Overall survival (OS) results in phase II trial of cabozantinib (CABO) plus durvalumab (DURVA) in patients with urothelial carcinoma (UC) or non-UC variant histologies (VH) after platinum chemotherapy (ARCADIA)

BackgroundCombining multitargeted receptor tyrosine kinase inhibitor (TKI) with checkpoint inhibitors has shown synergistic effect in pts with in various solid tumors due to the immunomodulatory propriety of VEGFR inhibitors. We aim to investigate the safety and efficacy of the combination of cabozantinib plus durvalumab in advanced UC and VHs (NCT03824691). Herein we present the overall survival results of the interim analysis.MethodsPatients affected by UC or non-urothelial carcinoma (VHs) recurred/progressed after at least one line of platinum-based chemotherapy for metastatic disease have been treated with CABO 40 mg daily, orally, and DURVA 1500 mg IV, q28 days, until disease progression (PD, by RECIST 1.1) or onset of unacceptable toxicity. Response was evaluated by RECIST criteria v.1.1 every 8 wks. The primary endpoint of the study was OS. Secondary endpoints included safety (CTCAE v.4.03), objective response-rate (ORR), duration of response (DoR), progression-free survival (PFS).ResultsAs of February 10, 2024 data cut, 61 pts were enrolled and were evaluable for response; median follow-up was 26 months (interquartile 16.38-35.82), median age was 64 yrs and 21 pts (24%) had pure/predominant VHs: 10 (47.6%) squamous differentiation/sarcomatoid tumor, 4 (19%) adenocarcinoma, 5 (24%) small-cell neuroendocrine tumor, 1 (4.7%) clear-cell tumor, and 1 nested VH (4.7%). 12/61 (20% liver mets.12 pts (20%) had ≥ 2 prior lines of therapies. Median OS and PFS were 12.9 months (95% CI, 7.1-25.5) and 6 months (95% CI, 3.9-9.4), respectively. Confirmed ORR was 42.6% (range 30-55.9),18% CR in 11 pts. For VHs subgroup, median OS and PFS were 17.6 months (95% CI, 5.3-NR), and 5.3 (95% CI, 2.8-NR), respectively and ORR was 31%. At analysis, 9 pts remained on treatment. 2/61(3%) pts received EV as subsequent therapy. 38/61 pts had treatment-related adverse events of any grade and 25 (41%) had grade 3/4.ConclusionsCABO in combination with DURVA suggests promising prolonged survival and acceptable tolerability in pts with advanced UC, especially those with VHs. Further randomized controlled studies will be required in a larger patient population.Clinical trial identificationNCT03824691.Legal entity responsible for the studyPatrizia Giannatempo.FundingAstraZeneca, Ipsen.DisclosureAll authors have declared no conflicts of interest.