title: The Role of Neoadjuvant Trials in Drug Development for Solid Tumors.
abstract: The relatively low success rate of phase II oncology trials in predicting success of novel drugs in phase III trials and in gaining regulatory approval may be due to reliance on the endpoint of response rate defined by the RECIST. The neoadjuvant treatment paradigm allows the antitumor activity of a novel therapy to be determined on a pathologic basis at the time of surgery instead of by RECIST, which was not developed to guide clinical decision making or correlate with long-term outcomes. Indeed, the FDA endorsed pathologic complete response (pCR) as a surrogate for overall survival (OS) in early-stage breast cancer and granted accelerated approval to pertuzumab based on this endpoint. We propose that pCR is a biologically rational method of determining treatment effect that may be more likely to predict OS. We discuss some advantages of the neoadjuvant trial design, review the use of neoadjuvant therapy as standards of care, and consider the neoadjuvant platform as a method for drug development. Clin Cancer Res; 22(10); 2323-8. ©2016 AACR.
authors: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
authors: Samuel A
authors: SA
authors: Funt
authors: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. chapmanp@mskcc.org.
authors: Paul B
authors: PB
authors: Chapman
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D006801:Humans; D020360:Neoadjuvant Therapy / Q000379:methods; D009369:Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents