Abstract 776P
Background
Bladder cancer is a disease of the elderly and this frail patient population, or patients with significant comorbidities, are ineligible for cystectomy or standard radiation and chemotherapy. We are conducting a study in a chemotherapy and cystectomy ineligible patient population with the combination of a programmed death (PD-1) inhibitor, nivolumab, and radiation therapy in localized/locally advanced urothelial cancer patients.
Methods
Eligible patients have muscle invasive bladder cancer (MIBC) and are not candidates for standard chemoradiation strategy due to at least one of the following criteria: performance status of 2, creatinine clearance < 60ml/min or cardiac disease, neuropathy, or intolerance to previous treatment that would render the patient ineligible for chemotherapy. The primary endpoint is progression free survival (PFS) rate at 12 months. Nivolumab is started within 3 days of radiation therapy and is administered at the dose of 240 mg intravenously every 2 weeks for a maximum of 6 months. Total radiation dose of 64 gray in 32 fractions was administered per standard of care for bladder cancer. If local lymph nodes were clinically involved, they had to be radiated.
Results
To date, 17 patients have been enrolled; median age is 78 years (range 54 to 95 years) 13 males and 4 females, Median creatinine clearance was 51ml/min (range 26-123ml/min). Four patients were clinical stage T3 /T4 and one patient had N1 disease. Nivolumab and radiation therapy toxicities were as expected: 5 patients needed steroids due to immune-mediated adverse events; diarrhoea in 2, thyroid dysfunction in 2 and immune cystitis in 1 patient. No treatment related deaths were noted. 6 of 14 patients demonstrated complete response, 4 had residual T1 disease or carcinoma in situ and 4 had disease progression. PDL-1 combined positive score (CPS) was <1% in all non responders except one patient with CPS of 5%. PFS and overall survival outcome data will be presented.
Conclusions
Concurrent nivolumab and radiation therapy is tolerable and showed promising early efficacy in an elderly population with multiple comorbidities. PDL-1 expression is a potential biomarker to guide patient selection.
Clinical trial identification
NCT03421652.
Editorial acknowledgement
Legal entity responsible for the study
Karmanos Cancer Center.
Funding
Bristol Myers Squibb Inc.
Disclosure
U.N. Vaishampayan: Honoraria (self), Research grant/Funding (institution): Bristol Myers Squibb; Honoraria (self): Bayer; Honoraria (self), Research grant/Funding (self): Exelixis; Honoraria (self): Pfizer; Honoraria (self), Research grant/Funding (institution): Astellas; Advisory/Consultancy, Research grant/Funding (institution): Alkermes; Advisory/Consultancy, Research grant/Funding (institution): Merck. S. George: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): BMS; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Merck; Research grant/Funding (institution): Agensys; Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy, Research grant/Funding (institution): Eisai; Advisory/Consultancy, Research grant/Funding (institution): Astellas; Research grant/Funding (institution): Calithera; Research grant/Funding (institution): Immunomedics; Advisory/Consultancy: EMD Serono; Advisory/Consultancy: Genentech; Advisory/Consultancy, Research grant/Funding (institution): Corvus; Advisory/Consultancy: Exelixis. All other authors have declared no conflicts of interest.