Australian consensus statement for best practice ROS1 testing in advanced non-small cell lung cancer

Pathology. 2019 Dec;51(7):673-680. doi: 10.1016/j.pathol.2019.08.006. Epub 2019 Oct 24.

Abstract

Lung cancer is the most commonly diagnosed malignancy and the leading cause of death from cancer globally. Diagnosis of advanced non-small cell lung cancer (NSCLC) is associated with 5-year relative survival of 3.2%. ROS proto-oncogene 1 (ROS1) is an oncogenic driver of NSCLC occurring in up to 2% of cases and commonly associated with younger age and a history of never or light smoking. Results of an early trial with the tyrosine kinase inhibitor (TKI) crizotinib that inhibits tumours that harbour ROS1 rearrangements have shown an objective response rate (ORR) of 72% (95% CI 58-83%), median progression free survival (PFS) of 19.3 months (95% CI 15.2-39.1 months) and median overall survival (OS) of 51.4 months (95% CI 29.3 months to not reached). Therefore, with the availability of highly effective ROS1-targeted TKI therapy, upfront molecular testing for ROS1 status alongside EGFR and ALK testing is recommended for all patients with NSCLC. We review the tissue requirements for ROS1 testing by immunohistochemistry (IHC) and fluorescent in situ hybridisation (FISH) and we present a testing algorithm for advanced NSCLC and consider how the future of pathology testing for ROS1 may evolve.

Keywords: Non-small cell lung cancer; ROS1; biomarker testing; consensus.

Publication types

  • Editorial
  • Review

MeSH terms

  • Australien
  • Biomarkers / analysis
  • Carcinoma, Non-Small-Cell Lung / diagnosis*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Crizotinib / pharmacology*
  • Gene Rearrangement
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Lung Neoplasms / diagnosis*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Protein Kinase Inhibitors / pharmacology*
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Protein-Tyrosine Kinases / genetics*
  • Protein-Tyrosine Kinases / metabolism
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins / antagonists & inhibitors
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism

Substances

  • Biomarkers
  • MAS1 protein, human
  • Protein Kinase Inhibitors
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins
  • Crizotinib
  • Protein-Tyrosine Kinases
  • ROS1 protein, human