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. 2020 Apr;27(2):e146-e155.
doi: 10.3747/co.27.6007. Epub 2020 May 1.

Canadian consensus: a new systemic treatment algorithm for advanced EGFR- mutated non-small-cell lung cancer

B Melosky  1 , S Banerji  2 , N Blais  3 , Q Chu  4 , R Juergens  5 , N B Leighl  6 , G Liu  6 , P Cheema  7
Affiliations

Canadian consensus: a new systemic treatment algorithm for advanced EGFR- mutated non-small-cell lung cancer

B Melosky et al. Curr Oncol. 2020 Apr.

Abstract

Background: Multiple clinical trials for the treatment of advanced EGFR-mutated non-small-cell lung cancer (nsclc) have recently been reported. As a result, the treatment algorithm has changed, and many important clinical questions have been raised:■ What is the optimal first-line treatment for patients with EGFR-mutated nsclc?■ What is preferred first-line treatment for patients with brain metastasis?■ What is the preferred second-line treatment for patients who received first-line first- or second-generation tyrosine kinase inhibitors (tkis)?■ What is the preferred treatment after osimertinib?■ What evidence do we have for treating patients whose tumours harbour uncommon EGFR mutations?

Methods: A Canadian expert panel was convened to define the key clinical questions, review recent evidence, and discuss and agree on practice recommendations for the treatment of advanced EGFR-mutated nsclc.

Results: The published overall survival results for osimertinib, combined with its central nervous system activity, have led to osimertinib becoming the preferred first-line treatment for patients with common EGFR mutations, including those with brain metastasis. Other agents could still have a role, especially when osimertinib is not available or not tolerated. Treatment in subsequent lines of therapy depends on the first-line therapy or on T790M mutation status. Treatment recommendations for patients whose tumours harbour uncommon EGFR mutations are guided mainly by retrospective and limited prospective evidence. Finally, the evidence for sequencing and combining tkis with chemotherapy, angiogenesis inhibitors, checkpoint inhibitors, and other new therapeutics is reviewed.

Conclusions: This Canadian expert consensus statement and algorithm were driven by significant advances in the treatment of EGFR-mutated nsclc.

Keywords: EGFR mutation; Non-small-cell lung cancer, advanced; acquired resistance; algorithms; mutations, common; mutations, uncommon; nsclc; sequencing.

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Conflict of interest statement

CONFLICT OF INTEREST DISCLOSURES We have read and understood Current Oncology’s policy on disclosing conflicts of interest, and we declare the following interests: BM has received honoraria for advisory board participation from Bayer, Pfizer, AstraZeneca, Boehringer Ingelheim, and Roche. SB has received honoraria for advisory board participation from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol–Myers Squibb, GlaxoSmithKline, Lilly, Merck, Novartis, Pfizer, Roche, and Takeda. NB has received honoraria for advisory board participation from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol–Myers Squibb, GlaxoSmithKline, Lilly, Merck, Novartis, Pfizer, Roche, and Takeda, and has received research funding from AstraZeneca. QC has received honoraria for advisory board participation from AbbVie, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol–Myers Squibb, Eisai, Eli Lilly, Merck, Novartis, Pfizer, Roche, and Takeda. RJ has received honoraria for advisory board participation from AstraZeneca, Bristol–Myers Squibb, Fusion, Merck, Novartis, Pfizer, Roche, and Takeda, and research funding from AstraZeneca, Bristol–Myers Squibb, and Merck. NBL is a beneficiary of institutional research funding from Guardant, Array, Novartis, Merck, and Roche; has received honoraria or travel expenses for independent continuing medical education from Roche, AstraZeneca, Merck Sharp and Dohme, and Bristol–Myers Squibb; and has acted as an advisor (compensated) for Xcovery and as a consultant for the Canadian Agency for Drugs and Technologies in Health. GL has received honoraria for advisory board participation from AstraZeneca, Roche, Pfizer, Takeda, Novartis, Merck, Bristol–Myers Squibb, Boehringer Ingelheim, and Bayer, and for providing education consulting services to AstraZeneca, Roche, emd Serono, and Takeda. GL has also received research funding from AstraZeneca, Roche, and Takeda. PC has received honoraria for advisory board participation from AstraZeneca, Boehringer Ingelheim, Roche, Pfizer, Takeda, Merck, and Bristol–Myers Squibb.

Figures

FIGURE 1
FIGURE 1
Canadian algorithm for the systemic treatment of patients with advanced EGFR-mutation positive non-small-cell lung cancer (NSCLC), from initial diagnosis of advanced disease, with confirmation of the mutation. The figure includes patients with common and uncommon mutations and with and without central nervous system metastasis. The grey-shaded area at the bottom of the algorithm represents progressive disease. Clinical trials, if available, are a first choice in all indications and all lines. aBased on FLAURA, gefitinib and erlotinib are not recommended in the first-line setting unless access to osimertinib is limited or unless they are combined with other agents.
See this image and copyright information in PMC

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