Invasive Urothelial Carcinoma in Phase 3 CheckMate -274 Trial. Bristol Myers Squibb. Posted September 24, 2020. Accessed September 24, 2020. https://bit.ly/3cs3mGM.
2. Nivolumab for Treatment of Urothelial Carcinoma. FDA. Published February 2, 2017. Accessed September 24, 2020. https://www.fda.gov/drugs/resources-information-approved-drugs/nivolumab-treatment-urothelial-carcinoma.