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

Background Optimal therapy following breast-conserving surgery (BCS) in older adults with low-risk, early-stage breast cancer remains uncertain. The EUROPA trial is a non-inferiority, phase 3 randomized study designed to compare the effects of radiation therapy (RT) and endocrine therapy (ET) as single-modality treatments on health-related quality of life (HRQOL) and ipsilateral breast tumour recurrence (IBTR) outcomes in this population.

Methods Eligible patients were women aged 70 years or older with histologically confirmed, stage I, luminal A-like breast cancer, who had undergone BCS and had an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomized 1:1 to receive single-modality ET or RT. ET consisted of daily oral aromatase inhibitors or tamoxifen, while RT was administered as either whole breast or partial breast irradiation, delivered in 5 to 15 fractions. Randomization was stratified by G8 health status and 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 EORTC QLQ-C30 at 24 months, and 5-year IBTR rates. This interim analysis reports results for the HRQOL endpoint based on data from 152 patients who completed the 24-month assessment. The study is ongoing and actively recruiting (ClinicalTrials.gov, NCT04134598).

Findings Between March 4, 2021, and June 14, 2024, 731 women were randomized to receive RT (n=365) or ET (n=366). This analysis included 104 patients in the RT arm and 103 in the ET arm, predominantly Caucasian (98%), with a median follow-up of 23·9 months (IQR 22·9–24·2). The mean baseline GHS score was 71·9 (SD 19·05) in the RT and 75·5 (SD 19·34) in the ET arm. At 24 months, GHS scores declined by -1·1 in the RT and -10·0 in the ET arm, with an age- and G8 score-adjusted mean difference of 6·39 favouring RT (95% CI 0·14 to 12·65; p=0·0453). Treatment-related adverse events (AEs) were less frequent in the RT (65 [67%]) compared to the ET arm (76 [85·4%]). The most common grade 1–2 AEs were breast pain (37 [38·1%]), fatigue (32 [33%]), and arthralgia (28 [28·9%]) in the RT arm, and arthralgia (62 [69·7%]), fatigue (40 [44·9%]), and hot flashes (29 [32·6%]) in the ET arm. The most frequent grade 3–4 AE was arthralgia in the ET arm (6 [6·7%]). Serious AEs were reported in 15 patients (15·5%) in the RT arm and 13 (14·6%) in the ET arm.

Interpretation ET was associated with a greater reduction in HRQOL GHS compared to RT at 24 months. While these interim results suggest RT may better preserve HRQOL in older women with low-risk early breast cancer, further data on disease control outcomes and final patient accrual are needed to draw definitive conclusions.