The FDA approved atezolizumab to treat advanced bladder cancer when cisplatin chemotherapy is contraindicated. The approval offers a potentially more effective alternative to carboplatin-based chemotherapy for frail, elderly patients.

The FDA has approved the PD-L1 checkpoint inhibitor atezolizumab (Tecentriq; Genentech) for patients with advanced bladder cancer when cisplatin chemotherapy is contraindicated. The drug could significantly extend survival compared with carboplatin-based chemotherapy, which until now has been the best option for patients who are too frail or sick to receive cisplatin.

“This is a landmark change in how we're treating metastatic bladder cancer,” says Jonathan Rosenberg, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York, NY. “Atezolizumab is now a very good first-line option for patients who cannot tolerate cisplatin.”

The approval, which is contingent upon a confirmatory trial, is based on findings from the phase II IMvigor210 trial, which evaluated safety and efficacy in 119 patients with cisplatin-ineligible, locally advanced or metastatic urothelial carcinoma. After a median follow-up of 14.4 months, the overall response rate was 23.5%, and median overall survival was 14.8 months, with 8 patients (6.7%) experiencing complete responses.

Atezolizumab is already approved to treat advanced bladder cancer following disease progression during or after carboplatin-based chemotherapy, based on data from another cohort of the same trial led by Rosenberg. When atezolizumab received the FDA's nod last year, it became the first drug approved for second-line therapy for this cancer in more than 20 years.

The fact that patients survived a median of almost 15 months is significant considering that carboplatin chemotherapy confers an average life expectancy of about 9 months, says Rosenberg. The drug also was well tolerated, with only 10% to 15% of patients experiencing grade 3 or 4 adverse events, including hypothyroidism, liver function abnormalities, rash, and diarrhea.

In general, immunotherapy seems to be better tolerated compared with chemotherapy in these patients, says Rosenberg. The PD-1 inhibitor pembrolizumab (Keytruda; Merck) is currently under FDA review and is expected to receive approval for this indication later this year.

“Patients with advanced bladder cancer tend to be elderly and have multiple comorbidities, such that cisplatin is frequently contraindicated,” Rosenberg notes. “Immunotherapy provides an acceptable safer—and potentially very effective—alternative.” –Janet Colwell

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