Canadian consensus: inhibition of ALK-positive tumours in advanced non-small-cell lung cancer

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Anaplastic lymphoma kinase (ALK) is an oncogenic driver in a subset of non-small cell lung cancer (NSCLC).
• ALK gene rearrangements occur in up to 4% of nonsquamous NSCLC, leading to pathway activation, and are more common in younger patients with frequent brain metastases.
• Targeted inhibition of the ALK pathway has shown efficacy in ALK-positive advanced NSCLC.

Purpose of the Study:

• To summarize the role of ALK rearrangements in NSCLC.
• To present evidence supporting targeted ALK inhibition.
• To provide recommendations for ALK testing and treatment in advanced NSCLC.

Main Methods:

• Review of recent clinical trials on ALK inhibitors (crizotinib, ceritinib).
• Analysis of patient demographics and metastatic patterns in ALK-positive NSCLC.
• Development of a consensus statement for Canadian oncologists.

Main Results:

• Targeted ALK inhibition prolongs progression-free survival in ALK-positive advanced NSCLC.
• Crizotinib and ceritinib demonstrate efficacy and safety benefits.
• ALK rearrangements are a targetable biomarker in NSCLC.

Conclusions:

• All patients with advanced nonsquamous NSCLC should be tested for ALK rearrangements.
• First-line treatment with ALK inhibitors is recommended for patients with ALK rearrangements.
• Second-generation ALK inhibitors should be considered for patients who develop resistance to first-generation therapies.