OT2-03-04: A Trial Model for the Future in the Search for Personalised Medicine – The UK POETIC and EPHOS-B Perioperative Trials Experience.

Abstract

Abstract Background Perioperative therapy offers the opportunity to measure biological response to treatment in the primary tumor in early breast cancer (EBC), enhancing prospects for personalised medicine. Perioperative trials form an expanding component of the UK national breast cancer trials portfolio. Unlike traditional neoadjuvant studies, activity dovetails around timelines for standard treatment with no planned delay to primary surgery. Tissue samples collected prior to randomisation (baseline) & again at surgery address key biological endpoints & are essential for perioperative studies. Methods: As the UK's largest perioperative trial, POETIC (ER+ve postmenopausal EBC, +/− aromatase inhibitor therapy, biomarker & disease outcome) aims to recruit 4000 patients from 100+ centres. EPHOS-B (HER2+ve EBC, +/− lapatinib or trastuzumab) focuses on biomarker endpoints & aims to recruit 250 patients. Barriers to recruitment included 1) integration of research protocols into busy breast surgical clinics, extending a clinical trials culture across a multidisciplinary breast diagnostic team, & ensuring appropriate GCP training, 2) satisfying requirements for storing research tissue, 3) complying with government cancer wait times, 4) obtaining biomarker results within required timelines 5) ensuring completeness & quality of tissue samples. Additional challenges for EPHOS-B include managing requirements for scheduling of oncological therapy (e.g. trastuzumab) in pre-operative setting, delivery of such therapy outside the randomising hospital & rapid access to cardiac screening before randomisation. Results: The following strategies were developed to overcome barriers 1) increasing collaborative working at sites & adopting a pragmatic approach to type of tissue required. Centres choose to provide both FFPE tissue & tissue in RNA-later, or FFPE tissue only; 2) working with national regulators to agree interpretation of current legislation in designation of when tissue is “in transit” (enabling it to reside outside a tissue bank) & “research” tissue (where transfer to a tissue bank is required); 3) agreement with government that procedures integral to perioperative trials comply with cancer wait times; 4) promoting reorganisation of site processes for obtaining essential biomarker results; 5) pilot lab work to inform site guidance on tissue collection procedures to ensure quality of samples received. A tracking database allows completeness of tissue samples to be monitored. Work to improve timelines for HER2 testing in EPHOS-B is ongoing, & challenges of delivering anti-HER2 therapy in this setting have been addressed. Conclusions: Assessment of biological response to therapy in the primary tumor in EBC within national trials is feasible. Many barriers faced by POETIC have been overcome, & with recruitment now 100+ patients per month, newer centres benefit from earlier experience. Lessons learnt in POETIC apply to EPHOS-B, allowing investigators to focus on resolving more challenging issues specific to that trial. In many centres both trials have been important drivers in improving timeliness of molecular testing & therefore benefited the patient pathway in general as well as securing high quality trial data. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT2-03-04.