Developing Safety Criteria for Introducing New Agents into Neoadjuvant Trials Journal Article

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Authors: DeMichele, A; Berry, D. A.; Zujewski, J.; Hunsberger, S.; Rubinstein, L.; Tomaszewski, J. E.; Kelloff, G.; Perlmutter, J; Buxton, M.; Lyandres, J.; Albain, K. S.; Benz, C.; Chien, A. J.; Haluska, P.; Leyland-Jones, B; Liu, M. C.; Munster, P.; Olopade, O; Park, J. W.; Parker, B. A.; Pusztai, L; Tripathy, D; Rugo, H; Yee, D; Esserman, L.
Article Title: Developing Safety Criteria for Introducing New Agents into Neoadjuvant Trials
Abstract: New approaches to drug development are critically needed to lessen the time, cost, and resources necessary to identify and optimize active agents. Strategies to accelerate drug development include testing drugs earlier in the disease process, such as the neoadjuvant setting. The U.S. Food and Drug Administration (FDA) has issued guidance designed to accelerate drug approval through the use of neoadjuvant studies in which the surrogate short-term endpoint, pathologic response, can be used to identify active agents and shorten the time to approval of both efficacious drugs and biomarkers identifying patients most likely to respond. However, this approach has unique challenges. In particular, issues of patient safety are paramount, given the exposure of potentially curable patients to investigational agents with limited safety experience. Key components to safe drug development in the neoadjuvant setting include defining a study population at sufficiently poor prognosis with standard therapy to justify exposure to investigational agents, defining the extent and adequacy of safety data from phase I, detecting potentially harmful interactions between investigational and standard therapies, improving study designs, such as adaptive strategies, that limit patient exposure to ineffective agents, and intensifying safety monitoring in the course of the trial. The I-SPY2 trial is an example of a phase II neoadjuvant trial of novel agents for breast cancer in which these issues have been addressed, both in the design and conduct of the trial. These adaptations of phase II design enable acceleration of drug development by reducing time and cost to screen novel therapies for activity without compromising safety. Clin Cancer Res; 19(11); 1-7. (c)2013 AACR.
Journal Title: Clinical cancer research : an official journal of the American Association for Cancer Research
Volume: 19
Issue: 11
ISSN: 1078-0432; 1078-0432
Publisher: AACR  
Date Published: 2013
Start Page: 2817-2823
Language: ENG
DOI/URL:

10.1158/1078-0432.CCR-12-2620
Notes: ID: 12987; JID: 9502500; 2013/03/07 [aheadofprint]; aheadofprint