Abstract
Anaplastic lymphoma kinase (alk) is an oncogenic driver in non-small-cell lung cancer (nsclc). Chromosomal rearrangements involving the ALK gene occur in up to 4% of nonsquamous nsclc patients and lead to constitutive activation of the alk signalling pathway. ALK-positive nsclc is found in relatively young patients, with a median age of 50 years. Patients frequently have brain metastasis. Targeted inhibition of the alk pathway prolongs progression-free survival in patients with ALK-positive advanced nsclc. The results of several recent clinical trials confirm the efficacy and safety benefit of crizotinib and ceritinib in this population. Canadian oncologists support the following consensus statement: All patients with advanced nonsquamous nsclc (excluding pure neuroendocrine carcinoma) should be tested for the presence of an ALK rearrangement. If an ALK rearrangement is present, treatment with a targeted alk inhibitor in the first-line setting is recommended. As patients become resistant to first-generation alk inhibitors, other treatments, including second-generation alk inhibitors can be considered.
Highlights
Standard first-line systemic treatment for advanced nonsmall-cell lung cancer is chemotherapy with a 2-drug combination including a platinum compound and a non-platinum drug
The most common is a rearrangement resulting in a small inversion within chromosome 2p, leading to the expression of a chimeric tyrosine kinase in which the N-terminal half of the echinoderm microtubule-associated protein-like 4 (EML4) is fused to the intracellular kinase domain of anaplastic lymphoma kinase (ALK)
The single-arm phase ii ascend-2 trial evaluated the efficacy of ceritinib in patients with advanced ALK-positive nsclc who had progressed on both standard chemotherapy and crizotinib
Summary
Standard first-line systemic treatment for advanced nonsmall-cell lung cancer (nsclc) is chemotherapy with a 2-drug combination including a platinum compound and a non-platinum drug. If an ALK rearrangement is present, treatment with a targeted alk inhibitor in the first-line setting is recommended. Testing for ALK gene rearrangements should be performed in all patients eligible for targeted therapy at time of diagnosis of advanced incurable nonsquamous nsclc in which a component of adenocarcinoma is noted or suspected[12].
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