Clinical outcomes and predictive factors of immunotherapy efficacy in non-small cell lung cancer brain metastases: A comparative study

Background Brain metastases (BMs) are common in patients with non-small cell lung cancer (NSCLC) and remain a major therapeutic challenge. While immune checkpoint inhibitors (ICIs) have improved systemic outcomes, their Intracranial efficacy and prognostic determinants in patients with BMs, particularly in comparison with chemotherapy, remain insufficiently characterized. Methods We conducted a multi-center, retrospective cohort study including NSCLC patients with BMs who received ICIs or chemotherapy alone. Propensity score matching was performed to balance baseline characteristics between treatment groups. Intracranial and extracranial responses, intracranial progression-free survival (iPFS), extracranial PFS (ePFS), and overall survival (OS) were compared. Logistic regression and Cox proportional hazards models were used to identify clinical and treatment-related prognostic factors associated with treatment response and survival. Results In the matched cohort, patients treated with immunotherapy achieved significantly longer median OS than those receiving chemotherapy (18.9 vs. 13.3 months, p  = 0.001), while intracranial and extracranial PFS were numerically but not significantly prolonged. The intracranial objective response rate (iORR) was 31.4% in the matched subset of immunotherapy cohort, comparable to 33.9% in the matched chemotherapy cohort. Concordance between intracranial and extracranial responses was about 70% across groups. In the immunotherapy cohort, development of immune-related adverse events (irAEs), receipt of stereotactic radiotherapy (SRT), and prior radiotherapy were associated with improved OS. Patients receiving intracranial radiotherapy before ICIs achieved a median OS of 32.3 months versus 19.0 months with concurrent therapy. In the chemotherapy cohort, age ≥ 65 years and multiple brain metastases were associated with inferior survival. Conclusions This real-world study suggests that immunotherapy may confer a survival advantage over chemotherapy in NSCLC patients with brain metastases, with efficacy less dependent on baseline factors such as age or performance status. Radiotherapy administered before ICIs appeared associated with favorable outcomes, although this observation remains hypothesis-generating given the study limitations.