Prospective screening for ALK: clinical features and outcome according to ALK status

Eur J Cancer. 2014 May;50(7):1239-46. doi: 10.1016/j.ejca.2014.02.001. Epub 2014 Feb 28.

Abstract

The aim of this study was to analyse the clinico-pathological characteristics and outcomes of a cohort of French patients who were prospectively screened for Anaplastic Lymphoma Kinase (ALK) rearrangement. One hundred and sixteen consecutive patients screened for ALK rearrangement to be recruited into a crizotinib registration trial were included from eight French centres. ALK rearrangement was detected by fluorescence in situ hybridization. Seventeen patients (14.6%) were positive for ALK. ALK+ patients were younger (p = 0.049) and more likely to be males (p=0.032), non- or light-smokers (p = 0.048) and without underlying respiratory disease (p=0.025) compared to ALK- patients. Thyroid-transcription factor-1 expression was present in all ALK+ tumours. ALK+ tumours tended to have lymph node and brain metastases. In multivariate analyses, gender, smoking history and N stage were independently associated with ALK status. Median overall survival (OS) was not reached for ALK+ patients and was significantly longer than for ALK- patients (hazard ratio for death for ALK- patients 2.98; 95% CI [1.29-6.90], p=0.01). French ALK+ patients present a specific phenotype. ALK rearrangement should be determined to improve OS with an effective targeted therapy.

Keywords: Adenocarcinoma; Crizotinib; EML4-ALK fusion protein; Lung neoplasms; Non-small-cell lung; Survival analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Analysis of Variance
  • Anaplastic Lymphoma Kinase
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Crizotinib
  • Disease-Free Survival
  • Female
  • Gene Rearrangement*
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Nuclear Proteins / metabolism
  • Prospective Studies
  • Protein Kinase Inhibitors / therapeutic use
  • Pyrazoles / therapeutic use
  • Pyridines / therapeutic use
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Risk Factors
  • Sex Factors
  • Smoking / adverse effects
  • Thyroid Nuclear Factor 1
  • Transcription Factors / metabolism

Substances

  • Antineoplastic Agents
  • NKX2-1 protein, human
  • Nuclear Proteins
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyridines
  • Thyroid Nuclear Factor 1
  • Transcription Factors
  • Crizotinib
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • Receptor Protein-Tyrosine Kinases