LAUSR

BACKGROUND A minority of phase III trials in gastrointestinal oncology are positive. We assessed the association between their outcome, and the level and characteristics of pre-existing evidence. METHODS EMBASE, PubMed, and proceedings from international meetings were searched for phase III gastrointestinal cancer trials (gastro-oesophageal [GEC], hepatocellular carcinoma [HCC], biliary tract [BTC], pancreatic [PC], small bowel [SBC], colorectal [CRC], anal [AC], stromal [GIST], and neuroendocrine [NET]) between 01/2000 and 06/2020. Trials investigating anti-cancer drugs for advanced disease, with superiority design, and standard treatments as control were eligible. The highest level of pre-existing evidence was retrieved from the main study report. RESULTS 193 phase III trials were included, and 69 (35.8%) met their primary endpoint. Positivity rates were: GEC 37%, CRC 48%, PC 17.1%, HCC 20%, NET 75%, BTC/GIST 60%. No information about pre-existing evidence was found for 44 trials (22.8%). For the remaining 149, this consisted of phase II studies in 123 (82.6%), and phase I studies in 26 cases (17.4%). The probability of success was 34.1%, 35.8% and 35.7%, respectively (p = 0.934). No parameter from prior studies predicted the outcome of phase III trials, except a β of < 0.2 (p = 0.048). A numerically increased success rate was observed for phase III trials preceded by positive phase II studies (41.9% vs 18.5%, p = 0.2). CONCLUSIONS There does not appear to be an association between level of prior evidence and success of phase III gastrointestinal cancer trials. These data, along with the high phase III failure rate, highlight the need to improve the drug development process in this setting.