Osimertinib Improves Overall Survival in Patients with Leptomeningeal Metastases Associated with EGFR-Mutated Non-Small-Cell Lung Cancer Regardless of Cerebrospinal Fluid T790M Mutational Status

Osimertinib has demonstrated promising efficacy against leptomeningeal metastasis (LM) associated with T790M-positive non-small-cell lung cancer (NSCLC). However, the effect of cerebrospinal fluid's (CSF's) epidermal growth factor receptor (EGFR) T790M mutation on osimertinib efficacy remains unclear.Seventy-eight patients were studied with EGFR-mutated NSCLC and LM. Case data were collected and EGFR mutation status of circulating cell-free DNA from paired CSF, and plasma of 23 patients with LM was detected using droplet digital PCR. The median overall survival (mOS) was 8.08 months (95% CI: 6.07–10.09) in the study. Forty-four osimertinib-treated patients had an improved mOS of 13.15 (95% CI: 5.74–20.57) and a median progression-free survival (PFS) of 9.50 months (95% CI: 6.77–12.23) when compared with patients treated with first- or second-generation EGFR-TKI (mOS = 3.00 months (95% CI: 1.32–4.68) and median PFS = 1.50 months (95% CI: 0.00–3.14)). In the osimertinib group, mOS values for CSF with and without T790M mutation were 22.15 months (95% CI: 9.44–34.87) and 13.39 months (95% CI: 7.01–19.76), respectively, with no statistical differences. Regardless of the CSF T790M mutation status, osimertinib demonstrated significant efficacy against LM associated with NSCLC.