Positive high-level results from the DESTINY-Breast11 Phase III trial showed Enhertu (trastuzumab deruxtecan) followed by paclitaxel, trastuzumab and pertuzumab (THP) demonstrated a statistically significant and clinically meaningful improvement in pathologic complete response (pCR) rate versus standard of care (dose-dense doxorubicin and cyclophosphamide followed by THP [ddAC-THP]) when used in the neoadjuvant setting (before surgery) in patients with high-risk, locally advanced HER2-positive early-stage breast cancer.

DESTINY-Breast11 III期试验的积极高层结果显示，在高风险、局部晚期HER2阳性早期乳腺癌患者的新辅助治疗（术前）中，使用Enhertu（trastuzumab deruxtecan）后接紫杉醇、曲妥珠单抗和帕妥珠单抗（THP）疗法，相较于标准治疗方案（密集剂量的阿霉素和环磷酰胺后接THP [ddAC-THP]），在病理完全缓解率（pCR）上显示出统计学显著性及临床意义上的改善。

Pathologic complete response is defined as no evidence of invasive cancer cells in the removed breast tissue and lymph nodes following treatment..

病理完全缓解的定义是，治疗后切除的乳腺组织和淋巴结中没有浸润性癌细胞的证据。

The secondary endpoint of event-free survival (EFS) was not mature at the time of analysis; however, EFS data showed an early positive trend favouring Enhertu followed by THP compared to standard of care. The trial will continue to follow EFS.

无事件生存期（EFS）的次要终点在分析时尚未成熟；然而，EFS数据显示早期有积极趋势，支持先使用Enhertu再使用THP，相较于标准治疗。试验将继续跟踪EFS。

Approximately one in three patients with early-stage breast cancer are considered high risk, as they are more likely to experience disease recurrence and have a poor prognosis.1,2 Achieving pCR in early-stage HER2-positive breast cancer is associated with improved long-term outcomes.2,3 The current standard of care in many regions of the world in this neoadjuvant setting involves combination chemotherapy regimens.2 These regimens often include anthracyclines, which can be challenging for patients to tolerate and may result in long-term cardiovascular side effects.4 Further, nearly half of patients who receive neoadjuvant treatment do not achieve pCR, reinforcing the need for new treatment options.2,3.

大约三分之一的早期乳腺癌患者被认为是高风险患者，因为他们更容易出现疾病复发且预后较差。1,2 在早期HER2阳性乳腺癌中实现病理完全缓解（pCR）与改善的长期预后相关。2,3 在世界许多地区，当前的新辅助治疗标准方案包括联合化疗方案。2 这些方案通常包含蒽环类药物，这类药物对患者来说可能较难耐受，并可能导致长期的心血管副作用。4 此外，近一半接受新辅助治疗的患者未能实现pCR，这进一步凸显了对新治疗选择的需求。2,3

Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: “The clinically meaningful improvement in pathologic complete response and the safety data seen in DESTINY-Breast11 highlight the potential of Enhertu to challenge the current standard of care in early-stage HER2-positive breast cancer.

阿斯利康肿瘤血液学研发执行副总裁苏珊·加尔布雷思表示：“DESTINY-Breast11 研究中看到的病理完全缓解具有临床意义的改善和安全性数据，突显了 Enhertu 挑战早期 HER2 阳性乳腺癌当前护理标准的潜力。”

Enhertu is already an important treatment option in the metastatic setting, and these data have the potential to allow this medicine to move into early stages of disease where cure is possible.”.

Enhertu在转移性环境中已经是一个重要的治疗选择，这些数据有可能使这种药物进入疾病的早期阶段，从而实现治愈。

Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said: “There are still many patients with early-stage breast cancer who do not achieve a pathologic complete response with treatment in the neoadjuvant setting, increasing the risk of disease recurrence. These topline results from DESTINY-Breast11 demonstrate that Enhertu followed by THP could offer patients with HER2-positive breast cancer a promising new treatment approach prior to surgery, setting more patients on a path towards a potential cure.'.

