8624 Background: The timing of brain radiation therapy (RT) in patients with oncogene-mutated NSCLC with asymptomatic brain metastases (ABM) has been a matter of debate. No level 1 evidence supports delayed brain RT in ABM. This phase III, open-label, RCT (NCT05236946) evaluates Upfront Cranial RT (U-CRT) versus Delayed CRT (D-CRT) in ABM of oncogene-mutated NSCLC. Methods: Eligible patients (≥18 years, ECOG ≤2), with EGFR mutation or ALK gene rearrangement and completely ABM, were randomized to U-CRT vs D-CRT at intracranial progression (ICP), stratified by GPA score (0-2 vs > 2) and BM presentation (Synchronous vs Metachronous). Key exclusions include symptomatic BM, brainstem metastases, and prior cranial RT. All pts received standard systemic therapy (TKI ± CT). The primary endpoint is intracranial PFS with death treated as a competing event. Secondary endpoints included OS, PFS, and treatment toxicity. All patients underwent MRI brain every 3 months for 1 st year and 6 months thereafter, unless indicated clinically. Cumulative incidence functions were estimated, and subdistribution hazards were compared using the Fine and Gray model. With a planned enrollment of 208 patients and 139 target events, the study had 80% power to detect a hazard ratio of 0.62 at a two-sided alpha of 0.05. The icPFS was analyzed in intention-to-treat populations using Kaplan-Meier estimates and log-rank tests. Results: A total of 208 patients were randomized (105-U-CRT; 103-D-CRT). Baseline characteristics were well-balanced in both arms. The median age was 53 years (range, 26-83). EGFR and ALK mutations were seen in 87.6% and 12.4% in U-CRT and 79.6% however, it did not improve the survival outcomes. The difference in survival may become more apparent as the OS data matures. Data on QOL, neurocognition, and molecular analysis will be reported later. Clinical trial information: NCT05236946 .
Tibdewal et al. (Thu,) studied this question.