A Cross-Sectional Study of Clinical Trials on Radiotherapy Combined with Immunotherapy for Lung Cancer

Abstract

For patients with lung cancer, remarkable advances have been made in Immune-Oncology (IO) therapy, especially immune checkpoint inhibitors (ICI). However, multi-modality treatment is needed to improve the efficacy or enlarge the beneficial populations of IO treatment. This study is to comprehensively summarize and analyze the clinical trials focusing on radiotherapy (RT) combined with IO therapy, explore the trend of research, as well as provide a view of the latest landscape of combination strategies. Trials registered on the electronic database (https://clinicaltrials.gov) between Jan.2009 and Jan.2019 were searched using “Radiotherapy AND Immunotherapy | Recruiting, Not yet recruiting, Active, not recruiting, Completed, Enrolling by invitation Studies | Interventional Studies | Lung Cancer”. Statistical analysis software was used to analyze the data. Totally 69 clinical trials of RT and IO combination therapy for lung cancer were recorded, including 54 active and 15 completed. Geographically, most of the trials were carried out in the USA (n=47, 68.1%), followed by the European countries (n=18, 26.1%). From timeline, the past 2 years has seen a soaring number of 40 clinical trials accounting for 58.0% of the total. The combination therapy trials were more often in non-small cell lung cancer (NSCLC) (n=52, 75.4%) than small cell lung cancer (SCLC) (n=10, 14.5%), with the remaining 7 trials unspecified. As for combination strategies, trials of tumor vaccine combined with RT were the most frequent before 2016. However, at present, ICI has exceeded tumor vaccine in the combination with RT and makes up the absolute most (n=62, 89.9%). On the whole, most of the combination therapy trials are in phase I/II (n=64, 92.8%). Although most trials are set for advanced or metastatic cancers (n=43, 62.3%), there are a few exploring the safety and effectiveness of combination therapy for early stage cancers or as adjuvant therapy (n=9, 13.0%). One trial was set as neo-adjuvant therapy. As for RT details, 22 trials were SBRT combined with IO therapy. Two trials were exploring the optimal sequence of RT and IO therapy. In addition, one trial is to compare high versus low dose RT in the combination with ICI in NSCLC. From the trials of RT and IO combination therapy for lung cancer, those of ICI combined with RT are increasing rapidly, although most are in phase I/II. Further studies are needed to explore the more detailed rational combination strategies, such as the sequencing, fractionation, and dose of RT, and the optimal IO agent.