Phase II clinical study of concurrent durvalumab and radiation therapy (DUART) followed by adjuvant durvalumab in patients with localized urothelial cancer of bladder: Results for primary analyses and survival. BTCRC-GU15-023.

Abstract

398 Background: Bladder cancer (BC) patients (pts) who are cisplatin ineligible/unfit for surgery, or locally advanced and unresectable have limited treatment options. DUART investigates if the combination of radiation therapy (RT) and checkpoint inhibitor, durvalumab (durva) is safe and effective in these pts. We recently reported that the combination was safe, tolerable and disease control rate (DCR) was 92% post durvaRT. Here we present interim efficacy data of our phase II study. Methods: Pts with pure or mixed urothelial bladder cancer (T2-4 N0-2 M0) were enrolled if their tumor was unresectable (35%), were unfit for surgery (50%) and/or cisplatin ineligible (89%). Primary endpoints: a) PFS at 1-yr b) DCR post adjuvant durva; Secondary endpoints: a) CR post durvaRT b) median PFS c) median 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 wks x 1 yr. Response was evaluated with CT scan and cystoscopy+biopsy. Sample size was based on assumption that this regimen would increase 1 yr PFS by 25% compared to RT alone (50% to 75%); we assumed DCR of 75%. A total of 26 pts were needed to reach a statistical power of at least 80% at one-sided alpha of 5% and to allow for 10% drop out rate. Results: Twenty-six pts (19 males, 7 females) were enrolled, median age 74 yr (51-94). Sixty two percent of pts had >T2 disease, 31% had positive lymph nodes; 62% with unresectable tumor or were unfit for surgery due to comorbidities. At data cut off (9/30/2020) 20/26 pts were evaluable for DCR post adjuvant durva (3 pts with CR post durvaRT, did not get adjuvant therapy; 1 pt withdrew after 3 cycles for adjuvant durva and was on f/u with unconfirmed CR; 2 pts are still on adjuvant durva) and 25/26 for PFS and all 26 pts for OS. Post completion of adjuvant durva, DCR was seen in 70 % (14/20 with 10 CR; 3 PR; 1 SD; 6 PD). One-year probability of PFS was 73% (95% CI 56.4%, 94.4%), median PFS was 18.5 months. One-year OS probability was 83.8% (95% CI 70.4%, 99.7%) with two-year OS probability of 76.8 (95% CI 60.2%, 98%). Median OS has not been reached. We did not observe any correlation between clinical outcome and baseline tumor PD-L1 expression. Conclusions: DurvaRT followed by adjuvant durva demonstrated promising efficacy with 1-year PFS probability of 73%, 1- year OS probability of 83.8% and DCR of 70% in MIBC and locally advanced BC pts with comorbidities. Results will be updated prior to the final presentation. Efficacy was also seen in node (+) pts which led to the design of prospective randomized NCTN study. Induction chemo followed by chemo+durvaRT+ adjuvant durva vs. chemoRT combination is being evaluated in the ongoing EA8185 clinical trial (ECOG-ACRIN/NRG study) for node (+) BC pts. Clinical trial information: NCT02891161.