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Highlights
- -The study design, distribution and characteristics of early-phase clinical trials (EPCTs) in supporting the FDA approved indications for targeted anti-cancer therapies were investigated.
- -Nearly 60% indications were approved by the FDA on the basis of EPCTs.
- -EPCTs mainly included two clinical trial types: dose-expansion cohort and single-arm phase 2 trials.
- -The indications approved on the basis of EPCTs had higher odds in receiving accelerated approval and lower odds in the number of entered patients of pivotal trials.
Abstract
Objective
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 3 randomized controlled trials (RCTs).
Study Design and Setting
We collected the publicly available FDA documents of targeted anti-cancer drugs approved between January 2012 and December 2021.
Results
We identified 95 targeted anti-cancer 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. Out of 112 EPCTs, 32 (28.6%) were dose-expansion cohort (DEC) trials and 75 (67.0%) were single-arm phase 2 trials (Phase 2 SATs), respectively, with a significant increase of 29.7% and 18.7% per year. Compared with indications approved on the basis of phase 3 RCTs, 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
DEC trials and phase 2 SATs played a critical role in EPCTs. EPCT was a major trial type in providing evidences for the FDA approvals of targeted anti-cancer drugs.
Graphical abstract
Graphical Abstract
Keywords
Abbreviations:
CDG (cancer driver gene), CI (confidence interval), DEC (dose-expansion cohort), DLT (dose-limiting toxicity), EPCT (early-phase clinical trial), FDA (US Food and Drug Administration), ICH (The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use), IQR (interquartile range), IRC (independent review committee), IRR (incidence rate ratio), NDA (new drug application), NSCLC (non-small cell lung cancer), OR (odds ratio), ORR (overall response rate), OS (overall survival), PFS (progression-free survival), Phase 2 SAT (single-arm phase 2 trial), RCT (randomized controlled trial), RP2D (recommended phase 2 dose)Article info
Publication history
Accepted:
March 6,
2023
Received in revised form:
January 29,
2023
Received:
October 18,
2022
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2023 The Author(s). Published by Elsevier Inc.
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