Giredestrant

编者按：2026年欧洲肿瘤内科学会（ESMO）年会于当地时间10月23-27日在西班牙马德里召开。会上，巴西阿雷格里港Moinhos de Vento医院Gustavo Werutsky教授汇报了III期lidERA BC研究的患者报告结局（PRO）数据（摘要号：538RO），该研究评估了口服选择性雌激素受体降解剂（SERD）giredestrant作为辅助治疗在雌激素受体阳性、HER2阴性（ER+/HER2-）早期乳腺癌患者中的疗效和安全性。PRO分析数据显示，giredestrant在显著改善无浸润性疾病生存期（iDFS）的同时，有效维持了患者的生活质量（HRQoL）与日常功能，并显著降低了副作用带来的困扰及停药风险。讲课结束后，肿瘤瞭望特邀采访了Gustavo Werutsky教授，请他就lidERA BC研究PRO数据中的关键发现、临床意义以及对未来辅助内分泌治疗格局的影响进行了深入解读。 ESMO 2026 研究者说 01 《肿瘤瞭望》：本届ESMO年会上您报告了lidERA BC研究患者报告结局（PRO）数据。能否请您先介绍一下，本次您公布了哪些患者治疗相关的内容和数据？ Gustavo Werutsky 教授 巴西阿雷格里港Moinhos de Vento医院 大家好，我是来自巴西阿雷格里港的肿瘤内科医生Gustavo Werutsky。本届ESMO 2026年会上，我报告了III期lidERA BC研究的患者报告结局（PRO）数据，该研究评估的是辅助giredestrant用于ER+/HER2-、I-III期早期乳腺癌患者的疗效和安全性。 正如大家此前所见，我们在2025年圣安东尼奥会议（SABCS）上公布了lidERA BC研究的主要终点结果，lidERA BC的主要终点结果显示，与标准内分泌治疗相比，giredestrant治疗使患者无浸润性疾病生存期（IDFS）取得了具有统计学意义的改善，3年IDFS提高了约3%（92.4% vs 89.6%）。此外，研究结果还显示，giredestrant的安全性特征表现为低级别、可管理的毒性，但有趣的是，giredestrant治疗患者因不良事件（AE）导致的停药率低于标准内分泌治疗组（5.3% vs 8.2%）。 在我报告的lidERA BC研究的PRO分析中，接受giredestrant治疗的患者，在整个治疗期间维持了生活质量，同时也维持了角色功能和躯体功能，且两组之间是相当的。正如大家所知，这对于长期治疗依从性至关重要。 我们还发现，患者关节疼痛较为常见，约60%的患者在入组试验时即有报告。然而，更多接受giredestrant的患者在研究期间从未报告过关节疼痛。有趣的是，当我们将giredestrant与标准内分泌治疗组进行比较时，我们发现，尽管研究中关节痛的不良事件发生率相似，但PRO数据显示出有意义的差异。在治疗的前六个月期间，接受giredestrant的患者中报告从未出现关节疼痛的比例高出标准内分泌治疗组约6.0%至7.5%。正如大家所了解的，这六个月正是早期内分泌治疗停药较常发生的时期。 因此，总体而言，lidERA BC研究PRO分析的结论是：在早期乳腺癌中，giredestrant相比标准内分泌治疗不仅提高了疗效，同时患者具有良好的耐受性并维持了生活质量。 上下滑动查看英文对话 At this year's ESMO Congress, you reported patient-reported outcome (PRO) data from the lidERA breast cancer trial. Could you start by walking us through what patient treatment-related content and data were presented at this meeting? Hello, I'm Gustavo Werutsky, medical oncologist from Porto Alegre, Brazil. And I'm here at the ESMO 2026 where I presented the patient-reported outcome results from the phase 3 lidERA clinical trial of adjuvant giredestrant in patients with estrogen receptor-positive, HER2-negative, stage 1 to 3 early breast cancer.  As you saw priorly, we presented the result, the primary endpoint results from lidERA BC in San Antonio last year, and the primary results of lidERA BC showed a statistical significance improvement in invasive disease-free survival by 3% with giredestrant versus the standard of care endocrine therapy. Also, we showed that the safety profile of giredestrant is characterized by low-grade, manageable toxicity, but interestingly, less drug discontinuation than standard of care endocrine therapy.  For this PRO analysis that I presented, we showed that patients on giredestrant, that received giredestrant, they maintained quality of life over the duration of treatment, but also role and physical functioning, and this was comparable between arms. And as you know, this is key for treatment adherence over time.  