First and only AKT inhibitor approved in the EU for breast cancer patients with specific biomarker alterations (PIK3CA, AKT1 or PTEN)

欧盟第一个也是唯一一个批准用于具有特定生物标志物改变（PIK3CA，AKT1或PTEN）的乳腺癌患者的AKT抑制剂

Approval based on CAPItello-291 results which showed this combination reduced the risk of disease progression or death by 50% vs. Faslodex alone in a biomarker-altered population

基于CAPItello-291结果的批准表明，在生物标志物改变的人群中，与单独使用Faslodex相比，这种组合将疾病进展或死亡的风险降低了50%

AstraZeneca’s Truqap (capivasertib) in combination with Faslodex (fulvestrant) has been approved in the European Union (EU) for the treatment of adult patients with estrogen receptor (ER)-positive, HER2‑negative locally advanced or metastatic breast cancer with one or more PIK3CA, AKT1, or PTEN-alterations following recurrence or progression on or after an endocrine-based regimen..

阿斯利康（AstraZeneca）的Truqap（capivasertib）联合Faslodex（氟维司群）已被欧盟（EU）批准用于治疗雌激素受体（ER）阳性，HER2阴性的局部晚期或转移性乳腺癌的成年患者，其中一种或多种PIK3CA，AKT1或PTEN改变是在内分泌方案复发或进展后发生的。。

The approval by the European Commission follows the positive opinion of the Committee for Medicinal Products for Human Use and is based on results from the CAPItello-291 Phase III trial published in The New England Journal of Medicine.1

欧盟委员会的批准遵循了人类使用药品委员会的积极意见，并基于《新英格兰医学杂志》1上发表的CAPItello-291 III期试验的结果

In the trial, Truqap in combination with Faslodex reduced the risk of disease progression or death by 50% versus Faslodex in combination with placebo in patients with tumours harbouring PI3K, AKT or PTEN alterations (based on hazard ratio of 0.50, 95% confidence interval 0.38-0.65; p=<0.001; median progression-free survival (PFS) 7.3 versus 3.1 months).1.

在该试验中，Truqap联合Faslodex与Faslodex联合安慰剂相比，携带PI3K，AKT或PTEN改变的肿瘤患者的疾病进展或死亡风险降低了50%（基于风险比0.50,95%置信区间0.38-0.65；p=<0.001；中位无进展生存期（PFS）7.3比3.1个月）。

In Europe, breast cancer remains the leading cause of cancer death, with more than 140,000 deaths in 2022 and more than 550,000 patients diagnosed in the same year.2 Hormone receptor (HR)-positive breast cancer (expressing estrogen or progesterone receptors, or both), is the most common subtype of breast cancer with 70% of tumours considered HR-positive and HER2-negative.3 More than 97% of HR-positive breast cancer tumours are ER-positive.4,5 Collectively, mutations in PIK3CA, AKT1 and alterations in PTEN occur frequently, affecting approximately 50% of patients with advanced HR-positive breast cancer.6-8.

在欧洲，乳腺癌仍然是癌症死亡的主要原因，2022年死亡人数超过140000人，同年确诊的患者超过550000人。2激素受体（HR）阳性乳腺癌（表达雌激素或孕激素受体，或两者兼有）是乳腺癌最常见的亚型，其中70%的肿瘤被认为是HR阳性和HER2阴性。3超过97%的HR阳性乳腺癌肿瘤是ER阳性的[4,5]。总的来说，PIK3CA突变，AKT1突变和PTEN改变频繁发生，影响约50%的晚期HR阳性乳腺癌患者[6-8]。

Mafalda Oliveira, MD, PhD, Vall d’Hebron University Hospital, and Senior Clinical Investigator of the Vall d’Hebron Institute of Oncology’s Breast Cancer Group in Barcelona, Spain, said: “Patients with advanced ER-positive breast cancer typically experience tumour progression or resistance with widely used endocrine-based treatment regimens, and there is an urgent need to provide them more time with their disease under control.

