title: Detecting overall survival benefit derived from survival postprogression rather than progression-free survival.
abstract: Broglio and Berry (2009) examined the impact of survival postprogression (SPP) on overall survival (OS) when progression-free survival (PFS) was used to assess treatment effect in metastatic cancer. Their simulation studies found no statistical difference in OS because of dilution effect from SPP, although there was a statistical difference in PFS between treatment arms. Recently, two phase III clinical trials showed efficacy of experimental treatments in OS, but not PFS. These results seem counterintuitive, because it may be reasonable to consider that the effect of treatment in prolonging PFS can influence OS prolongation. We conducted simulations to examine the role of SPP in OS under the assumption that only SPP, and not PFS, differed between treatment arms. We also explored the impact of patient heterogeneity on the OS analysis. Our study offers a reasonable explanation for the two phase III trials and recommends further discussion of PFS as an adequate endpoint and what role SPP might play in OS to evaluate current treatment regimens.
authors.affiliation: Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan (SM); Department of Biostatistics and Epidemiology, Yokohama City University Graduate School of Medicine, Yokohama, Japan (KS); Department of Statistics and Actuarial Science, The University of Hong Kong, Pokfulam Road, Hong Kong (GY). smorita@kuhp.kyoto-u.ac.jp.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Morita
authors.affiliation: Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan (SM); Department of Biostatistics and Epidemiology, Yokohama City University Graduate School of Medicine, Yokohama, Japan (KS); Department of Statistics and Actuarial Science, The University of Hong Kong, Pokfulam Road, Hong Kong (GY).
authors.forename: Kentaro
authors.initials: K
authors.lastname: Sakamaki
authors.affiliation: Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan (SM); Department of Biostatistics and Epidemiology, Yokohama City University Graduate School of Medicine, Yokohama, Japan (KS); Department of Statistics and Actuarial Science, The University of Hong Kong, Pokfulam Road, Hong Kong (GY).
authors.forename: Guosheng
authors.initials: G
authors.lastname: Yin
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D018572:Disease-Free Survival; D006801:Humans; D053208:Kaplan-Meier Estimate; D009369:Neoplasms / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology*; D016017:Odds Ratio
chemical_list: D000970:Antineoplastic Agents