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在期中分析中，giredestrant相较于标准内分泌单药治疗显示出统计学显著且具有临床意义的获益。
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这些前所未有的结果支持了其有望成为早期乳腺癌领域新的内分泌治疗标准方案。
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数据将在即将召开的医学会议上公布，并与全球卫生监管机构分享。
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继2025年ESMO大会上公布的evERA研究[1]之后，lidERA 是giredestrant第二个取得阳性结果的III期研究。
2025年11月18日，巴塞尔——罗氏宣布了lidERA 乳腺癌III期研究取得阳性结果。该研究评估了研究药物giredestrant作为辅助内分泌治疗，用于雌激素受体阳性(ER+)、人表皮生长因子受体2阴性(HER2-)的早期乳腺癌患者。该研究在预设的期中分析中，达到了其主要终点，结果显示giredestrant与标准内分泌治疗相比，在无浸润性疾病生存期方面取得了具有统计学显著性和临床意义的改善。lidERA是首次证实在早期乳腺癌阶段，通过选择性雌激素受体降解剂(SERD)辅助治疗，可以取得显著获益的III期试验。大多数乳腺癌患者在确诊时处于早期阶段。[2]
罗氏首席医学官罗氏全球药品开发负责人Levi Garraway博士：“研究结果进一步彰显了giredestrant的潜力，其将有望成为早期乳腺癌患者内分泌治疗的全新选择，并为早期乳腺癌患者带来治愈希望。鉴于ER阳性乳腺癌约占所有确诊病例的70%，这些结果，结合近期在晚期ER阳性乳腺癌领域的数据，提示giredestrant有潜力改善许多此类患者的预后。”
尽管期中分析时总生存期数据尚不成熟，但已观察到了明显的阳性趋势。Giredestrant的耐受性良好，不良事件与其已知的安全性特征一致，未观察到非预期的安全性发现。lidERA的数据将在即将召开的医学会议上公布，并与各国卫生监管机构分享，旨在将这一潜在的治疗方案带给全世界的患者。
ER阳性乳腺癌约占全部乳腺癌病例的70%[3]。目前，高达三分之一的早期乳腺癌患者在接受辅助内分泌治疗期间或之后，会经历复发[4-6]。此外，许多患者由于安全性或耐受性问题不得不提前中断或停止治疗，从而增加了死亡风险[7,8]。这些局限性凸显了对更有效、耐受性更好的治疗方案的需求，以提高治疗依从性，并预防或延迟疾病复发。
lidERA是giredestrant继evERA乳腺癌研究（已在2025年欧洲肿瘤内科学会大会上公布）之后的又一个阳性III期研究结果[1]。lidERA试验设计的科学性基于了既往新辅助治疗试验结果的支撑，包括coopERA在内试验已证明，giredestrant在降低恶性细胞分裂（Ki67水平）方面优于芳香化酶抑制剂[9]。越来越多的证据支持，在ER阳性早期和晚期乳腺癌中，与目前的标准内分泌治疗相比，giredestrant具有显著改善患者预后的潜力[1]。
罗氏为giredestrant开展的众多临床开发项目，涵盖了多种治疗阶段的多线治疗，体现了我们致力于为尽可能多的ER阳性乳腺癌患者提供创新药物的承诺。
关于lidERA乳腺癌研究
lidERA乳腺癌研究[NCT04961996]是一项III期、随机、开放标签的多中心研究，旨在评估在I-III期中高危雌激素受体阳性(ER+)、人表皮生长因子受体2阴性（HER2-)乳腺癌患者中，giredestrant辅助治疗相较于标准内分泌治疗的疗效和安全性。超过4,100名患者参加了该研究[10]。其主要终点是无浸润性疾病生存期(iDFS)，排除了其他器官的非相关癌症（即第二原发非乳腺癌）[10]。关键次要终点包括总生存期、包含第二原发非乳腺癌的iDFS、无病生存期和安全性[10]。
关于giredestrant
Giredestrant是一种在研的、口服、强效的新一代选择性雌激素受体降解剂和完全拮抗剂[11]。Giredestrant旨在阻止雌激素与雌激素受体结合，触发受体分解（称为降解），从而阻止或减缓癌细胞的生长[12]。
Giredestrant拥有广泛的临床开发项目，正在五项公司申办的 III期临床试验中进行研究，涵盖多种治疗阶段和治疗线，以尽可能多地惠及患者：
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Giredestrant对比标准内分泌治疗(SoC ET)用于ER阳性、HER2阴性早期乳腺癌的辅助治疗(lidERA Breast Cancer; NCT04961996)[10]。
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Giredestrant联合依维莫司对比SoC ET联合依维莫司，用于ER阳性、HER2阴性、局部晚期或转移性乳腺癌(evERA Breast Cancer; CT05306340)[13]。
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Giredestrant联合哌柏西利，对比来曲唑联合哌柏西利，用于ER阳性、HER2阴性、内分泌敏感、复发性局部晚期或转移性乳腺癌(persevERA Breast Cancer; NCT04546009)[14]。
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Giredestrant联合研究者选择的细胞周期蛋白依赖性激酶4/6 (CDK4/6)抑制剂对比氟维司群联合CDK4/6抑制剂，用于对辅助内分泌治疗耐药的ER阳性、HER2阴性晚期乳腺癌(pionERA Breast Cancer; NCT06065748)[15]。
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Giredestrant联合赫双妥®【帕妥珠曲妥珠单抗注射液（皮下注射）】对比赫双妥®，用于ER阳性、HER2阳性局部晚期或转移性乳腺癌(heredERA Breast Cancer; NCT05296798)[16]。
参考文献：
[1] Mayer E, et al. Giredestrant (GIRE), an oral selective oestrogen receptor (ER) antagonist and degrader, + everolimus (E) in patients (pts) with ER-positive, HER2-negative advanced breast cancer (ER+, HER2– aBC) previously treated with a CDK4/6 inhibitor (i): Primary results of the Phase III evERA BC trial. [cite: 46] Presented at: ESMO Congress; 2025 October 17-21; Berlin, Germany. LBA #16.
