Developing safety criteria for introducing new agents into neoadjuvant trials

Angela DeMichele, Donald A. Berry, Jo Anne Zujewski, Sally Hunsberger, Larry Rubinstein, Joseph E. Tomaszewski, Gary Kelloff, Jane Perlmutter, Meredith Buxton, Julia Lyandres, Kathy S. Albain, Chris Benz, A. Jo Chien, Paul Haluska, Brian Leyland-Jones, Minetta C. Liu, Pamela Munster, Olufunmilayo Olopade, John W. Park, Barbara A. ParkerLajos Pusztai, Debu Tripathy, Hope Rugo, Douglas Yee, Laura Esserman

Research output: Contribution to journalReview articlepeer-review

19 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)2817-2823
Number of pages7
JournalClinical Cancer Research
Issue number11
StatePublished - Jun 1 2013


Dive into the research topics of 'Developing safety criteria for introducing new agents into neoadjuvant trials'. Together they form a unique fingerprint.

Cite this