title: FDA Approval: Alectinib for the Treatment of Metastatic, ALK-Positive Non-Small Cell Lung Cancer Following Crizotinib.
abstract: On December 11, 2015, the FDA granted accelerated approval to alectinib (Alecensa; Genentech) for the treatment of patients with anaplastic lymphoma receptor tyrosine kinase (ALK)-positive, metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib. This approval was based on two single-arm trials including 225 patients treated with alectinib 600 mg orally twice daily. The objective response rates (ORR) by an independent review committee in these studies were 38% [95% confidence interval (CI), 28-49] and 44% (95% CI, 36-53); the median durations of response (DOR) were 7.5 months and 11.2 months. In a pooled analysis of 51 patients with measurable disease in the central nervous system (CNS) at baseline, the CNS ORR was 61% (95% CI, 46-74); the CNS DOR was 9.1 months. The primary safety analysis population included 253 patients. The most common adverse reactions were fatigue (41%), constipation (34%), edema (30%), and myalgia (29%). The most common laboratory abnormalities were anemia (56%), increased aspartate aminotransferase (51%), increased alkaline phosphatase (47%), increased creatine phosphokinase (43%), hyperbilirubinemia (39%), hyperglycemia (36%), increased alanine aminotransferase (34%), and hypocalcemia (32%). Dose reductions due to adverse reactions occurred in 12% of patients, whereas 27% of patients had alectinib dosing interrupted for adverse reactions. Permanent discontinuation of alectinib due to adverse reactions occurred in only 6% of patients. With the clinically meaningful ORR and DOR as well as the safety profile observed in these trials, alectinib was determined to have a favorable benefit-risk profile for the treatment of the indicated population. Clin Cancer Res; 22(21); 5171-6. ©2016 AACR.
authors.affiliation: Office of Hematology and Oncology Products, U.S. Food and Drug Administration, Silver Spring, Maryland. erin.larkins@fda.hhs.gov.
authors.forename: Erin
authors.initials: E
authors.lastname: Larkins
authors.affiliation: Office of Hematology and Oncology Products, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Gideon M
authors.initials: GM
authors.lastname: Blumenthal
authors.affiliation: Office of Biostatistics, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Huanyu
authors.initials: H
authors.lastname: Chen
authors.affiliation: Office of Biostatistics, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Kun
authors.initials: K
authors.lastname: He
authors.affiliation: Office of Pharmaceutical Quality, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Agarwal
authors.affiliation: Office of Pharmaceutical Quality, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Gerlie
authors.initials: G
authors.lastname: Gieser
authors.affiliation: Office of Pharmaceutical Quality, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Olen
authors.initials: O
authors.lastname: Stephens
authors.affiliation: Office of Hematology and Oncology Products, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Eias
authors.initials: E
authors.lastname: Zahalka
authors.affiliation: Office of Hematology and Oncology Products, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Ringgold
authors.affiliation: Office of Hematology and Oncology Products, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Whitney
authors.initials: W
authors.lastname: Helms
authors.affiliation: Office of Translational Sciences, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Stacy
authors.initials: S
authors.lastname: Shord
authors.affiliation: Office of Translational Sciences, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Jingyu
authors.initials: J
authors.lastname: Yu
authors.affiliation: Office of Translational Sciences, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Office of Hematology and Oncology Products, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Gina
authors.initials: G
authors.lastname: Davis
authors.affiliation: Office of Hematology and Oncology Products, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Amy E
authors.initials: AE
authors.lastname: McKee
authors.affiliation: Office of Hematology and Oncology Products, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Patricia
authors.initials: P
authors.lastname: Keegan
authors.affiliation: Office of Hematology and Oncology Products, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Richard
authors.initials: R
authors.lastname: Pazdur
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D001219:Aspartate Aminotransferases / Q000378:metabolism; D002227:Carbazoles / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism; D000077547:Crizotinib; D017277:Drug Approval / Q000379:methods; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D010880:Piperidines / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011720:Pyrazoles / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D002227:Carbazoles; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D000077547:Crizotinib; D001219:Aspartate Aminotransferases; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases; C582670:alectinib