Treatment with Opdivo (nivolumab) after surgery significantly delays disease recurrence or death in patients with muscle-invasive urothelial carcinoma, a form of bladder cancer that has spread to nearby muscles, according to data from a Phase 3 clinical trial.
These beneficial effects were seen in the overall population of patients in the CheckMate-274 trial (NCT02632409), as well as in a subgroup whose tumors contained at least 1% of PD-L1 protein.
CheckMate-274 is the first Phase 3 trial to demonstrate Opdivo’s effectiveness as an adjuvant therapy for this specific type of bladder cancer. Adjuvant treatments are those given after surgery to prevent cancer from returning.
The trial’s findings were presented in an oral presentation, “First results from the phase 3 CheckMate 274 trial of adjuvant nivolumab vs placebo in patients who underwent radical surgery for high-risk muscle-invasive urothelial carcinoma (MIUC),” at the American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, held online, Feb. 11–13.
Developed and marketed by Bristol Myers Squibb, Opdivo is an immune checkpoint inhibitor that has been approved, both alone and in combination with other medications, to treat different types of cancers.
Since the therapy works by interfering with the PD-1/PD-L1 signaling cascade, which is used by cancer cells to avoid being targeted and eliminated by the immune system, it tends to be more effective in patients whose tumors produce the PD-L1 protein.
CheckMate-274 is a randomized, double-blind, Phase 3 trial that is assessing the safety and effectiveness of Opdivo as an adjuvant therapy in adults with muscle-invasive urothelial cancer, who are at a high risk of seeing their disease return after undergoing surgery to remove their bladder.
The trial enrolled 709 patients, who were assigned randomly to receive either 240 mg of Opdivo or a placebo every two weeks for one year.
The study’s main goal is to assess if Opdivo prolongs the time patients live without seeing their cancer return. This particular study goal is meant to be evaluated in the overall population, as well as in the subgroup of patients whose tumors produce the PD-L1 protein.
Additional goals include the safety, overall survival, and the time patients live without signs of cancer outside the urinary tract.
The recent data from CheckMate-274 show that patients treated with Opdivo lived much longer without their cancer reappearing than those given a placebo (median of 21 vs. 10.9 months). This corresponded to a 30% reduction in the risk of cancer recurrence or death, a percentage that was even higher (47%) in patients who had PD-L1 in their tumors.
Opdivo also extended the time patients lived without having signs of cancer recurrence in regions outside the urinary tract — from a median of 13.7 months (on a placebo) to 24.6 months, lowering the risk of non-urinary tract disease recurrence or death by 28%.
Again, patients whose tumors produced PD-L1, Opdivo lowered this risk even further — by 46% — compared with the placebo.
“People with muscle-invasive urothelial carcinoma often undergo major surgery to remove their bladders as a life-saving measure, but still face a probability of about 50 percent that their cancer will recur,” Dean Bajorin, MD, genitourinary oncologist at the Memorial Sloan Kettering Cancer Center, New York, said in a press release.
“In the CheckMate-274 trial, patients who received nivolumab lived almost twice as long without their disease recurring compared to those treated with placebo. These clinically meaningful results have the potential to change the way physicians treat muscle-invasive urothelial carcinoma, helping address the pressing unmet need for efficacious, tolerable therapies following surgery,” he added.
Opdivo’s safety profile in CheckMate-274 was consistent with that of previous studies in other solid tumors. Treatment-related side effects were more frequent with Opdivo than with placebo (77.5% vs. 55.5%). Likewise, severe or life-threatening treatment-related side effects were more common with Opdivo (17.9% vs. 7.2%).
According to trial investigators, these findings support the use of Opdivo as a standard adjuvant treatment for patients with muscle-invasive urothelial carcinoma who are at a high risk of disease recurrence, even after having radical surgery.
“We are excited for what the results of CheckMate-274 may mean for patients, and we thank the patients and investigators who participated in the trial. We look forward to working with regulatory authorities globally with the goal of bringing this treatment option to those who may benefit,” said Dana Walker, MD, vice president and development program lead of genitourinary cancers at Bristol Myers Squibb.