Thromboembolism in ALK+ and ROS1+ NSCLC patients: A systematic review and meta-analysis

Lung Cancer. 2021 Jul:157:147-155. doi: 10.1016/j.lungcan.2021.05.019. Epub 2021 May 20.

Abstract

Introduction: Increased thromboembolism (TE) has been reported in ALK+ and ROS1+ non-small cell lung cancer (NSCLC).

Materials and methods: Odds ratios (OR) and hazard ratios (HR) of TE were calculated from meta-analysis and time-to-event analysis respectively for either ALK+ or ROS1+ NSCLC patients.

Results: We identified eight studies (766 ALK+, 143 ROS1+, 2314 non-ALK+ and non-ROS1+ NSCLC patients) for the meta-analysis. For ALK+ NSCLC, the pooled OR was 2.00 (95% CI: 1.60-2.50) for total TE (TTE) by random-effects model, 2.10 (95% CI: 1.70-2.60) for venous thromboembolism (VTE), and 1.24 (95% CI: 0.80-1.91) for arterial thromboembolism (ATE). For ROS1+ NSCLC, the pooled OR was 3.08 (95% CI: 1.95-4.86) for TTE, and 3.15 (95% CI: 1.83-5.43) for VTE. Six studies (739 ALK+, 137 ROS1+, 561 EGFR+, 714 "wildtype" NSCLC patients) were included in the time-to-event analysis. The TTE incidence rate was 17.4 (95% CI: 15.3-19.5) per 100 pateint-years for ALK+ NSCLC, and 32.1 (95% CI: 24.6-39.6) per 100 patient-years for ROS1+ NSCLC with a 50 % cumulative incidence rate at year 3 of diagnosis. HR for TTE was 2.35 (95% CI: 1.90-2.92, p < 0.001) and 3.23 (95% CI: 2.40-4.34, p < 0.001) for ALK+ and ROS1+ NSCLC, respectively. Comparing ROS1+ NSCLC to ALK+ NSCLC, HR for TTE was 1.37 (95% CI: 1.05-1.79, p = 0.020).

Conclusions: ALK+ and ROS1+ NSCLC patients had an increased risk of TE. ROS1+ NSCLC had further increased risk of TE over ALK+ NSCLC.

Keywords: ALK+ NSCLC; Cumulative incidence; Deep vein thrombosis; Meta-analysis; Pulmonary embolism; ROS1+ NSCLC; Systematic review; Thromboembolism.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Carcinoma, Non-Small-Cell Lung* / complications
  • Carcinoma, Non-Small-Cell Lung* / epidemiology
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Gene Rearrangement
  • Humans
  • Lung Neoplasms* / complications
  • Lung Neoplasms* / epidemiology
  • Lung Neoplasms* / genetics
  • Protein-Tyrosine Kinases / genetics
  • Proto-Oncogene Proteins / genetics
  • Receptor Protein-Tyrosine Kinases / genetics

Substances

  • Proto-Oncogene Proteins
  • Protein-Tyrosine Kinases
  • ROS1 protein, human
  • Receptor Protein-Tyrosine Kinases