西班牙巴塞罗那瓦尔德希布伦大学医院医学博士、博士、瓦尔德希布伦肿瘤研究所乳腺癌研究小组高级临床研究员马法尔达·奥利维拉（MafaldaOliveira）说：“晚期ER阳性乳腺癌患者通常会因广泛使用的内分泌治疗方案而出现肿瘤进展或耐药性，迫切需要为他们提供更多的时间来控制疾病。

Today’s approval is welcome news for approximately half of ER-positive breast cancer patients in Europe who have tumours with these biomarkers, and it is important for clinicians to test and identify eligible patients who may be able to benefit from this combination.”.

今天的批准对于欧洲大约一半患有这些生物标志物肿瘤的ER阳性乳腺癌患者来说是一个好消息，临床医生测试和确定可能从这种组合中受益的合格患者非常重要。”。

Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: “Truqap is now the first and only AKT inhibitor approved in the European Union for patients with ER-positive breast cancer who have tumours harbouring these specific biomarkers. Breast cancer continues to be the leading cause of cancer-related death in Europe, and today’s news represents a significant step forward in providing an important new treatment option for patients in need of new, innovative therapies.”.

阿斯利康肿瘤业务部门执行副总裁戴夫·弗雷德里克森（DaveFredrickson）表示：“Truqap现在是欧盟批准用于ER阳性乳腺癌患者的第一种也是唯一一种AKT抑制剂，这些患者的肿瘤中含有这些特定的生物标志物。乳腺癌仍然是欧洲癌症相关死亡的主要原因，今天的新闻代表着在为需要新的创新疗法的患者提供重要的新治疗选择方面迈出了重要的一步。”。

In the CAPItello-291 trial, the safety profile of Truqap plus Faslodex was similar to that observed in previous trials evaluating this combination.1

在CAPItello-291试验中，Truqap加Faslodex的安全性与之前评估这种组合的试验中观察到的相似。1

Regulatory applications are currently under review in China and several other countries. Similar indications for Truqap in combination with Faslodex are already approved in the US, Japan and several other countries based on the CAPItello-291 trial.

中国和其他几个国家目前正在审查监管申请。根据CAPItello-291试验，美国，日本和其他几个国家已经批准了Truqap联合Faslodex的类似适应症。

Financial considerations

财务考虑

Following this approval in the EU, Astex Therapeutics is eligible to receive a milestone payment from AstraZeneca on first commercial sale of the drug in the EU as well as royalties on future sales in line with the agreement between the two companies.

在欧盟获得此项批准后，Astex Therapeutics有资格从阿斯利康获得该药物在欧盟首次商业销售的里程碑付款，以及根据两家公司之间的协议收取未来销售的版税。

Notes

注意事项

HR-positive breast cancer

HR阳性乳腺癌

The growth of HR-positive breast cancer cells is often driven by estrogen receptors, and endocrine therapies that target ER-driven disease are widely used as 1st-line treatment in the advanced setting, and often paired with CDK4/6 inhibitors.9-11 However, resistance to CDK4/6 inhibitors and current endocrine therapies develops in many patients with advanced disease.10 Once this occurs, treatment options are limited – with chemotherapy being the current standard of care – and survival rates are low with approximately 35% of patients anticipated to live beyond five years after diagnosis.3,10,12.

HR阳性乳腺癌细胞的生长通常是由雌激素受体驱动的，针对ER驱动的疾病的内分泌治疗被广泛用作晚期患者的一线治疗，并且通常与CDK4/6抑制剂配对[9-11]。然而，许多晚期疾病患者对CDK4/6抑制剂和目前的内分泌治疗产生了耐药性[10]。一旦发生这种情况，治疗选择就会受到限制-化疗是目前的护理标准-生存率很低，大约35%的患者预计在诊断后存活五年以上[3,10,12]。

The optimisation of endocrine therapy and overcoming resistance to enable patients to continue benefiting from these treatments, as well as identifying new therapies for those who are less likely to benefit, are active areas of focus for breast cancer research.

