Efficacy and safety of intrathecal pemetrexed in the treatment of leptomeningeal metastases from ALK-mutant NSCLC: A prospective, multi-center, single-arm, phase II clinical trial.

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Background: This study aimed to evaluate the efficacy and safety of intrathecal pemetrexed (IP) in the treatment of leptomeningeal metastases (LM) from ALK-mutant non-small-cell lung cancer (NSCLC). Methods: This prospective, multi-center, single-arm, phase II clinical trial enrolled 25 patients with ALK-mutant NSCLC and LM who had failed multi-line treatments. Patients had failed multi-line treatments received IP twice during the first week (Day 1 and Day 5), followed by once every 3-4 weeks until disease progression (PD), intolerance, or refusal of further treatment. The primary endpoint was overall survival (OS), and secondary endpoints included objective response rate (ORR) and adverse events (AEs). LM response was assessed using the Response Assessment in Neuro-Oncology (RANO) criteria. Results: The median overall survival (mOS) was 18.0 months (95% confidence interval [CI]: 13.0–23.6 months), with the RANO-assessed response rate of 76% (19/25). The most common adverse event was myelosuppression (n = 13; 52%), which was reversible with symptomatic treatment. Conclusions: This study demonstrates that IP is a safe and effective treatment for ALK-mutant NSCLC-LM, with a median OS exceeding 18 months. To our knowledge, this is the first prospective study to evaluate IP in this patient population, highlighting its potential as a promising therapeutic option for LM. Clinical trial information: ChiCTR1800016615 .