武田健，第一三共全球研发主管表示：“在新辅助治疗环境中，仍有许多早期乳腺癌患者未能达到病理完全缓解，这增加了疾病复发的风险。DESTINY-Breast11的这些初步结果表明，对于HER2阳性乳腺癌患者，在手术前采用Enhertu后接THP的治疗方案可能提供一种前景广阔的新治疗选择，为更多患者铺平潜在治愈的道路。”

Enhertu followed by THP showed an improved safety profile compared to ddAC-THP. The safety profiles of Enhertu and THP were consistent with the known profiles of each individual medicine with no new safety concerns identified. Rates of interstitial lung disease were similar across the Enhertu followed by THP and the ddAC-THP arms as determined by an independent adjudication committee..

Enhertu序贯THP相比ddAC-THP显示出更好的安全性。Enhertu和THP的安全性与每种药物已知的安全性特征一致，未发现新的安全性问题。根据独立评审委员会的判定，Enhertu序贯THP组和ddAC-THP组的间质性肺病发生率相似。

Following a recommendation by the Independent Data Monitoring Committee, patient enrolment in a third arm of the trial evaluating Enhertu alone was closed after a previous interim efficacy assessment of the trial arms.

根据独立数据监查委员会的建议，在对试验组进行先前的中期疗效评估后，单独评估Enhertu的试验第三组的患者入组已经停止。

Data from DESTINY-Breast11 will be presented at an upcoming medical meeting and shared with regulatory authorities.

DESTINY-Breast11 的数据将在即将举行的医学会议上公布，并分享给监管机构。

Enhertu is a specifically engineered HER2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.

Enhertu 是由第一三共发现的专门设计的HER2导向DXd抗体药物偶联物（ADC），阿斯利康和第一三共正在联合开发和商业化。

Enhertu has demonstrated improved outcomes in six Phase III breast cancer trials across different subtypes and stages of disease, including the recently announced DESTINY-Breast09 Phase III trial in the 1st-line HER2-positive metastatic setting. Enhertu is also being studied in several ongoing breast cancer trials including the DESTINY-Breast05 Phase III trial which is evaluating Enhertu in the high-risk adjuvant early HER2-positive setting..

Enhertu在六项三期乳腺癌试验中展示了改善的结果，这些试验涵盖了不同类型和阶段的疾病，包括最近宣布的DESTINY-Breast09三期试验，该试验针对一线治疗HER2阳性转移性乳腺癌。Enhertu还在几个正在进行的乳腺癌试验中进行研究，其中包括DESTINY-Breast05三期试验，该试验正在评估Enhertu在高风险辅助早期HER2阳性环境中的效果。

Notes

注释

HER2-positive early breast cancer

HER2阳性早期乳腺癌

Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide.5 More than two million breast cancer cases were diagnosed in 2022, with more than 665,000 deaths globally.5

乳腺癌是第二大常见癌症，也是全球癌症相关死亡的主要原因之一。2022年，全球诊断出超过两百万例乳腺癌病例，导致超过665,000人死亡。

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumours including breast cancer.6 HER2 protein overexpression may occur as a result of HER2 gene amplification and is often associated with aggressive disease and poor prognosis in breast cancer.7 Approximately one in five cases of breast cancer are considered HER2-positive.8.

HER2是一种酪氨酸激酶受体生长促进蛋白，表达于多种肿瘤表面，包括乳腺癌。HER2蛋白过表达可能是由于HER2基因扩增引起的，常与侵袭性疾病和乳腺癌预后不良相关。大约五分之一的乳腺癌病例被认为是HER2阳性。

DESTINY-Breast11

DESTINY-乳腺癌11

DESTINY-Breast11 is a global, multicentre, randomised, open-label, Phase III trial evaluating the efficacy and safety of neoadjuvant Enhertu (5.4mg/kg) monotherapy or Enhertu followed by THP vs. the standard of care regimen in patients with high-risk (lymph node positive [N1-3] or primary tumour stage T3-4), locally advanced or inflammatory HER2-positive early-stage breast cancer..

DESTINY-Breast11是一项全球性、多中心、随机、开放标签的III期试验，评估新辅助治疗Enhertu（5.4mg/kg）单药或Enhertu后接THP对比标准治疗方案在高风险（淋巴结阳性[N1-3]或原发肿瘤分期T3-4）、局部晚期或炎性HER2阳性早期乳腺癌患者中的疗效和安全性。

Patients were randomised 1:1:1 to receive either eight cycles of Enhertu monotherapy; four cycles of Enhertu followed by four cycles of THP; or four cycles of ddAC (dose-dense doxorubicin and cyclophosphamide) followed by four cycles of THP.

