Chinese perspectives on clinical efficacy and safety of alectinib in patients with ALK-positive advanced non-small cell lung cancer

Abstract

The incidence of lung cancer is increasing in China, in contrast to trends in Western countries, due to the increasing numbers of smokers and high levels of air pollution. Non-small-cell lung cancer (NSCLC) is the most common form of lung cancer, accounting for approximately 85% of lung cancers. Better understanding of the pathogenesis of NSCLC has led to the identification of multiple genetic mutations and chromosomal translocations such as those in the anaplastic lymphoma kinase (ALK) gene. To facilitate the identification of treatment targets, multiple guidelines (European Society for Medical Oncology, National Comprehensive Cancer Network, and American Society of Clinical Oncology) now recommend screening for genetic factors to help guide treatment decisions. In recent years, multiple ALK inhibitors have been developed to treat NSCLC, including the first-generation tyrosine kinase inhibitor (TKI) crizotinib; second-generation TKIs such as ceritinib, ensartinib, brigatinib, and alectinib; the thirdgeneration TKI lorlatinib; and the fourth-generation TKI repotrectinib. These agents differ in structure, potency, and activity, both systemically and their effects on central nervous system (CNS) metastases. Recently, alectinib was approved in China to treat patients with locally advanced or metastatic NSCLC that were ALK+. Alectinib has demonstrated activity against NSCLC, including metastases within the CNS, with better tolerability than crizotinib. These ALK inhibitors represent significant advances in the treatment of NSCLC and yet patients will likely still exhibit disease progression. Alectinib offers greater potency with greater specificity as well as a better toxicity profile than many other TKIs that are currently available. Here, we review the role of ALK as a therapeutic target in NSCLC, the testing methods for identifying ALK-rearranged NSCLC, and the various TKIs currently being used or explored for treatment in this setting, with a focus on alectinib from a Chinese perspective.