Milestone Survival: A Potential Intermediate Endpoint for Immune Checkpoint Inhibitors

Recent advancements in cancer immunotherapies offer diverse strategies for cancer treatment. Among the most promising approaches is the blockade of immune checkpoint molecules to activate antitumor immunity. With targeted immunotherapies of new mechanisms of action come greater challenges in study design and statistical analysis, as well as the need for refining clinical trial endpoints. The long-term survival and delayed clinical effects demonstrated by these therapies could result in substantial prolongation of study duration and loss of statistical power if these key attributes are not accounted for in the study design and statistical analyses. In the Brookings Conference on Clinical Cancer Research held in Washington, DC, in November 2013, several intermediate clinical endpoints, including milestone overall survival, were proposed for the evaluation of cancer immunotherapies to take into account the possibility of delayed treatment effect and to better characterize the clinical activity profile of such agents, particularly immune checkpoint inhibitors. In this manuscript, the use of milestone survival is described as a potential efficacy endpoint for immune checkpoint inhibitors in late-stage drug development that could potentially mitigate the challenge of accelerating the drug development process when the strength of this class of agents is derived from long-term follow-up.