Journal
EUROPEAN JOURNAL OF CANCER
Volume 121, Issue -, Pages 19-28Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.ejca.2019.08.006
Keywords
Treatment effect; Phase II trials; Phase III trials; Randomised controlled trials
Categories
Ask authors/readers for more resources
Purpose: We aimed to determine whether treatment effect size differed between randomised controlled phase II trials and subsequent phase III trials and examine potential predictor of positive phase III trials. Methods: We searched MEDLINE for randomised controlled phase II studies published from January 2006 to December 2015. Matched phase III trials that investigated same intervention in the same setting of the same cancer were identified through Web of Science, ClinicalTrials. gov and conference proceedings. For each pair of phase II and phase III trials, we extracted hazard ratios (HRs) with 95% confidence intervals (CIs) for both overall survival (OS) and progression-free survival (PFS) and evaluated the differences by ratio of HRs (rHRs): the HR for phase II trial to that for phase III trial. A summary rHR was obtained through a random-effect meta-analysis. Univariable analyses were conducted to identify predictors of positive phase III trials. Results: We identified 57 pairs of phase II and phase III trials. Compared with phase III trials, treatment effect sizes of PFS were, on average, 26% larger in phase II trials (rHR Z 0.74, P < 0.001, 95% CI: 0.68-0.80). Treatment effect sizes of OS were 27% greater in phase II trials than in phase III trials (rHR Z0.73, P < 0.001, 95% CI: 0.66-0.79). Fifteen (26.3%) phase III trials were positive, and the only predictor of positive phase III trials was positive phase II trials Conclusion: Treatment effects in randomised controlled phase II trials were greater than those in matched phase III trials. Caution must be taken when interpreting promising results from randomised controlled phase II trials. (C) 2019 Elsevier Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available