患者被随机分为1:1:1三组，分别接受八个周期的Enhertu单药治疗；四个周期的Enhertu后接四个周期的THP；或四个周期的ddAC（剂量密集型多柔比星和环磷酰胺）后接四个周期的THP。

The primary endpoint of DESTINY-Breast11 is pCR (absence of invasive disease in the breast and lymph nodes). Secondary endpoints include EFS, invasive disease-free survival, overall survival and safety.

DESTINY-Breast11 的主要终点是 pCR（乳腺和淋巴结中无侵袭性疾病）。次要终点包括 EFS、无侵袭性疾病生存期、总生存期和安全性。

DESTINY-Breast11 enrolled 927 patients across multiple sites in Asia, Europe, North America and South America. For more information about the trial, visit ClinicalTrials.gov.

DESTINY-Breast11 在亚洲、欧洲、北美和南美的多个地点招募了 927 名患者。有关该试验的更多信息，请访问 ClinicalTrials.gov。

Enhertu

Enhertu

Enhertu is a HER2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, Enhertu is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme in AstraZeneca’s ADC scientific platform. Enhertu consists of a HER2 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers..

Enhertu是一种靶向HER2的抗体药物偶联物（ADC）。Enhertu采用第一三共株式会社专有的DXd ADC技术设计，是第一三共肿瘤产品组合中的主要ADC，也是阿斯利康ADC科学平台中最先进的项目。Enhertu由一种HER2单克隆抗体通过四肽可裂解连接子连接到多个拓扑异构酶I抑制剂有效载荷（依沙替康衍生物，DXd）组成。

Enhertu (5.4mg/kg) is approved in more than 75 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2-positive (immunohistochemistry [IHC 3+ or in-situ hybridisation [ISH]+) breast cancer who have received a (or one or more) prior anti-HER2-based regimen, either in the metastatic setting or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial..

Enhertu（5.4mg/kg）已在全世界70多个国家获批，用于治疗接受过一种（或一种以上）既往抗HER2治疗方案的不可切除或转移性HER2阳性（免疫组织化学[IHC 3+]或原位杂交[ISH]+）乳腺癌成年患者。这些患者在接受新辅助或辅助治疗期间或完成治疗后六个月内出现疾病复发，依据的是DESTINY-Breast03试验的结果。

Enhertu (5.4mg/kg) is approved in more than 75 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ ISH-) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial..

Enhertu（5.4mg/kg）已在全世界70多个国家获得批准，用于治疗患有不可切除或转移性HER2低表达（IHC 1+或IHC 2+/ISH-）的乳腺癌成年患者。这些患者在转移性环境中接受过先前的系统治疗，或在完成辅助化疗期间或六个月内出现疾病复发，基于DESTINY-Breast04试验的结果。

Enhertu (5.4mg/kg) is approved in more than 30 countries for the treatment of adult patients with unresectable or metastatic hormone receptor (HR)-positive, HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer, as determined by a locally or regionally approved test, that have progressed on one or more endocrine therapies in the metastatic setting based on the results from the DESTINY-Breast06 trial..

Enhertu（5.4mg/kg）已在30多个国家获批，用于治疗成年不可切除或转移性激素受体（HR）阳性、HER2低表达（IHC 1+ 或 IHC 2+/ISH-）或HER2极低表达（IHC 0且有膜染色）的乳腺癌患者。这些患者经局部或地区批准的检测方法确认，并基于DESTINY-Breast06试验结果，在转移性环境中接受一种或多种内分泌治疗后出现疾病进展。

Enhertu (5.4mg/kg) is approved in more than 50 countries worldwide for the treatment of adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumours have activating HER2 (ERBB2) mutations, as detected by a locally or regionally approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 and/or DESTINY-Lung05 trials.

