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. 2019 Aug;26(4):e551-e557.
doi: 10.3747/co.26.5137. Epub 2019 Aug 1.

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

D G Bebb  1 , J Agulnik  2 , R Albadine  2 , S Banerji  3 , G Bigras  1 , C Butts  1 , C Couture  2 , J C Cutz  4 , P Desmeules  2 , D N Ionescu  5 , N B Leighl  4 , B Melosky  5 , W Morzycki  6 , F Rashid-Kolvear  1   2   3   4   5   6   7 , Clin Lab  1 , H S Sekhon  4 , A C Smith  4 , T L Stockley  4 , E Torlakovic  7 , Z Xu  6 , M S Tsao  4
Affiliations

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

D G Bebb et al. Curr Oncol. 2019 Aug.

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

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Conflict of interest statement

CONFLICT OF INTEREST DISCLOSURES We have read and understood Current Oncology’s policy on disclosing conflicts of interest, and we declare the following interests: JA, SB, ACS have received personal fees from Pfizer, outside the submitted work; RA received personal fees from Pfizer during the conduct of the study; DGB received grants from Pfizer during the conduct of the study and personal fees from AstraZeneca, Roche, Bristol–Myers Squibb, Boehringer Ingelheim, Pfizer, Merck, Bayer, Lilly, and Takeda outside the submitted work; GB and WM are members of the Pfizer advisory board; CB and CC have received other consideration from Pfizer outside the submitted work; PD received grants from Pfizer during the conduct of the study and other consideration from Bayer, Bristol–Myers Squibb, AstraZeneca, and Pfizer outside the submitted work; HSS has received other consideration from Pfizer Canada, Bayer, Merck, and EMD Serono Canada outside the submitted work; TLS has received grants and personal fees from AstraZeneca and personal fees from Bristol–Myers Squibb, Janssen, Pfizer, and Novartis outside the submitted work; ET has received grants from, and been an advisory board member for, Pfizer, Bristol–Myers Squibb, Merck, AstraZeneca, Roche, and Janssen outside the submitted work; MST received grants and personal fees from Pfizer during the conduct of the study and has received grants and personal fees from AstraZeneca and Merck, and personal fees from Bristol–Myers Squibb and Bayer outside the submitted work; JCC, DNI, NBL, BM, FRK, and ZX have no conflicts to disclose.

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