First-Line Anaplastic Lymphoma Kinase (ALK) Inhibitors for ALK-Positive Lung Cancer in Asian Populations: Systematic Review and Network Meta-Analysis.

Kuan-Li Wu,Hsiao-Ling Chen,Hsiu-Mei Chang,Jen-Yu Hung,Inn-Wen Chong,Chih-Jen Yang,Yong-Chieh Chang,Yu-Chen Tsai,Yu-Kang Tu,Ying-Ming Tsai,Tai-Huang Lee,Cheng-Hao Chuang

doi:10.3390/jcm10194376

Abstract

Various anaplastic lymphoma kinase inhibitors (ALKIs) have been approved for first-line use in treating anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC). To date, no head-to-head comparison of these newer generation ALKIs has been made, and different efficacies of ALKIs may present across ethnicity. This study aims to compare newer generation ALKIs for treatment efficacy in Asian groups using network meta-analysis. Phase II/III trials that enrolled treatment-naïve Asian ALK-rearranged NSCLC patients treated by ALKIs were included. Progression-free survival (PFS) and overall response rate (ORR) of each trial were extracted as indicators of drug efficacy. Surfaces under cumulative ranking curves (SUCRAs) were calculated as a numeric presentation of the overall ranking associated with each agent. After a systematic literature review, six phase III clinical trials were included. Our results showed that newer generation ALKIs, such as alectinib, brigatinib, ensartinib, and lorlatinib, all demonstrated superior efficacy to crizotinib. Among those, ensartinib exhibited the best overall SUCRA value and ranked first among all agents. According to our network meta-analysis, ensartinib may currently be the most effective first-line treatment for Asian patients with ALK-positive NSCLC. However, this conclusion needs further validation by a larger scale of clinical trials or posthoc analysis of Asian populations. Moreover, in our comparison, low-dose alectinib (300 mg twice daily) exhibited an efficacy profile similar to a higher dose regimen in Asian populations.

Highlights

In 2020, lung cancer accounted for 1.8 million deaths globally, ranking first among all causes of cancer death [1]
The search terms used in the search strategy included non-small cell lung cancer (NSCLC), anaplastic lymphoma kinase (ALK) inhibitors, and tyrosine kinase inhibitors
Since the results were robust, no trials have focused on the efficacy of newer anaplastic lymphoma kinase inhibitors (ALKIs), such as alectinib, brigatinib lorlatinib, and ensartinib, compared with chemotherapy

Summary

Introduction

In 2020, lung cancer accounted for 1.8 million deaths globally, ranking first among all causes of cancer death [1]. Among all forms of lung cancer, 85% of cases are histologically sorted as non-small cell lung cancer (NSCLC) and 15% as small cell lung cancer (SCLC). Interpatient heterogeneity for genetic alteration is well recognized. Some of these so-called targetable driver mutations have been linked to the susceptibility of molecular-targeted therapy, creating a new era for lung cancer treatment [4]. Seven targetable genetic alterations in lung cancer have been listed in the latest National Comprehensive Cancer Network (NCCN) guidelines. Such genetic alterations exist exclusively among NSCLC patients [5]

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