Main Session
Sep
27
PQA 01 - Gastrointestinal Cancer and Central Nervous System
2176 - ICON-RT: Intracranial Consolidation and Deferral of Radiation Therapy in Patients Receiving Approved CNS-Active Systemic Therapeutics
Presenter(s)
Luke Pike, MD, DPhil - Memorial Sloan Kettering Cancer Center, New York, New York
L. R. G. Pike1, M. Jeng1, E. Wo2, E. Miao3, H. Walch4, L. A. Boe1, R. Kotecha5, E. Carbone1, L. Nystrom1, N. Siegel1, C. G. Rusthoven6, and H. Yu1; 1Memorial Sloan Kettering Cancer Center, New York, NY, 2Memorial Sloan Kettering Cancer Center, New York City, NY, 3Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, 4Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, 5Miami Cancer Institute, Baptist Health South Florida, Miami, FL, 6Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, CO
Purpose/Objective(s):
Brain metastases (BM) are common in patients with EGFR-mutant non–small cell lung cancer (NSCLC). Modern central nervous system (CNS)-active EGFR tyrosine kinase inhibitors, particularly osimertinib, achieve high intracranial response rates and durable disease control, leading many clinicians to defer upfront stereotactic radiosurgery (SRS). However, deferral of local therapy may increase the risk of subsequent intracranial progression, neurologic morbidity, and need for salvage CNS-directed interventions. Preliminary data indicate that consolidative SRS to residual brain metastases after CNS-active systemic therapy may enhance intracranial control while sparing patients unnecessary upfront radiation, yet this strategy has not been prospectively validated. ICON-RT was designed to address this gap by prospectively evaluating a response-adapted, radiation-sparing strategy that selectively applies SRS to residual viable disease following initial systemic therapy, while incorporating patient-reported outcomes and correlative analyses to inform patient selection.Materials/Methods:
ICON-RT is a multicenter, phase II randomized controlled trial evaluating the role of consolidative SRS following an initial course of CNS-active EGFR-targeted therapy in patients with EGFR-mutant NSCLC and brain metastases. Eligible patients are adults (=18 years) with one or more intact brain metastases identified on contrast-enhanced brain MRI prior to initiation of first-line CNS-active systemic therapy. Key exclusion criteria include prior brain-directed radiotherapy, radiographic leptomeningeal disease, or intracranial lesions requiring urgent local intervention. After approximately 3 months of systemic therapy, patients with residual contrast-enhancing brain metastases without intracranial progression are randomized 1:1 to continued systemic therapy with MRI surveillance (Arm A) or consolidative SRS to all residual intracranial lesions followed by continued systemic therapy (Arm B). Randomization is stratified by systemic therapy regimen (osimertinib monotherapy versus combination therapy) and EGFR mutation subtype. The primary endpoint is intracranial progression-free survival from randomization, assessed using RANO-BM criteria with brain MRI every 3 months. Secondary endpoints include time-to-CNS progression, overall survival, patient-reported quality of life using validated instruments, neurologic outcomes, and patterns of intracranial failure. Exploratory endpoints include rates of salvage CNS-directed interventions and correlative biospecimen analyses. Enrollment began on 12/13/24. Clinical trial registry number: NCT06741085.Results:
N/AConclusion:
N/A