Phase III randomized trial of stereotactic ablative radiotherapy (SAbR) for oligometastatic advanced renal carcinoma (EA8211-SOAR).

Abstract

TPS489 Background: Optimal strategies for managing oligometastatic renal cell carcinoma (RCC) are unclear. While systemic therapy is the accepted standard, Stereotactic Ablative Radiation (SAbR) is a promising alternative based on retrospective and limited prospective data1-3. SAbR may spare patients from systemic therapy toxicity, but progression of occult micrometastasis remains a concern. This prospective ECOG-ACRIN phase 3 randomized trial will compare SAbR to systemic therapy for oligometastatic RCC. Co-primary endpoints are overall survival (OS) and toxicity. Methods: Patients with RCC (any histology except for sarcomatoid) with an ECOG performance 0-2, International Metastatic RCC Database Consortium (IMDC) favorable and intermediate-risk, and 2-5 extracranial metastases are eligible. The exclusion criteria include prior systemic therapy (except for adjuvant therapy) and brain metastases. Patients with intact primary are eligible after definitive treatment of the primary site. Stratification factors include 1) number of metastases (2-3 vs 4-5), 2) histology (clear cell vs non-clear cell), 3) IMDC (0 vs 1-2), 4) prior adjuvant systemic therapy (yes vs no), and 5) time from treatment of primary disease (<1yr vs >1yr). Patients will be randomized to up front systemic therapy (the type of systemic therapy will be chosen at the discretion of the investigator) versus SAbR (and additional SAbR of up to a total of 6 metastasis while disease remains amenable) followed by systemic therapy. Co-primary endpoints are OS and toxicity (≥grade 3). Target accrual goal is 472 patients which will provide 85% power to test non-inferiority in OS from a non-inferiority hybrid design, assuming a null hazard ratio of 1.24 and alternative hazard ratio of 0.85. If it is concluded that SAbR arm has non-inferior OS, superiority in toxicity will be tested. Secondary endpoints include health-related quality of life (QOL) as measured with NFKSI-19 and EQ-5D-5L and progression free survival (PFS). Exploratory endpoints include PFS of 1st line systemic therapy, local control with SAbR and cost-effectiveness. The trial has been open for enrollment since September 2023.