编者按：在2024年SABCS大会上，意大利佛罗伦萨大学附属医院的Icro Meattini教授分享了EUROPA试验的重要研究成果。这项III期随机对照试验聚焦于70岁及以上、I期Luminal型乳腺癌女性患者，旨在比较仅接受放射治疗（RT）与仅接受内分泌治疗（ET）对健康相关生活质量（HRQoL）和同侧乳腺肿瘤复发率（IBTR）的影响。肿瘤瞭望特邀采访了Icro Meattini教授，请他就该项研究的设计及未来的研究方向进行了介绍。

 

Icro Meattini教授：我是来自意大利佛罗伦萨大学的Icro Meattini。EUROPA是一项针对70岁及以上患者群体的III期临床试验。这些患者是一个非常特殊的群体，因为她们的治疗有时需要进一步优化，所以目前的指南建议这些患者接受保乳手术。如果乳腺癌患者为雌激素受体阳性（Luminal型乳腺癌），大多数患者会接受内分泌治疗，同时也通常会接受术后放射治疗。因此，EUROPA试验的目标是探索在仅使用内分泌治疗或放疗作为单一治疗方案时，对患者健康相关生活质量的具体影响。值得一提的是，生活质量是我们研究中采用的一个全新的主要终点。

 

 

Oncology Frontier:How did you decide to include women 70 years of age or older with stage I Luminal breast cancer in the design of the EUROPA trial?What do you think are the special needs or challenges in treatment options for patients in this age group and disease type?

 

Prof.Icro Meattini:I’m Icro Meattini from University of Florence，Florence，Italy.The EUROPA trial is a phase 3 trial based on this cohort of patients，that it’s really a peculiar cohort of patients，70 years old，that sometimes optimization of treatment can be required.So for that reason currently the guidelines recommend breast conserving surgery and the majority of patients receive endocrine therapy if estrogen receptor positive and the majority of patients also receive post-operative radiation therapy.So the aim of the EUROPA trial is to try to identify the health-related quality of life impact of both endocrine and radiation therapy as a single modality option.And the quality of life is the quite brand new primary endpoint that we use in our study.

 

Icro Meattini教授：这是一项针对本试验中前152例招募并随机分组的患者进行的中期分析，该试验的最终样本量预计将达到约1000例患者。我们已经观察到一个重要信号，即相比仅接受放射治疗的患者，接受内分泌治疗的患者在健康相关生活质量方面显著下降。这一结果并不完全出乎意料。我们认为，这些可能较为脆弱的患者更适合选择两种治疗方案中的一种，而放射治疗可能在改善健康相关生活质量方面表现出更优的效果。

 

 

Oncology Frontier:In preplanned interim analysis of the EUROPA trial，patients treated with endocrine therapy(ET)had a significant decrease in health-related quality of life(HRQoL)compared with those treated with radiation therapy(RT).How do you interpret this result?Is this more than you expected?

 

Prof.Icro Meattini:Yeah，this is an interim analysis on the first 152 patients recruited and randomised in this trial.The final sample size of the trial will be around 1，000 patients.We already see an important signal in terms of decrease of health-related quality of life in patients receiving endocrine therapy as compared to patients receiving only radiotherapy.It’s not really unexpected.We do believe that probably these potentially fragile patients may be suitable for one of the two treatment options and probably radiotherapy might be related to better outcomes in terms of health-related quality of life.

 

Icro Meattini教授：这是该项研究的另外一个关键点。我们在研究中平衡了健康相关生活质量和同侧乳腺肿瘤复发率（IBTR）。首先，我们希望确保在省略内分泌治疗或放射治疗的情况下，局部控制率能够保持相当。所以局部控制效果是通过同侧乳腺肿瘤复发率来衡量的，这也是该研究的两个主要终点之一。不良事件无疑是这些患者中一个至关重要的因素，因为它与健康相关生活质量息息相关。事实上，接受内分泌治疗的患者中，约有20%在试验期间出现了新发不良事件，这或许可以解释健康相关生活质量下降的原因。

 

 

Oncology Frontier:How do you balance the efficacy of treatment with patient safety in the EUROPA trial?What do you think are the safety issues that need special attention，especially in elderly patients?

 

Prof.Icro Meattini:That’s another important point.We balance both health-related quality of life and ipsilateral breast tumour recurrence.So first of all，we want to assure that omitting endocrine or radiation therapy，the local control will be equivalent.So local control as measured by ipsilateral breast tumour recurrence，rate recurrence，is one of the two primary endpoints of the study.Of course，adverse events is a crucial feature in these patients because it’s strictly related to health-related quality of life.In fact，around 20%of patients more in the endocrine therapy treated patients had adverse events emergent during the trials.This might explain this effect in health-related quality of life.

 

Icro Meattini教授：当然，目前这项研究还不足以改变临床实践，因为它只是一个预设的中期分析。下一步是完成针对1000名患者的五年随访，以获取完整的研究结果。这需要一定的时间，但我们相信，这将为患者带来更多的治疗选择。一些患者可能适合同时接受内分泌治疗和放射治疗，而对于较为脆弱的患者，在经过充分的患者咨询后，我们可以根据具体情况选择仅采用内分泌治疗，或更有利于改善生活质量的放射治疗。

 

Oncology Frontier:Based on the results of the current interim analysis，what do you think will be the future changes or trends in the treatment strategy for older patients with breast cancer?How do you plan to further advance this study to gain a more complete understanding of the effects of different treatment options on patients’long-term quality of life?

 

Prof.Icro Meattini:Of course，this is not a practice-changing study at this point because this is a pre-planned interim analysis.So the next step is having the full results on all the 1，000 patients at five years.So we need time，but we do believe that we’ll increase the options for these patients，that some patients will be suitable for receiving both treatment，endocrine and radiation therapy.But in case of fragile patients，we can decide after an important patient counseling to prescribe endocrine therapy or maybe better impacting on quality of life，radiation therapy only.

 

Icro Meattini教授：当然，我们预计局部复发率会非常高，但我们仍将努力识别与患者复发相关的潜在生物标志物。不过，这是一项子研究，需在明确最终事件发生率后再进一步深入探索。

 

Oncology Frontier:In the meantime，do you plan to explore other factors or biomarkers that might influence patient outcomes?

 

Prof.Icro Meattini:We are not expecting very high rate of local relapse，of course，but then we will try to identify potential biomarkers related to the patient their recourse.But this is a sub-study，of course，and when we’ll have an idea of the final events rate.

 

Icro Meattini教授

意大利佛罗伦萨大学附属医院乳腺科及乳腺癌MDT主任