In order to perform a clinical trial in oncology, the choice of the primary endpoint is a major concern, not only for sample size calculation but also regarding the clinical meaning of the results which represents treatment utility for patients or public health system. Endpoints could be classified in two categories: “clinical endpoints” including overall survival and health related quality of life (QoL); “biological markers” including, for example, progression free survival (PFS). If conceptual and methodological limits of quality of life are well identified with dedicated researches, limits of progression free survival remain less targeted and known by clinicians. Numerous clinical trials having only demonstrated a progression free survival benefit could be discussed according to clinical benefit. In this context, quality of life constitutes an available and a useful alternative endpoint for trials to ensure treatment benefit in a patient or public health point of view. As quality of life, methodological researches should be pursued to improve scientific robustness for assessments and analyses of progression free survival.