2,109 randomized oncology trials map continuous, meager improvements in progression-free and overall survival over 50 years

Objectives: To assess the patterns and time trends in overall survival and progression-free survival treatment effects across randomized controlled trials (RCTs) in oncology. Study Design and Setting: A PubMed search for oncology network meta-analyses (NMAs) was carried (to September 30, 2021). Relevant hazard ratios were extracted for systemic treatments from RCTs in the NMAs. After removing duplicate results, relationships between treatment effects, year of publication, trial design, and other features were explored. Results: From 241 oncology NMAs, 2,109 unique eligible RCTs provided analyzable data. On average, there was a 12%–14% reduction in hazard for overall survival and 27%–30% reduction for progression-free survival, with substantial heterogeneity across different malignancies. Correlation between overall survival and progression-free survival treatment effects was modest (r = 0.60, 95% confidence interval, 0.56–0.64). Over time, there was a suggestive trend of increased progression-free survival treatment effect, although overall survival treatment effects remained steady. Only one in five trials met criteria for clinically meaningful improvements in overall survival. Among 300 randomly selected trials, mean absolute improvement was 1.6 months for median progression-free survival and 1.4 months for median overall survival. Conclusion: Broad patterns across the past 50 years of oncology research suggest continuous progress has been made, but few results meet clinically meaningful thresholds for overall survival improvement.