title: Osimertinib for the Treatment of Metastatic EGFR T790M Mutation-Positive Non-Small Cell Lung Cancer.
abstract: On November 13, 2015, the FDA granted accelerated approval to osimertinib (TAGRISSO; AstraZeneca), a breakthrough therapy-designated drug for the treatment of patients with metastatic EGFR T790M mutation-positive non-small cell lung cancer, as detected by an FDA-approved test, with progression on or after EGFR tyrosine kinase inhibitor therapy. Approval was based on durable tumor response rates in two single-arm, multicenter trials: the dose extension cohort of a first-in-human trial (FIH; AURA extension;n= 201) and a fixed-dose, activity-estimating trial (AURA2;n= 210). Osimertinib was administered at 80 mg orally once daily. The objective response rates (ORR) per blinded independent committee review were 57% [95% confidence interval (CI), 50-64) in AURA extension and 61% (95% CI, 54-68) in AURA2. Median duration of response (DOR) could not be estimated. Supportive efficacy data from 63 patients in the dose-finding part of the FIH trial demonstrated an ORR of 51% (95% CI, 38-64), with a median DOR of 12.4 months. Common adverse events (AE) evaluated in 411 patients included diarrhea (42%), rash (41%), dry skin (31%), and nail toxicity (25%). Grade 3 to 4 AEs occurred in 28% of patients, and 5.6% discontinued treatment due to AEs.Clin Cancer Res; 23(9); 2131-5. ©2016 AACR.
authors.affiliation: U.S. Food and Drug Administration, Silver Spring, Maryland. Sean.Khozin@fda.hhs.gov.
authors.forename: Sean
authors.initials: S
authors.lastname: Khozin
authors.affiliation: U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Chana
authors.initials: C
authors.lastname: Weinstock
authors.affiliation: U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Gideon M
authors.initials: GM
authors.lastname: Blumenthal
authors.affiliation: U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Joyce
authors.initials: J
authors.lastname: Cheng
authors.affiliation: U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Kun
authors.initials: K
authors.lastname: He
authors.affiliation: U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Luning
authors.initials: L
authors.lastname: Zhuang
authors.affiliation: U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhao
authors.affiliation: U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Rosane
authors.initials: R
authors.lastname: Charlab
authors.affiliation: U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Fan
authors.affiliation: U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Patricia
authors.initials: P
authors.lastname: Keegan
authors.affiliation: U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Richard
authors.initials: R
authors.lastname: Pazdur
mesh_terms: D000178:Acrylamides; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000814:Aniline Compounds; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D017277:Drug Approval; D064420:Drug-Related Side Effects and Adverse Reactions; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D007211:Indoles; D011743:Pyrimidines
chemical_list: D000178:Acrylamides; D000814:Aniline Compounds; D066246:ErbB Receptors; D010879:Piperazines; D047428:Protein Kinase Inhibitors; C000596361:osimertinib; D007211:Indoles; D011743:Pyrimidines; C512478:EGFR protein, human