Cabozantinib plus durvalumab in patients with advanced and chemotherapy-treated urothelial carcinoma (UC) and variant histology (VH): An open-label, phase II, single-arm proof-of-concept trial: ARCADIA study. Subgroup analysis for bone metastasis

BackgroundPreliminary results from the phase II ARCADIA trial (NCT03824691) showed promising activity of cabozantinib (CABO) in combination with durvalumab (DURVA) in patients with advanced or metastatic UC and in non-UC VH after previous chemotherapy exposure. Herein we report the preliminary results of the subgroup analysis for Bone metastasis (BM).MethodsPatients affected by UC and VHs recurred or progressed after failure of at least one line of platinum-based chemotherapy have been treated with CABO 40 mg daily, orally, and are administered DURVA 1500 mg IV, q28 days, until disease progression (PD), by RECIST v.1.1, or onset of unacceptable toxicity. Response was evaluated by RECIST criteria v.1.1 every 8 weeks and by EORTC PET response criteria by 18FDG PET/CT scan. The primary endpoint of the study was OS whereas secondary endpoints included FDG-PET responses in BM.ResultsBetween September 2019 and April 2024, the ARCADIA study enrolled 88 patients: this interim analysis was performed after obtaining at least one post-baseline tumor assessment data from 61 patients. The median follow-up was 26.8 mo (95%CI 19.4-39.2). 22/61 (36%) patients had BM. Patients were evaluated with 18FDG PET/CT scan and CT scan. Complete Metabolic Response was described in 4/22 (18%) patients, Partial Metabolic Response in 3/22 (13.6%), Stable Metabolic Disease in 2/22 (9%) patients whereas 4/22 (18%) patients had Progressive Metabolic Disease as best response. 9/25 (36%) patients experienced disease clinical progression after the 2nd doses of study intervention. mPFS was 4.7 months (95%CI 2.0-7.0) whereas mOS was 6.7 (95%CI 5.1-NR). Smoking habit, liver metastasis, ECOG PS, line of tratment ARCADIA trial, WBC, LDH and AEs were significantly associated with OS in patients with BM. 4/22 (18%) received Bone Target Agents concomitantly and SREs were described in 11/22 (50%).ConclusionsCABO-DURVA has activity in pretreated, platinum-refractory mUC patients with BM with interesting results in term of metabolic response. More mature results including larger sample of BM patients and with longer follow-up are awaited.Clinical trial identificationNCT03824691.Legal entity responsible for the studyFondazione IRCCS Istituto Nazionale dei Tumori di Milano.FundingIpsen, AstraZeneca.DisclosureAll authors have declared no conflicts of interest.