Feasibility and safety results from RAD-IO: A multi-stage trial of durvalumab (Medi4736) with chemoradiotherapy with 5-fluorouracil and mitomycin C in patients with muscle-invasive bladder cancer.

Abstract

778 Background: Immune checkpoint inhibitors have a substantial and growing role in all stages of care for bladder cancer. Durvalumab (Durva) is a humanised monoclonal antibody that inhibits binding of PD-L1. Recent phase 3 results with peri-operative durvalumab show a 25% reduction in the risk of death compared to standard of care. Methods: RADIO is a multi-stage trial comparing standard chemoradiotherapy (CRT) with 5FU & mitomycin C (MMC) +/- durvalumab given pre-CRT x1, during CRT x1 and post CRT for up to 12 months. Eligible patients T2-T4aN0-2M0 bladder cancer, neo-adjuvant chemotherapy was encouraged for suitable participants. Switch to single arm occurred after achieving feasibility criteria. We report here feasibility and toxicity data up to 3 months post randomisation. Recruitment continues in the single arm efficacy phase with results to be reported later. Results: Between Oct 2020 and May 2023, 29 participants were randomised. Median age 68 (IQR 61-75) years, 26 male, 3 female. Casemix: T2N0 21 (72.4%), T3N0 8 (27.6%), T4N0 0 (0%). 23 (79.3%) had received prior neoadjuvant chemotherapy. 10 (34.5%) were recruited to receive CRT only, 19 (65.5%) to receive CRT + Durva. All participants completed 55Gy/20# RT, 25 (86.2%) without any delays and 4 participants completed RT but with delay (1-5 days), 2 due to toxicity, 2 due to external factors. Median intensity of planned dose received: RT; 1 (IQR 1-1), MMC; 0.97 (IQR 0.94-0.99), 5FU; 0.8 (IQR 0.49-0.96), Durva; 0.97 (IQR 0.88-1). Toxicity for patients on the CRT + Durva arm, between informed consent and 3 months post the end of CRT:6 SAEs were reported, 3 of which were SARs and 0 were SUSARs. Of these SAEs, 3 were related to trial treatment (2 related to Durva, 2 related to 5FU & MMC, 1 being related to both regimens), 3 lead to discontinuation (RT; 0, MMC; 0, 5FU; 2, Durva; 1), and 2 SAEs lead to dose delays (RT; 0, MMC; 0, 5FU; 0, Durva; 2). In the CRT + Durva arm there were 9 AEs grade ≥3 (6 related to trial treatment). Results split by CRT only or CRT + Durva will be available at the time of the conference, and all figures are provisional on subsequent rounds of data cleaning. Conclusions: The schedule of neo-adjuvant, synchronous and adjuvant durvalumab was deliverable with full dose CRT to bladder. Most participants completed CRT as planned, none discontinued Durva due to toxicity, only 3 incurred toxicity related delays but continued treatment. Clinical trial information: 43698103.