Use of expansion cohorts in phase I trials and probability of success in phase II for 381 anticancer drugs

Diogo D.G. Bugano, Kenneth Hess, Denis L.F. Jardim, Alona Zer, Funda Meric-Bernstam, Lillian L. Siu, Albiruni R.A. Razak, David S. Hong*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Purpose: Evaluate the association between the use of phase I expansion cohorts (ECs) and drug performance in phase II as well as time to approval by the FDA. Experimental Design: We performed a systematic search of MEDLINE for single-agent dose-finding adult oncology phase I trials published in 2006 to 2011 and subsequent phase II trials. Successful phase II trials were those that met their primary endpoints. Dates of approval were obtained from the Drugs@FDA website in April 2014. A logistic regression model was used to determine the associations between variables and success in phase II. Results: We identified 533 phase I trials evaluating 381 drugs; 112 drugs had at least one phase I trial with an expansion cohort. Phase I trials with expansion cohorts of two to 20 patients were associated with a higher rate of successful phase II trials than those with no expansion cohort [48% vs. 27%; OR, 2.1; 95% confidence interval (CI), 1.1–4.0; P = 0.037]. Phase II success rates were the same for expansion cohort with two to 20 and more than 20 patients (48% vs. 52%). Other positive associations were disease-specific trials (OR, 1.7; 95% CI, 1.0–2.9; P = 0.037), industry sponsorship (OR, 2.9; 95% CI, 1.5–5.7; P = 0.0024), and response rate of 6% to 20% (OR, 2.89; 95% CI, 1.6–5.2; P = 0.0007). Drugs tested in phase I trials with expansion cohorts had a higher rate of 5-year approval (19% vs. 5%; HR, 4.4; 95% CI, 2.2–8.8; P < 0.001). Conclusions: The use of expansion cohorts in phase I trials was associated with success of subsequent phase II trials. However confounders may play a role in this association.

Original languageEnglish
Pages (from-to)4020-4026
Number of pages7
JournalClinical Cancer Research
Issue number15
StatePublished - 1 Aug 2017
Externally publishedYes


FundersFunder number
National Institutes of Health
National Cancer InstituteP30CA016672
National Center for Advancing Translational SciencesUL1 TR000371
University of Texas MD Anderson Cancer Center


    Dive into the research topics of 'Use of expansion cohorts in phase I trials and probability of success in phase II for 381 anticancer drugs'. Together they form a unique fingerprint.

    Cite this