Combination of antiangiogenic and systemic therapy in advanced non-small cell lung cancer: before and after progression to leptomeningeal metastasis

Leptomeningeal metastasis (LM) is the most devastating complication of non-small cell lung cancer (NSCLC), and its incidence is increasing. We investigated the survival outcomes of patients with NSCLC who received combined antiangiogenic and systemic therapies before and after LM progression and explored survival-associated factors. Patients with epidermal growth factor receptor (EGFR)-mutant or wild-type NSCLC-LM receiving systemic therapy were included. 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). The mLFS and mOS of the 77 enrolled patients after receiving EGFR-tyrosine kinase inhibitor (TKI) plus antiangiogenic drugs were 19.0 and 21.9 months, respectively, which were significantly longer than those of the patients in the EGFR-TKI monotherapy group (14.0 and 8.3 months, respectively; P values for mLFS and mOS were 0.035 and 0.038, respectively). In patients receiving platinum-based chemotherapy, significantly longer mLFS and mOS were not dependent on antiangiogenic therapy. Metastatic counts at more than three sites were associated with a shorter LFS, and liver metastasis was an independent predictor of worse OS. Combining antiangiogenic and systemic therapies, particularly EGFR-TKIs, may prolong LFS and OS in NSCLC-LM, whereas metastatic counts at more than three sites and liver metastasis may be adverse prognostic factors.