Single-modality endocrine therapy versus radiotherapy after breast-conserving surgery in women aged 70 years and older with luminal A-like early breast cancer (EUROPA): a preplanned interim analysis of a phase 3, non-inferiority, randomised trial

• Published in: The lancet oncology 2024-12
• Main Authors: Meattini, Icro, De Santis, Maria Carmen, Visani, Luca, Scorsetti, Marta, Fozza, Alessandra, Meduri, Bruno, De Rose, Fiorenza, Bonzano, Elisabetta, Prisco, Agnese, Masiello, Valeria, La Rocca, Eliana, Spoto, Ruggero, Becherini, Carlotta, Blandino, Gladys, Moscetti, Luca, Colciago, Riccardo Ray, Audisio, Riccardo A, Brain, Etienne, Caini, Saverio, Hamaker, Marije, Kaidar-Person, Orit, Lambertini, Matteo, Marrazzo, Livia, Saieva, Calogero, Spanic, Tanja, Strnad, Vratislav, Wheelwright, Sally, Poortmans, Philip M P, Livi, Lorenzo, Kaidar Person, Orit, Martella, Francesca, Vinante, Lorenzo, Ramella, Sara, Gatti, Marco, Pedretti, Sara, Vici, Patrizia, Di Muzio, Nadia G, Pastorino, Alice, Leonardi, Maria Cristina, Ratosa, Ivica, Verbancic, Jure
• Format: Article
• Language: English
• ISSN: 1470-2045; 1474-5488; 1474-5488
• DOI: 10.1016/S1470-2045(24)00661-2

Optimal therapy following breast-conserving surgery in older adults with low-risk, early-stage breast cancer remains uncertain. The EUROPA trial aims to compare the effects of radiotherapy and endocrine therapy as single-modality treatments on health-related quality of life (HRQOL) and ipsilateral breast tumour recurrence (IBTR) outcomes in this population. This non-inferiority, phase 3, randomised study was conducted at 18 academic hospitals across Italy (17 centres) and Slovenia (one centre). Eligible patients were women aged 70 years or older with histologically confirmed, stage I, luminal A-like breast cancer, who had undergone breast-conserving surgery and had an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (1:1) to receive single-modality endocrine therapy or radiotherapy. Endocrine therapy consisted of daily oral aromatase inhibitors or tamoxifen, for a total planned duration of 5–10 years as per clinical discretion, while radiotherapy was administered as either whole breast or partial breast irradiation, delivered in 5–15 fractions. Randomisation was stratified by health status according to the Geriatric 8 (G8) screening tool and by age, with allocation concealed and no blinding. The co-primary endpoints were the change in HRQOL, assessed by the global health status (GHS) scale of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire 30-item core module at 24 months, and 5-year IBTR rates (not reported here). This preplanned interim analysis was performed once at least 152 patients completed the 24-month GHS HRQOL assessment. The safety population comprised patients who received the study intervention at least once after randomisation. The study is registered with ClinicalTrials.gov, NCT04134598, and is ongoing and actively recruiting. Between March 4, 2021, and June 14, 2024, 731 women were randomly assigned to receive radiotherapy (n=365) or endocrine therapy (n=366). This analysis included 104 patients in the radiotherapy group and 103 in the endocrine therapy group, with a median follow-up of 23·9 months (IQR 22·9–24·2). Patients were predominantly White (204 [99%] of 207) and the median age was 75·0 years (IQR 73·0–80·0) in the radiotherapy group and 74·0 years (72·0–80·0) in the endocrine therapy group. 86 patients in the radiotherapy group and 75 in the endocrine therapy group completed the 24-month HRQOL assessment. The mean baseline GHS score was 71·