Progression-free survival rate as primary end point for phase II cancer clinical trials: application to mesothelioma--The EORTC Lung Cancer Group

J Clin Oncol. 2006 Jul 1;24(19):3007-12. doi: 10.1200/JCO.2005.05.1359.

Abstract

Purpose: Phase II cancer clinical trials play a key role in the development of new drugs. These trials should be designed to accurately determine if the drug should be abandoned or if it is sufficiently promising for further investigation in phase III trials. With new cytostatic agents or when the response assessment is difficult, using the progression-free survival rate (PFSR) at a fixed time point, such as 3, 4, 5, or 6 months, instead of the response rate (RR) as the primary end point is an alternative approach. To design future phase II trials, reference values for PFSRs that correspond to drugs with insufficient (P0) and sufficient (P1) clinical activity (CA) are necessary. This article provides these values in mesothelioma.

Materials and methods: The European Organisation for Research and Treatment of Cancer database registered ten closed mesothelioma trials (nine phase II trials and one phase III trial) with 523 total patients. Trials were grouped into three categories according to the published RR: significant (n = 259), moderate (n = 142), and insufficient (n = 122) CA.

Results: The PFSRs at 3, 4, 5, and 6 months, respectively, were as follows: 72%, 67%, 51%, and 43% in the group with significant CA; 59%, 51%, 42%, and 35% with moderate CA; and 52%, 40%, 34%, and 28% with insufficient CA.

Conclusion: These values may be used to define relevant P0 and P1 values in future phase II mesothelioma trials that use PFSR as the primary end point.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Clinical Trials, Phase II as Topic*
  • Disease Progression
  • Endpoint Determination*
  • Female
  • Humans
  • Male
  • Mesothelioma / drug therapy*
  • Middle Aged
  • Reference Values
  • Research Design
  • Retrospective Studies
  • Survival Analysis*