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

• Published in: Clinical lung cancer Vol. 25; no. 5; pp. 417 - 423.e1
• Main Authors: Mills, Matthew N., Uno, Akihiro, Li, Pinxue, Liveringhouse, Casey, Kim, Youngchul, Oliver, Daniel E., Perez, Bradford A., Creelan, Benjamin C., Yu, Michael, Forsyth, Peter A., Pina, Yolanda, Ahmed, Kamran A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2024
• Subjects: EGFR-targeted therapy; Immune checkpoint blockade; Leptomeningeal disease; Non-small cell lung cancer; Radiation therapy; Leptomeningeal disease; EGFR-targeted therapy; Radiation therapy; Immune checkpoint blockade; Non-small cell lung cancer
• ISSN: 1525-7304; 1938-0690; 1938-0690
• DOI: 10.1016/j.cllc.2024.04.005

•Patients with NSCLC LMD have a poor prognosis, with a 6-month OS of 35%.•EGFR-positive NSCLC LMD who received targeted therapy have improved OS.•EGFR-positive NSCLC LMD who received targeted therapy have improved CS-PFS. NSCLC LMD is a challenging diagnosis. We assessed 80 NSCLC LMD patients treated at our institution with EGFR-targeted therapy, immune checkpoint blockade, intrathecal chemotherapy or radiation therapy alone. Significant differences were noted in both CS-PFS and OS between treatment groups. With the best OS in patients receiving EGFR targeted therapy (P = .03) and the highest 6-month CSF-PFS of 43% (P = .04). 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). 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). 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 = .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 = .049). Upon univariate analysis, receipt of ETT compared to RT alone reached significance for OS (HR 0.35, P = .006) and CS-PFS (HR 0.39, P = .013). 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.