Intrathecal pemetrexed improves survival outcomes in previously treated EGFR-mutant advanced non-small-cell lung cancer with leptomeningeal metastases.

OBJECTIVE

This study assessed the impact of intrathecal pemetrexed (IP) in managing leptomeningeal metastases (LM) in previously treated patients with -mutant advanced non-small cell lung cancer (NSCLC).

METHODS

We analyzed the clinical and survival outcomes of 50 patients with LM who received 50 mg IP after disease progression with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) treatment between September 2021 and September 2023 at the Hunan Cancer Hospital. Treatment response was evaluated based on improvement in neurological symptoms/signs and Karnofsky Performance Status (KPS) scores. We also evaluated the overall survival (OS), intracranial progression-free survival (I-PFS), and extracranial progression-free survival (E-PFS). Next generation sequencing (NGS) was employed to explore the underlying mechanisms of LM after EGFR-TKIs resistance.

RESULTS

IP treatment was associated with a 64 % clinical response rate, median I-PFS of 5.3 months (95 % confidence intervals [CI], 1.4-9.2), E-PFS of 8.0 months (95 % CI, 2.2-13.8), and OS of 12.0 months (95 % CI, 9.6-14.4). Compared with non-responders, responders to IP demonstrated significantly prolonged I-PFS (11.2 months vs. 1.0 month; hazard ratio [HR]: 0.15, 95 % CI: 0.06-0.39), E-PFS (11.2 months vs. 3.0 months; HR: 0.24, 95 % CI: 0.10-0.57), and OS (15.5 months vs. 3.8 months; HR: 0.22, 95 % CI: 0.08-0.58) (all P < 0.001). Adverse events(AEs) primarily consisted of myelosuppression (54 %) and hepatic damage (24 %), but were manageable and did not result in any deaths. mutations were consistent between cerebrospinal fluid (CSF) and primary tumors in 100 % of cases. CSF also exhibited genetic variations such as mutations/amplifications and alterations in , , , and .

CONCLUSION

IP represents a potentially viable treatment option for managing LM in patients with EGFR-TKI-resistant -mutant advanced NSCLC. Clinical responses as measured by the improvement of neurological symptoms/signs and KPS scores were associated with favorable survival outcomes.