Les essais cliniques en oncologie thoracique à l'ère de la médecine de précision : comment les réaliser en pratique ?

Randomized controlled trials (RCTs) are the benchmark for evaluating the effectiveness of an intervention. The clinical development of the drug aligned with this methodology in order to obtain a marketing authorization by requiring successive completion of Phase I, II and III trials. Nevertheless, as the human and financial costs become considerable and the need to maintain the level of remuneration of the pharmaceutical industry's shareholders has led to the emergence of phase I / II and II / III trials in order to shorten the development period and to limit the costs. Moreover, the emergence of the precision medicine resulting from the research of a couple of predictive biomarker / targeted therapy made ethically difficult to continue RCTs in this situation and allowed to the development of new therapeutic trial study design such as stratified trials, basket and umbrella trials, adaptive and finally molecular algorithm trials. These new designs have allowed rapid access to marketing authorization for rare diseases (dabrafenib + trime-tinib / BRAFV600, crizotinib / ROS) but they have also been used in the initial development of certain immunotherapies. Their disadvantages are: the multiplicity of arms; the complexity of statistical analysis; the lack of evaluation of the targeted molecule in the general population; the small number of patients included with a risk of ignoring rare adverse events; the absence of comparison with the therapeutic standard and finally, the lack of evaluation of the impact of treatment on overall survival.