Analysis of phase II studies on targeted agents and subsequent phase III trials: What are the predictors for success?
Analysis of phase II studies on targeted agents and subsequent phase III trials: What are the predictors for success?
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DOI：
10.1200/jco.2007.14.8874
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发表时间：
2008-03-20
影响因子：
45.3
通讯作者：
Kapp, Daniel S.
中科院分区：
文献类型：
--
作者：
Chan, John K.;Ueda, Stefanie M.;Kapp, Daniel S.
PurposeTo identify the characteristics of phase II studies that predict for subsequent "positive" phase III trials (those that reached the proposed primary end points of study or those wherein the study drug was superior to the standard regimen investigating targeted agents in advanced tumors.MethodsWe identified all phase III clinical trials of targeted therapies against advanced cancers published from 1985 to 2005. Characteristics of the preceding phase II studies were reviewed to identify predictive factors for success of the subsequent phase III trial. Data were analyzed using the chi(2) test and logistic regression models.ResultsOf 351 phase II studies, 167 (47.6%) subsequent phase III trials were positive and 184 (52.4%) negative. Phase II studies from multiple rather than single institutions were more likely to precede a successful trial (60.4% v 39.4%; P < .001). Positive phase II results were more likely to lead to a successful phase III trial (50.8% v 22.5%; P = .003). The percentage of successful trials from pharmaceutical companies was significantly higher compared with academic, cooperative groups, and research institutes (89.5% v 44.2%, 45.2%, and 46.3%, respectively; P = .002). On multivariate analysis, these factors and shorter time interval between publication of phase II results and III study publication were independent predictive factors for a positive phase III trial.ConclusionIn phase II studies of targeted agents, multiple-versus single-institution participation, positive phase II trial, pharmaceutical company-based trials, and shorter time period between publication of phase II to phase III trial were independent predictive factors of success in a phase III trial. Investigators should be cognizant of these factors in phase II studies before designing phase III trials.
