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

[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.

[学科分类] 肿瘤学

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