Next-generation epidermal growth factor receptor tyrosine kinase inhibitors for leptomeningeal carcinomatosis

Introduction: Epidermal growth factor receptor (EGFR) mutation status is strongly correlated with leptomeningeal carcinomatosis in non-small cell lung cancer. Historically, patients were treated with radiotherapy, intrathecal chemotherapy or first-generation EGFR tyrosine kinase inhibitors (TKIs); however, most would eventually develop resistance and disease progression. Therefore, recent interest has sparked in investigating next-generation EGFR-TKI monotherapy. Case reports: We describe 2 patients with non-small cell lung adenocarcinoma who later presented with leptomeningeal disease, treated with next-generation EGFR-TKI monotherapy, independent of whole-brain radiotherapy, with favorable response and outcome. Conclusions: The next-generation EGFR-TKIs may have improved success in treatment of leptomeningeal metastases in non-small cell lung adenocarcinoma when compared with the first-generation and second-generation EGFR-TKIs. Next-generation EGFR-TKI monotherapy should be considered in select patients with leptomeningeal metastases from lung adenocarcinoma. More research is needed to review this potential therapeutic option, especially for use as first-line therapy.