Benchmarks of success in radiotherapy vs systemic therapy: National Clinical Trials Network (NCTN) randomized controlled trials sponsored by the National Cancer Institute (NCI).

Abstract

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