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Volume 26
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Article

Crizotinib Inhibition of ROS1-Positive Tumours in Advanced Non-Small-Cell Lung Cancer: A Canadian Perspective

by
D.G. Bebb
1,2,*,
J. Agulnik
3,
R. Albadine
4,
S. Banerji
5,
G. Bigras
6,
C. Butts
7,8,
C. Couture
9,
J.C. Cutz
10,
P. Desmeules
9,
D.N. Ionescu
11,
N.B. Leighl
12,
B. Melosky
13,
W. Morzycki
14,15,
F. Rashid-Kolvear
16,17,
H.S. Sekhon
18,
A.C. Smith
19,20,
T.L. Stockley
19,20,
E. Torlakovic
21,22,
Z. Xu
14,15 and
M.S. Tsao
23
1
Alberta Tom Baker Canc Ctr, Calgary, AB, Canada
2
Univ Calgary, Calgary, AB, Canada
3
McGill Univ, Quebec Sir Mortimer B Davis Jewish Gen Hosp, Montreal, PQ, Canada
4
Ctr Hosp Univ Montreal, Dept Pathol, Montreal, PQ, Canada
5
Univ Manitoba, Manitoba Dept Med Oncol, Winnipeg, MB, Canada
6
Univ Alberta, Dept Lab Med & Pathol, Edmonton, AB, Canada
7
Cross Canc Inst, Edmonton, AB, Canada
8
Univ Alberta, Edmonton, AB, Canada
9
Univ Laval, Inst Univ Cardiol Pneurnol Quebec, Serv Natomopathol & Cytol, Quebec City, PQ, Canada
10
McMaster Univ, Dept Pathol & Mol Med, Hamilton Reg Lab Med Program, Ontario St Josephs Healthcare, Hamilton, ON, Canada
11
Univ British Columbia, British Columbia Dept Pathol & Lab Med, Vancouver, BC, Canada
12
Univ Toronto, Princess Margaret Canc Ctr, Toronto, ON, Canada
13
BC Canc Vancouver Ctr, Vancouver, BC, Canada
14
Nova Scotia Queen Elizabeth II Hlth Sci Ctr, Halifax, NS, Canada
15
Dalhousie Univ, Halifax, NS, Canada
16
Univ Calgary, Cumming Sch Med, Dept Pathol & Lab Med, Calgary, AB, Canada
17
Calgary Lab Serv, Calgary, AB, Canada
18
Univ Ottawa, Dept Pathol & Lab Med, Ottawa, ON, Canada
19
Univ Hlth Network, Dept Clin Lab Genet, Lab Med Program, Toronto, ON, Canada
20
Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada
21
Saskatchewan Hlth Author, Saskatchewan Dept Pathol & Lab Med, Saskatoon, SK, Canada
22
Univ Saskatchewan, Saskatoon, SK, Canada
23
Princess Margaret Canc Ctr, Dept Lab Med & Pathobiol, Toronto, ON, Canada
 
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*
Author to whom correspondence should be addressed.
Curr. Oncol. 2019, 26(4), 551-557; https://doi.org/10.3747/co.26.5137
Submission received: 11 May 2019 / Revised: 2 June 2019 / Accepted: 5 July 2019 / Published: 1 August 2019

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 nsclc. 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.
Keywords: ROS1; oncogenic drivers; non-small-cell lung cancer, advanced; nsclc, advanced; targeted therapy; crizotinib; molecular testing; nsclc, nonsquamous ROS1; oncogenic drivers; non-small-cell lung cancer, advanced; nsclc, advanced; targeted therapy; crizotinib; molecular testing; nsclc, nonsquamous

Share and Cite

MDPI and ACS Style

Bebb, D.G.; Agulnik, J.; Albadine, R.; Banerji, S.; Bigras, G.; Butts, C.; Couture, C.; Cutz, J.C.; Desmeules, P.; Ionescu, D.N.; et al. Crizotinib Inhibition of ROS1-Positive Tumours in Advanced Non-Small-Cell Lung Cancer: A Canadian Perspective. Curr. Oncol. 2019, 26, 551-557. https://doi.org/10.3747/co.26.5137

AMA Style

Bebb DG, Agulnik J, Albadine R, Banerji S, Bigras G, Butts C, Couture C, Cutz JC, Desmeules P, Ionescu DN, et al. Crizotinib Inhibition of ROS1-Positive Tumours in Advanced Non-Small-Cell Lung Cancer: A Canadian Perspective. Current Oncology. 2019; 26(4):551-557. https://doi.org/10.3747/co.26.5137

Chicago/Turabian Style

Bebb, D.G., J. Agulnik, R. Albadine, S. Banerji, G. Bigras, C. Butts, C. Couture, J.C. Cutz, P. Desmeules, D.N. Ionescu, and et al. 2019. "Crizotinib Inhibition of ROS1-Positive Tumours in Advanced Non-Small-Cell Lung Cancer: A Canadian Perspective" Current Oncology 26, no. 4: 551-557. https://doi.org/10.3747/co.26.5137

APA Style

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), 551-557. https://doi.org/10.3747/co.26.5137

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