Durvalumab-Based Combination Therapy in Non–Muscle Invasive Bladder Cancer
Posted: Friday, February 5, 2021
Noah M. Hahn, MD, of Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center, Baltimore, and colleagues conducted the ADAPT-BLADDER trial to determine the efficacy and safety of combining the immunotherapy durvalumab with BCR or radiation therapy in patients who have Bacillus Calmette-Guérin (BCG)-unresponsive non–muscle invasive bladder cancer. Presented at the 2020 Annual Meeting of the Society of Urologic Oncology (SUO; Abstract 22), their findings suggest the combination therapy is safe, with “promising” complete response rates in this patient population.
This phase I, multistage study enrolled 28 patients with BCG-unresponsive non–muscle invasive bladder cancer. Patients were administered durvalumab alone, durvalumab plus BCG therapy, or durvalumab plus external-beam radiotherapy (EBRT). Durvalumab was administered intravenously at 1,200 mg on day 1 of each 3-week cycle for at most 8 cycles. Every week for 6 weeks, 50 mg of BCG therapy was given intravenously with maintenance therapy for selected individuals. Those patients given EBRT received three separate 6-Gy fractions on days 1, 3, and 5 of the first cycle alone.
Participants' median age was 74, with 82% male; 15 patients had carcinoma in situ, 9 had high-grade Ta/T1 disease, and 4 had high-grade Ta/T1 plus carcinoma in situ. The median number of prior BCG regimens was two. Grade 3 to 4 treatment-related events such as hyperglycemia, elevated transaminase levels, rash, and elevated lipase levels affected one patient.
In one patient given durvalumab and EBRT, dose-limiting toxicity occurred, leading to a recommended phase II dose of 1,120 mg of durvalumab intravenously every 21 days combined with 50 mg of BCG therapy weekly or three 6-Gy fractions of EBRT. Complete response rates at 3 and 6 months for durvalumab alone, durvalumab plus BCG therapy, and durvalumab plus EBRT were 33% and 0%, 83% and 71%, and 55% and 33%, respectively. Translational biomarker analyses are yet to be presented.
Disclosure: For full disclosures of the study authors, visit suo-abstracts.secure-platform.com.