Leptomeningeal metastasis (LM) is an almost universally fatal complication of solid tumors. Intrathecal pemetrexed (IP) has preliminary activity; however, robust efficacy and safety data are lacking. Data of 112 patients with newly diagnosed, cytologically and/or radiologically confirmed LM from solid tumors between May 2021 and June 2024 were retrospectively analyzed. All patients received IP as first-line intrathecal therapy. The efficacy and safety of IP were evaluated, and prognostic factors associated with overall survival in the entire cohort and a non-small-cell lung cancer (NSCLC) subgroup were identified. The primary tumor types were NSCLC (63.4%), small-cell lung cancer (14.3%), breast cancer (9.8%), and colorectal cancer (5.4%). The median overall survival (mOS) for the entire cohort was 8.0 months (95% confidence interval CI, 6.5–9.5), with an overall clinical response rate of 75% (84/112). In the NSCLC subgroup, the mOS was 6.0 months (95% CI, 3.6–8.4). Multivariable analysis identified three independent predictors of improved survival: >6 IP administrations (hazard ratio HR, 0.38; 95% CI, 0.23–0.62; P 6 IP cycles, the mOS was 16 months. Treatment-related adverse events were predominantly grades 1–2. The most common symptoms were myelosuppression (41.1%) and elevated hepatic transaminase levels (36.6%). Intrathecal pemetrexed could confer clinically meaningful survival benefits with acceptable toxicity in patients with solid tumor LM.
Wang et al. (Thu,) studied this question.