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

B. Melosky, P. Cheema, J. Agulnik, R. Albadine, D. G. Bebb, N. Blais, R. Burkes, C. Butts, P. B. Card, A.M Y. Chan, V. Hirsh, D. N. Ionescu, R Juergens, W. Morzycki, Z. Poonja, R. Sangha, M. Tehfe, M. S. Tao, M. Vincent, Z. Xu, G. Liu

Abstract


Background

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 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 nsclc.

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:

  • Patients with advanced nonsquamous nsclc have to be tested for the presence of an ALKrearrangement.

  • 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.

Summary

Multiple lines of alk inhibition are now recommended for patients with advanced nsclc with an ALKrearrangement.


Keywords


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

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DOI: http://dx.doi.org/10.3747/co.25.4379






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ISSN: 1198-0052 (Print) ISSN: 1718-7729 (Online)