EML4-ALK Fusion Detected by RT-PCR Confers Similar Response to Crizotinib as Detected by FISH in Patients with Advanced Non-Small-Cell Lung Cancer

J Thorac Oncol. 2015 Nov;10(11):1546-52. doi: 10.1097/JTO.0000000000000668.

Abstract

Introduction: Reverse transcriptase polymerase chain reaction (RT-PCR) assay has been proved to have high sensitivity and specificity to detect anaplastic lymphoma kinase (ALK) rearrangements. The aim of this study was to investigate the response to crizotinib in patients of advanced non-small-cell lung cancer (NSCLC) with ALK rearrangements detected by RT-PCR.

Methods: Only patients with advanced NSCLC who had their ALK rearrangement status detected by RT-PCR were included in this analysis. The utility of RT-PCR and fluorescence in situ hybridization (FISH) assay were compared in patients who were treated with crizotinib based on their positive ALK rearrangements.

Results: One thousand ten patients were included in this study. Among them, 104 patients were ALK RT-PCR positive and 53 of them received crizotinib treatment. Among 255 tumors simultaneously analyzed by FISH and RT-PCR, the latter successfully detected all the 25 tumors with arrangements, including two cases that were missed by FISH. The overall response rate and median progression-free survival of the 53 patients with ALK rearrangements who received crizotinib treatment were 60.4% (95% confidence interval [CI], 47.2-73.6) and 8.4 months (95% CI, 6.75-10.05), respectively, which were similar to the 21 patients detected by FISH with overall response rate of 57.1% (95% CI, 33.3-76.2; p = 0.799) and median progression-free survival of 7.4 months (95% CI, 4.43-10.38; p = 0.833) after crizotinib treatment. Interestingly, there were two patients responded to crizotinib had their ALK rearrangement detected by RT-PCR but not FISH.

Conclusions: RT-PCR should be considered as an alternative/supplemental approach to detect ALK fusion oncogene in NSCLC patients who might benefit from crizotinib treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Crizotinib
  • Female
  • Humans
  • In Situ Hybridization, Fluorescence / methods*
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Oncogene Proteins, Fusion / genetics*
  • Oncogene Proteins, Fusion / metabolism*
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrazoles / administration & dosage
  • Pyrazoles / therapeutic use*
  • Pyridines / administration & dosage
  • Pyridines / therapeutic use*
  • Reverse Transcriptase Polymerase Chain Reaction / methods*
  • Survival Analysis
  • Young Adult

Substances

  • EML4-ALK fusion protein, human
  • Oncogene Proteins, Fusion
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyridines
  • Crizotinib