Phase II Trial of Concurrent Nivolumab and Radiation Therapy for Muscle-Invasive Bladder Cancer of Older or Chemotherapy-Ineligible Patients

Background Bladder cancer is predominantly a disease of the elderly. Concurrent chemotherapy and radiation is a bladder sparing strategy for management of muscle invasive bladder cancer (MIBC), however many patients are not candidates for chemotherapy due to comorbidities or impaired performance status. We conducted a study in a chemotherapy ineligible patient population with the objectives of evaluating the safety, efficacy and quality of life impact of the combination of nivolumab and radiation therapy in localized/locally advanced urothelial cancer patients. Patients and Methods Eligible patients had MIBC, were not candidates for standard chemoradiation strategy due to at least one of the following; performance status of 2, creatinine clearance ≤ 60ml/min, cardiac disease, neuropathy, or intolerance to previous treatment. Creatinine clearance ≥40ml/min, normal marrow and liver function were required. The primary endpoint was progression free survival rate at 12 months. Nivolumab was started within 3 days of radiation therapy and administered at the dose of 240 mg intravenously every 2 weeks for a maximum of 6 months. Radiation therapy was per standard of care for bladder cancer. Imaging and cystoscopy and biopsy evaluation was required at months 3, 6 and 12 and then annually until progression. Results 20 patients were enrolled; median age of 78.5 years (range 58-95 years), 80% of patients were above 70 years of age and eight (40%) were above 80 years of age. Median creatinine clearance was 52 ml/min. Nine patients (48%) were progression free at 12 months. Median PFS was 11.4 months (90% CI: 7.5- 23.7 months) and median OS was 15.6 months (90% confidence interval 9.1-26.1 months). Conclusion Concurrent nivolumab and radiation therapy is tolerable but demonstrated limited efficacy in an elderly population with multiple comorbidities. Immune correlates demonstrated that patients with baseline PD-L1 combined prognostic score (CPS) ≥5% had numerically longer PFS.