Smith B Douglas, DeZern Amy E, Bastian Alex W, Durie Brian G M
Kimmel Cancer Center/Johns Hopkins, Baltimore, Maryland.
GfK Market Access, San Francisco, California.
Cancer. 2017 May 15;123(10):1689-1694. doi: 10.1002/cncr.30622. Epub 2017 Feb 21.
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.
总生存期（OS）被认为是肿瘤学试验中确定治疗效果的金标准，但由于研究持续时间长以及后续治疗对结果的影响，治疗与OS之间的关系可能难以评估。对于血液系统恶性肿瘤（HM）的新疗法，使用OS可能尤其困难。
进行这项回顾性分析，以描述2002年1月至2015年7月期间用于支持美国食品药品监督管理局（FDA）批准新药或新型HM适应症的主要终点。批准数据从FDA和CenterWatch网站以及FDA批准时各产品的处方信息中检索。
确定了63项FDA批准，涉及35种药物和16种HM。在这63项批准中，45项（71.4%）包括缓解率（RR），17项（27%）包括无进展生存期（PFS；n = 14）或疾病进展时间（n = 3），1项批准包括OS。23项批准（36.5%）包括有活性对照臂的试验。与对照相比，获益的相对中位幅度为改善71%（范围，26% - 127%），中位风险比为0.55（范围，0.16 - 0.72）。
FDA对新药或新型HM适应症的批准通常基于OS以外的终点，如RR和PFS。确定HM临床获益程度和治疗价值的工具应考虑RR、PFS和其他非OS终点的重要性。《癌症》2017年；123:1689 - 1694。© 2017美国癌症协会。
