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

Date 24 November 2018
Event ESMO Asia 2018 Congress
Session Poster display - Cocktail
Topics Anticancer Agents
Personalised/Precision Medicine
Thoracic Malignancies
Presenter Xiaoyan Liu
Citation Annals of Oncology (2018) 29 (suppl_9): ix150-ix169. 10.1093/annonc/mdy425
Authors X. Liu1, M. Chen2, Y. Xu2, J. Zhao3, W. Zhong3, M. Wang2
  • 1Deparment Of Pulmonary Medicine, Lung Cancer Centre, PUMCH, 100730 - Beijing/CN
  • 2Deparment Of Pulmonary Medicine, Lung Cancer Centre, PUMCH, beijing/CN
  • 3Deparment Of Pulmonary Medicine, Lung Cancer Centre, PUMCH, Beijing/CN

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.

Editorial acknowledgement

Clinical trial identification

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.