Abstract
BACKGROUND: Central nervous system (CNS) metastases occur frequently in oncogene-driven non-small cell lung cancer (NSCLC). Standard treatment (i.e surgery, whole brain radiation therapy or stereotactic radiosurgery) approaches can potentially delay systemic treatment and/or result in neurocognitive impairment. Recently, next generation tyrosine kinase inhibitors (TKIs) have demonstrated a remarkable intracranial activity. However, most clinical trials did not enroll patients with neurological symptoms. Our study aims to assess the CNS activity of targeted therapy in this patient population. METHOD: We present a case series of nine NSCLC patients with either EGFR mutation of ALK rearrangement and symptomatic CNS metastases that were treated with TKIs, without radiation therapy or surgery. Clinicopathological characteristics, treatment and outcome were analyzed. RESULTS: Most patients presented with symptomatic CNS metastases at time of metastatic disease presentation (6/9 patients). Additionally, the majority of patients had leptomingeal disease (6/9 patients) and multiple parenchymal metastases. Patients presented with a variety of CNS symptoms with the most common being nausea, vomiting, headache and confusion. Five patients were treated with Osimertinib. One patient with ALK rearrangement was treated with Lorlatinib. The remaining 3 patients received either Gefitinib or Afatinib. Most patients (6/9 patients) responded rapidly both clinically and radiographically to the targeted treatment, with a marked correlation between systemic and intracranial radiographic response. CONCLUSION: Upfront use of next generation TKIs in patients with oncogene-driver NSCLC with symptomatic CNS metastases is associated with reasonable intracranial activity and represents a valuable treatment option.