Originally published as JCO Early Release 10.1200/JCO.2007.14.8874 on February 19 2008

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chan, J. K. Articles by Kapp, D. S. Search for Related Content PubMed PubMed Citation Articles by Chan, J. K. Articles by Kapp, D. S. Social Bookmarking                            What's this?

Analysis of Phase II Studies on Targeted Agents and Subsequent Phase III Trials: What Are the Predictors for Success?

John K. Chan, Stefanie M. Ueda, Valerie E. Sugiyama, Christopher D. Stave, Jacob Y. Shin, Bradley J. Monk, Branimir I. Sikic, Kathryn Osann, Daniel S. Kapp

From the Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of California, San Francisco, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco; Department of Radiation Therapy, Division of Medical Oncology; Lane Medical Library & Knowledge Management Center, Stanford Cancer Center, Stanford University School of Medicine, Stanford; and the Chao Family Comprehensive Cancer Center, University of California, Irvine, Medical Center, Orange, CA

Corresponding author: John K. Chan, MD, University of California, San Francisco, UCSF Helen Diller Family Comprehensive Cancer Center, 1600 Divisadero St, Room A747, Box 1702, San Francisco, CA 94143-1702; e-mail: chanjohn{at}obgyn.ucsf.edu

Purpose To 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.

Methods We 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 ² test and logistic regression models.

Results Of 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.

Conclusion In 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.

published online ahead of print at www.jco.org on February 19, 2008.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				N. Dhani, D. Tu, D. J. Sargent, L. Seymour, and M. J. Moore Alternate Endpoints for Screening Phase II Studies Clin. Cancer Res., March 15, 2009; 15(6): 1873 - 1882. [Abstract] [Full Text] [PDF]