A comprehensive analysis of clinical trials including both immunotherapy and radiation therapy

Abstract

Purpose Radiation therapy (RT) may work synergistically with cancer immunotherapies but clinical trial data is needed to validate this paradigm. We isolated the portfolio of trials that investigate the primary immunomodulatory properties of RT and examined recent trends in clinical trials that combine immunotherapy and RT (ITRT). MethodsWe queried clinicaltrials.gov for trials initiated since 2002 using both radiation and immunotherapy as mandated interventions. We designated the trials that examine the specific aspects of RT or its abscopal properties as "Primary RT Immunomodulation" trials. Chi-squared analysis determined differences between primary RT immunomodulation trials and those that incorporate RT as a secondary intervention. Joinpoint regression modeling determined the rate of change of the introduction of new trials over time. ResultsOne hundred and ninety trials met inclusion criteria. Targeted immunostimulatory agents, including checkpoint inhibitors, were the most common immunotherapy (n = 79 [41.6%]). Sixty-six (34.7%) trials included RT as the primary intervention, with 50 (75.6%) of these utilizing stereotactic body radiation (SBRT). All ITRT trials increased at a rate of 14.8% per year. Primary RT immunomodulation trials increased at a rate of 26.8% per year. Primary RT immunomodulation trials were more likely to utilize targeted immunostimulatory agents (p < 0.01), and SBRT (p < 0.01), and more likely to involve metastatic sites (p < 0.01). The number of ITRT studies increased drastically in the latest two years of the study. ConclusionThe number of new ITRT clinical trials is increasing rapidly. This increase in quantity may improve the clinical application of the immunomodulatory properties of RT.