Intrathecal pemetrexed chemotherapy combined with systemic therapy in patients with non-small cell lung cancer and leptomeningeal metastases: a retrospective study.

Background: Leptomeningeal metastases (LM) in non-small cell lung cancer (NSCLC) present a challenging prognosis, with systemic therapies often limited by the blood-brain barrier. However, intrathecal pemetrexed injections can increase intracranial drug concentrations, aiding in disease control. Objective: To evaluate the efficacy and safety of combining intrathecal pemetrexed with systemic therapy in patients with NSCLC and LM. Methods: Thirty-one patients with NSCLC and LM who received intrathecal pemetrexed chemotherapy between 2018 and 2022 at First Affiliated Hospital of Gannan Medical College were retrospectively reviewed. Results: Of the 31 patients enrolled, six had LM at initial diagnosis. The median number of intrathecal pemetrexed injections was 4 (2-26), with an intracranial control rate of 87.1% (27/31). Median iPFS was 9 months (95% CI: 2.77-15.23), and median iOS was 12 months (95% CI: 5.94-18.06 months). Most adverse events (AEs) were grade 1-2, with four (12.9%) grade 3 AEs (including two cases of grade 3 leukopenia; one, grade 3 diarrhea; one, grade 3 interstitial pneumonitis). Univariate and multivariate analyses showed that the combination of bevacizumab (p<0.05) and an Eastern Cooperative Oncology Group(ECOG) score of ≤ 1 (p<0.05) were favorable prognostic factors for survival. Conclusion: Intrathecal pemetrexed injections combined with systemic treatment demonstrated significant therapeutic efficacy and manageable safety in NSCLC patients with LM.