Progression-free survival rate as primary endpoint for phase-II cancer clinical trialsapplication to mesothelioma

The main objective of this project was to estimate progression-free survival rates \nat different fixed time points in order to design future phase-II trials targeting \n\nthe progression-free survival rate as primary endpoint in mesothelioma. \n\nResponse 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 \n\nthe response is expected to be low. \n\nThe 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 \n\nnot reproducible, and the response rate is usually low. \n\nIn 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 \n\nthe progression-free survival rate at fixed time point. \n\nData 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 \n\nthe 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 \n\na potentially interesting therapy by considering non-progressive diseases as successes.