Impact of Immune Checkpoint Inhibitor-Combined Chemotherapy as First-Line Treatment for Non-Small Cell Lung Cancer...

Immune checkpoint inhibitor-combined chemotherapy (chemo-ICI) is a cornerstone treatment for metastatic non-small cell lung cancer (NSCLC) without oncogenic addictions. However, immunotherapy's efficacy in patients with brain metastases remains unclear. This multicenter retrospective study assessed NSCLC patients with brain metastases who received first-line chemo-ICI between January 2020 and December 2022. The primary outcome was the 12-week intracranial control (IC) rate. Progression-free survival (PFS), overall survival (OS), and neurological tolerance were also evaluated. Of 338 patients from 11 French hospitals, most were male (n = 196, 58%), with a median age of 60 (IQR 54-66) years, and an ECOG performance status (ECOG-PS) of 0 or 1 in 267 (79%) patients. Most (n = 291, 86%) had adenocarcinoma, and 130 (38.6%) had programmed death-ligand 1 (PD-L1) expression <1%. At diagnosis, 174 (51.5%) received steroids. Sixty-six (19.8%) underwent prior brain radiotherapy. Of 240 evaluable patients, the 12-week ICC rate was 74.2%. Median OS and PFS were 22.1 (95% CI 16.5-29.3) and 7.3 months (95% CI 5.9-8.5), respectively. Variables independently associated with CNS progression were ECOG-PS >1 (vs. 0; OR 12.15; 95% CI 3.93-37.54) and extracerebral metastases (OR 3.52; 95% CI 1.55-7.99). Conversely, high PD-L1 expression (≥50%) (vs. 0; OR 0.41; 95% CI 0.19-0.90) and prior brain radiotherapy (OR 0.25; 95% CI 0.10-0.68) were associated with better ICC. No new toxicity was observed. Chemo-ICI was effective and safe in NSCLC patients with CNS metastases, including corticosteroid-treated symptomatic patients. High PD-L1 expression and early brain radiotherapy were favorable prognostic factors.