title: Meaningful endpoints for therapies approved for hematologic malignancies.
abstract: Overall survival (OS) is considered the gold standard for determining treatment efficacy in oncology trials, but the relation between treatment and OS can be challenging to assess because of long study durations and the impact of subsequent therapies on outcome. Using OS can be particularly difficult for new therapies in hematologic malignancies (HMs).
  
  
  
  This retrospective analysis was conducted to characterize the primary endpoints used to support US Food and Drug Administration (FDA) approvals for new drug or novel HM indications between January 2002 and July 2015. Data on approvals were retrieved from the FDA and CenterWatch websites, and from the FDA prescribing information on respective products at the time of approval.
  
  
  
  Sixty-three FDA approvals involving 35 drugs and 16 HMs were identified. Of the 63 approvals, 45 (71.4%) included response rate (RR), and 17 (27%) included progression-free survival (PFS; n = 14) or time to progression (n = 3), and 1 approval included OS. Twenty-three approvals (36.5%) included trials with an active comparator arm. The median relative magnitude of benefit versus comparator was 71% improvement (range, 26%-127%), with a median hazard ratio of 0.55 (range, 0.16-0.72).
  
  
  
  FDA approvals for new drug or novel HM indications are often based on endpoints other than OS, such as RR and PFS. Tools for determining the magnitude of clinical benefit and treatment value in HMs should take into account the importance of RR, PFS, and other non-OS endpoints. Cancer 2017;123:1689-1694. © 2017 American Cancer Society.
authors.affiliation: Kimmel Cancer Center/Johns Hopkins, Baltimore, Maryland.
authors.forename: B Douglas
authors.initials: BD
authors.lastname: Smith
authors.affiliation: Kimmel Cancer Center/Johns Hopkins, Baltimore, Maryland.
authors.forename: Amy E
authors.initials: AE
authors.lastname: DeZern
authors.affiliation: GfK Market Access, San Francisco, California.
authors.forename: Alex W
authors.initials: AW
authors.lastname: Bastian
authors.affiliation: Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute, Los Angeles, California.
authors.forename: Brian G M
authors.initials: BGM
authors.lastname: Durie
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018572:Disease-Free Survival; D017277:Drug Approval; D023381:Endpoint Determination; D019337:Hematologic Neoplasms / Q000188:drug therapy*; D006801:Humans; D017063:Outcome Assessment, Health Care; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000970:Antineoplastic Agents
keywords: US Food and Drug Administration; cancer; drug approval; endpoints; hematologic malignancies; medical oncology; overall survival; progression-free survival