The FDA has granted accelerated approval to nivolumab for patients with locally advanced or metastatic urothelial carcinoma whose disease has progressed on platinum chemotherapy. This is the second PD-1–targeting agent in less than a year to get the agency's nod for bladder cancer.

The PD-1 inhibitor nivolumab (Opdivo; Bristol-Myers Squibb) has received accelerated approval from the FDA for patients with locally advanced or metastatic urothelial carcinoma—the most common type of bladder cancer—whose disease has progressed on platinum chemotherapy. This marks the sixth tumor type for which treatment with nivolumab is now an option.

The agency based its decision on data from the phase II CheckMate-275 study evaluating nivolumab in 270 patients. The objective response rate (ORR) to nivolumab was 19.6%, including seven complete responses. Among 124 patients who had PD-L1 expression in at least 1% of their tumor cells, the ORR was 25%; six of the seven complete responses occurred in this subset. The drug was largely well tolerated, with fatigue, musculoskeletal pain, nausea, and decreased appetite being the most common side effects.

Nivolumab is the second immune checkpoint inhibitor in less than a year to gain approval for urothelial carcinoma. Last May, the FDA greenlighted atezolizumab (Tecentriq; Genentech)—which targets the PD-L1 ligand rather than the PD-1 receptor—for this disease, also on the basis of a single-arm phase II trial. Jonathan Rosenberg, MD, a genitourinary cancer specialist at Memorial Sloan Kettering Cancer Center in New York, NY, notes that the study data are similar for nivolumab and atezolizumab, but cautions against cross-trial comparisons, because of “subtle differences in enrolled patient populations that can influence the results.”

“It's difficult to differentiate these drugs on clinical grounds at this time—both are reasonable and appropriate choices,” he says. Atezolizumab's every-three-weeks dosing plan may be more favorable to patients, he observes, versus nivolumab's fortnightly schedule. As well, there are potential biological differences that merit further study: Receptor inhibition with nivolumab blocks both PD-L1 and PD-L2; meanwhile, atezolizumab's mode of action leaves the PD-1/PD-L2 interaction intact. However, the latter also blocks signaling through CD80, “leading to another way of restoring T-cell function,” Rosenberg adds.

Arjun Balar, MD, director of genitourinary oncology at Perlmutter Cancer Center in New York, NY, agrees that either drug is a good option, “given the currently available evidence.” Besides these two immunotherapies, pembrolizumab (Keytruda; Merck) may soon be a third contender in the urothelial carcinoma space: Compared to chemotherapy, the PD-1 blocker was recently shown to improve overall survival in a randomized phase III trial, and its application for FDA approval is under review.

“This is a testament to the durable activity and tolerable safety of immune checkpoint inhibitors, and reflects how desperately we've needed better treatments for a disease that was until now uniformly and rapidly fatal after progression on platinum chemotherapy,” Balar says. “Moving forward, we're seeing a dramatic shift in how we'll manage urothelial carcinoma.” –Alissa Poh

©2017 American Association for Cancer Research.
2017
American Association for Cancer Research.