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Review
. 2023 May 23;12(2):LMT59.
doi: 10.2217/lmt-2022-0018. eCollection 2023 Jun.

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

Daniel Samacá-Samacá  1 , Laura Prieto-Pinto  2 , Andrés Yepes Peréz  3 , Carolina Valderrama  1 , Fabián Hernández  1
Affiliations
Review

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

Daniel Samacá-Samacá et al. Lung Cancer Manag. .

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.

Keywords: anaplastic lymphoma kinase; carcinoma; neoplasm metastasis; network meta-analysis; non-small-cell lung.

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.

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Conflict of interest statement

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Figures

Figure 1.
Figure 1.. Flow diagram for the evidence identification and selection process.
Figure 2.
Figure 2.. Risk of bias assessment.
(A) Risk of bias summary. (B) Risk of bias graph. All studies included in this assessment were open-label studies; however, considering the objective nature of the outcomes and assessment by independent reviewers, participants' knowledge of the allocation group was judged not to affect the study results.
Figure 3.
Figure 3.. Network geometry and forest plot for overall survival and progression-free survival comparing alectinib 600 mg with the other ALK inhibitors.
(A) Network geometry for OS. (B) Forest plot for OS for alectinib 600 mg compared to other ALK inhibitors. (C) Network geometry for PFS. (D) Forest plot for PFS for alectinib 600 mg compared to other ALK inhibitors. HR: Hazard ratio; OS: Overall survival; PFS: Progression-free survival.
Figure 4.
Figure 4.. Network geometry and forest plot for progression-free survival comparing alectinib 600 mg with the other ALK inhibitors among subgroups with/without CNS metastasis at baseline.
(A) Network geometry for progression-free survival of patients with CNS metastasis at baseline. (B) Forest plot for PFS for alectinib 600 mg compared to other ALK inhibitors among patients with CNS metastasis at baseline. (C) Network geometry for PFS of patients without CNS metastasis at baseline. (D) Forest plot for PFS for alectinib 600 mg compared to other ALK inhibitors among patients without CNS metastasis at baseline. HR: Hazard ratio; PFS: Progression-free survival.
Figure 5.
Figure 5.. Network geometry and forest plot for serious adverse events comparing alectinib 600 mg with the other ALK inhibitors.
(A) Geometry for the network for SAEs. (B) Forest plot for SAEs for alectinib 600 mg compared to other ALK inhibitors. RR: Relatvie risk; SAE: Serious adverse event.
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