Alectinib Together with Intracranial Therapies Improved Survival Outcomes in Untreated ALK-Positive Patients with Non-Small-Cell Lung Cancer and Symptomatic and Synchronic Brain Metastases: A Retrospective Study

PURPOSE: The performance of alectinib and crizotinib in untreated anaplastic lymphoma kinase (ALK)-positive patients with non-small-cell lung cancer (NSCLC) and symptomatic and synchronic brain metastases is largely unknown. This retrospective study assessed the effectiveness of alectinib and crizotinib, together with intracranial therapies in a cohort of these patients. PATIENTS AND METHODS: This study included 34 previously untreated ALK-positive NSCLC patients with three or fewer intracranial metastases. Of these patients, 13 received oral alectinib 600 mg twice daily, and 21 received oral crizotinib 250 mg twice daily, until progressive disease, unacceptable toxicity, or death. All intracranial metastases were treated with craniotomy, CyberKnife, or both. RESULTS: Median overall progression-free survival (PFS) was 32.8 months (95% CI 24.4–41.2 months) in patients treated with alectinib and 8.0 months (95% CI 7.3–8.7 months) in patients treated with crizotinib. Median PFS of brain lesions was not yet reached with alectinib (95% CI 30.1 months–not estimated) and was 8.5 months (95% CI 7.2–12.3 months) with crizotinib. Median PFS of lung lesions was 38.5 months (95% CI 27.5–49.5 months) with alectinib and 9.2 months (95% CI 7.4–11.0 months) with crizotinib. Median overall survival was not yet reached with alectinib (95% CI 31.0 months–not estimated) and 30.3 months (95% CI 27.3–37.1 months) with crizotinib. CONCLUSION: Compared with crizotinib, alectinib showed superior efficacy and lower toxicity in the treatment of ALK-positive patients with NSCLC and symptomatic and synchronic brain metastases. The inclusion of intracranial therapies such as craniotomy or CyberKnife further improved the brain PFS and overall survival of these patients.