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 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. Summary Multiple lines of alk inhibition are now recommended for patients with advanced nsclc with an ALK rearrangement.
| Original language | English |
|---|---|
| Pages (from-to) | 317-328 |
| Number of pages | 12 |
| Journal | Current Oncology |
| Volume | 25 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - Oct 2018 |
| Externally published | Yes |
Bibliographical note
Funding Information:BM serves on advisory boards for Novartis, Pfizer, and Roche; JA serves on advisory boards for Novartis, Pfizer, Takeda, and Roche, and has given talks for, or served on advisory boards for, Astra-Zeneca, Boehringer Ingelheim, Bristol–Meyers Squibb, Merck, Novartis, and Pfizer; RA serves on advisory boards for Novartis, Pfizer, and Roche; DGB serves on advisory boards for Novartis, Pfizer, and Roche; NB serves on advisory boards for Takeda, No-vartis, Pfizer, and Roche; RB serves on advisory boards for Roche, Takeda, Merck, and AstraZeneca; CB serves on advisory boards for AstraZeneca, Boehringer Ingelheim, Bristol–Meyers Squibb, Merck, and Pfizer; VH serves on advisory boards for Amgen, Astra-Zeneca, Boehringer Ingelheim, Bristol–Meyers Squibb, Eli Lilly, Merck, Novartis, Roche, and Pfizer; RJ serves on advisory boards for Novartis, Pfizer, and Roche; DNI has received honoraria from, or has been part of an advisory board for, AstraZeneca, Boehringer Ingelheim, Bristol–Myers Squibb, Eli Lilly, Merck, Novartis, and Pfizer; WM serves on advisory boards for Novartis, Pfizer, and Roche; ZP has served on advisory boards for AstraZeneca, Merck, and Roche; RS serves on advisory boards for AstraZeneca, Boehringer Ingelheim, Bristol–Myers Squibb, Merck, Novartis, AbbVie, Roche, and Takeda; MT has served on advisory boards for Takeda; MST has received research funding from Roche; MV serves on advisory boards for Amgen, AstraZeneca, Bristol–Myers Squibb, Boehringer Ingelheim, Celgene, Novartis, Eli Lilly, Takeda, Taiho, Hoffman–La Roche, Pfizer, and Merck, and is a member of the speaker’s bureau for AstraZeneca, Boehringer Ingelheim, Amgen, Merck and Eli Lilly; ZX serves on the advisory board for and has received grants from Pfizer; GL serves on advisory boards for and has received honoraria from AstraZeneca, Novartis, Pfizer, Roche, Merck, AbbVie, Bristol–Myers Squibb, and Takeda, and has received grants from AstraZeneca and Roche; the remaining authors have no conflicts of interest to disclose.
Publisher Copyright:
© 2018 Multimed Inc.
ASJC Scopus Subject Areas
- Oncology
