Clinical Outcomes of Patients with Non-Small Cell Lung Cancer Leptomeningeal Disease Following Receipt of EGFR-Targeted Therapy, Immune-Checkpoint Blockade, Intrathecal Chemotherapy, or Radiation Therapy Alone

Background : EGFR-targeted therapy (ETT) and immune-checkpoint blockade (ICB) have shown promising results in treating NSCLC brain metastases (BM). However, little is known of their effect in treating leptomeningeal disease (LMD). Patients and Methods : This is a retrospective review of 80 patients diagnosed with NSCLC LMD from January 2014 to March 2021. Patients were grouped based on initial LMD treatment: radiotherapy (RT) alone, ETT, ICB, and intrathecal chemotherapy (ITC). Results : EGFR mutation was present in 22 patients (28%). Twenty patients had positive cytology in cerebrospinal fluid, while 60 patients were diagnosed based on MRI with clinical correlation. The RT alone group consisted primarily of whole brain radiation (n=20; 77%), stereotactic radiation (n=3; 12%), and palliative spine radiation (n=2; 7%). There were no significant differences amongst the treatment groups in age, performance status, or neurologic symptoms. Overall, the 6-month overall survival (OS) and craniospinal progression free survival (CS-PFS) were 35% and 24%, respectively. The 6-month OS for the ETT, ICB, ITC, and RT alone groups was 64%, 33%, 57%, and 29% respectively (log-rank p=0.026). The 6-month CS-PFS for the ETT, ICB, ITC, and RT alone groups was 43%, 33%, 29%, and 19% respectively (log-rank p=0.049). Upon univariate analysis, receipt of ETT compared to RT alone reached significance for OS (HR 0.35, p=0.006) and CS-PFS (HR 0.39, p=0.013). Conclusions : The prognosis for patients with NSCLC LMD remains poor overall. However, the receipt of ETT for patients with EGFR-positive disease was associated with improved outcomes.