T. Bachelot1, F. Dalenc2, S. Chabaud3, P.H. Cottu4, D. Allouache5, E. Brain6, J.P. Jacquin7, J. Grenier8, L. Venat Bouvet9, M. Brunt10, M. Campone11, F. Del Piano12, M. Debled13, A.C. Hardy Bessard14, S. Giacchetti15, J. Bliss16, J.L. Canon17, J. Lemonnier18, D. Cameron19, F. André20
Everolimus (EVE) in combination with hormone therapy (HT) has been shown to improve progression free survival for advanced HR+/HER2- breast cancer (BC). The double blind randomized UNIRAD trial aimed to investigate the benefit of adjuvant EVE in combination with standard adjuvant HT versus HT alone for women with high-risk HR+/HER2- early BC.
Women with high-risk HR+/HER2- early BC (>4 N+ or 1-3 N+ and EPclin score ≥ 3.3) who had completed initial treatment and started adjuvant HT for < 3 years were randomly allocated (1:1) to placebo (P-HT) or EVE (E-HT) for 2 years. HT treatment was investigator’s choice. The primary endpoint was disease-free survival (DFS) from randomization. Secondary endpoints included metastasis free survival (MFS), overall survival (OS) and toxicity. UNIRAD is registered with ClinicalTrials.gov (NCT01805271).
1278 patients (pts) were randomized between June 2013 and March 2020 in 72 centers/3 countries; 641 in the P-HT arm, and 637 in the E-HT arm. The present final analysis was conducted after decision of stopping the study for futility at the first pre-planned interim analysis in March 2020. Median duration of HT before randomization was 15 months (IQR: 4.9-29.9). 700 (55%) and 544 pts (44%) received aromatase inhibitor and tamoxifen, respectively. After a median follow up of 35.7 months (range: 0.7-85), 147 events were recorded. Median 3 years DFS was 88% in both arms (HR=0.95; 95%CI: 0.69-1.32)). MFS (HR=0.88; 95%CI: 0.62-1.25) and OS (HR=1.09, 95CI: 0.62-1.92) did neither differ. 187 pts (30%) vs 101 pts (16%) presented at least one grade 3-4 adverse event in the E-HT and P-HT arms, respectively. There was 1 toxic death in the E-HT arm. Dose reduction and early treatment discontinuation due to AEs respectively occurred in 34% and 35% of pts in the E-HT arm, vs 12% and 10% in the P-HT arm (p<0.001). Median duration of EVE exposition was 9.2 months (IQR=2.1-23.4).
Everolimus given in combination with adjuvant HT for high risk early BC did not improve 3-year DFS compared with HT alone. Follow-up will continue to evaluate long-term outcomes.
Clinical trial identification
- 1 Oncology Department, Centre Léon Bérard, 12345 - Lyon/FR
- 2 Oncology Department, Centre Claudius-Regaud, 31052 - Toulouse/FR
- 3 Department Of Clinical Research And Innovation, Centre Léon Bérard, 12345 - Lyon/FR
- 4 Oncology Department, Curie Site Paris, 75005 - Paris/FR
- 5 Oncology Department, Centre Francois Baclesse, 14076 - Caen/FR
- 6 Oncology Department, Curie Site Saint-Cloud, Saint-Cloud/FR
- 7 Oncology Department, Institut de Cancérologie Lucien Neuwirth, 42270 - Saint-Étienne/FR
- 8 Oncology Department, Institut Ste Catherine, 84082 - Avignon/FR
- 9 Oncology Department, Chu de Limoges - Hopital Dupuytren, Limoges/FR
- 10 Oncology Department, Royal Stoke Hospital, Stoke-on-Trent/GB
- 11 Medical Oncology Department, ICO Institut de Cancerologie de l'Ouest René Gauducheau, 44805 - Saint-Herblain/FR
- 12 Oncology Department, Hopitaux du Leman - Site Georges Pianta, Thonon-les-Bains/FR
- 13 Oncology Department, Institut Bergonié, 33076 - Bordeaux/FR
- 14 Oncology Department, Centre CARIO - HPCA, Plérin sur Mer/FR
- 15 Oncology Department, Hopital Saint Louis, Paris/FR
- 16 Clinical Trials And Statistics Unit, ICR - The Institute of Cancer Research, London/GB
- 17 Oncology Department, Centre Hospitalier Notre Dame et Reine Fabiola - Grand Hopital de Charleroi, Charleroi/BE
- 18 R&d Department, UNICANCER - UCBG, Le Kremlin-Bicêtre/FR
- 19 Oncology Department, Western General Hospital, Edinburgh/GB
- 20 Oncology Department, Gustave Roussy, Villejuif/FR