Concurrent Durvalumab And Radiation Therapy (DUART) followed by Adjuvant Durvalumab in Patients with Localized Urothelial Cancer of Bladder: BTCRC-GU15-023

Abstract

Bladder cancer (BC) patients (pts) who are cisplatin ineligible/unfit for surgery or unresectable have limited treatment options. In this study, we investigate if the combination of radiation therapy (RT) and checkpoint inhibitor, durvalumab (durva), is safe and effective in these pts. Our results from phase (ph) Ib suggested that the combination was safe. Here we present the updated response rate post durvaRT and updated treatment related adverse events (TRAEs) amongst our evaluable pts in ph II. This is a single arm ph Ib-II study for T2-4 N0-2 M0 BC pts. The ph II primary endpoints a) PFS rate at 1 yr b) disease control rate (DCR); secondary endpoints were a) CR post durvaRT b) PFS c) OS. Pts were treated with durva (1500mg) Q4 wks x2 doses along with definitive RT (64.8Gy, 36 fractions over 7 wks) to the bladder and involved nodes followed by adjuvant durva Q4 wk x 1 yr. Response was evaluated with CT scan and cystoscopy+biopsy post durvaRT. We anticipated that durvaRT followed by durva would increase PFS at 1 yr from 50% to 75% when compared to RT; we assumed DCR of about 75%. A total of 26 pts was needed to reach a statistical power of at least 80% at one-sided alpha of 5% and to allow for 10% drop out rate. Total N = 26 patients (Male 19; Female 7, median age 74yr). Node positive patients were 30.8%. At the time of data cut off (1/2020) 24/26 pts were evaluable for response post durvaRT. 2 pts withdrew from active Rx before 1st response evaluation. Post completion of durvaRT, clinical CR was seen in 17/24 pts (70.8%); PR 3/24 pts (12.5%); SD 3/24 (12.5%); PD 1/21 (4.7%). DCR was seen in 23/24 pts (95.8%) post durvaRT. Mean follow up from D1 to last follow up was 11.2 mos. Grade ≥ 3 TRAE amongst 26 pts: anemia (1/26), lipase/amylase (1/26), immune nephritis (1/26), dyspnea (gr 4- COPD/immune), fatigue (1/26), lymphopenia (6/26). Median no. of doses of durva was 8.0 from D1 (range 2-15); median no. of adjuvant durva doses was 6.0 (range 0-13). DurvaRT followed by durva demonstrated promising efficacy with 95.8% DCR and clinical CR of 70.8% in unresectable, cisplatin ineligible locally advanced BC. Efficacy was also seen in node positive patients. It was generally well tolerated. Ph II study has completed accrual and longer follow up with PFS, OS and DCR post adjuvant treatment will further our understanding of this regimen’s efficacy in locally advanced BC.