Future of ALK inhibition in non-small-cell lung cancer

Progress in defining molecular targets of oncogenesis and drugs to inhibit cancer growth in specific populations has led to augmented outcomes for patients and new expectations in the development of treatments. The EML4–ALK fusion protein was identified in patients with non-small-cell lung cancer (NSCLC) in 2007. 1 Soda M Choi YL Enomoto M et al. Identification of the transforming EML4–ALK fusion gene in non-small-cell lung cancer. Nature. 2007; 448: 561-566 Crossref PubMed Scopus (4263) Google Scholar Rearrangements in the ALK gene lead to constitutive signalling, triggering transforming properties. Up to now, two drugs have been approved by the US Food and Drug Administration for ALK-rearranged NSCLC—crizotinib and ceritinib. Safety and activity of alectinib against systemic disease and brain metastases in patients with crizotinib-resistant ALK-rearranged non-small-cell lung cancer (AF-002JG): results from the dose-finding portion of a phase 1/2 studyAlectinib was well tolerated, with promising antitumour activity in patients with ALK-rearranged NSCLC resistant to crizotinib, including those with CNS metastases. On the basis of activity, tolerability, and pharmacokinetic data, we chose alectinib 600 mg twice a day as the recommended dose for phase 2. Full-Text PDF Correction to Lancet Oncol 2014; 15: 1047–48Reckamp KL. Future of ALK inhibition in non-small-cell lung cancer. Lancet Oncol 2014; 15: 1047–48—In this Comment, the fourth sentence of the second paragraph should read “Crizotinib was superior to chemotherapy as second-line treatment for ALK-positive NSCLC, with similar response rate and progression-free survival to the phase 1 trial.3”. This correction has been made as of Sept 29, 2014. Full-Text PDF