We also showed that joint pain was frequent, about in 60% of the patients when they entered in the trial. However, more patients on giredestrant never reported during the duration of the study. Interestingly, when we compare giredestrant to aromatase inhibitor, we saw that despite adverse events for arthralgia were similar in the trial, the PRO data showed a meaningful difference. About 6 to 7.5% more patients on giredestrant reported never experiencing joint pain over the six months duration of treatment, the first six months. And as you know, this is the period of time where the early endocrine therapy discontinuation may occur more frequently.  So in general, the conclusion of the lidERA clinical trial PRO is that giredestrant is improved the efficacy over standard of care endocrine therapy in early breast cancer, but also with a favorable tolerability and preserved quality of life. 02 《肿瘤瞭望》：lidERA BC研究的PRO数据显示，giredestrant（GIRE组）与标准内分泌在治疗（SOC ET）两组在躯体/角色功能和HRQoL方面均维持基线水平，关键症状的发生频率和严重程度也基本相当；但GIRE组报告“完全不受”副作用困扰的患者比例在每个访视点高出2-8%。您如何解读这一“症状负担相当、困扰程度更低”的现象？这是否提示giredestrant在患者耐受性体验上具有独特优势？ Gustavo Werutsky 教授 巴西阿雷格里港Moinhos de Vento医院 关于患者自我报告耐受性的问题，我们看到了一些非常有趣的发现。首先，与标准内分泌治疗相比，超过50%接受giredestrant治疗的患者报告完全没有受到giredestrant副作用的困扰。此外，约80%的患者报告完全没有受到副作用困扰，或者仅受到一点点困扰，并且在整个治疗过程中，giredestrant组的这一比例高于标准内分泌治疗组。因此，患者自我报告结局进一步印证了giredestrant的良好耐受性。 上下滑动查看英文对话 The PRO data from lidERA BC showed that both the giredestrant（GIRE）and standard-of-care endocrine therapy (SOC ET) arms maintained baseline physical/role function and HRQoL, with comparable frequency and severity of key symptoms. However, a 2–8% higher proportion of patients in the GIRE arm reported being "not at all" bothered by side effects at each visit. How do you interpret this phenomenon of "comparable symptom burden but less bother"? Does this suggest that giredestrant has a distinct advantage in the patient tolerability experience? For the second question about the self-report tolerability, we saw very interesting findings. First of all, about more than 50% of the patients on giredestrant reported not being bothered at all with giredestrant versus standard of care endocrine therapy.  Also, about 80% of the patients reported not being at all bothered by side effects or a little bit, and this was increased high in giredestrant over the treatment than standard endocrine therapy. So this reinforce the tolerability of giredestrant by self-reported outcomes.  03 《肿瘤瞭望》：辅助内分泌治疗需长期坚持，副作用困扰程度直接影响患者依从性与治疗结局。结合lidERA BC已证实的疗效获益与本次PRO数据，您认为这些发现将如何影响临床实践中ER+/HER2-早期乳腺癌辅助内分泌治疗的选择与患者沟通？后续是否计划开展更长期的PRO随访或患者偏好研究？ Gustavo Werutsky 教授 巴西阿雷格里港Moinhos de Vento医院 我认为lidERA BC研究表明，giredestrant作为单药治疗用于I-III期、中高危ER+/HER2-乳腺癌患者，在已公布的三年主要终点疗效中期分析中显示出了明确的疗效。 当我们分析PRO时，我们发现与标准内分泌治疗相比，患者报告的结局事件更少，尤其是关节痛，并且自我报告的耐受性更好。这就解释了为什么在临床试验中，我们看到giredestrant组的停药率低于标准内分泌治疗组。 