{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["25(5)"],"submitter":["Melosky B"],"pubmed_abstract":["<h4>Background</h4>Inhibition 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 <i>ALK-</i>positive patients, recommending use of the alk inhibitor crizotinib in the first line. New scientific literature warrants a consensus update.<h4>Methods</h4>Clinical trials of alk inhibitor were reviewed to assess benefits, risks, and implications relative to current Canadian guidance in patients with <i>ALK-</i>positive nsclc.<h4>Results</h4>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:■ Patients with advanced nonsquamous nsclc have to be tested for the presence of an <i>ALK</i> rearrangement.■ Treatment-naïve patients with <i>ALK-</i>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.<h4>Summary</h4>Multiple lines of alk inhibition are now recommended for patients with advanced nsclc with an <i>ALK</i> rearrangement."],"journal":["Current oncology (Toronto, Ont.)"],"pagination":["317-328"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6209554"],"repository":["biostudies-literature"],"pubmed_title":["Canadian perspectives: update on inhibition of <i>ALK</i>-positive tumours in advanced non-small-cell lung cancer."],"pmcid":["PMC6209554"],"pubmed_authors":["Agulnik J","Blais N","Chan AMY","Bebb DG","Morzycki W","Vincent M","Juergens R","Albadine R","Tsao MS","Tehfe M","Burkes R","Poonja Z","Hirsh V","Melosky B","Butts C","Ionescu DN","Cheema P","Sangha R","Card PB","Xu Z","Liu G"],"additional_accession":[]},"is_claimable":false,"name":"Canadian perspectives: update on inhibition of <i>ALK</i>-positive tumours in advanced non-small-cell lung cancer.","description":"<h4>Background</h4>Inhibition 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 <i>ALK-</i>positive patients, recommending use of the alk inhibitor crizotinib in the first line. New scientific literature warrants a consensus update.<h4>Methods</h4>Clinical trials of alk inhibitor were reviewed to assess benefits, risks, and implications relative to current Canadian guidance in patients with <i>ALK-</i>positive nsclc.<h4>Results</h4>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:■ Patients with advanced nonsquamous nsclc have to be tested for the presence of an <i>ALK</i> rearrangement.■ Treatment-naïve patients with <i>ALK-</i>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.<h4>Summary</h4>Multiple lines of alk inhibition are now recommended for patients with advanced nsclc with an <i>ALK</i> rearrangement.","dates":{"release":"2018-01-01T00:00:00Z","publication":"2018 Oct","modification":"2024-11-05T15:17:32.854Z","creation":"2019-03-27T00:08:37Z"},"accession":"S-EPMC6209554","cross_references":{"pubmed":["30464681"],"doi":["10.3747/co.25.4379"]}}