Gandhi L, et al. – Alectinib, a central nervous system (CNS)–active anaplastic lymphoma kinase(ALK) inhibitor was assessed for its efficacy in central nervous system metastases in crizotinib–resistant ALK–positive non–small–cell lung cancer (NSCLC). Regardless of the assessment criteria used, for this group of patients, alectinib demonstrated promising efficacy in the CNS.

Methods

• Patients aged ≥18 years who had previously received crizotinib were incorporated in both studies.
• Researchers performed NP28761 in North America.
• It was noted that NP28673 was a global study.
• 600 mg oral alectinib was administered in all patients twice daily.
• These individuals had baseline CNS imaging.
• An independent review committee delineated CNS response for those with baseline CNS metastases.

Results

• By Response Evaluation Criteria in Solid Tumours (RECIST), baseline measurable CNS disease was identified in 50 patients and by Response Assessment in Neuro-Oncology high-grade glioma (RANO-HGG) it was determined in 43.
• Furthermore, CNS objective response rate was 64.0% by RECIST (95% confidence interval [CI]: 49.2–77.1; 11 CNS complete responses [CCRs]) and 53.5% by RANO-HGG (95% CI: 37.7–68.8; eight CCRs).
• With consistent estimates of median duration of 10.8 months with RECIST and 11.1 months with RANO-HGG, CNS responses were durable.
• They observed CNS progression according to one criteria but not the other (92% concordance rate) in only three (8%), among the 39 patients with measurable CNS disease by both RECIST and RANO-HGG.