Early phase clinical trial played a critical role in the Food and Drug Administration-approved indications for targeted anticancer drugs: a cross-sectional study from 2012 to 2021.

Objectives: To characterize the indications approved by the US Food and Drug Administration (FDA) on the basis of early phase clinical trials (EPCTs) and compared with that of phase three randomized controlled trials.

Study Design And Setting: We collected the publicly available FDA documents of targeted anticancer drugs approved between January 2012 and December 2021.

Results: We identified 95 targeted anticancer drugs with 188 indications approved by the FDA. One hundred and twelve (59.6%) indications were approved on the basis of EPCTs, with a significant increase of 22.2% per year. Of 112 EPCTs, 32 (28.6%) were dose-expansion cohort trials and 75 (67.0%) were single-arm phase 2 trials, respectively, with a significant increase of 29.7% and 18.7% per year. Compared with indications approved on the basis of phase three randomized controlled trials, the indications approved on the basis of EPCTs had significantly higher odds in receiving accelerated approval and lower odds in the number of entered patients of pivotal trials.

Conclusions: Dose-expansion cohort trials and single-arm phase 2 trials played a critical role in EPCTs. EPCT was a major trial type in providing evidences for the FDA approvals of targeted anticancer drugs.