Progression-free survival effect sizes in randomized controlled trials of targeted cancer therapies with positive outcomes

Improvement in progression-free survival (PFS) is increasingly used by health authorities for cancer drug approvals. We analyzed 106 randomized controlled trials (RCTs) with positive PFS outcomes published in JAMA Oncology, Lancet Oncology, Journal of Clinical Oncology, and Annals of Oncology during 2020 – 2023. RCTs were categorized as ‘targeted’ (n = 83) or ‘conventional’ (n = 23) by their interrogated treatment variables. Two measures of PFS effect sizes were analyzed: hazard ratio (HR) and PFS increment. Among the RCTs of targeted therapies, the 25th-percentile value (Q1) of HR increased significantly (slope = 0.05 per year; P = .02) during the study period whilst Q1 of PFS increment decreased significantly (slope = –9.1 percentage points per year; P = .03). Similar trends were not observed among the RCTs of conventional therapies. Our analyses suggest a potential bias in accepting RCTs of targeted therapies despite decreased PFS effect sizes.