526P - Correlation between the response to critzotinib and concomitant genetic alterations in advanced lung cancer patients with ALK rearrangement

Abstract

Background: The fusion gene echinoderm microtubule-associated protein-like 4 (EML4) - anaplastic lymphoma kinase (ALK) was found to be a driver mutation in lung cancer in 2007. Crizotinib can significantly prolong a patient’s survival and improve the quality of life in patients harboring ALK fusion gene. Methods: The specimens enrolled in the study underwent next generation sequencing. The types of ALK fusion gene and contaminant mutations were identified and their correlation with crizotinib efficacy was explored. Results: 197 patients with advanced ALK-positive lung cancer received crizotinib treatment at Peking Union Medical College Hospital and Peking University Cancer Hospital from January 2013 to December 2017. After excluding cases with incomplete medical records and inadequate tissue samples, 16 cases were enrolled in the study and the specimen underwent next-generation sequencing. The main ALK fusion type was V1 fusion (37.5%); followed by V3 fusion (31.25%). No difference was found in clinical characteristics and crizotinib efficacy between patients with different types of ALK fusion genes. Patients with shorter progression free survival (PFS) have a larger number of genetic mutations (p = 0.048). According to the mutation types, three mutational signatures were identified, namely, signature A, B and C. Patients with mutation signature A have a prolonged PFS (p = 0.026). Conclusions: No association between crizotinib efficacy and types of ALK fusion variant was found. However, crizotinib efficacy was associated with mutation signature and mutation number. Legal entity responsible for the study: Peking Union Medical College Hospital. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.