Progression-free survival rate as primary endpoint for phase-II cancer clinical trials
(2010)
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- Abstract
- (en) The main objective of this project was to estimate progression-free survival rates at different fixed time points in order to design future phase-II trials targeting the progression-free survival rate as primary endpoint in mesothelioma. Response rate has traditionally been used as an endpoint in many phase-II trials of oncology therapies. However, progression-free survival could be a more appropriate endpoint in rapidly progressing disease, at least in three situations: (1) when testing cytostatic agents, (2) when the response to a regimen is difficult to assess, (3) when the response is expected to be low. The use of progression-free survival as an endpoint instead of the response rate is relevant in mesothelioma for two primary reasons. Firstly, the global incidence of mesothelioma is increasing and current treatments yield disappointingly poor results. The development of more active treatments is thus highly desirable and new targeted therapies, including cytostatic agents, are currently the main focus of mesothelioma research. Secondly, in mesothelioma the assessment of response is difficult and not reproducible, and the response rate is usually low. In order to evaluate a novel therapy using progression-free survival rate as the primary endpoint, we need data about the progression of patients and especially about the progression-free survival rate at fixed time point. Data on 523 patients included in 10 mesothelioma trials conducted by the European Organisation for Research and Treatment of Cancer were analysed. Values of progression-free survival rate at 3, 4, 5 and 6 months in groups of different levels of therapeutic activity and in different risk groups were calculated. Our work also provides a prognostic index which allows the definition of more homogeneous groups of patients that avoids dilution of results between groups. Based on these results, the size of future mesothelioma trials can be calculated and designs can be adapted to improve the assessment of the activity of a new therapy. Furthermore the use of progression-free survival rate rather than response rate as a primary endpoint would not require much more time to assess the endpoint. It would also decrease the probability to reject a potentially interesting therapy by considering non-progressive diseases as successes.
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Citations
Francart, J. (2010). Progression-free survival rate as primary endpoint for phase-II cancer clinical trials. https://hdl.handle.net/2078.5/203537