Ten-year update of HOBOE phase III trial comparing triptorelin plus either tamoxifen or letrozole or zoledronic acid + letrozole in premenopausal hormone receptor-positive early breast cancer patients
Adriano Gravina, P. Gargiulo, Michelino De Laurentiis, Laura Arenare, Sabino De Placido, M. Orditura, Saverio Cinieri, F Riccardi, Angela Stefania Ribecco, Carlo Putzu, Lucia Del Mastro, Emma Rossi, F. Ciardiello, Francesca Di Rella, Francesco Nuzzo, Carmen Pacilio, R. Caputo, Daniela Cianniello, Valeria Forestieri, Mario Giuliano, Grazia Arpino, Luís Orlando, Carmela Mocerino, Carla Schettino, M.C. Piccirillo, Ciro Gallo, Federica Perrone
Abstract
BACKGROUND: The Hormonal Bone Effects (HOBOE) study tested whether adjuvant triptorelin plus either letrozole (L) or zoledronic acid (Z) plus L (ZL) was more effective than tamoxifen (T) in premenopausal patients with hormone receptor-positive (HR+) early breast cancer (BC). Here we report the long-term follow-up analysis. PATIENTS AND METHODS: HOBOE (ClinicalTrials.gov number NCT00412022) is an open-label, three-arm, randomised, phase III trial that involved 16 centres in Italy. One thousand and sixty-five premenopausal patients with HR+ early BC receiving triptorelin were randomly assigned (1 : 1 : 1) to adjuvant T, L or ZL for 5 years. Cancer recurrence, second breast or non-breast cancer and death were considered events for the intention-to-treat disease-free survival (DFS) analysis. RESULTS: As of 24 October 2024 at a median follow-up of 9.2 years, 199 DFS events and 79 deaths were reported. Both ZL and L improved DFS over T, with a hazard ratio (HR) of 0.58 [95% confidence interval (CI) 0.41-0.82; P = 0.002] for ZL versus T and 0.69 (95% CI 0.49-0.97, P = 0.030) for L versus T. No statistically significant difference in OS was reported (global log-rank P = 0.103). The previously reported statistically significant interaction with human epidermal growth factor receptor 2 (HER2) status was confirmed for ZL versus T comparison (P = 0.007). CONCLUSION: In this updated analysis, L plus triptorelin, with or without Z, demonstrated a statistically significant DFS improvement over T plus triptorelin for the adjuvant treatment of early BC in premenopausal patients.