Nivolumab monotherapy administered after surgery demonstrated a significant improvement in disease-free survival compared with placebo in patients with high-risk, muscle-invasive urothelial carcinoma, for all patients randomized in the phase 3 CheckMate-274 trial and those with PD-L1 ≥1% in their tumors, meeting the primary end point of the study.
Nivolumab (Opdivo) monotherapy administered after surgery demonstrated a significant improvement in disease-free survival (DFS) compared with placebo in patients with high-risk, muscle-invasive urothelial carcinoma, for all patients randomized in the phase 3 CheckMate-274 trial (NCT02632409) and those with PD-L1 ≥1% in their tumors, meeting the primary end point of the study.
This pivotal trial is the first and only phase 3 study to show reduced risk of relapse after surgery with immunotherapy. Patients were also observed to have a consistent safety profile with nivolumab compared with previous solid tumor trials.
“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 codirector of the Center of Excellence for Bladder Cancer at The Tisch Cancer Institute and the Icahn School of Medicine at Mount Sinai, said in a statement.
“The positive results from CheckMate 274 point to the potential for nivolumab to become a new standard of care in the adjuvant setting, extending DFS for post-surgery patients with muscle-invasive urothelial cancer without the use of chemotherapy.”
For CheckMate 274, a randomized, double-blind, multicenter trial, 709 patients who were at a high risk of recurrence after radical surgery were randomized 1:1 to receive nivolumab or placebo for up to 1 year. Some patients may or may not have been given neoadjuvant chemotherapy prior to resection based on patient characteristics.
The primary end point of DFS, which was defined as the time between the date of randomization and the date of first recurrence or death of any cause, was looked at in the intent-to-treat population, as well as patients whose tumors express PD-L1 of 1% or more. Secondary end points included overall survival, non-urothelial tract recurrence-free survival, and disease-specific survival.
Eligible patients were 18 years or older, who had radical surgery within 120 days of going on the trial. They had to have disease-free status determined through imaging within 4 weeks of dosing with nivolumab or placebo. Patients also had to have available tumor tissue for biomarker analysis.
If a patient had a partial bladder or kidney removal and/or had secondary treatment following surgical removal of bladder cancer, they could not be enrolled on this study. Those with autoimmune disease, hepatitis B virus surface antigen, or hepatitis C virus ribonucleic acid were also not allowed on the trial. Unless it was a locally curable cancer that was cured, patients who had an active prior malignancy in the last 3 years were not enrolled.
Nivolumab has been observed to have clinically meaningful efficacy as adjuvant treatment for patients with bladder cancer, melanoma, and esophageal/gastroesophageal junction cancer.
“As we advance the science of immunotherapy, we’re discovering that these treatments may play an important role in earlier stages of cancer, when the immune system is generally more intact and potentially more responsive,” Mark Rutstein, the vice president of Opdivo Development at Bristol Myers Squibb, said in a press release. “With the positive results from CheckMate 274, Opdivo has now demonstrated improved efficacy in the adjuvant treatment of 3 tumor types, including bladder cancer, melanoma and esophageal/gastroesophageal junction cancer, as part of our broad development program across earlier stages of cancer.”
The investigators will be completing a full evaluation and the CheckMate 274 data and will present the results at an upcoming medical conference, and continued follow-up will take place for the analysis of the secondary end points, including overall and disease-specific survival.
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. News release. Bristol Myers Squibb. September 24, 2020. Accessed September 28, 2020. https://bit.ly/3iaHhxQ