Crizotinib inhibition of ROS1-positive tumours in advanced non-small-cell lung cancer: a Canadian perspective

  • D. G. Bebb Tom Baker Cancer Centre, University of Calgary
  • J. Agulnik Sir Mortimer B. Davis Jewish General Hospital, McGill University
  • R. Albadine Centre hospitalier de l’Université de Montréal
  • S. Banerji University of Manitoba
  • G. Bigras University of Alberta
  • C. Butts Cross Cancer Institute and University of Alberta
  • C. Couture Institut universitaire de cardiologie et de pneumologie de Québec–Université Laval
  • J. C. Cutz St. Joseph’s Healthcare, Hamilton Regional Laboratory Medicine Program, McMaster University
  • P. Desmeules Institut universitaire de cardiologie et de pneumologie de Québec-Université Laval
  • D. N. Ionescu University of British Columbia, Vancouver
  • N. B. Leighl Princess Margaret Cancer Centre, University of Toronto
  • B. Melosky British Columbia Cancer Agency, Vancouver Centre
  • W. Morzycki Queen Elizabeth II Health Sciences Centre and University of Dalhousie
  • F. Rashid-Kolvear Cumming School of Medicine, University of Calgary, Calgary Laboratory Services
  • H. S. Sekhon Medicine, University of Ottawa
  • A. C. Smith University Health Network, University of Toronto
  • T. L. Stockley University Health Network and Department of Laboratory Medicine and Pathobiology, University of Toronto
  • E. Torlakovic Saskatchewan Health Authority, University of Saskatchewan
  • Z. Xu Queen Elizabeth II Health Sciences Centre and University of Dalhousie
  • M. S. Tsao Princess Margaret Cancer Centre
Keywords: ROS1, oncogenic drivers, non-small-cell lung cancer, advanced, NSCLC, targeted therapy, crizotinib, molecular testing, nonsquamous

Abstract

The ROS1 kinase is an oncogenic driver in non-small-cell lung cancer (NSCLC). Fusion events involving the ROS1 gene are found in 1%–2% of NSCLC patients and lead to deregulation of a tyrosine kinase–mediated multi-use intracellular signalling pathway, which then promotes the growth, proliferation, and progression of tumour cells. ROS1 fusion is a distinct molecular subtype of NSCLC, found independently of other recognized driver mutations, and it is predominantly identified in younger patients (<50 years of age), women, never-smokers, and patients with adenocarcinoma histology.

    Targeted inhibition of the aberrant ros1 kinase with crizotinib is associated with increased progression-free survival (PFS) and improved quality-of-life measures. As the sole approved treatment for ROS1-rearranged NSCLC, crizotinib has been demonstrated, through a variety of clinical trials and retrospective analyses, to be a safe, effective, well-tolerated, and appropriate treatment for patients having the ROS1 rearrangement.

    Canadian physicians endorse current guidelines which recommend that all patients with nonsquamous advanced NSCLC, regardless of clinical characteristics, be tested for ROS1 rearrangement. Future integration of multigene testing panels into the standard of care could allow for efficient and cost-effective comprehensive testing of all patients with advanced NSCL. If a ROS1 rearrangement is found, treatment with crizotinib, preferably in the first-line setting, constitutes the standard of care, with other treatment options being investigated, as appropriate, should resistance to crizotinib develop.

Author Biographies

R. Albadine, Centre hospitalier de l’Université de Montréal
Department of Pathology
S. Banerji, University of Manitoba
Department of Medical Oncology
G. Bigras, University of Alberta
Department of Laboratory Medicine & Pathology
C. Couture, Institut universitaire de cardiologie et de pneumologie de Québec–Université Laval
Service d’anatomopathologie et de cytologie
J. C. Cutz, St. Joseph’s Healthcare, Hamilton Regional Laboratory Medicine Program, McMaster University
Department of Pathology and Molecular Medicine
P. Desmeules, Institut universitaire de cardiologie et de pneumologie de Québec-Université Laval
Service d’anatomopathologie et de cytologie
D. N. Ionescu, University of British Columbia, Vancouver
Department of Pathology and Laboratory Medicine
F. Rashid-Kolvear, Cumming School of Medicine, University of Calgary, Calgary Laboratory Services
Department of Pathology and Laboratory Medicine
H. S. Sekhon, Medicine, University of Ottawa
Department of Pathology and Laboratory
A. C. Smith, University Health Network, University of Toronto
Department of Clinical Laboratory Genetics, Laboratory Medicine Program, Department of Laboratory Medicine and Pathobiology
T. L. Stockley, University Health Network and Department of Laboratory Medicine and Pathobiology, University of Toronto
Department of Clinical Laboratory Genetics, Laboratory Medicine Program
E. Torlakovic, Saskatchewan Health Authority, University of Saskatchewan
Department of Pathology and Laboratory Medicine
M. S. Tsao, Princess Margaret Cancer Centre
Department of Laboratory Medicine and Pathobiology
Published
2019-08-29
How to Cite
Bebb, D. G., Agulnik, J., Albadine, R., Banerji, S., Bigras, G., Butts, C., Couture, C., Cutz, J. C., Desmeules, P., Ionescu, D. N., Leighl, N. B., Melosky, B., Morzycki, W., Rashid-Kolvear, F., Sekhon, H. S., Smith, A. C., Stockley, T. L., Torlakovic, E., Xu, Z., & Tsao, M. S. (2019). Crizotinib inhibition of ROS1-positive tumours in advanced non-small-cell lung cancer: a Canadian perspective. Current Oncology, 26(4). https://doi.org/10.3747/co.26.5137
Section
Practice Guideline