因此，随着一种能够维持生活质量、更有效且具有良好安全性特征的新型内分泌药物的出现，我认为这肯定将成为早期乳腺癌的重大进展之一，就像20年前芳香化酶抑制剂获批一样，现在我们将拥有另一个疗效确切、安全性好、停药率低，并能以更好耐受性维持生活质量的治疗选择。 上下滑动查看英文对话 Adjuvant endocrine therapy requires long-term adherence, and the degree to which side effects bother patients directly affects adherence and treatment outcomes. Building on the efficacy benefit already demonstrated in lidERA BC and the current PRO data, how do you think these findings will influence the choice of adjuvant endocrine therapy and patient communication in clinical practice for ER+/HER2- early breast cancer? Are there plans for longer-term PRO follow-up or patient preference studies? So how we build this information about the PRO results in terms of the lidERA BC efficacy data and also the safety. I think lidERA BC showed that giredestrant as monotherapy for patients with stage 1 and 3 intermediate and high-risk ER-positive HER2-negative breast cancer showed a clear efficacy with three years primary endpoint where the efficacy interim analysis was released.  When we look to the PRO, we found fewer patient-reported outcomes than standard of care endocrine therapy, particularly for joint pain, and also more self-reported tolerability. And this is explain why in the clinical trial we saw less discontinuation in the arm of giredestrant versus standard of care endocrine therapy.  So, with a new endocrine agent that maintains quality of life, is more efficacious, and have a safety profile, I think this will certainly will be one of the major advancements in early breast cancer as aromatase inhibitors were approved 20 years ago, and now we are going to have another option that is efficacious, have a good safety profile, less discontinuation, and maintain the quality of life with a better tolerability.  ESMO 2026 研究简介 研究背景 在早期乳腺癌的辅助治疗（tx）中，了解患者体验至关重要，因为长期耐受性和健康相关生活质量（HRQoL）直接影响依从性和结局。III期lidERA BC研究（NCT04961996；Bardia SABCS 2025）显示，与标准内分泌治疗（SOC ET）相比，giredestrant（一种口服选择性雌激素受体降解剂及完全雌激素受体拮抗剂）具有显著的疗效获益。为补充该研究的临床疗效数据，本PRO分析从患者角度评估了功能、HRQoL、毒性和治疗负担。 研究方法 接受过手术和（新）辅助化疗（如果适合）的ER+/HER2-早期乳腺癌患者按1:1随机分配至每日一次30 mg GIRE或SOC ET（他莫昔芬/芳香化酶抑制剂）。通过EORTC QLQ-C30、PRO-CTCAE和FACT-G条目GP5在预定时间点评估预设的次要和探索性PRO终点。对随时间变化的数据进行描述性分析。 研究结果 在数据截止时（中位随访32.3个月），基线时4170例患者的问卷完成率>75%，且在大多数周期中保持>75%。两组患者在治疗期间均维持基线体力/角色功能和HRQoL，未观察到具有临床意义的恶化（变化≥10分）。两组耐受性特征相似，大多数患者报告关键症状（如关节痛、潮热、疲乏）为“偶尔/轻微/有一点”或更轻。关键症状恶化至高严重程度水平（评分3或4）的患者比例在两组间相当，包括关节痛（GIRE 43% vs SOC ET 43%）、潮热（32% vs 31%）和疲乏（19% vs 20%）。截至42个周期，在每个访视点，giredestrant组较SOC ET组报告“完全不受”副作用困扰的患者比例高出2-8%。 研究结论 lidERA BC研究的PRO数据表明，giredestrant治疗早期乳腺癌患者可维持患者的日常功能和HRQoL。虽然关键症状的频率和严重程度在两组间相当，但giredestrant组患者持续报告副作用带来的困扰更少。总之，PRO数据提示，giredestrant相较SOC ET的疗效改善并未以牺牲耐受性或HRQoL为代价。 Gustavo Werutsky 教授 巴西阿雷格里港Moinhos de Vento医院肿瘤内科医生‌‌ 拉丁美洲肿瘤合作组织（LACOG）执行主任 欧洲癌症研究与治疗组织（EORTC）乳腺癌指导委员会成员 （来源：《肿瘤瞭望》编辑部） 声 明 凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。