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Review

Canadian Perspectives: Update on Inhibition of ALK-Positive Tumours in Advanced Non-Small-Cell Lung Cancer

1
BC Cancer–Vancouver Centre, Vancouver, BC, Canada
2
William Osler Health System, University of Toronto, Brampton, ON, Canada
3
Sir Mortimer B. Davis Jewish General Hospital, McGill University, Montreal, QC, Canada
4
Centre hospitalier de l’Université de Montréal, Montreal, QC, Canada
5
Tom Baker Cancer Centre and University of Calgary, Calgary, AB, Canada
6
Mount Sinai Hospital, Toronto, ON, Canada
7
Cross Cancer Institute and University of Alberta, Edmonton, AB, Canada
8
Kaleidoscope Strategic, Inc., Toronto, ON, Canada
9
Royal Victoria Hospital, McGill University Health Centre, Montreal, QC, Canada
10
Juravinski Cancer Centre, McMaster University, Hamilton, ON, Canada
11
QEII Health Sciences Centre, Halifax, NS, Canada
12
BC Cancer–Vancouver Island Center, Victoria, BC, Canada
13
University Health Network, Princess Margaret Cancer Centre, Toronto, ON, Canada
14
University of Western Ontario, London, ON, Canada
*
Author to whom correspondence should be addressed.
Curr. Oncol. 2018, 25(5), 317-328; https://doi.org/10.3747/co.25.4379
Submission received: 12 July 2018 / Revised: 3 August 2018 / Accepted: 10 September 2018 / Published: 1 October 2018

Abstract

Background: Inhibition of the anaplastic lymphoma kinase (ALK) oncogenic driver in advanced non-small-cell lung carcinoma (NSCLS) improves survival. In 2015, Canadian thoracic oncology specialists published a consensus guideline about the identification and treatment of ALK-positive patients, recommending use of the ALK inhibitor crizotinib in the first line. New scientific literature warrants a consensus update. Methods: Clinical trials of ALK inhibitor were reviewed to assess benefits, risks, and implications relative to current Canadian guidance in patients with ALK-positive NSCLS. Results: Randomized phase III trials have demonstrated clinical benefit for single-agent alectinib and ceritinib used in treatment-naïve patients and as second-line therapy after crizotinib. Phase II trials have demonstrated activity for single-agent brigatinib and lorlatinib in further lines of therapy. Improved responses in brain metastases were observed for all second- and next/third-generation ALK tyrosine kinase inhibitors in patients progressing on crizotinib. Canadian recommendations are therefore revised as follows: (1) Patients with advanced nonsquamous NSCLS have to be tested for the presence of an ALK rearrangement. (2) Treatment-naïve patients with ALK-positive disease should initially be offered single-agent alectinib or ceritinib, or both sequentially. (3) Crizotinib-refractory patients should be treated with single-agent alectinib or ceritinib, or both sequentially. (4) Further treatments could include single-agent brigatinib or lorlatinib, or both sequentially. (5) Patients progressing on ALK tyrosine kinase inhibitors should be considered for pemetrexed-based chemotherapy. (6) Other systemic therapies should be exhausted before immunotherapy is considered. Summary: Multiple lines of ALK inhibition are now recommended for patients with advanced NSCLS with an ALK rearrangement.
Keywords: non-small-cell lung cancer; nsclc; anaplastic lymphoma kinase; ALK; tyrosine kinase inhibitors; tkis; cns; metastases non-small-cell lung cancer; nsclc; anaplastic lymphoma kinase; ALK; tyrosine kinase inhibitors; tkis; cns; metastases

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MDPI and ACS Style

Melosky, B.; Cheema, P.; Agulnik, J.; Albadine, R.; Bebb, D.G.; Blais, N.; Burkes, R.; Butts, C.; Card, P.B.; Chan, A.M.Y.; et al. Canadian Perspectives: Update on Inhibition of ALK-Positive Tumours in Advanced Non-Small-Cell Lung Cancer. Curr. Oncol. 2018, 25, 317-328. https://doi.org/10.3747/co.25.4379

AMA Style

Melosky B, Cheema P, Agulnik J, Albadine R, Bebb DG, Blais N, Burkes R, Butts C, Card PB, Chan AMY, et al. Canadian Perspectives: Update on Inhibition of ALK-Positive Tumours in Advanced Non-Small-Cell Lung Cancer. Current Oncology. 2018; 25(5):317-328. https://doi.org/10.3747/co.25.4379

Chicago/Turabian Style

Melosky, B., P. Cheema, J. Agulnik, R. Albadine, D.G. Bebb, N. Blais, R. Burkes, C. Butts, P.B. Card, A.M.Y. Chan, and et al. 2018. "Canadian Perspectives: Update on Inhibition of ALK-Positive Tumours in Advanced Non-Small-Cell Lung Cancer" Current Oncology 25, no. 5: 317-328. https://doi.org/10.3747/co.25.4379

APA Style

Melosky, B., Cheema, P., Agulnik, J., Albadine, R., Bebb, D. G., Blais, N., Burkes, R., Butts, C., Card, P. B., Chan, A. M. Y., Hirsh, V., Ionescu, D. N., Juergens, R., Morzycki, W., Poonja, Z., Sangha, R., Tehfe, M., Tsao, M. S., Vincent, M., ... Liu, G. (2018). Canadian Perspectives: Update on Inhibition of ALK-Positive Tumours in Advanced Non-Small-Cell Lung Cancer. Current Oncology, 25(5), 317-328. https://doi.org/10.3747/co.25.4379

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