Background:Multi-parameter tumour gene expression assays (MPAs) are widely used to estimate individual patient residual risk and to guide chemotherapy use in hormone-sensitive, HER2-negative early breast cancer. The TAILORx trial supports MPA use in a node-negative population. Evidence for MPA use in node-positive breast cancer is limited. OPTIMA (Optimal Personalised Treatment of early breast cancer usIng Multi-parameter Analysis) (ISRCTN42400492) aims to validate MPAs as predictors of chemotherapy sensitivity in a largely node-positive breast cancer population where prospective RCT (Randomised Controlled Trial) evidence is lacking. Methods: OPTIMA is a partially blinded multi-center RCT with an adaptive two-stage design. The main eligibility criteria are women and men age 40 or older with resected ER-positive, HER2-negative invasive breast cancer and up to 9 involved axillary lymph nodes. Randomisation is to standard management (chemotherapy and endocrine therapy) or to MPA-directed treatment using the Prosigna (PAM50) test. Those with a Prosigna tumour score (ROR_PT) >60 receive standard management whilst those with a low score (≤60) are treated with endocrine therapy alone. Endocrine therapy for pre-menopausal women includes ovarian suppression. The co-primary outcomes are (1) Invasive Disease Free Survival (IDFS) and (2) cost-effectiveness of test-directed treatment. Secondary outcomes include IDFS in patients with low-score tumours and quality of life. An integrated qualitative recruitment study addresses challenges to consent and recruitment and will build on experience from the feasibility study that a multidisciplinary approach at sites is important for recruitment success. Tumour blocks will be banked to allow evaluation of additional MPA technologies. Recruitment of 4500 patients over 5 years will permit demonstration of 3% non-inferiority of test-directed treatment, assuming 5-year IDFS of 85% with standard management, equivalent to a HR of 1.22. Inclusion of patients from the feasibility study will increase the power to test for non-inferiority. Results: The OPTIMA main trial opened in January 2017. Overall recruitment (including the feasibility study) will reach 1000 in August 2018. Recruitment in Norway will commence in July 2018. Characteristics of the OPTIMA main participants recruited to 31st May 2018 are shown in the table. Main study patient characteristicsCharacteristic %Median age in years (range)57 (40-80) Menopause statusPre34 Post66 Male1Tumour size<30mm58 >=30mm42Node statuspN04 pN1mi(sn)7 pN1(sn)20 pN155 pN214Historic grade16 258 336 Conclusion: OPTIMA is one of two large scale prospective trials validating the use of test-guided chemotherapy decisions in node-positive early breast cancer. It is expected to have a global impact on breast cancer treatment. Experience from the preliminary study and close engagement with centres will aid trial success. Funding: OPTIMA is funded by the UK NIHR HTA Programme (10/34/501). Views expressed are those of the authors and not those of the HTA Programme, NIHR, NHS or the DoH. Citation Format: Stein RC, Hughes-Davies L, Makris A, Macpherson IR, Conefrey C, Rooshenas L, Pinder SE, Thomas J, Hall PS, Cameron DA, Earl HM, Naume B, Poole CJ, Rea DW, MacIntosh SA, Harmer V, Morgan A, Hulme C, McCabe C, Stallard N, Higgins H, Donovan JL, Bartlett JM, Marshall A, Dunn JA. OPTIMA: A prospective randomized trial to validate the clinical utility and cost-effectiveness of gene expression test-directed chemotherapy decisions in high clinical risk early breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT1-05-02.

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Introduction Febrile neutropenia (FN) is a recognised complication of adjuvant systemic chemotherapy which leads to hospitalisation, treatment delays and dose reductions which ultimately may compromises treatment efficacy and patient (pt) outcomes. The use of granulocyte-colony stimulating factor (G-CSF) is recommended within clinical guidelines as routine prophylaxis if the chemotherapy regimen is likely to cause FN rates of >20%.For regimens associated with FN rates of 10-20%, pt may increase the risk.(Aapro et al, 2006). Following the publication of Jones et al (2006), the Beatson West of Scotland Cancer Centre (BWOSCC) adopted TC chemotherapy as an option for patients with intermediate/high risk breast cancer as an alternative to anthracyline based regimens. This was primarily for patients who had major co-morbidities precluding anthracycline use, had prior exposure to anthracylines or who were deemed unable to tolerate a protracted course of treatment for clinical reasons. The study by Jones et al (2006) described an overall FN rate of 5% with an increased rate of FN (8%) in patients > 65 yrs, with a 4% rate in those <65yrs. Recently Soong et al (2009) reported a higher rate of FN of 50% within the first cohort of patients (6/12 pts) treated within their centre, which resulted in subsequent prophylactic G-CSF usage. A recent paper by Chan et al (2010) concluded that Asian patients who have a recognised higher incidence of Docetaxel induced myelosuppresion warranted G-CSF propylaxis. Their experience of using TC resulted in FN rates of 25% in those patients who didn't receive G-CSF, 6.3% FN rates in those who did with an absolute risk reduction of FN events by 18.7%. With this in mind, an audit of our local practice and usage of TC chemotherapy was conducted. Methods A retrospective/prospective case note review of patients treated using (neo) adjuvant TC within the BWOSCC and satellite units between October 2007 and October 2010 is being undertaken. Data in respect to the first 51 consecutive pts identified from pharmacy records, treated between October 2007 and October 2009 is available. The median age was 58 (range 27 — 81): female 50, male 1: adjuvant 50, neo-adjuvant 1. All patients received Docetaxel 75mg/m2 and Cyclophosphamide 600mg/m2 at first cycle. Results 5/51 pts (9.8%) had an episode of FN, 2 pts at cycle 1, with 1 pt at cycles 2, 3 and 4. No pt had more than 1 episode of FN.22 pts (43%) received primary G-CSF prophylaxis whilst 29pts (57%) did not. The rate of FN in the primary prophylactic group was 9% (2/22 pts) and 10% (3/29pts) in those who didn't receive G-CSF. In the G-CSF group, 1 patient required a dose reduction and 5 patients had dose delays whilst 5 patients had a dose reduction and 3 required dose delays in the non G-CSF group. Conclusion The overall rate of FN observed was approximately 10% and for a substantial proportion of patients, primary prophylaxis with G-CSF is not required. Results of ongoing data collection will be presented with regard to patient characteristics, outcomes, and indications for G-CSF primary prophylaxis in this group of patients. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-10-25.