Phase III randomized trial of stereotactic ablative radiotherapy (SAbR) for oligometastatic advanced renal carcinoma (EA8211-SOAR).
Authors: Hannan Raquibul , Kim Se Eun , Cole Suzanne , Wulff-Burchfield Elizabeth Marie , Wentland Andrew , Hannan Mu-Han , Kapur Payal , Shevrin Daniel , Gurley Tami , Lin John Kent , Brugarolas James , Timmerman Robert D. , McKay Rana R. , Wagner Lynne I. , Haas Naomi B. , Carducci Michael Anthony 
Published: February 2024

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. References: 1. Hannan R, Christensen M, Christie A, et al: Stereotactic Ablative Radiation for Systemic Therapy-naïve Oligometastatic Kidney Cancer. Eur Urol Oncol, 2022; 2. Zhang Y, Schoenhals J, Christie A, et al: Stereotactic Ablative Radiation Therapy (SAbR) Used to Defer Systemic Therapy in Oligometastatic Renal Cell Cancer. Int J Radiat Oncol Biol Phys 105:367-375, 2019; 3. 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. Clinical trial information: NCT05863351 .