Enhertu（5.4mg/kg）已在全世界50多个国家获批，用于治疗肿瘤携带激活型HER2（ERBB2）突变的不可切除或转移性非小细胞肺癌（NSCLC）成年患者。这些患者的突变通过当地或地区批准的检测方法确认，并且基于DESTINY-Lung02和/或DESTINY-Lung05试验的结果，已接受过先前的系统治疗。

Continued approval in China and the US for this indication is contingent upon verification and description of clinical benefit in a confirmatory trial..

在中国和美国，这一适应症的持续批准取决于在确证性试验中对临床益处的验证和描述。

Enhertu (6.4mg/kg) is approved in more than 65 countries worldwide for the treatment of adult patients with locally advanced or metastatic HER2-positive (IHC 3+ or 2+/ISH+) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01, DESTINY-Gastric02 and/or DESTINY-Gastric06 trials.

Enhertu（6.4mg/kg）已在全世界65多个国家获得批准，用于治疗先前接受过基于曲妥珠单抗治疗方案的局部晚期或转移性HER2阳性（IHC 3+ 或 2+/ISH+）胃癌或胃食管交界处（GEJ）腺癌成年患者，这一批准是基于DESTINY-Gastric01、DESTINY-Gastric02和/或DESTINY-Gastric06试验的结果。

Continued approval in China for this indication will depend on whether a randomised controlled confirmatory clinical trial can demonstrate clinical benefit in this population..

在中国，这一适应症的持续批准将取决于随机对照确证性临床试验是否能够证明在这一人群中的临床益处。

Enhertu (5.4mg/kg) is approved in the US and other countries for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumours who have received prior systemic treatment and have no satisfactory alternative treatment options based on the results from the DESTINY-PanTumor02, DESTINY-Lung01 and DESTINY-CRC02 trials.

Enhertu（5.4mg/kg）在美国和其他国家获批，用于治疗不可切除或转移性HER2阳性（IHC 3+）实体瘤的成年患者，这些患者既往接受过系统治疗，并且基于DESTINY-PanTumor02、DESTINY-Lung01和DESTINY-CRC02试验结果，无满意的替代治疗方案。

Continued approval for this indication in the US is contingent upon verification and description of clinical benefit in a confirmatory trial..

在美国，继续批准该适应症取决于在确证性试验中对临床益处的验证和描述。

Enhertu development programme

Enhertu开发计划

A comprehensive global clinical development programme is underway evaluating the efficacy and safety of Enhertu as monotherapy or in combination or sequentially with other anti-cancer therapies across multiple HER2-targetable cancers.

一项全面的全球临床开发计划正在进行中，评估Enhertu作为单一疗法或与其他抗癌疗法联合或序贯使用的疗效和安全性，涵盖多种HER2靶向癌症。

Daiichi Sankyo collaboration

第一三共合作

AstraZeneca and Daiichi Sankyo entered into a global collaboration to jointly develop and commercialise Enhertu in March 2019 and Datroway (datopotamab deruxtecan) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of Enhertu and Datroway..

2019年3月，阿斯利康和第一三共达成全球合作，共同开发和商业化Enhertu，并于2020年7月就Datroway（datopotamab deruxtecan）展开合作，但日本市场除外，在日本第一三共对每种ADC拥有独家权利。第一三共负责Enhertu和Datroway的生产和供应。

AstraZeneca in breast cancer

阿斯利康在乳腺癌领域

Driven by a growing understanding of breast cancer biology, AstraZeneca is challenging, and redefining, the current clinical paradigm for how breast cancer is classified and treated to deliver even more effective treatments to patients in need – with the bold ambition to one day eliminate breast cancer as a cause of death..

基于对乳腺癌生物学的日益深入的理解，阿斯利康正在挑战并重新定义当前乳腺癌分类和治疗的临床模式，致力于为有需要的患者提供更有效的治疗方案——其宏伟目标是终有一天消除乳腺癌这一致死原因。

AstraZeneca has a comprehensive portfolio of approved and promising compounds in development that leverage different mechanisms of action to address the biologically diverse breast cancer tumour environment.

阿斯利康拥有一个全面的已批准和有前景的在研化合物组合，这些化合物利用不同的作用机制来应对生物多样性乳腺癌肿瘤环境。

With Enhertu, AstraZeneca and Daiichi Sankyo are aiming to improve outcomes in previously treated HER2-positive, HER2-low and HER2-ultralow metastatic breast cancer, and are exploring its potential in earlier lines of treatment and in new breast cancer settings.