内分泌治疗的优化和克服阻力，使患者继续从这些治疗中受益，以及为那些不太可能受益的患者确定新的治疗方法，是乳腺癌研究的活跃重点领域。

CAPItello-291

第291章

CAPItello-291 is a Phase III, double-blind, randomised trial evaluating the efficacy of Truqap in combination with Faslodex versus placebo plus Faslodex for the treatment of locally advanced (inoperable) or metastatic HR-positive (ER-positive and ER-positive, progesterone receptor-positive), HER2-low or negative (immunohistochemistry (IHC) 0 or 1+, or IHC 2+/in-situ hybridisation (ISH)-negative) breast cancer..

CAPItello-291是一项III期双盲随机试验，评估Truqap联合Faslodex与安慰剂联合Faslodex治疗局部晚期（无法手术）或转移性HR阳性（ER阳性和ER阳性，孕酮受体阳性），HER2低或阴性（免疫组织化学（IHC）0或1+，或IHC 2+/原位杂交（ISH）阴性）乳腺癌的疗效。。

The global trial enrolled 708 adult patients with histologically confirmed HR-positive, HER2-low or negative breast cancer whose disease has recurred or progressed during or after aromatase inhibitor therapy, with or without a CDK4/6 inhibitor, and up to one line of chemotherapy for advanced disease.

该全球试验招募了708名经组织学证实为HR阳性，HER2低或阴性乳腺癌的成年患者，这些患者在芳香化酶抑制剂治疗期间或之后复发或进展，有或没有CDK4/6抑制剂，以及多达一种晚期疾病的化疗方案。

The trial has dual primary endpoints of PFS in the overall patient population and in a population of patients whose tumours have qualifying alterations in the PI3K/AKT pathway (PIK3CA, AKT1 or PTEN genes). In the trial, approximately 40% of tumours had these alterations and approximately 70% of patients received a prior CDK4/6 inhibitor..

该试验在总体患者人群和肿瘤在PI3K/AKT途径（PIK3CA，AKT1或PTEN基因）中具有合格改变的患者人群中具有PFS的双重主要终点。在试验中，大约40%的肿瘤有这些改变，大约70%的患者接受了先前的CDK4/6抑制剂。。

Truqap

Truqap

Truqap is a first-in-class, potent, adenosine triphosphate (ATP)-competitive inhibitor of all three AKT isoforms (AKT1/2/3). Truqap 400mg is administered twice daily according to an intermittent dosing schedule of four days on and three days off. This was chosen in early phase trials based on tolerability and the degree of target inhibition..

Truqap是所有三种AKT亚型（AKT1/2/3）的一流，有效的三磷酸腺苷（ATP）竞争性抑制剂。Truqap 400mg每天两次，根据间歇给药时间表，分四天服用，休息三天服用。这是根据耐受性和靶向抑制程度在早期试验中选择的。。

Truqap is approved in the US, EU, Japan and several other countries for the treatment of adult patients with HR-positive (or ER-positive), HER2-negative locally advanced or metastatic breast cancer with one or more biomarker alterations (PIK3CA, AKT1 or PTEN) following recurrence or progression on or after an endocrine-based regimen based on the results from the CAPItello-291 trial.

Truqap在美国，欧盟，日本和其他几个国家被批准用于治疗HR阳性（或ER阳性），HER2阴性局部晚期或转移性乳腺癌的成年患者，其具有一种或多种生物标志物改变（PIK3CA，AKT1或PTEN），根据CAPItello-291试验的结果，在基于内分泌的方案上或之后复发或进展。

Truqap is also approved in Australia for the treatment of adult patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer following recurrence or progression on or after an endocrine based regimen based on these trial results..

Truqap在澳大利亚也被批准用于治疗基于这些试验结果的内分泌方案复发或进展后HR阳性，HER2阴性的局部晚期或转移性乳腺癌的成年患者。。

Truqap is currently being evaluated in Phase III trials for the treatment of breast cancer (CAPItello-292) and prostate cancer (CAPItello-280 and CAPItello-281) in combination with established treatments.

