Combination of Anti-Angiogenic and Systemic Therapy in Advanced Non-Small Cell Lung Cancer: Before and After Progression to Leptomeningeal Metastasis

Abstract

Abstract Background Leptomeningeal metastasis (LM) is the most devastating complication of non-small cell lung cancer (NSCLC), and its incidence is increasing. We investigated survival outcomes of patients with NSCLC who received a combination of anti-angiogenic and systemic therapies before and after progression to LM and explored the factors associated with their survival. Methods Patients with EGFR-mutant or wild-type NSCLC-LM who received defined systemic therapy from January 2015 to March 2023 were included. The baseline characteristics of the patients were collected. Survival outcomes were analyzed separately for patients who received different therapies before and after LM progression. The primary outcomes were the median time from NSCLC diagnosis to LM (LM-free survival, mLFS) and overall survival (mOS). Prognostic factors were also analyzed. Results We enrolled 77 patients with NSCLC-LM. Their mLFS and mOS after EGFR-tyrosine kinase inhibitor (TKI) plus anti-angiogenic drugs were 19.0 and 21.9 months, respectively, and were significantly longer than that of the EGFR-TKI monotherapy group (14.0 and 8.3 months). mOS was also longer in patients who received platinum-based chemotherapy with anti-angiogenic therapy than in those who did not receive anti-angiogenic therapy, although without statistical significance. One- and two-year LFS rates and OS rates were higher with combination therapy than with chemotherapy or EGFR-TKI monotherapy. Multivariate analysis revealed that metastatic counts at > 3 sites were associated with a shorter LFS, and liver metastasis was an independent predictor of worse OS. Conclusions Combination of anti-angiogenic therapy with systemic therapy, particularly EGFR-TKIs, may prolong LFS and OS in patients with NSCLC-LM. Metastasis counts at > 3 sites and liver metastasis may serve as adverse prognostic factors for NSCLC-LM.