Outcomes and endpoints in trials of cancer treatment: the past, present, and future

Cancer treatment should allow patients to live better or longer lives, and ideally, both. Trial endpoints should show clinically meaningful improvements in patient survival or quality of life. Alternative endpoints such as progression-free survival, disease-free survival, and objective response rate have been used to identify benefit earlier, but their true validity as surrogate endpoints is controversial. In this Review we discuss the measurement, assessment, and benefits and limitations of trial endpoints in use for cancer treatment. Many stakeholders are affected, including regulatory agencies, industry partners, clinicians, and most importantly, patients. In an accompanying Review, reflections from individual stakeholders are incorporated into a discussion of what the future holds for clinical trial endpoints and design.