Effectiveness and prognostic factors of first-line crizotinib treatment in patients with ROS1-rearranged non-small cell lung cancer: A multicenter retrospective study

Lung Cancer. 2020 Sep;147:130-136. doi: 10.1016/j.lungcan.2020.07.016. Epub 2020 Jul 16.

Abstract

Introduction: ROS1 rearrangements are seen in 1-2 % of non-small cell lung cancer (NSCLC) patients. The aim of this study was to determine the effectiveness of crizotinib as first-line treatment in patients with ROS1 rearranged NSCLC.

Methods: The data of 56 patients with ROS1-rearranged advanced NSCLC who received first-line crizotinib treatment from 5 hospitals in China were retrospectively reviewed. The clinical characteristics, outcomes of first-line crizotinib therapy and prognostic factors were evaluated. In addition, mechanisms of resistance to crizotinib were analyzed in a cohort of crizotinib-resistant patients.

Results: The median age of the cohort was 53.0 years and most patients (91.1 %) had adenocarcinomas. The median progression free survival (mPFS) after first-line crizotinib therapy was 23.0 months, and the median overall survival (mOS) was 60.0 months. In the univariate analysis, mPFS was significantly shorter in female patients compared to males (12.0 months versus 24.0 months; p = 0.015) and in patients with >2 baseline metastatic organ involvement compared to those with ≤2 baseline metastatic organ involvement (4.0 months vs 24.0 months; p < 0.001).In addition, the mOS was significantly shorter in patients with >2 baseline metastatic organ involvement relative to that in patients with ≤2 baseline metastatic organ involvement (6.0 months vs 60.0 months; p < 0.001). Multivariable analysis further showed that >2 baseline metastatic organ involvement was the only independent prognostic factor of PFS (p = 0.008). Four out of 8 patients (50 %) with crizotinib resistance harbored a G2032R mutation in the ROS1 kinase domain.

Conclusions: First-line crizotinib treatment is beneficial in Chinese patients with ROS1-rearranged advanced NSCLC. Resistance to crizotinib correlated with the G2032R mutation in the ROS1 kinase domain.

Keywords: Crizotinib; Effectiveness; First-line treatment; Non-small cell lung cancer; Prognostic factors; Resistance mechanisms.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • China
  • Crizotinib / therapeutic use
  • Female
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Male
  • Middle Aged
  • Prognosis
  • Protein Kinase Inhibitors / therapeutic use
  • Protein-Tyrosine Kinases / genetics
  • Proto-Oncogene Proteins / genetics
  • Retrospective Studies

Substances

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