Onkológia 6/2015

Treatment of ALK-rearranged non-small cell lung cancer

Lung cancer is the leading cause of cancer-related mortality that results in more than one million death each year in the world. Standard chemotherapeutic regimen for treatment of advanced and metastatic non–small cell lung cancer (NSCLC) patients includes platinumbased chemoterapy. Nowadays, histological subtype is considered as an important predictive factor in selecting from different cytotoxic drugs. The monoclonal antibody anti-VEGF bevacizumab is also indicated for the first-line treatment of advanced or metastatic nonsquammous NSCLC in combination with platinum-based chemotherapy. Testing advanced NSCLC for the presence of somatic targetable genetic alterations, including EGFR (epidermal growth factor receptor ) mutation and ALK rearrangements, which predicts responsiveness to specific targeted therapies, is a crucial factor for selecting the most appropriate treatment option for patients. Crizotinib is the firstin-class ALK TKI and it is standard therapy for patients with ALK-rearranged non-small cell lung cancer. Acquired resistance, defined as tumor progression after initial response, seems to be an inevitable consequence of this treatment approach. The tyrosine kinase inhibitors (TKI) therapy frequently induces dramatic clinical responses in molecularly defined cohorts of patients with lung cancer. Several next-generation ALK-TKI have shown promising activity in crizotinib-resistant patients. Ceritinib, alectinib and brigatinib are highly selective ALK inhibitors in crizotinib-resistant patients, including those with CNS metastases. This brief review provides an overview of ALK-rearranged NSCLC treatment, complex and heterogeneous problem of acquired resistance to TKI therapy in NSCLC, with a focus on ALK-rearranged NSCLC.

Keywords: non-small cell lung cancer, EML4-ALK, aquired resistance to crizotinib, ceritinib, alectinib.