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

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  • 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.


  • Melosky, B
  • Cheema, P
  • Agulnik, J
  • Albadine, R
  • Bebb, DG
  • Blais, N
  • Burkes, R
  • Butts, C
  • Card, PB
  • Chan, AMY
  • Hirsh, V
  • Ionescu, DN
  • Juergens, Rosalyn
  • Morzycki, W
  • Poonja, Z
  • Sangha, R
  • Tehfe, M
  • Tsao, MS
  • Vincent, M
  • Xu, Z
  • Liu, G

publication date

  • October 2018