Benchmarks of Success in Radiotherapy versus Systemic Therapy National Clinical Trials Network (NCTN) Randomized Controlled Trials Sponsored by the National Cancer Institute (NCI)

Abstract

Background The National Clinical Trials Network (NCTN) is the largest government sponsored organization in the United States tasked with funding randomized controlled trials (RCTs) in oncology. It is unknown whether there are differences in study design by treatment modality. We evaluated differences in methodology between trials testing radiotherapy versus systemic therapy. Methods The Clinical Trials Support Unit website was used to identify active RCTs of systemic or radiotherapy across NCTN cooperative groups through December 31, 2023. Studies in disease sites with > 5 radiotherapy trials were included. Each trial’s protocol was reviewed to obtain key design information that were descriptively compared: primary endpoint, hypothesis testing type (superiority vs non-inferiority), non-inferiority margin, hypothesized effect size, power, and significance level. Results A total of 186 RCTs (142 systemic therapy, 44 radiotherapy) were examined. Comparing primary endpoints, 59.1% vs 26.8% of radiotherapy vs systemic therapy trials, respectively, had a primary endpoint of overall survival. Nearly 1/3 of radiotherapy trials (31.2%) were non-inferiority vs 6.3% of systemic therapy trials. Among breast cancer trials, 75% of radiotherapy studies were non-inferiority vs 11.1% systemic. Target effect size, power, and significance level were similar by treatment modality within tumor types and disease settings. Conclusion Among NCTN cooperative group RCTs, there were marked differences in study design between radiotherapy vs systemic therapy trials. A higher benchmark for defining success for radiotherapy interventions was observed with greater emphasis on overall survival as primary endpoint. This may reflect differences in therapeutic mechanism by modality and types of study questions posed.