The agents have demonstrated a remarkable intracranial activity.
November 19, 2020—Houston, Texas—Upfront use of next generation tyrosine kinase inhibitors in oncogene-driver non-small cell lung cancer (NSCLC) with symptomatic central nervous system (CNS) metastases has been associated with reasonable intracranial activity and represents a valuable treatment option.
This outcome of a case series was reported at the 2020 Society for Neuro-Oncology (SNO) Virtual Meeting.
Tali Siegal, MD, of the Tel Aviv Sourasky Medical Center and Tel Aviv University Sackler School of Medicine, Israel, and colleagues set out to assess the CNS activity of targeted therapy in patients with CNS metastases of oncogene-driven NSCLC.
Nine patients with NSCLC harboring either an EGFR mutation or ALK rearrangement and symptomatic CNS metastases and were treated with TKIs without radiation therapy or surgery. Clinicopathological characteristics, treatments, and outcomes were analyzed.
Most patients presented with symptomatic CNS metastases at the time of presentation with metastatic disease (6 of 9 patients).
The majority of patients harbored leptomeningeal disease (6 of 9 patients) and multiple parenchymal metastases. Patients presented with a variety of CNS symptoms, 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 of 9) responded rapidly, both clinically and radiographically, to targeted treatment. A marked correlation between systemic and intracranial radiographic response.
Dr. Siegal explained that CNS metastases are frequent in oncogene-driven NSCLC. They are associated with significant morbidity and poor survival outcomes. They occur in 10% to 20% of patients with NSCLC at presentation, and in up to 50% of patients during the course of their illness.
Brain metastases occur most frequently in patients with adenocarcinomas and tumors harboring epidermal growth factor receptor (EGFR) mutations or ALK rearrangements.
Standard treatment (that is, surgery, whole brain radiation therapy, or stereotactic radiosurgery) can potentially delay systemic treatment and/or result in neurocognitive impairment.
The brain appears to be a site of metastatic disease where responses, even complete responses, are obtainable with most of the currently used chemotherapy regimens.
Little data are available, however, on the correlation among response rates, progression-free survival, overall survival, and long-term functionality.
Penetration of the blood-brain barrier by tyrosine kinase inhibitors, including erlotinib and gefitinib, has been demonstrated.
Drug concentrations in cerebrospinal fluid, however, were lower than in plasma. This lower concentration in cerebrospinal fluid raises the question of whether higher doses are required for effective intracranial activity. Such activity is limited by dose-related toxicities.
Recently, next-generation tyrosine kinase inhibitors demonstrated remarkable intracranial activity. Most clinical trials, however, did not enroll patients with neurological symptoms.
Dr. Siegal concluded that upfront use of next-generation tyrosine kinase inhibitors in oncogene-driven NSCLC with symptomatic CNS metastases is associated with reasonable intracranial activity and represents a valuable treatment option.