Clinical management of advanced lung adenocarcinoma with ALK rearrangement: Real-world treatment outcomes and long-term survival

Abstract

Background: Anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs) have been demonstrated to be effective in ALK-rearranged, advanced lung adenocarcinoma patients. However, data from a real-world setting is very limited. The aim of the study was to: a) determine long-term survival in these patients and investigate factors associated with their prognosis; and b) analyze the clinical outcomes of patients who were sequentially treated with next-generation ALK-TKIs. Methods: ALK-rearranged, advanced lung adenocarcinoma patients who were treated with crizotinib were included between January 2013 and December 2016. Progression- free survival (PFS) and overall survival (OS) were calculated by the Kaplan-Meier method. The hazard ratio (HR) for the risk of progression or death was calculated using multivariate Cox regression model. Results: A total of 5286 patients were screened and 176 eligible patients were included. Median PFS and OS were 12.4 months (95% CI, 10.3-14.6 months) and 45.6 months (95% CI, 37.6-53.7 months), respectively. 36.3% of patients were 5-year survivors. Extrathoracic metastasis before crizotinib treatment was independently associated with worse PFS (HR, 1.77, 95% CI, 1.24-2.53, P<0.01) and OS (HR, 1.61, 95% CI, 1.02- 2.54, P=0.04). 45 patients were sequentially treated with newer-generation ALK-TKIs, obtaining a statistically longer OS (54.8 months, 95% CI, not calculable) than patients who were solely treated with crizotinib during clinical management (36.6 months, 95% CI, 29.2-43.9months, P<0.01). Conclusions: Our study provides useful information about ALK-rearranged, advanced lung adenocarcinoma patients treated with ALK-TKIs in a real-world setting.