Abstract OT3-1-10: ASTER 70s (UNICANCER phase III trial): Is personalized adjuvant treatment for women over 70 with luminal breast cancer the way to go?
Authors: Dubot C , Bourbouloux E , Tazi Y , Cure H , Ferrero J-M , Romieu G , Rigal O , Allouache D , Abadie-Lacourtoisie S , Kirscher S , Ladoire S , Malaurie E , Blot E , Rollot F , Terret C , Baffert S , Lacroix-Triki M , Falandry C , Poggionovo C , Peyro Saint Paul HP , Orsini C , Latouche A , Bonnetain F , Girre V , Brain E 
Published: August 2014

Abstract
Background
The question of the additional benefit of adjuvant chemotherapy (CT) compared to hormonal therapy alone (HT) for women &gt;70 with ER+ / HER2- breast cancer (BC) and aggressive characteristics is still unsolved. This trial compares the impact of both strategies on overall survival (OS).
Trial design
Following surgery, ∼2,000 patients will have a Genomic Grade (GG) centrally performed on FFPE specimens. Those with a high or equivocal GG will be randomized HT alone vs HT+CT. Patients with low GG will be followed as an observational cohort. The study, on-going in France since April 2012, has been recently activated in Belgium.
Eligibility criteria
Any ER+ HER2- BC after complete surgery, M0, any pT or pN. Normal organ functions. No specific BC treatment before surgery. Contralateral BC, invasive BC after ductal carcinoma in situ and isolated local invasive relapse when adjuvant systemic treatment is considered are all eligible. Multifocal or bilateral are eligible according to focus with worst GG. The G8 screening tool is used as stratification criteria for randomization.
Specific aims
OS (all deaths) is the primary endpoint. Secondary objectives include competing events, cost-effectiveness and Q-TWiST analysis, geriatric dimension, acceptability/willingness and health-related quality of life including specific ELD15. The Lee's 4-year mortality score is calculated. Translational research will focus on prognostic biomarkers and pharmacogenetic, investigating also the impact of treatments on putative ageing biomarkers as CRAMP, stathmin, EF-1α and chitinase and telomeres length.
Statistical methods
Sample size based on 4-year OS (87.5 vs 80%), bilateral test, α = 0.05, β = 0.20 and HR = 0.60.
In total, 129 events are expected, requiring 340 patients/arm. Considering those lost to follow-up, ∼700 patients in total should be included (5 extra patients/year).
Present accrual and target accrual
As of May 2013, 43 centres have included 406 Patients aged 70-88.
Only 14 GG evaluations were not performed for the following reasons: Patients consent withdrawal (n = 3), tumour block not available for the GG test (n = 5), CT not a treatment option anymore (patients or investigator's decision) (n = 2) or tumour status (ER+/HER2-) not confirmed by central review (n = 4). 8 GG evaluations are on-going.
Of 384 cases with GG report, 160 (42%), 151 (39%) and 65 (17%) were respectively GG-1 (low risk), GG-3 (high risk) and GG-EQ (equivocal); 8 (2%) tests failed for technical reasons. The proportion of high GG in the study (53%) is similar to those observed in previous studies in general BC populations (40% to 60%).
Of 216 GG-3/-EQ cases, 4 were not randomized because of distant metastases detected during extensive work-up (n = 3) and Patient refusal of CT treatment before randomization (n = 1). Five randomizations are on-going.
GG determination was obtained in 384 leading to randomization in 207, totalizing so far 30% of the projected recruitment for the primary objective. This confirms the feasibility of such multicentre strategic program with an innovative prognostic signature in the elderly BC population.
Contact information
c-orsini@unicancer.fr.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr OT3-1-10.