通过Enhertu，阿斯利康和第一三共旨在改善先前治疗过的HER2阳性、HER2低表达以及HER2超低表达转移性乳腺癌的治疗效果，并正在探索其在更前线治疗和新的乳腺癌环境中的潜力。

In HR-positive breast cancer, AstraZeneca continues to improve outcomes with foundational medicines Faslodex (fulvestrant) and Zoladex (goserelin) and aims to reshape the HR-positive space with first-in-class AKT inhibitor, Truqap (capivasertib), the TROP2-directed ADC, Datroway (datopotamab deruxtecan), and next-generation oral SERD and potential new medicine camizestrant..

在HR阳性的乳腺癌治疗领域，阿斯利康继续通过基础药物Faslodex（氟维司群）和Zoladex（戈舍瑞林）改善患者的治疗效果，并致力于通过首创的AKT抑制剂Truqap（capivasertib）、靶向TROP2的抗体偶联药物Datroway（datopotamab deruxtecan）、下一代口服SERD以及潜在的新药camizestrant重新定义HR阳性乳腺癌的治疗格局。

PARP inhibitor Lynparza (olaparib) is a targeted treatment option that has been studied in early and metastatic breast cancer patients with an inherited BRCA mutation. AstraZeneca with MSD (Merck & Co., Inc. in the US and Canada) continue to research Lynparza in these settings and to explore its potential in earlier disease.

PARP抑制剂Lynparza（奥拉帕利）是一种靶向治疗选择，已在携带遗传性BRCA突变的早期和转移性乳腺癌患者中进行了研究。阿斯利康与MSD（美国和加拿大的默克公司）继续在这些环境中研究Lynparza，并探索其在更早期疾病中的潜力。

AstraZeneca is also exploring the potential of saruparib, a potent and selective inhibitor of PARP1, in combination with camizestrant in BRCA-mutated, HR-positive, HER2-negative advanced breast cancer..

阿斯利康还在研究强效且选择性的PARP1抑制剂saruparib与camizestrant联合使用在BRCA突变、激素受体阳性、HER2阴性的晚期乳腺癌中的潜力。

To bring much-needed treatment options to patients with triple-negative breast cancer, an aggressive form of breast cancer, AstraZeneca is collaborating with Daiichi Sankyo to evaluate the potential of Datroway alone and in combination with immunotherapy Imfinzi (durvalumab).

为了给三阴性乳腺癌（一种侵袭性乳腺癌）患者带来亟需的治疗选择，阿斯利康正与第一三共合作，评估Datroway单药以及与免疫疗法Imfinzi（durvalumab）联合使用的潜力。

AstraZeneca in oncology

阿斯利康在肿瘤学领域

AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.

阿斯利康正引领一场肿瘤学革命，其雄心在于为各种形式的癌症提供治愈方案，遵循科学以理解癌症及其所有复杂性，从而发现、开发并交付改变生命的药物给患者。

The Company's focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.

公司的重点是一些最具挑战性的癌症。正是通过不懈的创新，阿斯利康建立了业内最多样化的产品组合和研发管线之一，有望催化医疗实践的变革，并改善患者的体验。

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.

阿斯利康有重新定义癌症护理并有朝一日消除癌症作为死亡原因的愿景。

AstraZeneca

阿斯利康

AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology.

阿斯利康（LSE/STO/Nasdaq：AZN）是一家全球领先的、以科学为导向的生物制药公司，专注于肿瘤学、罕见病以及包括心血管、肾病与代谢、呼吸与免疫学在内的生物制药领域的处方药的研发、生产和商业化。

Based in Cambridge, UK, AstraZeneca’s innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on social media @AstraZeneca..

总部位于英国剑桥的阿斯利康创新药物在全球125多个国家销售，被全球数百万患者使用。请访问astrazeneca.com，并在社交媒体上关注该公司@AstraZeneca。

Contacts

联系人

For details on how to contact the Investor Relations Team, please click here. For Media contacts, click here.

如需了解如何联系投资者关系团队的详细信息，请点击这里。如需联系媒体，请点击这里。

References

参考文献

Source: astrazeneca.com

来源：astrazeneca.com