Background

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.

Methods

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.

Findings

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 71·9 (SD 19·1) in the radiotherapy group and 75·5 (19·3) in the endocrine therapy group. At 24 months, the age-adjusted, G8 score-adjusted mean change from baseline in GHS was –3·40 (95% CI –7·82 to 1·03; p=0·13) in the radiotherapy group and –9·79 (–14·45 to –5·13; p<0·0001) in the endocrine therapy group, with an adjusted mean difference of 6·39 (0·14 to 12·65; p=0·045) favouring radiotherapy. Treatment-related adverse events were less frequent in the radiotherapy group (65 [67%] of 97 patients) compared with the endocrine therapy group (76 [85%] of 89). The most common grade 3–4 adverse events were arthralgia (six [7%] of 89 in the endocrine therapy group vs 0 of 97 in the radiotherapy group), pelvic organ prolapse (three [3%] vs 0), fatigue, hot flashes, myalgia, bone pain, and fractures (two [2%] vs 0 for each). Serious adverse events were reported in 15 (15%) patients in the radiotherapy group and 13 (15%) in the endocrine therapy group. There were no treatment-related deaths in either group.

Interpretation

Endocrine therapy was associated with a greater reduction in HRQOL, as measured by GHS, compared with radiotherapy at 24 months. While these interim results suggest radiotherapy might 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.

Funding

Fondazione Radioterapia Oncologica.

中文翻译：

---

70 岁及以上管腔 A 样早期乳腺癌 （EUROPA） 女性保乳手术后单模式内分泌治疗与放疗的比较：一项 3 期、非劣效性、随机试验的预先计划中期分析

 背景

对于患有低风险早期乳腺癌的老年人，保乳手术后的最佳治疗仍不确定。EUROPA 试验旨在比较放疗和内分泌治疗作为单一模式治疗对该人群健康相关生活质量 （HRQOL） 和同侧乳腺肿瘤复发 （IBTR） 结局的影响。

 方法

这项非劣效性 3 期随机研究在意大利 （17 个中心） 和斯洛文尼亚 （1 个中心） 的 18 家学术医院进行。符合条件的患者是 70 岁或以上经组织学证实的 I 期管腔 A 样乳腺癌的女性，她们接受了保乳手术，并且东部肿瘤合作组体能状态为 0 或 1。患者被随机分配 （1：1） 接受单模式内分泌治疗或放疗。内分泌治疗包括每日口服芳香化酶抑制剂或他莫昔芬，根据临床判断，计划总持续时间为 5-10 年，而放疗以全乳或部分乳腺照射的形式进行，分 5-15 次进行。根据老年 8 （G8） 筛查工具按健康状况和年龄进行随机分组，分配隐藏且无盲法。共同主要终点是 HRQOL 的变化，根据欧洲癌症研究与治疗组织生活质量问卷 30 项核心模块的全球健康状况 （GHS） 量表在 24 个月时进行评估，以及 5 年 IBTR 率（此处未报告）。在至少 152 名患者完成 24 个月的 GHS HRQOL 评估后，进行这项预先计划的中期分析。安全人群包括随机分组后至少接受一次研究干预的患者。该研究已在 ClinicalTrials.gov、NCT04134598 注册，并且正在进行并积极招募。

 发现

在 2021 年 3 月 4 日至 2024 年 6 月 14 日期间，731 名女性被随机分配接受放疗 （n=365） 或内分泌治疗 （n=366）。该分析包括放疗组 104 例患者和内分泌治疗组 103 例患者，中位随访时间为 23·9 个月 （IQR 22·9–24·2）。患者以白人为主 （207 人中的 204 [99%]），放疗组的中位年龄为 75·0 岁 （IQR 73·0–80·0），内分泌治疗组为 74·0 岁 （72·0–80·0）。放疗组 86 例患者和内分泌治疗组 75 例患者完成了 24 个月的 HRQOL 评估。放疗组平均基线 GHS 评分为 71·9 （SD 19·1），内分泌治疗组为 75·5 （19·3）。在 24 个月时，放疗组经年龄调整的 G8 评分调整后 GHS 相对于基线的平均变化为 -3·40（95% CI -7·82 至 1·03;p=0·13），内分泌治疗组为 -9·79（-14·45 至 -5·13;p<0·0001），调整后的平均差为 6·39（0·14 至 12·65;p=0·045）有利于放疗。与内分泌治疗组 （89 例中的 76 例 [85%] 相比，放疗组 （97 例患者中的 65 例 [67%]）与治疗相关的不良事件发生率较低。最常见的 3-4 级不良事件是关节痛（内分泌治疗组 89 例中有 6 例 [7%] 发生，放疗组 97 例中有 0 例）、盆腔器官脱垂（3 例 [3%] 对 0 例）、疲劳、潮热、肌痛、骨痛和骨折（各 2 例 [2%] 对 0 例）。放疗组 15 例 （15%） 患者和内分泌治疗组 13 例 （15%） 患者报告了严重不良事件。两组均无治疗相关死亡。

 解释

与放疗相比，内分泌治疗与 24 个月时 HRQOL 的更大降低相关，通过 GHS 测量。虽然这些中期结果表明，放疗可能更好地保留患有低风险早期乳腺癌的老年女性的 HRQOL，但需要有关疾病控制结果和最终患者应计的进一步数据来得出明确的结论。

 资金

Fondazione Radioterapia Oncologica.