First-line immunotherapy ± chemotherapy with or without upfront stereotactic radiotherapy (SRT) in patients with Non-Small cell lung cancer (NSCLC) with asymptomatic brain metastases.

Background The role and optimal timing of SRT for patients with advanced NSCLC and asymptomatic brain metastases treated with immune checkpoint inhibitors (ICI) are controversial.Methods Efficacy and safety outcomes of patients with newly diagnosed non oncogene- addicted NSCLC with asymptomatic brain metastases (1-10 lesions, max. diameter of lesions 3 cm) treated with a first-line ICI-containing regimen at 11 Swiss cancer centers were retrospectively analyzed.Results A total of 128 patients in two cohorts (58 patients with upfront SRT and 69 patients without upfront SRT) were included in this analysis. The median intracranial progression-free survival (PFS) was significantly longer in patients with upfront SRT (12.6 vs. 8.2 months, Hazard ratio (HR) 0.62 [95 % CI 0.41 vs. 0.95], p = 0.026). This benefit remained significant after correcting for number and size of lesions and programmed cell death 1 ligand (PD-L1) status. The proportion of patients with symptomatic progression of brain metastases and of patients receiving further local treatment to the brain was similar between cohorts (3 % vs. 12 %, p = 0.11 and 33 % vs. 42 %, p = 0.3). No significant difference in median overall survival (OS) was observed between the cohorts (22.8 vs. 21.7 months, p = 0.4). Only two patients with upfront SRT experienced a clinically significant Central Nervous System (CNS) adverse event (AE).Conclusion In this multicentric retrospective analysis of patients with asymptomatic brain metastases upfront SRT was associated with an improved intracranial PFS and was well tolerated but median OS and the rate of patients developing symptomatic brain progression were similar to patients without upfront SRT.