title: Ceritinib: a Review in ALK-Positive Advanced NSCLC.
abstract: Ceritinib (Zykadia™) is an oral, selective inhibitor of the anaplastic lymphoma kinase (ALK), a receptor tyrosine kinase which, after genetic rearrangement, acts as an oncogenic driver in a proportion of non-small cell lung cancers (NSCLCs). The drug is approved in several countries worldwide for the treatment of patients with ALK-positive, advanced NSCLC who have previously received the first-generation ALK inhibitor crizotinib (indication details may vary by country). Approval was based on its clinical benefit in this setting in the phase I and II trials known as ASCEND-1 and -2. Across these noncomparative studies, 36-56 % of patients achieved a response with ceritinib (at the recommended dosage of 750 mg once daily) and the responses were durable, lasting up to a median of 10 months. Patients survived free from progression for a median of up to 7 months and had a median overall survival of up to 17 months. Moreover, efficacy outcomes in patients with brain metastases were generally consistent with those of the overall study populations. Ceritinib has an acceptable tolerability profile, with gastrointestinal issues, fatigue and liver test abnormalities being the most common adverse reactions. Thus, ceritinib is a valuable treatment option for patients with ALK-positive advanced NSCLC who have already received crizotinib therapy.
authors.affiliation: Springer, Private Bag 65901, Mairangi Bay 0754, Auckland, New Zealand. demail@springer.com.
authors.forename: Emma D
authors.initials: ED
authors.lastname: Deeks
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D013450:Sulfones / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D011743:Pyrimidines; D013450:Sulfones; C586847:ceritinib