Abstract 148P
Background
The double blind randomized UNIRAD trial (NCT01805271) showed that adding Everolimus (EVE) to adjuvant endocrine therapy (ET) for high-risk early breast cancer (BC) does not improve 3-year disease-free survival (iDFS) compared with ET alone. We report the subgroup analysis focusing on the pre-specified stratification factors.
Methods
Women with high-risk HR+/HER2- early BC who had completed initial treatment and started adjuvant ET were randomly allocated (1:1) to placebo (Pbo) or EVE for 2 years. Primary endpoint was iDFS from randomization. ET treatment was investigator’s choice. Pre-specified stratification factors included ET treatment: tamoxifen (TAM) or aromatase inhibitor (AI); adjuvant or neo-adjuvant chemotherapy; progesterone receptor (PR) status; duration of adjuvant ET before inclusion (≤3 Years/>3 years); inclusion based on tumor stage (≥4 N+ or ≥ 1N+ after neoadjuvant treatment) or on the Endopredict test ® (≥ 1N+ and EPclin score ≥ 3.3).
Results
1278 pts were randomized between June 2013 and March 2020; 641 in the Pbo arm, and 637 in the EVE arm. 773 (60.4%) and 505 (39.4%) received AI or TAM as adjuvant ET, respectively. After a median follow up of 35.7 months, 3 years iDFS rate (iDFS-3y) was 88% in both arms (HR=0.95; 95%CI: 0.69-1.32). The only significant interaction between stratification factors and treatment group was ET backbone (p= 0.044). In TAM treated patients, iDFS-3y was 91% and 86% in the EVE and Pbo arms, respectively (HR=0.63; 95%CI: 0.369-1.05). In AI treated patients, iDFS-3y was 87% and 91% in the EVE and Pbo arms, respectively (HR=1.25; 95%CI: 0.82-1.9). Proportion of dose reduction was similar in TAM and AI patients, but early treatment discontinuation was less frequent in TAM than in AI patients: 48.0% vs 56.9%, respectively (p=0.028). Accordingly, median duration of EVE exposition was 12.8 months when combined with TAM and only 7.7 months when combined with an AI (p=0.007).
Conclusions
This subgroup analysis suggest that in patients with high risk early HR+/HER2- BC adjuvant EVE may be associated with different tolerability and therapeutic effect when combined with TAM or AI. Interaction with age or menopausal status is worth exploring.
Clinical trial identification
NCT01805271.
Editorial acknowledgement
Legal entity responsible for the study
UNICANCER.
Funding
Novartis, Myriad Genetics, French Ministry of Health (PHRC 2012).
Disclosure
P.H. Cottu: Financial Interests, Personal and Institutional, Advisory Role: Pfizer; Financial Interests, Personal and Institutional, Advisory Role: Lilly; Financial Interests, Institutional, Advisory Role: Roche Genentech; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Novartis; Non-Financial Interests, Personal, Other, Travel: Roche; Non-Financial Interests, Personal, Other, Travel: Pfizer; Financial Interests, Institutional, Advisory Role: NanoString Tech; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Pierre Fabre; Financial Interests, Institutional, Advisory Role: Novartis. F. Dalenc: Financial Interests, Institutional, Advisory Role: Novartis; Financial Interests, Institutional, Advisory Role: Roche; Financial Interests, Institutional, Advisory Role: AstraZeneca; Financial Interests, Institutional, Advisory Role: Pfizer; Financial Interests, Institutional, Advisory Role: MSD; Financial Interests, Institutional, Advisory Role: Pierre Fabre; Non-Financial Interests, Personal, Other, Travel accommodation: Roche; Non-Financial Interests, Personal, Other, Travel accommodation: Pfizer; Non-Financial Interests, Personal, Other, Travel accommodation: Novartis; Non-Financial Interests, Personal, Other, Travel accommodation: Amgen. D. Cameron: Financial Interests, Institutional, Advisory Role: Novartis; Financial Interests, Institutional, Advisory Role: Pfizer; Financial Interests, Institutional, Advisory Role: Lilly. A. Hardy-Bessard: Financial Interests, Personal and Institutional, Advisory Role: Novartis; Financial Interests, Personal and Institutional, Advisory Role: Pfizer; Financial Interests, Personal and Institutional, Advisory Role: AstraZeneca; Financial Interests, Personal and Institutional, Advisory Role: MSD; Financial Interests, Personal and Institutional, Advisory Role: Clovis; Non-Financial Interests, Institutional, Other, Travel: Roche. S. Giacchetti: Financial Interests, Personal and Institutional, Advisory Role: Pfizer; Financial Interests, Personal and Institutional, Advisory Role: Novartis. J. Bliss: Financial Interests, Institutional, Advisory Role: Novartis; Financial Interests, Institutional, Advisory Role: AstraZeneca; Financial Interests, Institutional, Advisory Role: Clovis Oncology; Financial Interests, Institutional, Advisory Role: Janssen Cilag; Financial Interests, Institutional, Advisory Role: Merck; Financial Interests, Institutional, Advisory Role: Puma Biotech; Financial Interests, Institutional, Advisory Role: Pfizer; Financial Interests, Institutional, Advisory Role: Medivation; Financial Interests, Institutional, Advisory Role: Eli Lilly. F. André: Financial Interests, Personal and Institutional, Advisory Role: Pfizer; Non-Financial Interests, Personal, Other, Travel: Pfizer; Financial Interests, Institutional, Research Grant: Pfizer; Non-Financial Interests, Personal, Other, Travel: Roche; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Personal and Institutional, Advisory Role: Roche; Financial Interests, Personal and Institutional, Advisory Role: Lilly; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Genentech; Financial Interests, Institutional, Advisory Role: NanoString Technologies. T. Bachelot: Non-Financial Interests, Personal, Other, Travel: Roche; Non-Financial Interests, Personal, Other, Travel: Novartis; Non-Financial Interests, Personal, Other, Travel: AstraZeneca; Non-Financial Interests, Personal, Other, Travel: Pfizer; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Personal and Institutional, Advisory Role: Pfizer; Financial Interests, Personal and Institutional, Advisory Role: Roche; Financial Interests, Personal and Institutional, Advisory Role: Genentech; Financial Interests, Personal and Institutional, Advisory Role: Lilly. All other authors have declared no conflicts of interest.