FDA approves immunotherapy drug for advanced bladder cancer

Bladder cancer patients with advanced disease have a new option for treatment after the Food and Drug Administration (FDA) this week approved a drug that launches an immune response against the disease.

The FDA approval of the checkpoint inhibitor nivolumab, known commercially as Opdivo, was based on a Phase II multi-center clinical trial led by Padmanee Sharma, M.D., Ph.D., professor of Genitourinary Medical Oncology and Immunology at MD Anderson.

“Nearly 20 percent of patients had their tumors shrink substantially, with some complete responses, which is a significant improvement over other second-line options for these patients,” Sharma said. 

Under its breakthrough therapy designation and priority review status, the FDA granted accelerated approval of nivolumab for patients with locally advanced urothelial carcinoma whose disease progresses during or after platinum-based chemotherapy treatment, which remains frontline standard of care.

The trial was a single-arm study of 270 patients. Of 265 patients who were able to be evaluated, six (2%) had complete response, 46 (17%) had a partial response, defined as tumor shrinkage of at least 30%, and 60 (23%) had stable disease, meaning their cancer neither grew nor shrunk.

Nivolumab unleashes an immune system attack on cancer by blocking activation of a protein called PD-1 on T cells, white blood cells that find and attack abnormal cells, viruses or bacteria that have specific targets. PD-1 acts as a brake, or checkpoint, to shut down activated T cells.

Responses have been durable, with 40 of 52 responding patients (77%) still confirmed at the time of analysis. Median duration of response, a common measure noting the point in time in which half of patients still respond to treatment, had not been reached.

“Durable responses are a hallmark of cancer immunotherapy,” Sharma said. “Research remains under way at MD Anderson and other cancer centers to extend the effectiveness of these drugs to more patients.”

Results of the international clinical trial were published in late January by Lancet Oncology.

Sharma leads a clinical trial that combines nivolumab with ipilimumab, the original immune checkpoint-inhibiting drug that blocks another brake, called CTLA-4. She presented early findings of the study at a scientific meeting in November showing response rates of 26% and 38% of patients treated with different doses of the combination.

Patients with advanced bladder cancer are treated first with cisplatin-based chemotherapy, with about 50% experiencing short responses. According to Sharma, toxicities from treatment also leave these patients in a fragile state, so it’s important that nivolumab was relatively well-tolerated.

The most common adverse reactions, reported in at least 20% of patients, were fatigue, musculoskeletal pain, nausea and decreased appetite. Seventeen percent of patients had to discontinue treatment due to adverse reactions. Fourteen patients died from causes other than disease progression, including four who died from lung inflammation or cardiovascular failure attributed to nivolumab.

The clinical trial was funded by Bristol-Myers Squibb, which developed and produces nivolumab.

Until last year, no second-line treatments for these patients had been approved by the FDA. Most attempts had involved single-agent chemotherapy drugs with response rates around 10%.

The FDA approved another immunotherapy, atezolizumab, in May. That drug blocks PD-L1, a ligand found on tumor and other cells that activates the PD-1 brake on T cells, and elicited a tumor response in 15% of patients treated.

Sharma is scientific director of MD Anderson’s immunotherapy platform and an investigator with the Parker Institute for Cancer Immunotherapy at MD Anderson. The platform is part of MD Anderson’s Cancer Moon Shots Program™ to reduce cancer deaths by accelerating development of therapies, prevention efforts and early detection based on scientific discoveries.