Non-Small Cell Lung Cancer Coverage from Every Angle

Retrospective Analysis of Brain Metastases in Patients With Stage IV NSCLC

By: Joseph Cupolo
Posted: Monday, August 13, 2018

Although brain metastases are common in patients with treatment-naive stage IV ROS1-positive non–small cell lung cancer (NSCLC), a retrospective study revealed that the incidence does not differ from other oncogene cohorts (such as ALK, EGFR, KRAS, and BRAF). The study, published in the Journal of Thoracic Surgery by Tejas Patil, MD, of the University of Colorado School of Medicine, Aurora, and colleagues, also centered on the rate of central nervous system (CNS) disease progression in patients with stage IV NSCLC receiving crizotinib.

The investigators analyzed 579 patients with stage IV NSCLC, 33 of whom were identified as having ROS1-positive disease and 115, as having ALK-positive disease. The incidence of brain metastases in patients with treatment-naive, stage IV ROS1-positive and ALK-positive NSCLC was 36% (12 of 33) and 34% (39 of 115), respectively. There were no statistically significant differences in the incidence of brain metastases across ROS1 (36%), ALK (34%), EGFR (28%), KRAS (28%), BRAF (19%), or other mutations (22%).

Although the investigators noted that positive systemic responses to crizotinib therapy are seen in patients with ALK-positive NSCLC, CNS disease progression is common due to the reduced penetrance of crizotinib through the blood-brain barrier. In this study, 95 patients (16 with ROS1-positive disease and 79 with ALK-positive disease) experienced disease progression on crizotinib therapy. The median treatment duration for all ROS1-positive and ALK-positive patients in this analysis was 11 months and 13 months, respectively.

“Our data demonstrate that brain metastases are common in stage IV, treatment-naive, ROS1-positive NSCLC, a finding in contrast with other studies that report a reduced incidence of brain metastasis,” the investigators noted. As for the data analyzed on crizotinib therapy in these patients, “these observations reinforce the importance of CNS-penetrant [tyrosine kinase inhibitors] for patients with ALK-positive and ROS1-positive NSCLC,” they concluded.

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