Crizotinib efficacy in advanced non-squamous NSCLC patients with ALK or ROS1 rearrangement

Sci Rep. 2021 Oct 22;11(1):20939. doi: 10.1038/s41598-021-00309-3.

Abstract

In patients with advanced non-small cell lung cancer (NSCLC), comprehensive genetic diagnostics is currently carried out in order to qualify for molecularly targeted therapies and immunotherapy. The aim of the study was to assess the usefulness of the reverse transcriptase (RT-PCR) method in the diagnosis of gene rearrangements, the effectiveness of EGFR, ALK, ROS1, and PD-L1 inhibitors in first-line treatment in NSCLC patients. We enrolled 95 non-squamous NSCLC patients with known status of EGFR, ALK, ROS1, MET and RET genes and PD-L1 protein expression. We used the real time PCR, fluorescence in situ hybridization (FISH), immunohistochemistry (IHC) and RT-PCR techniques for determination of predictive factors. In patients with ALK and ROS1 genes alteration, the median overall survival was 34 months in crizotinib treated patients and 6 months in patients who received chemotherapy (HR = 0.266, p = 0.0056). The risk of death was lower in patients treated with molecularly targeted therapies or immunotherapy compared to patients with predictive factors without personalized treatment (HR = 0.265, 95% CI 0.116-0.606) and to patient without predictive factors who received chemotherapy (HR = 0.42, 95% CI 0.162-1.09). Diagnosis of predictive factors and implementation of personalized treatment are key to prolonging the survival in advanced NSCLC patients.

MeSH terms

  • Aged
  • Anaplastic Lymphoma Kinase / metabolism*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Crizotinib / therapeutic use*
  • Female
  • Humans
  • Immunohistochemistry / methods
  • Immunotherapy / methods
  • In Situ Hybridization, Fluorescence / methods
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism*
  • Male
  • Protein Kinase Inhibitors / therapeutic use*
  • Protein-Tyrosine Kinases / metabolism*
  • Proto-Oncogene Proteins / metabolism*

Substances

  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins
  • Crizotinib
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • Protein-Tyrosine Kinases
  • ROS1 protein, human