Optimal first-line treatment for metastatic ALK+ non-small cell lung cancer—a narrative review

Abstract

Background and Objective: First-line treatment options for patients with advanced non-small cell lung cancer (aNSCLC) whose tumors harbour anaplastic lymphoma kinase (ALK) gene rearrangements have rapidly evolved from chemotherapy, to the first in class ALK-targeted tyrosine kinase inhibitor (TKI) crizotinib in 2011, and now include no fewer than five FDA-approved ALK inhibitors. However, while superiority to crizotinib has been established, head-to-head clinical trials comparing newer generation ALK inhibitors are lacking, and decisions on optimal first-line treatment must be based on analysis of the relevant trials, with attention to systemic and intracranial efficacy, toxicity profile as well as consideration of patient factors and preferences. Here we aim to synthesise findings from review of these trials and to describe options for optimal first-line treatment for ALK+ NSCLC.Methods: A literature review of relevant randomised clinical trials was undertaken using Embase database. There were no limitations to time frame or language applied.

Unraveling the Potential of ALK-Targeted Therapies in Non-Small Cell Lung Cancer: Comprehensive Insights and Future Directions

“…Studies comparing various ALK inhibitors for advanced NSCLC have highlighted distinct efficacy profiles and safety concerns associated with each medication. Examining the efficacy of crizotinib, alectinib, brigatinib, ceritinib, and lorlatinib in treating ALK+ NSCLC has provided valuable insights into their performance, safety, and unique adverse event profiles [80].…”

Analysis on the pathogenesis and treatment progress of NRG1 fusion-positive non-small cell lung cancer

“…Identifying these fusions through molecular profiling is crucial, as it can render the tumor susceptible to targeted therapeutic therapies. The potential strategy involves the use of tyrosine kinase inhibitors (TKIs) targeting the ERBB receptor family, which has demonstrated efficacy in certain cases of NRG1 fusion-positive NSCLC (50)(51)(52).…”

Commemorating the 20th anniversary of the discovery of epidermal growth factor receptor mutation in lung cancer: Translational research at its best

“…9 Now, at least four generations of ALK inhibitors are in clinical use/development. 10 Soon, the molecular classification of lung adenocarcinoma was completed, with identification of a driver event in nearly two thirds of patients. The most common driver events are KRAS, EGFR, ALK, and mesenchymal epithelial transition factor (MET); a plethora of less common but treatable alterations including RET, ROS1, HER2, BRAF V600E, and neurotropic tyrosine receptor kinase were also identified.…”

“…Anaplastic lymphoma kinase (ALK) gene rearrangement was soon identified in a subset of lung adenocarcinomas; disruption of downstream pathways with an ALK inhibitor resulted in improved clinical outcomes for patients 9 . Now, at least four generations of ALK inhibitors are in clinical use/development 10 . Soon, the molecular classification of lung adenocarcinoma was completed, with identification of a driver event in nearly two thirds of patients.…”