Nivolumab Approved for Bladder Cancer by European Commission

Troy Brown, RN


June 05, 2017

The European Commission approved nivolumab (Opdivo, Bristol-Myers Squibb) for adults with locally advanced unresectable or metastatic urothelial carcinoma that has failed to respond to prior platinum-containing therapy.

Nivolumab — a programmed cell death (PD)-1 (PD-1) immune checkpoint inhibitor —  is now the first immune-oncology agent approved in the European Union for this type of bladder cancer. This is the eighth indication in six separate types of tumor for nivolumab. The US Food and Drug Administration approved  nivolumab for the same indication on February 2.

"Bladder cancer has an estimated 151,000 new cases diagnosed annually in Europe, yet there have been few advancements in treatment for advanced bladder cancer during the last few decades," Margitta Retz, MD, director of the Division of Uro-Oncology of the Department of Urology, Technical University Munich, Germany, said in a company news release. "The European Commission's approval of nivolumab marks a significant advancement, with a notable objective response rate, and provides an important option to help patients with previously treated locally advanced unresectable or metastatic urothelial cancer."

The approval follows consideration of data from CheckMate-275. That phase 2, open-label, single-arm, multicenter trial evaluated nivolumab in patients with locally advanced or metastatic urothelial carcinoma that progressed during or after treatment with a platinum-containing chemotherapy or patients whose disease progressed within 12 months of neoadjuvant or adjuvant therapy with platinum-containing chemotherapy.

Study patients (n = 270) received nivolumab 3 mg/kg intravenously every 2 weeks until their disease progressed or they experienced unacceptable toxicity.

The trial's primary endpoint was objective response rate. One fifth (20% [54 of 270]; 95% confidence interval [CI], 15.4% - 25.3%) of patients responded to treatment with nivolumab. Three percent (8 of 270) of patients experienced a complete response and 17% (46 of 270) experienced a partial response to treatment.

Tumor PD-ligand 1 (PD-L1) expression was at least 1% in 46% of patients, and efficacy was seen across tumor PD-L1 expressors and nonexpressors. The response rate was 25% in patients with tumor PD-L1 expression of 1% or higher (95% CI, 17.7% - 33.6%) and 15.8% (95% CI, 10.3% - 22.7%) in patients with PD-L1 expression lower than 1%.

The trial's secondary outcomes included progression-free survival and overall survival. The median progression-free survival duration was 2 months and the 12-month overall survival rate was 41% (95% CI, 34.8% - 47.1%). The median overall survival duration was 8.6 months (95% CI, 6.1 - 11.3 months).

The most commonly reported treatment-related adverse events (AEs) included fatigue (16.7%), pruritus (9.3%), diarrhea (8.9%), decreased appetite (8.1%), hypothyroidism (7.8%), nausea (7%), asthenia (5.9%), rash (5.9%), and pyrexia (5.6%). Overall, 4.8% of patients stopped therapy as a result of treatment-related AEs.

Grade 3 or 4 treatment-related AEs were experienced by 17.8% of patients who received nivolumab. The most common of these were fatigue (1.9%), diarrhea (1.9%), asthenia (1.5%), and rash (1.1%). Overall, 3.0% of patients stopped therapy as a result of grade 3 or 4 treatment-related AEs.

Four patients experienced treatment-related death from pneumonitis or cardiovascular failure.

Patients taking nivolumab should be monitored for signs and symptoms of pneumonitis and undergo radiographic imaging. Nivolumab can cause immune-mediated colitis, and clinicians should monitor patients for colitis. Nivolumab can cause immune-mediated hepatitis, and patients should be monitored for abnormal liver test results before and periodically during therapy. Patients should also be observed for other immune-mediated adverse events, including endocrinopathies, nephritis and renal dysfunction, skin adverse reactions and dermatitis, and encephalitis.

Urothelial carcinoma is the most common type of bladder cancer, occurring in about 90% of patients. It is the fifth most frequently diagnosed cancer in Europe. Most cases are diagnosed early, but it has high rates of recurrence and progression, with approximately 78% of patients experiencing a recurrence within 5 years. The 5-year survival rate for patients with stage IV bladder cancer is 15%.

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