Trial of perioperative endocrine therapy: Individualizing care (POETIC).

Abstract

TPS117 Background: The neoadjuvant IMPACT trial suggested Ki67 levels after 2 weeks endocrine therapy predicts long-term outcome. Major changes in gene expression have also been seen in ER+ breast cancer after aromatase inhibitor (AI) treatment. POETIC evaluates whether changes in Ki67 level after 2 weeks treatment predicts for relapse-free survival (RFS) more effectively than the baseline value. It also tests whether gene expression profile at this timepoint provides more accurate prognostic and predictive information than the pre-treatment profile. Experimental evidence suggests peri-operative endocrine therapy may improve disease outcome. This hypothesis is also addressed in POETIC. (ISRCTN63882543) With a sample size of 4000, an improvement in 5 year relapse from 10% to 7% could be detected with 91% power (two sided alpha of 5%), as would a 1.3 fold difference in the ability of Ki67 to predict RFS (90% power, two sided 5% significance level). Target recruitment is 4000 patients from 100 UK hospitals over 3-4 years. Methods: Patients are randomised in the ratio of 2:1 to perioperative AI (letrozole 2.5mg or anastrozole 1mg daily) starting 2 weeks before planned surgery until 2 weeks after surgery. FFPE and RNA-later samples are taken prior to trial entry (baseline) and at surgery. Eligible patients are postmenopausal with ER+ invasive breast cancer. Consent to take additional research tissue is sought from patients undergoing diagnostic biopsy. Consenting patients donate tumour tissue in RNA-later and/or a FFPE research sample and enter POETIC following diagnosis of ER+ breast cancer. Matching tumour tissue is taken at surgery. Where an RNA-later sample at baseline is unavailable, consenting patients may undergo a further biopsy for research tissue immediately before study entry. Where consent procedures at diagnosis present logistical challenges, sites may provide FFPE tissue left over from diagnosis only. The 1st patient was entered in September 2008, and by January 2011 102 UK hospitals open and 1200 patients were entered. 182 optional RNA-later samples at both timepoints are available. Current success is due to a flexible approach to tissue sample collection and overcoming local and national logistical challenges.