In high-risk muscle-invasive urothelial carcinoma, the use of nivolumab after surgery cut patients’ risk of disease returning or death by 30% over placebo. The data was released for presentation at the American Society of Clinical Oncology Genitourinary Cancers Symposium.
The CheckMate-274 win marks the first positive phase 3 readout for a checkpoint inhibitor in this particular bladder cancer setting.
It’s estimated that about 50% of patients diagnosed with muscle-invasive bladder cancer will see their cancer return after surgery. In CheckMate-274, though, nivolumab almost doubled the time patients lived without recurrence; the BMS drug helped patients stay disease-free for a median of 21.0 months, versus 10.9 months for placebo.
The benefit was even more pronounced in patients whose tumors expressed biomarker PD-L1, with the risk reduction expanding to 47%. In that subpopulation, the median time before the disease returned hadn’t been reached for nivolumab , compared with 10.8 months for placebo.
Opdivo cut the risk of disease recurrence outside the bladder, ureters or renal pelvis by 28% in the wider patient group and by 46% among PD-L1-positive patients. That secondary endpoint is important because oncologists want to know if the recurrence is more distant, making it more challenging to keep patients alive, Jonathan Cheng, M.D., BMS’ head of oncology development, explained in an interview.
The company is talking to the FDA about the data. Disease-free survival data in bladder cancer has been a clinically relevant endpoint used to support FDA filings in the past, Cheng said, and meanwhile, investigators are still following the patients to see if nivolumab can prolong lives.
The bladder cancer arena is full of PD-1/L1 competition. So far, the drugs have mostly managed to find their niche markets, but it may not be long until they have challengers to face.
nivolumab , for its part, has been approved in previously treated locally advanced or metastatic bladder cancer since 2017. pembrolizumab quickly followed into the second-line setting and simultaneously added a front-line use in cisplatin-ineligible patients. But the FDA soon limited that first-line use to PD-L1-positive patients after noting pembrolizumab might perform worse than chemotherapy in other cases.
An update last year showed neither solo pembrolizumab nor a pembrolizumab -chemo combo was able to stall the progression of tumors or prolong patients’ lives compared with chemo. The dual immuno-oncology regimen pembrolizumab and ipilimumab against chemo has been conducted in previously untreated patients in the CheckMate-901 phase 3 trial.
