Abstract
Brain metastases are common in patients with advanced non–small cell lung cancer (NSCLC). Approximately 1% of NSCLC patients have ROS1-rearranged, and these patients achieved prolonged survival when treated with crizotinib, which is approved for the treatment of ROS1-rearranged NSCLC. However, this efficacy might not translate to intracranial control of disease. Herein, we evaluated the clinical impact of crizotinib on brain metastases in patients with advanced ROS1-rearranged NSCLC. Between April 2014 and October 2016, 53 ROS1-rearranged NSCLC patients treated with crizotinib were retrospectively evaluated for baseline characteristics, brain metastases status, progression patterns and the overall prognosis. Of the 53 ROS1-rearranged NSCLC patients who received crizotinib as treatment, 13 (24.5%) patients had baseline brain metastases before crizotinib treatment. Among patients without baseline brain metastases who developed progressive disease after initiation of crizotinib (n=27), 22.2% were diagnosed with brain metastases. Among patients without baseline brain metastases, systemic progression-free survival (PFS) and overall survival (OS) after initiation of crizotinib was significantly longer than that of patients with brain metastases (median PFS: 20.4 months vs. 11.0 months, p = 0.003; median OS: not reached vs. 16.5 months, p = 0.027). There was no significant difference in systemic PFS and OS between patients developing brain metastases before and after crizotinib treatment (median PFS: 11.0 months vs. 6.4 months, p = 0.469; median OS: 16.5 months vs. not reached, p = 0.605). Among the patients with baseline brain metastases, 6 had received prior brain radiotherapy and 7 had received no prior radiotherapy. A total of 2 patients in the treated group had an event of brain metastases progression, as compared with 4 patients in the untreated group (33.3% vs 57.1%, p = 0.592). There was no significant difference in intracranial PFS in the previously brain treated patients versus the untreated patients before crizotinib treatment (median intracranial PFS: 12.5 months vs. 11.0 months, p = 0.790). Brain metastases status before crizotinib treatment was significantly associated with both PFS and OS in crizotinib-treated ROS1-rearranged NSCLC patients. Patients with brain metastases received prior radiotherapy have not prolonged survival compared with the patients treated with crizotinib alone.
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