Evolution of therapy for ALK-positive lung carcinomas: Application of third-generation ALK inhibitors in real clinical practice

Abstract

Lung cancer is currently a heterogeneous group of diseases, whose heterogeneity is determined not only by its phenotypic, but also by its genetic profile. A special place is occupied by subtypes that have driver mutations. Due to new antitumor agents – small molecule inhibitors – it has become possible to significantly increase patients’ chances of survival. The diagnostic panel most often includes mutations in the EGFR, ALK, ROS1, BRAF genes; somewhat less frequently, genetic changes in MET, KRAS, HER2, NTRK, etc. are determined. This distribution is most likely explained by the availability of appropriate inhibitors. The article provides an overview of different generations of ALK inhibitors known in the Russian Federation, among them the most famous: crizotinib, ceritinib, alectinib and lorlatinib. These drugs are included in the clinical guidelines for the treatment of ALK-positive lung carcinomas of all major oncology societies. The article describes the results of registration studies proving the advantage of ALK inhibitors over standard therapy, including the results of the CROWN study. In this study, the latest generation of ALK inhibitors, lorlatinib, demonstrates superiority over crizotinib, with a 73% reduction in the risk of progression or death and better intracranial response rates. A description of a clinical case of treatment of metastatic lung cancer using the third generation ALK inhibitor lorlatinib is provided. The drug was prescribed in the first line of therapy. The patient’s treatment outcome indicates high efficacy of lorlatinib in the first-line treatment of ALK translocation-positive lung cancer, along with low toxicity. The treatment period has already been more than 70 months and the patient continues therapy at the time of the last control. A complete response to lorlatinib therapy was recorded. During treatment, the following adverse events were recorded: hypertriglyceridemia, grade 1 toxicity, hypercholesterolemia, grade 2 toxicity, increased liver transaminases, grade 1 toxicity.