Crizotinib: From discovery to accelerated development to front-line treatment

Abstract

Non-small-cell lung cancer (NSCLC) is associated with a poor prognosis and low survival rates, providing a strong rationalefor the development of new treatment options. The discovery of ALK gene rearrangements in a subset of NSCLCspecimens and the identification and development of the first-in-class ALK inhibitor crizotinib provided a personalisedtreatment option for patients with advanced ALK-positive NSCLC. Crizotinib demonstrated rapid and durable responsesin advanced ALK-positive NSCLC patients in phase I and II studies, leading to accelerated FDA approval. Subsequentevaluation in phase III studies showed that crizotinib improved progression-free survival compared with platinum-baseddoublet chemotherapy in previously untreated patients and compared with pemetrexed or docetaxel in previously treatedpatients. Crizotinib was shown to have an acceptable safety profile and also to improve quality of life and symptomscores. Overall, crizotinib has been shown to provide a valuable first-and second-line treatment option and is now thefirst-line standard of care for patients with advanced ALK-positive NSCLC.