The ITALIC-RCC study: A randomized study of clinical and humoral impact of primary tumor ablation in metastatic renal cell carcinoma treated with immunotherapy.

Abstract

TPS584 Background: The role and optimal timing of cytoreductive nephrectomy (CN) have long been subject of debate in the management of metastatic renal cell carcinoma (mRCC) due to the potential role in control of bleeding and pain and also in reducing the risk of future metastatic spread by removing a potential source of immunosuppressive or tumor-promoting growth factors. In the VEGFR-TKIs era, the CARMENA and SURTIME trials, investigated the role of the CN: the CARMENA study compared immediate CN + sunitinib over sunitinib alone showing similar overall survival (OS) in intermediate- and poor-risk patients, except for those with only one IMDC risk factor who benefited from CN. The SURTIME trial assessed deferred CN after sunitinib versus upfront CN followed by sunitinib. Deferred CN was associated with improved OS compared to upfront CN (HR 0.57, 95% CI 0.34–0.95; p = 0.03). Nowadays, CheckMate 214, Keynote 426, CheckMate 9ER and the CLEAR studies showed that immunotherapy (IT)-based combinations therapies significantly improve OS and progression-free survival (PFS) compared to the previous standard of care (SOC) with sunitinib. Furthermore, radiotherapy (RT) in RCC has demonstrated excellent renal function and oncological outcomes in several clinical trials: safety data reported a low risk of high-grade toxicity, accounting for only 3.8% of cases. This trial investigates the potential role of CN and RT in the therapeutic algorithm of mRCC. Methods: The ITALIC-RCC study (NCT06903312) is a phase IV, randomized, multi-arm, multicenter, low- interventional clinical trial, aiming to evaluate whether intensifying treatment by adding local therapy of the primary tumor to the standard IT-based therapy, improves OS in patients with mRCC. The study aims to enroll 409 patients affected by metastatic or locally advanced renal cell carcinoma with predominantly clear cell histology, aged ≥18 years, with ECOG performance status 0–1 and without evidence of progressive disease after at least 24 weeks, but not more than 52 weeks from the time of the signed informed consent. Eligible patients will be randomized 1:1:1 to receive deferred cytoreductive nephrectomy + SOC or RT on primary tumor + SOC (only in those with primary kidney cancer ≤ 4 cm) or SOC alone. The primary endpoint of the study is to assess the difference in OS between patients who undergo CN and those who do not, while receiving therapy with SOC for mRCC. Secondary endpoints include the difference in PFS between patients who receive or not the deferred CN or the RT during SOC therapy for mRCC, the difference in OS between patients who receive or not the RT on primary tumor while on therapy with SOC for mRCC among those with primary tumor up to 4 cm, as well as assessments of quality of life and safety. Exploratory biomarkers analysis will also be performed. The trial is currently actively enrolling participants. Clinical trial information: NCT06903312 .