1. Treatment with alectinib reduced CNS lesion sizes and significantly improved symptoms, ECOG performance scores and requirements for mannitol and corticosteroids in patients with metastases from non-small cell lung cancer.
Evidence Level Rating: 2 (Good)
Central nervous system metastases are highly prevalent in patients with ALK gene mutations driving advanced non-small cell lung cancer despite existing treatments with ALK-targeted tyrosine kinase inhibitors (TKIs). Alectinib is a second-generation ALK-TKI with very high blood-brain barrier penetration rates and has demonstrated efficacy in patients with CNS metastases. Data has been limited, however, in patients who are symptomatic or unstable from their disease. This multicenter retrospective analysis included 65 patients with brain metastases (BM) or leptomeningeal metastases (LM) undergoing alectinib treatment, subgrouped into 3 cohorts. Cohort 1 (n=20) was comprised of ALK-TKI-naive patients, cohort 2 (n=32) included patients with intracranial progression ± extracranial progression after treatment with crizotinib, and cohort 3 (n=13) included patients with CNS-limited disease following treatment with other second-generation ALK-TKIs (ceritinib, CT707, WX-0593). Of these patients, most had uncontrolled CNS metastases before treatment with alectinib (cohort 1: n=19, cohort 2: n= 30, cohort 3: n=12). Overall objective response rates (o-ORR), overall disease control rates and tumor shrinkage rates in CNS target lesions were recorded. For the overall population and patients with uncontrolled CNS metastases, similar intracranial response in CNS target lesions was observed: cohort 1: 81.8% and 80%; cohort 2: 76.5% and 86.7%; cohort 3: 42.8% and 33.3%. Significant improvement in CNS-related symptoms was noted in 75% (6/8), 78.6% (11/14), and 83.3% (5/6), respectively, in these cohorts. A significant decrease in the number of patients requiring mannitol or corticosteroids was found following treatment with alectinib (P<0.001), in addition to a steep decline in the number of patients with ECOG score ≥2 points before and after the administration of alectinib (P=0.003). Overall, alectininb may be effective in reducing lesion and symptom burden in non-small cell lung cancer patients with CNS metastases, but further investigation with larger sample sizes is necessary.
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