P3.02a-027 A Retrospective Analysis of the Efficacy and Safety of ALK Inhibitors in ALK-Positive Lung Cancer Patients: Topic: ALK Clinical

Abstract

Patients with non-small cell lung cancer (NSCLC) harboring ALK rearrangements have been shown to exhibit a good response to ALK-inhibitor treatment. However, serious adverse events are observed in some patients. Therefore, it is important to precisely evaluate severity of adverse events and treat properly. We performed a retrospective study of the efficacy and safety of ALK inhibitors in ALK-positive lung cancer patients. Between September 2013 and April 2016, 9 patients receiving ALK inhibitors in our department were analyzed. All patients gave informed consent for the use of their clinical data. The median age was 67 years (range, 54-74 years), and the histological type of cancer was adenocarcinoma in all cases. One patient had stage IIIB, four patients had stage IV and four patients had postoperative recurrence. Seven cases were fluorescence in situ hybridization (FISH) positive / immunohistochemistry (IHC) positive, and two cases were FISH positive / IHC negative. Crizotinib and alectinib were administered orally to seven and eight patients, respectively. In evaluable cases, the disease control rate was more than 80% both crizotinib and alectinib. The median progression-free survival was longer in alectinib treatment than in crizotinib treatment (133 days (range, 8-635 days) vs 51 days (range, 3-452 days)). Among 7 patients received crizotinib, the adverse events included grade 4 increased ALT and AST levels in 1, grade 3 pneumonitis in 2, grade 2 edema in 1, and grade 2 increased creatinine level in 1. Among 8 patients received alectinib, the adverse events were included grade 2 pneumonitis in 2 and grade 2 skin disorder (drug eruption) in 1. Severe adverse events such as pneumonitis and liver dysfunction were observed within 40 days, and in these cases, treatment could not be continued. Visual disorder, gastrointestinal symptoms such as nausea, vomiting and constipation were more frequent in crizotinib treatment, but these symptoms were reduced by switching from crizotinib to alectinib. Drug discontinuation rate because of adverse events was higher in crizotinib treatment than in alectinib treatment (71% vs 50%). No treatment-related death occurred. Although ALK inhibitors have therapeutic effect against ALK-positive NSCLCs, severe adverse events occur in some patients. Based on these adverse events as well as the efficacy in each agent, alectinib treatment may be recommended in first line setting for ALK-positive NSCLC patients.