title: Applications for oncologic drugs: a descriptive analysis of the oncologic drugs advisory committee reviews.
abstract: BACKGROUND
  Despite advances in cancer research, the majority of drug applications submitted to the U.S. Food and Drug Administration (FDA) are not approved. It is important to identify the concerns of the Oncologic Drugs Advisory Committee (ODAC) from rejected applications.
  
  
  METHODS
  All applications referred to the ODAC from 2001 to 2012 were reviewed.
  
  
  RESULTS
  Of 46 applications, 31 (67%) were for full and 15 (33%) were for supplemental approval, 34 (74%) were for solid and 12 (26%) were for hematologic tumors. In all, 22 (48%) were not approved. ODAC comments addressed missing or inadequate data (65%), excessive toxicity (55%), inappropriate study endpoints (45%), poor study design (40%), and insufficient sample size (30%). To define efficacy, 19 applications used response rates (RR) (median = 38%), and 19 applications used hazard ratios (HR) (median = 0.67). For all organ systems combined, the median cumulative grade 3 or 4 toxicity was 64%. Drugs with higher RR, lower HR, and lower toxicity were more likely to be approved versus other drugs (89% vs. 45%; p = .02). Over time (2001-2004, 2005-2008, 2009-2012), there was an increase in the following: number of applications submitted for review (from 11 to 12 to 23, respectively), number of approvals (from 6 to 6 to 12, respectively), and proportion of trials using progression-free survival as a primary endpoint (from 0% to 50% to 70%, respectively; p = .01).
  
  
  CONCLUSIONS
  Of all applications, common ODAC concerns included inadequate data, excessive toxicity, and inappropriate study endpoints. Over time, there was an approximate doubling of FDA application submissions and approved oncology drugs.
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California, USA; Division of Gynecologic Oncology, Creighton University School of Medicine, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA; Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California, USA; Palo Alto Medical Foundation Research Institute, Palo Alto, California, USA.
authors.forename: John K
authors.initials: JK
authors.lastname: Chan
authors.forename: Tuyen K
authors.initials: TK
authors.lastname: Kiet
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Monk
authors.forename: Nichole
authors.initials: N
authors.lastname: Young-Lin
authors.forename: Kevin
authors.initials: K
authors.lastname: Blansit
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Kapp
authors.forename: Idoroenyi
authors.initials: I
authors.lastname: Amanam
mesh_terms: D026683:Advisory Committees; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D004358:Drug Therapy / Q000592:standards; D006801:Humans; D008495:Medical Oncology / Q000592:standards*; D009369:Neoplasms / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents
keywords: Clinical trial study design; Oncologic Drugs Advisory Committee; Oncology drug applications; U.S. Food and Drug Administration