A selective ALK inhibitor in ALK-rearranged patients

摘要

ALK was first identified as a fusion protein with nucleophosmin (NPM-ALK) in CD30(kil)-anaplastic lymphoma.1 Soda and colleagues2 discovered the EML4-ALK fusion protein in 6-7% (five of 75) of patients with non-small-cell lung cancer (NSCLC) and showed that EML4-ALK protein was oncogenic in preclinical models. A phase 1 study3 of PFO2341O66 (crizotinib), a small molecule inhibitor of MET, ALK, and ROS1, enrolled predominantly patients with ALK-rearranged NSCLC and showed an objective response of 60-8% (87 of 143) and median progression-free survival of 9-7 months. A phase 3 randomised study4 further showed the superior progression-free survival of crizotinib over docetaxel or pemetrexed chemotherapy (median progression-free survival 7-7 months vs 3-0 months, hazard ratio 0-49).