Immune Checkpoint Inhibitors +/- Chemotherapy for Patients With NSCLC and Brain Metastases: A Systematic Review and Network Meta-Analysis

Background: Multiple studies have demonstrated the intracranial efficacy of immune checkpoint inhibitors (ICI) +/- chemotherapy. The efficacy of chemoimmunotherapy compared to ICI alone in patients with metastatic NSCLC and brain metastases (BM) remains unknown.

Methods: A systematic review and network meta-analysis were performed to evaluate ICI efficacy and the influence of additional chemotherapy on survival outcomes in treatment-naïve metastatic NSCLC with BM. Randomized phase II/III studies with at least one treatment arm with an ICI were eligible. Overall survival (OS) and progression-free survival (PFS) in patients with and without BM were assessed.

Results: Ten studies were included, totaling 6560 patients, 770 with BM. Pairwise meta-analysis revealed that patients with BM treated with ICI +/- chemotherapy had improved PFS (hazard ratio [HR] 0.49; 95% CI 0.40-0.60) and OS (HR 0.55; 95% CI 0.44-0.68) versus chemotherapy alone. Patients without BM treated with ICI +/- chemotherapy also had improved PFS and OS compared to chemotherapy alone. In the network meta-analysis of patients with BM, chemoimmunotherapy demonstrated improved PFS compared to ICI alone (HR 0.64; 95% CI 0.43-0.96; p = 0.03). No significant difference was observed in OS. In the population of patients without BM, no significant differences in PFS or OS were observed between chemoimmunotherapy versus ICI alone.

Conclusion: This meta-analysis confirms that ICIs with or without chemotherapy are superior to chemotherapy alone for the first-line management of metastatic NSCLC with and without BM. This network meta-analysis suggests combination chemoimmunotherapy offers PFS benefit over ICI monotherapy in BM patients, warranting direct comparisons in clinical trials.

Trial registration: PROSPERO: CRD42024501345.