Alectinib for treating patients with metastatic ALK-positive NSCLC: systematic review and network metanalysis

Abstract

Aim: To compare the efficacy and safety of alectinib with other ALK inhibitors in treating patients with metastatic or locally advanced ALK-positive NSCLC. Methods: A systematic literature review was conducted up to November 2021. Network meta-analyses were performed using the frequentist method (random effects). GRADE evidence profile was conducted. Results: 13 RCTs were selected. For overall survival, alectinib was found to reduce the risk of death compared with crizotinib. In progression-free survival, alectinib reduced the risk of death or progression compared with crizotinib and ceritinib. Subgroup analysis by brain metastasis at baseline showed the superiority of alectinib over crizotinib and a similar effect compared with second-and third-generation inhibitors. Alectinib showed a good safety profile compared with the other ALK inhibitors. Plain language summary This article reports the results of a systematic literature review with network meta-analysis (NMA) that aimed to compare the efficacy and safety of alectinib with other ALK inhibitors in treating patients with metastatic or locally advanced ALK-positive NSCLC. The results show that alectinib reduces the risk of death and the risk of progression compared with crizotinib. For progression-free survival, further significant reductions were observed when compared with ceritinib. For the other ALK inhibitors, no statistically significant differences were found. Subgroup analysis according to the presence of CNS metastases at baseline were consistent in showing the superiority of alectinib over crizotinib and the absence of statistically significant differences compared with second-and third-generation inhibitors. Alectinib showed a good safety profile compared with the other ALK inhibitors, reducing the frequency of adverse events (AEs) compared with ceritinib, and with no statistically significant differences compared with lorlatinib, brigatinib, ensartinib and crizotinib for the frequency of serious AEs or discontinuation of treatment due to AEs. The results of this study suggest clinically relevant insights in decision-making based on patient survival and progression-free survival. Furthermore, considering the importance of reducing the risk of intracranial progression and the need for available therapies for patients who will inevitably progress, alectinib could be considered as a first-line treatment for patients with ALK-positive NSCLC.