The characteristics of oncological clinical trials investigating the synergistic effect of radiotherapy and immune checkpoint inhibitors: a cross-sectional study

Abstract

Background: The combined use of radiotherapy (RT) and immune checkpoint inhibitors (ICIs) is a promising strategy in the treatment of cancer patients. We sought to comprehensively summarize the characteristics of oncological trials investigating the synergistic effect of RT and ICIs registered at ClinicalTrials.gov. Methods:In this cross-sectional study, oncological trials investigating the synergistic effect of RT and ICIs registered at ClinicalTrials.gov from database inception to November 30, 2021 were retrieved. The characteristics of the included trials were assessed.Results: Overall, 403 registered trials were identified for analysis. Of these trials, 393 (97.5%) were interventional trials and 10 (2.5%) were observational trials. The top 3 most-studied conditions were gastrointestinal cancer (25.8%), head and neck cancer (18.6%), and non-small cell lung cancer (NSCLC) (17.9%). Approximately, 60.0% of the trials comprised ≤50 participants and 22.6% of the trials comprised >100 participants. More than half of the registered trials were prospective phase 2 trials (54.3%). In relation to trial location, 39.7% of the trials were conducted in the United States, which was the most common registered area, followed by China (33.7%) and Europe (19.4%). In relation to the radiation fractionation, the conventional fractionation size of 1.8-2.0 Gy was comparable to the ultra-hypofractionation size of ≥5 Gy (46.4% vs. 32.8%), and the most commonly used ultra-hypofractionation regimen was 24 Gy/3 Fx (24%), followed by 25 Gy/5 Fx (11%) and 30 Gy/5 Fx (11%). Additionally, the most commonly used ICI in the registered trials was pembrolizumab (20.1%), followed by durvalumab (11.4%) and nivolumab (9.2%). Among all the registered trials, only 4% of the trials had been completed, but 61.5% of the completed trials had reported their results on ClinicalTrials.gov. The conventional fractionation trials were more likely to be phase 3 trials, located in China, and performed in patients with head and neck cancer or gynecological cancer (all P values <0.05), while the ultra-hypofractionation trials were more likely to be phase 1 trials, stopped early, located in the United States, and performed in patients with lung cancer (all P values <0.05). Conclusions:The number of prospective trials investigating the synergistic effect of RT and ICIs registered at ClinicalTrials.gov has increased significantly over the past decade. The ultra-hypofractionation size of the registered trials varies, but the 24 Gy/3 Fx regimen is commonly used. The clinical results of registered trials examining the synergistic effect of RT in combination with ICIs, specifically in terms of ultra-hypofractionation, remain limited. Highlight box Key findings• Prospective oncological trials investigating the synergistic effect of RT and ICIs registered at ClinicalTrials.gov had been significantly increased, but most of these trials were small sample size, nonrandomized trials and were uncompleted. The fraction size of ultra-hypofractionation size used also varied. What...