Canadian perspectives: update on inhibition of ALK-positive tumours in advanced non-small-cell lung cancer

Current oncology

B. Melosky¹  D. N. Ionescu²  R. Albadine³  R. Burkes⁴  A.M Y. Chan⁵  C. Butts⁶  N. Blais⁷  V. Hirsh⁸  P. B. Card⁹  J. Agulnik^1,10  D. G. Bebb^1,11  R Juergens^1,12  W. Morzycki^1,13  P. Cheema^1,14 

[1] BC Cancer–Vancouver Centre;BC Cancer–Vancouver Island Center;Centre hospitalier de l’Université de Montréal;Cross Cancer Institute and University of Alberta;Juravinski Cancer Centre, McMaster University;Kaleidoscope Strategic, Inc.;Mount Sinai Hospital;QEII Health Sciences Centre;Royal Victoria Hospital, McGill University Health Centre;Sir Mortimer B. Davis Jewish General Hospital, McGill University;Tom Baker Cancer Centre and University of Calgary;University Health Network, Princess Margaret Cancer Centre;University of Western Ontario;William Osler Health System, University of Toronto

关键词: Non-small-cell lung cancer;    nsclc;    anaplastic lymphoma kinase;    ALK;    tyrosine kinase inhibitors;    tkis;    cns;    metastases;   

DOI  :  10.3747/co.25.4379

学科分类：肿瘤学

来源: Multimed, Inc.

【 摘 要 】

BackgroundInhibition of the anaplastic lymphoma kinase ( alk ) oncogenic driver in advanced non-small-cell lung carcinoma ( nsclc ) 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.MethodsClinical trials of  alk  inhibitor were reviewed to assess benefits, risks, and implications relative to current Canadian guidance in patients with  ALK- positive  nsclc .ResultsRandomized 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:Patients with advanced nonsquamous  nsclc  have to be tested for the presence of an  ALK rearrangement.Treatment-naïve patients with  ALK- positive disease should initially be offered single-agent alectinib or ceritinib, or both sequentially.Crizotinib-refractory patients should be treated with single-agent alectinib or ceritinib, or both sequentially.Further treatments could include single-agent brigatinib or lorlatinib, or both sequentially.Patients progressing on  alk  tyrosine kinase inhibitors should be considered for pemetrexed-based chemotherapy.Other systemic therapies should be exhausted before immunotherapy is considered.SummaryMultiple lines of  alk  inhibition are now recommended for patients with advanced  nsclc  with an  ALK rearrangement.

【 授权许可】

Unknown