Systemic therapy combined with radiotherapy versus systemic therapy alone for oligometastatic kidney cancer (STROKER): A multicenter, randomized controlled phase III trial.

Abstract

TPS576 Background: The value of local therapy for oligometastatic renal cell carcinoma (RCC) remains undefined. Several single-arm phase II studies suggest that stereotactic body radiotherapy (SBRT) may delay disease progression 1,2 . In our previous phase II trial, SBRT + sunitinib improved response and PFS versus sunitinib alone 3 . However, these studies are constrained by small sample sizes and phase II methodology, limiting the robustness and generalizability of their conclusions. The phase III STROKER trial was therefore designed to verify whether combining SBRT with systemic therapy offers additional benefit over systemic therapy alone in patients with oligometastatic RCC. Methods: This open-label, multicenter, randomized phase III trial enrolls patients with oligometastatic RCC (≤5 lesions), an ECOG performance status of 0 to 2. Patients must have received definitive treatment of the primary tumor, and no more than two prior lines of systemic therapy. Key exclusion criteria include intracranial metastases, prior high-dose irradiation to target lesions, or target lesions unamenable to SBRT. Eligible patients are randomized in a 1:1 ratio to receive systemic therapy alone, consisting of tyrosine kinase inhibitors (TKIs) or TKIs combined with immune checkpoint inhibitors (ICIs), versus SBRT+ systemic therapy. The primary endpoint is progression-free survival (PFS). Based on existing clinical data, the median PFS is estimated at 12 months in the control arm and expected to reach 18 months in the experimental arm. With a two-sided α of 0.05 and 80% power, a total of 113 patients per arm is required. Accounting for a 10% dropout rate, 126 patients per arm (252 total) will be enrolled over 4 years with a 2-year follow-up. One interim analysis will be conducted after 60% of the total sample size has been accrued, applying the O'Brien–Fleming α-spendin g function for type I error adjustment. Secondary endpoints include overall survival, cancer-specific survival, local control, post-treatment PFS, PFS2, adverse events, and Health-related quality of life as measured with NFKSI-19 and EQ-5D-5L. The trial has been open for patient enrollment since December 2024. References: 1. Tang C, Msaouel P, Hara K, et al. Definitive radiotherapy in lieu of systemic therapy for oligometastatic renal cell carcinoma: a single-arm, single-centre, feasibility, phase 2 trial. Lancet Oncol. 2021;22. 2. Siva S, Bressel M, Wood ST, et al. Stereotactic Radiotherapy and Short-course Pembrolizumab for Oligometastatic Renal Cell Carcinoma-The RAPPORT Trial. Eur Urol. 2022;81. 3. Liu Y, Wei W, Zhang Z, et al. Preliminary results from a phase II study comparing sunitinib alone or with stereotactic body radiotherapy (SBRT) for newly diagnosed oligometastatic renal cell carcinoma. J Clin Oncol. 2023;41. Clinical trial information: NCT06726421 .