A Review of studies examining the relationship between progression-free survival and overall survival in advanced or metastatic cancer / Sarah Davis [and three others].

Format:

Book

Author/Creator:

Davis, Sarah, author.

Language:

English

Subjects (All):

Cost effectiveness.

Outcome assessment (Medical care).

Physical Description:

1 online resource (41 pages) : illustrations

Place of Publication:

London, England : National Institute for Health and Care Excellence (NICE), 2012.

Summary:

Introduction Progression-free survival (PFS), time-to-progression (TTP) and overall survival (OS) are commonly used endpoints in randomised controlled trials (RCTs) and observational studies of treatments for metastatic disease in solid tumour cancers. Within health economic models of cancer interventions, disease- and treatment-related health states are often defined according to whether the patient has experienced disease progression since starting a particular line of therapy. Such models typically estimate the mean sojourn time in these health states and therefore information is needed on both PFS/TTP and OS. PFS or TTP are sometimes regarded as valid surrogate outcomes when establishing the clinical benefit of a treatment in the absence of mature data on OS, but an estimate of OS is still needed within the economic analysis. Some quantification of the relationship between PFS/TTP and OS may be used to populate the economic model as an alternative to directly modelling OS from the trial data. Objectives The aim of this review was to examine the evidence available concerning the relationship between PFS/TTP and OS in advanced or metastatic cancer, with a view to determining the extent to which PFS/TTP can be considered a robust surrogate endpoint for OS. Methods A review was conducted of papers using meta-regression or other meta-analytic techniques to examine the statistical relationship between OS and either PFS or TTP. Studies were identified through citation searching as a systematic search was not considered feasible. The review focuses on advanced or metastatic cancer where the treatment intent is palliative rather than curative and therefore the surrogate outcome of interest is progression-free rather than disease-free survival. Results Nineteen papers were included in the review covering eight different tumour types. Four studies used aggregate data from multiple trials to examine the relationship between PFS and OS for individual trial arms. Seven studies used individual patient data to examine the relationship between PFS and OS for individual patients. Thirteen studies examined the trial level relationship between treatment effect on PFS and treatment effect on OS with three using individual patient data, whilst the remainder used aggregate data from multiple trials. A variety of statistical techniques were employed within these studies, with the most commonly used being rank correlation coefficients, linear regression and landmark analysis. The lack of a standardised approach made it difficult to establish whether there is a consistent relationship between PFS/TTP and OS. The majority of the studies found a positive correlation between PFS/TTP and OS for individual patients, individual trial arms and the treatment effect between trial arms, although, the size of the correlation and its statistical significance varied considerably across studies. This is not surprising given the variety of methods employed and the variation in studies characteristics such as differences in the tumour type and the line of therapy considered. Conclusion This review suggests that the level of evidence available supporting a relationship between PFS/TTP and OS varies considerably by cancer type and is not always consistent even within one specific cancer type. Furthermore, even where strong consistent evidence supporting a correlation between the treatment effects (i.e Level 1 evidence according to Elston and Taylor's framework) is available, it is unclear how that should be converted into a quantified relationship between PFS and OS treatment effects within a cost-effectiveness model. Therefore, any cost-effectiveness analysis which makes a strong assumption regarding the relationship between PFS and OS should be treated with caution. We would support Elston and Taylor in recommending that any cost-effectiveness analysis based on a surrogate relationship between PFS and OS should be supported with a transparent explanation of how the relationship is quantified in the model and should be accompanied by sensitivity analysis exploring the uncertainty associated with that relationship and a systematic review of papers examining the relationship between PFS and OS in the relevant setting. This would allow decision makers to judge the appropriateness of the model in light of the evidence available in that specific disease area.

Notes:

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