Clinical and biomarker endpoint analysis in neoadjuvant endocrine therapy trials.
Neoadjuvant endocrine therapy trials for breast cancer are now a widely accepted investigational approach for oncology cooperative group and pharmaceutical company research programs. However, there remains considerable uncertainty regarding the most suitable endpoints for these studies, in part, because short-term clinical, radiological or biomarker responses have not been fully validated as surrogate endpoints that closely relate to long-term breast cancer outcome. This shortcoming must be addressed before neoadjuvant endocrine treatment can be used as a triage strategy designed to identify patients with endocrine therapy "curable" disease. In this summary, information from published studies is used as a basis to critique clinical trial designs and to suggest experimental endpoints for future validation studies. Three aspects of neoadjuvant endocrine therapy designs are considered: the determination of response; the assessment of surgical outcomes; and biomarker endpoint analysis. Data from the letrozole 024 (LET 024) trial that compared letrozole and tamoxifen is used to illustrate a combined endpoint analysis that integrates both clinical and biomarker information. In addition, the concept of a "cell cycle response" is explored as a simple post-treatment endpoint based on Ki67 analysis that might have properties similar to the pathological complete response endpoint used in neoadjuvant chemotherapy trials.
Siteman Cancer Center and Washington University in St. Louis, Campus Box 8506, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Yu
Y
Tao
Andreas
A
Klause
Andrew
A
Vickers
Kyongtae
K
Bae
Matthew
M
Ellis
D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000601:surgery; D002986:Clinical Trials as Topic; D023381:Endpoint Determination; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D000077289:Letrozole; D020360:Neoadjuvant Therapy; D009570:Nitriles / Q000627:therapeutic use; D013629:Tamoxifen / Q000627:therapeutic use; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use
D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D009570:Nitriles; D014230:Triazoles; D013629:Tamoxifen; D000077289:Letrozole