Superior Effectiveness of PD‐1 Inhibitor Plus Chemotherapy versus Bevacizumab Plus Chemotherapy as First‐Line Treatment for Non‐Small Cell Lung Cancer with Brain Metastases

Abstract Optimal first‐line treatment approaches for non‐small cell lung cancer (NSCLC) with brain metastases (BMs) without driver gene alterations remain unclear. Recently, some studies preliminarily have suggested that immunotherapy plus chemotherapy (ICI+Chemo) may be superior to bevacizumab plus chemotherapy (Beva+Chemo). However, no study directly compares the effectiveness of two treatment approaches for NSCLC patients with BMs without driver gene alterations. NSCLC patients are retrospectively identified with BMs lacking sensitizing mutations, and patients are divided into ICI+Chemo and Beva+Chemo groups based on the front‐line treatment approach. It is aimed to compare the efficacy for two treatments. All 155 eligible patients between March 2017 and May 2022 have been enrolled. Median intracranial progression‐free survival (iPFS) and systemic PFS (sPFS) in ICI+Chemo group are 14.4 and 12.1 months compared with those in Beva+Chemo group (10.0 and 8.4 months) (hazard ratio (HR), 0.626; P = 0.035; and HR, 0.634; P = 0.022). The PFS benefit of ICI+Chemo over Beva+Chemo is significant in those with programmed cell death‐ligand 1(PD‐L1)‐positive expression. Median overall survival (OS) is similar between the ICI+Chemo and Beva+Chemo groups (26.9 versus 23.1 months, HR, 0.790; P = 0.335). The objective response rates (ORR) are similar in both groups, and both of the regimens are well tolerated without newly reported adverse events (AEs). Sixty‐three patients (40%) received locoregional therapy for BMs including radiotherapy or surgery throughout the course of treatment. The subsequent treatment is analyzed after progression and it is found that patients who receive immunotherapy throughout the course of treatment have significantly improved OS compared with those who are naïve to immunotherapy ( P < 0.001). OS is comparable in patients who receive immunotherapy compared with those who receive both immunotherapy and bevacizumab ( P = 0.394). The ICI+Chemo significantly improves iPFS and sPFS for PD‐L1‐positive NSCLC patients with BMs lacking driver gene alterations. Immunotherapy provides the vital contribution to improving OS of NSCLC patients with BMs.