Abstract GS1-03: Peri-operative aromatase inhibitor treatment in determining or predicting longterm outcome in early breast cancer – The POETIC* Trial (CRUK/07/015)
Authors: Robertson JFR , Dowsett M , Bliss JM , Morden JP , Wilcox M , Evans A , Holcombe C , Horgan K , Kirwan C , Mallon E , Sibbering M , Skene A , Vidya R , Cheang M , Banerji J , Kilburn L , Dodson A , Smith I 
Published: February 2018

Background

Experimental evidence (Fisher et al, 1989) & a small clinical trial (IMPACT) respectively suggested peri-operative endocrine therapy (ET) may improve long-term disease-related outcome in patients undergoing primary surgery for ER positive (ER+) breast cancer (BC) & that tumor Ki67 levels after 2 weeks of peri-operative aromatase inhibitor (POAI) therapy might offer an effective way of predicting outcome & the need for additional adjuvant treatment. POETIC (*Peri-Operative Endocrine Therapy - Individualising Care) is a phase III randomized controlled trial designed to test these hypotheses & provide data to determine whether 2 week Ki67 improves prediction beyond that by baseline Ki67 of the group who have a higher risk of relapse in the first years after diagnosis in spite of best current standard of care.

Patients & methods

Postmenopausal patients with ER+ BC were randomised 2:1 to either, POAI (centre choice: letrozole 2.5mg or anastrozole 1mg daily) for 14 days prior to & 14 days following surgery or no POAI (Control). Randomization was stratified by treating center; adjuvant treatment was per UK routine practice. Tissue samples were collected at baseline & surgery (FFPE) for blinded Ki67 testing. Primary endpoint was Time to Recurrence (TTR: time from randomization to loco-regional or distant recurrence or BC death). A secondary endpoint was Ki67 at baseline & after 2 weeks of AI.

Results

Between 2008 & 2014, 4480 patients (2976 AI, 1504 Control) were randomized from 130 UK centers. Median age was 67 (IQR 62-75), 18% had grade 3 tumors, 39% were node positive and 61% had tumor size&gt;2cm. For adjuvant ET 314 patients (7.2%) received tamoxifen (Tam), 3695 (84.6%) an AI, 251 (5.7%) Tam changing to AI and 109 (2.5%) changing from AI to Tam. On 8 August 2017, median follow-up was 60.7 months (IQR 49.5 to 72.2).

408/4480 (9.1%) patients have had a TTR event; 263 (8.8%) allocated to POAI compared to 145 (9.6%) controls: HR=0.91 (95%CI: 0.74, 1.12) Log-rank p=0.37. Adjusted HR=0.91 (95%CI: 0.74, 1.11).

The relationship of Ki67 (baseline & after 2 weeks) with TTR in both the POAI & control groups will be presented for the overall ER+ population & HER2 defined sub-groups.

Discussion

There was no significant evidence that four weeks of POAI improved TTR compared with no POAI. POETIC will provide definitive evidence on the role of 2 week POAI-treated Ki67 to inform future practice & trials in terms of the potential to identify a group of patients for whom current standard of care appears insufficient in the few years post diagnosis.

Citation Format: Robertson JFR, Dowsett M, Bliss JM, Morden JP, Wilcox M, Evans A, Holcombe C, Horgan K, Kirwan C, Mallon E, Sibbering M, Skene A, Vidya R, Cheang M, Banerji J, Kilburn L, Dodson A, Smith I. Peri-operative aromatase inhibitor treatment in determining or predicting longterm outcome in early breast cancer – The POETIC* Trial (CRUK/07/015) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr GS1-03.