The effects of brain radiotherapy combined with immunotherapy and chemotherapy for driver gene-negative non-small-cell lung cancer with brain metastases

Objective Brain metastases (BM) are highly prevalent in advanced non-small cell lung cancer (NSCLC); however, therapeutic options remain limited and suboptimal for driver gene-negative NSCLC BM patients. This study aimed to explore the efficacy and prognostic risk factors of brain radiotherapy combined with immunotherapy and chemotherapy in real-world for these patients. Methods This study included 222 driver gene-negative NSCLC patients with BM. Inverse Probability of Treatment Weighting (IPTW) was employed to reduce the impact of selection bias and confounding factors. Prognostic risk factors were identified using Cox regression analysis. Survival outcomes were evaluated using Kaplan–Meier curves, and subgroup analyses were performed to explore the associations between treatment and survival results. Results Based on the use of immunotherapy, patients were divided into the RT+CT+ICI group (received brain radiotherapy combined with immunotherapy and chemotherapy, n=117) and the RT+CT group (received brain radiotherapy combined with chemotherapy alone, n=105). The median overall survival (mOS) longer in the RT+CT+ICI group (19.6 vs. 15 months, Hazard Ratio [HR] 0.57, 95% confidence interval [CI] 0.41–0.79, P < 0.001). Multivariable adjustments confirmed prolonged OS (HR 0.58, 95% CI 0.41–0.81, P = 0.002) and progression-free survival (PFS) (HR 0.72, 95% CI 0.53–0.98, P = 0.038) in the RT+CT+ICI group. Stereotactic radiosurgery (SRS) is a protective factor for OS in patients with driver gene-negative NSCLC BM; while PD-L1 expression is a protective factor for PFS and intracranial progression-free survival (IPFS) in these patients. Conclusions This study demonstrates that brain radiotherapy combined with immunotherapy and chemotherapy is effective and predictive in driver gene-negative NSCLC BM patients. In addition, SRS and PD-L1 expression may be associated with better prognosis in such patients.