ASCO GU 2021: 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
The authors enrolled patients with pure or mixed urothelial bladder cancer (T2-4 N0-2 M0) if their tumor was unresectable (35%), they were deemed unfit for surgery (50%) and/or deemed cisplatin-ineligible (89%).
The authors assessed the primary endpoints of progression-free survival (PFS) at 1-yr and disease control rate (DCR) following post adjuvant durvalumab. The authors further assessed a number of secondary endpoints including CR following durvalumab and RT, median PFS, and median OS.
Patients were treated with durvalumab (1500mg) Q4 weeks x2 doses along with definitive RT (64.8Gy, 36 fractions over 7 weeks) to the bladder and involved nodes followed by adjuvant durvalumab every 4 weeks for 1 year. Response was evaluated with CT scan and cystoscopy and biopsy. The authors powered the sample size was based on assumption that this regimen would increase 1-year PFS by 25% compared to RT alone (50% to 75%) with an assumed DCR of 75%. As a result, 26 patients 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.
The authors, therefore, enrolled 26 patients (19 men and 7 women) with a median age of 74 years (51-94). Most patients (62%) had >T2 disease, while 31% had positive lymph nodes. The majority (62%) had unresectable tumors or were unfit for surgery due to comorbidities.
As of the data cut-off of September 30, 2020, 20 of 26 patients were evaluable for DCR following adjuvant durvalumab: 3 patients with CR following durvalumab + RT did not receive adjuvant therapy; 1 patient withdrew after 3 cycles for adjuvant durvalumab and continued on follow-up with an unconfirmed CR, and a further 2 patients are still on adjuvant durvalumab. All 26 patients were evaluable for OS and 25 of 26 were evaluable for PFS.
Following initial durvalumab plus RT, 19 patients (79.1%) had CR, 1 had PR, 2 had SD, and 2 had PD for a total ORR of 83% and DCR of 92%. Following the completion of adjuvant durvalumab, DCR was seen in 73% of patients, and ORR was seen in 68%, of whom 12 had CR, 3 had PR, 1 had SD, and 6 had PD.
The 1-year probability of PFS was 73% (95% CI 56.4%, 94.4%) with a median PFS of 18.5 months. The 1-year OS probability was 83.8% (95% CI 70.4%, 99.7%) with a two-year OS probability of 76.8 (95% CI 60.2%, 98%) and median OS not yet reached. Interestingly, the authors did not observe a correlation between clinical outcomes and baseline tumor PD-L1 expression.
The authors conclude that durvalumab + RT followed by adjuvant durvalumab is associated with promising efficacy in patients with localized MIBC who are unable to undergo surgery. A related approach with induction chemotherapy followed by durvalumab + RT followed by adjuvant durvalumab, as compared to chemo RT is currently being examined in the ongoing EA8185 clinical trial (ECOG-ACRIN/NRG study) for node (+) bladder cancer patients.
Presented by: Monika Joshi, MD, MRCP, Penn State Cancer Institute
Written by: Christopher J.D. Wallis, Urologic Oncology Fellow, Vanderbilt University Medical Center Contact: @WallisCJD on Twitter during the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium (#GU21), February 11th-February 13th, 2021