Phase II trial of Concurrent Nivolumab and Radiation therapy in Elderly or Chemotherapy ineligible Muscle Invasive Bladder Cancer.

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.

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.

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).

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.

International journal of radiation oncology, biology, physics. 2023 Nov 17 [Epub ahead of print]

Ulka N Vaishampayan, Lance Heilbrun, Nitin Vaishampayan, Felicity Wk Harper, Dongping Shi, Daryn Smith, Kelly Green, Khurshid Guru, Qiang Li, Michael Kuettel, Gurkamal Chatta, Jordan Maier, Brenda Dickow, Tanina Foster Moore, Saby George

University of Michigan, Ann Arbor MI. Electronic address: ., Karmanos Cancer Center/Wayne State University Detroit, MI., Roswell Park Cancer Center, Buffalo NY.