Clinicopathologic characteristics and therapeutic responses of Chinese patients with non-small cell lung cancer who harbor an anaplastic lymphoma kinase rearrangement.

Sha Fu,Hai-Yun Wang,Ma-Yan Huang,Jian-Yong Shao,Ling Deng,Xiao Zhang,Fang Wang,Zu-Lu Ye

doi:10.1186/s40880-015-0032-8

Abstract

IntroductionThe rearrangement of the anaplastic lymphoma kinase (ALK) gene accounts for approximately 1%–6% of lung adenocarcinoma cases and defines a molecular subgroup of tumors characterized by clinical sensitivity to ALK inhibitors such as crizotinib. This study aimed to identify the relationship between ALK rearrangement and the clinicopathologic characteristics of non-small cell lung cancer (NSCLC) and to analyze the therapeutic responses of crizotinib and conventional chemotherapy to ALK rearrangement in NSCLC patients.MethodsA total of 487 lung cancer patients who underwent testing for ALK rearrangement in our department were included in this study. ALK rearrangement was examined by using fluorescence in situ hybridization (FISH) assay.ResultsAmong the 487 patients, 44 (9.0%) were diagnosed with ALK rearrangement by using FISH assay. In 123 patients with adenocarcinoma who were non-smokers and of a young age (≤58 years old), the frequency of ALK rearrangement was 20.3% (25/123). Short overall survival (OS) was associated with non-adenocarcinoma tumor type (P = 0.006), poorly differentiated tumors (P = 0.001), advanced-stage tumors (P < 0.001), smoking history (P = 0.008), and wild-type epidermal growth factor receptor (EGFR) (P = 0.008). Moreover, patients with poorly differentiated and advanced-stage tumors had a shorter time to cancer progression compared with those with well differentiated (P = 0.023) and early-stage tumors (P = 0.001), respectively.ConclusionsALK-rearranged NSCLC tends to occur in younger individuals who are either non-smokers or light smokers with adenocarcinoma. Patients with ALK rearrangement might benefit from ALK inhibitor therapy.

Highlights

The rearrangement of the anaplastic lymphoma kinase (ALK) gene accounts for approximately 1%–6% of lung adenocarcinoma cases and defines a molecular subgroup of tumors characterized by clinical sensitivity to ALK inhibitors such as crizotinib
The echinoderm microtubule-associated protein like 4 (EML4)-ALK in non-small cell lung cancer (NSCLC) was first discovered as an oncogenic driver gene in 2007; the EML4-ALK fusion gene was generated by an inversion in the short arm of chromosome 2 [6]
Patients with ALK rearrangement are highly sensitive to crizotinib, an oral tyrosine kinase inhibitor (TKI) of the c-Met proto-oncogene (c-Met), ALK, and ros oncogene 1 (ROS1) genes

Summary

Introduction

The rearrangement of the anaplastic lymphoma kinase (ALK) gene accounts for approximately 1%–6% of lung adenocarcinoma cases and defines a molecular subgroup of tumors characterized by clinical sensitivity to ALK inhibitors such as crizotinib. This study aimed to identify the relationship between ALK rearrangement and the clinico‐ pathologic characteristics of non-small cell lung cancer (NSCLC) and to analyze the therapeutic responses of crizotinib and conventional chemotherapy to ALK rearrangement in NSCLC patients. A randomized phase III study reported that, in the subgroup of ALK-rearranged NSCLC, patients treated with crizotinib showed higher response rate and longer progression-free survival (PFS) compared with those treated with the standard second-line chemotherapies (docetaxel or pemetrexed) [14]. Other studies showed dramatic clinical benefits associated with crizotinib in patients with ALK-rearranged NSCLC [15, 16]

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