The Past, Present, and Future of Pancreatic Cancer Clinical Trials

Abstract

Upper gastrointestinal malignancies comprise half of the deadliest cancers as defined by those with a 5-year survival rate less than 50%. Using pancreatic adenocarcinoma (PAC) as an example, we retrospectively evaluated the success of phase III clinical trials, examined the current landscape of clinical trials, and identified emerging areas that foretell the future for this disease. Pancreatic and liver cancers are on the rise and will be the second and third leading causes of cancer deaths in 2030. A total of 35 different agents or combinations have been tested in randomized phase III clinical trials for patients with advanced PAC over the past 25 years, but only 11% have been incorporated into clinical practice. There has been a 37% increase in the number of PAC trials open in the United States between 2011 to 2012 and 2014 to 2015. Enrollment has also increased slightly, from 3.85% of the newly diagnosed cases in 2011 to 4.15% in 2014. However, the demand for patients far exceeds the number of patients available for these trials. On the horizon is the realization that stratification of patients with PAC using biomarkers that predict a high probability of a response could reallocate patients to faster, smaller trials with a greater chance of a survival benefit. The current landscape of PAC clinical trials and the launch of the Pancreatic Cancer Action Network’s Know Your Tumor initiative indicate this shift is starting to occur, with particular emphasis on targeted therapies, immunotherapies, and agents that disrupt the stroma.