Intrathecal Pemetrexed for Leptomeningeal Metastasis in EGFR-Mutant NSCLC
Status:
Not yet recruiting
Trial end date:
2025-05-01
Target enrollment:
Participant gender:
Summary
Leptomeningeal metastasis (LM) is a complication of advanced non-small cell lung cancer
(NSCLC). The incidence of LM in NSCLC patients is around 3-5 %, reaching 9.4 % of those with
an epidermal growth factor receptor (EGFR) mutation. Generally, the efficacy of systemic
treatment for LM is limited due to the blood-brain barrier. Osimertinib has a high central
nervous system penetration rate, making it the preferred first-line treatment for EGFR-mutant
NSCLC. Previous studies indicated that osimertinib had shown promising efficacy in pretreated
patients harboring EGFR mutations and LM. However, intracranial disease progression
eventually develops, and the prognosis of patients with LM progression after osimertinib is
poor. Recently, intrathecal chemotherapy with pemetrexed (IP) was reported to be an
alternative treatment in patients with NSCLC and LM. The results from a phase I/II trial
examining the efficacy and safety of IP in patients with EGFR-mutant NSCLC after the failure
of previous TKI, and 83% of study enrollees received osimertinib before IP. The clinical
response rate was 84.6%, and the median overall survival was 9.0 months. Despite initial
promising efficacy, further trials are needed to verify these results. Therefore, the
investigators plan to conduct a prospective study to examine the safety and effectiveness of
IP combined with EGFR-TKI for patients with EGFR mutant NSCLC after osimertinib failure.