Pemetrexed in the Treatment of Leptomeningeal Metastasis in Patients With EGFR-mutant Lung Cancer

Leptomeningeal metastasis (LM), still an area of unmet need, has frequently been observed in patients with EGFR-mutant non-small-cell lung cancer (NSCLC). Because the antitumor efficacy of systemic cytotoxic agents against LM is unclear, we explored the role of pemetrexed in the treatment of patients with LM from EGFR-mutant NSCLC.We retrospectively reviewed the medical records of patients with LM from EGFR-mutant NSCLC treated between 2006 and 2016. Post-LM survival was evaluated as well as clinical factors.In our patient cohort with EGFR-mutant NSCLC (n = 631), 17.4% (n = 110) developed LM. Their median post-LM survival was 5.7 months (95% confidence interval, [CI], 0.0-12.0 months). Post-LM survival was significantly longer with pemetrexed use after LM (median, 13.7 months; 95% CI, 4.1-23.2 months) than without pemetrexed use after LM (median, 4.0 months; 95% CI, 2.2-5.7 months; P = .008). In the multivariate analyses, no pemetrexed use after LM (vs. use) and no EGFR tyrosine kinase inhibitor use after LM (vs. use) were independently associated with a poor post-LM survival with a hazard ratio of 3.1 (95% CI, 1.5-6.3; P = .002) and 3.0 (95% CI, 1.6-5.8; P = .001), respectively.Pemetrexed use after LM was independently associated with a longer post-LM survival in patients with EGFR-mutant NSCLC with LM. Prospective studies are warranted to validate this finding.