[2] Benitez Fuentes JD, et al. Global Stage Distribution of Breast Cancer at Diagnosis. A Systematic Review and Meta-Analysis. JAMA Oncol. 2024;10(1):71-78.
[3] Kinslow C, et al. Prevalence of Estrogen Receptor Alpha (ESR1) Somatic Mutations in Breast Cancer. JNCI Cancer Spectrum; 2022 Oct;6(5):pkac060.
[4] O’Shaughnessy J, et al. Real-world risk of recurrence and treatment outcomes with adjuvant endocrine therapy in patients with stage II-III HR+/HER2- early breast cancer. Breast. 2025; 81:104437.
[5] Pan H, et al. 20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years. NEJM. 2017;377:1836–1846.
[6] Khatpe AS, et al. Nexus between PI3K/AKT and Estrogen Receptor Signaling in Breast Cancer. Cancers (Basel). 2021;13(3):369.
[7] Hershman DL, et al. Early discontinuation and non-adherence to adjuvant hormonal therapy are associated with increased mortality in women with breast cancer. Breast Cancer Res Treat. 2011;126:529–537.
[8] Rosso R, et al. Adherence to Adjuvant Endocrine Therapy in Breast Cancer Patients. Curr Oncol. 2023 Jan 21;30(2):1461-1472.
[9] Hurvitz SA, et al. Neoadjuvant palbociclib plus either giredestrant or anastrozole in oestrogen receptor-positive, HER2-negative, early breast cancer (coopERA Breast Cancer): an open-label, randomised, controlled, phase 2 study. Lancet Oncol. 2023;24:1029–1041.
[10] ClinicalTrials.gov. A Study Evaluating the Efficacy and Safety of Adjuvant Giredestrant Compared With Physician's Choice of Adjuvant Endocrine Monotherapy in Participants With Estrogen Receptor-Positive, HER2-Negative Early Breast Cancer (lidERA Breast Cancer) [Internet; cited 2025 November]. Available from: [https://clinicaltrials.gov/study/NCT04961996](https://clinicaltrials.gov/study/NCT04961996).
[11] Martin M, et al. Giredestrant (GDC-9545) vs physician choice of endocrine monotherapy (PCET) in patients (pts) with ER+, HER2– locally advanced/metastatic breast cancer (LA/mBC): Primary analysis of the phase 2, randomised, open-label acelERA BC study. Presented at: The European Society for Medical Oncology Annual Meeting; 2022 September 9-13; Paris, France. Abstract #211MO.
[12] Metcalfe C, et al. GDC-9545: A novel ER antagonist and clinical candidate that combines desirable mechanistic and pre-clinical DMPK attributes. Presented at: San Antonio Breast Cancer Symposium; 2018 December 4-8; San Antonio, Texas, USA. Abstract #P5-04-07.
[13] ClinicalTrials.gov. A Study Evaluating the Efficacy and Safety of Giredestrant Plus Everolimus Compared With the Physician's Choice of Endocrine Therapy Plus Everolimus in Participants With Estrogen Receptor-Positive, HER2-Negative, Locally Advanced or Metastatic Breast Cancer (evERA Breast Cancer) [Internet; cited 2025 November]. Available from: [https://clinicaltrials.gov/study/NCT05306340](https://clinicaltrials.gov/study/NCT05306340).
[14] ClinicalTrials.gov. A Study Evaluating the Efficacy and Safety of Giredestrant Combined With Palbociclib Compared With Letrozole Combined With Palbociclib in Participants With Estrogen Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer (persevERA Breast Cancer) [Internet; cited 2025 November]. Available from: [https://clinicaltrials.gov/study/NCT04546009](https://clinicaltrials.gov/study/NCT04546009).
[15] ClinicalTrials.gov. A Study to Evaluate Efficacy and Safety of Giredestrant Compared With Fulvestrant (Plus a CDK4/ 6 Inhibitor), in Participants With ER-Positive, HER2-Negative Advanced Breast Cancer Resistant to Adjuvant Endocrine Therapy (pionERA Breast Cancer) [Internet; cited 2025 November]. Available from: [https://clinicaltrials.gov/study/NCT06065748](https://clinicaltrials.gov/study/NCT06065748).
[16] ClinicalTrials.gov. A Study to Evaluate the Efficacy and Safety of Giredestrant in Combination With Phesgo (Pertuzumab, Trastuzumab, and Hyaluronidase-zzxf) Versus Phesgo in Participants With Locally Advanced or Metastatic Breast Cancer (heredERA Breast Cancer) [Internet; [cite: 73] cited 2025 November]. Available from: [https://clinicaltrials.gov/study/NCT05296798](https://clinicaltrials.gov/study/NCT05296798).