Truqap目前正在III期临床试验中进行评估，用于治疗乳腺癌（CAPItello-292）和前列腺癌（CAPItello-280和CAPItello-281），并结合已建立的治疗方法。

Truqap was discovered by AstraZeneca subsequent to a collaboration with Astex Therapeutics (and its collaboration with the Institute of Cancer Research and Cancer Research Technology Limited).

Truqap是阿斯利康在与Astex Therapeutics（及其与癌症研究所和癌症研究技术有限公司的合作）合作后发现的。

Faslodex

Phalodex

Faslodex is an endocrine therapy indicated for the treatment of ER-positive, locally advanced or metastatic breast cancer in postmenopausal women not previously treated with endocrine therapy, or with disease relapse on or after adjuvant anti-estrogen therapy, or disease progression on anti-estrogen therapy..

Faslodex是一种内分泌疗法，用于治疗绝经后女性ER阳性，局部晚期或转移性乳腺癌，这些女性以前没有接受过内分泌治疗，或者在辅助抗雌激素治疗时或之后疾病复发，或者在抗雌激素治疗中疾病进展。。

In the US, EU and Japan, Faslodex is also approved in combination with CDK4/6 inhibitors for the treatment of women with HR-positive, HER2-negative advanced or metastatic breast cancer, whose cancer has progressed after endocrine medicine. Faslodex represents a hormonal treatment approach that helps to slow tumour growth by blocking and degrading the estrogen receptor – a key driver of disease progression..

在美国，欧盟和日本，Faslodex也被批准与CDK4/6抑制剂联合用于治疗HR阳性，HER2阴性晚期或转移性乳腺癌的女性，这些女性的癌症在内分泌医学后进展。Faslodex代表了一种激素治疗方法，通过阻断和降解雌激素受体（疾病进展的关键驱动因素）来帮助减缓肿瘤生长。。

Faslodex is approved as monotherapy or in combination with medicines from various drug classes including CDK4/6, PI3K and AKT inhibitors for the treatment of patients with HR-positive advanced breast cancer and is being evaluated in combination with medicines from other drug classes.

Faslodex被批准为单一疗法或与包括CDK4/6，PI3K和AKT抑制剂在内的各种药物类别的药物联合用于治疗HR阳性晚期乳腺癌患者，目前正在与其他药物类别的药物联合评估。

AstraZeneca in breast cancer

阿斯利康治疗乳腺癌

Driven by a growing understanding of breast cancer biology, AstraZeneca is starting to challenge, and redefine, 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..

在对乳腺癌生物学越来越了解的推动下，阿斯利康开始挑战并重新定义当前乳腺癌分类和治疗的临床范例，以便为有需要的患者提供更有效的治疗方法-大胆的目标是有朝一日消除乳腺癌作为死亡原因。。

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.

阿斯利康在开发中拥有一系列经过批准且有前景的化合物，这些化合物利用不同的作用机制来解决生物学上多样化的乳腺癌肿瘤环境。

With Enhertu (trastuzumab deruxtecan), a HER2-directed antibody drug conjugate (ADC), AstraZeneca and Daiichi Sankyo are aiming to improve outcomes in previously treated HER2-positive and HER2-low metastatic breast cancer and are exploring its potential in earlier lines of treatment and in new breast cancer settings...

阿斯利康和第一三共正致力于通过HER2定向抗体药物共轭物（ADC）Enhertu（曲妥珠单抗-德鲁司坦）改善既往接受过治疗的HER2阳性和HER2低下转移性乳腺癌患者的治疗效果，并探索其在早期治疗和新的乳腺癌治疗中的潜力

In HR-positive breast cancer, AstraZeneca continues to improve outcomes with foundational medicines Faslodex and Zoladex (goserelin) and aims to reshape the HR-positive space with first-in-class AKT inhibitor, Truqap, and next-generation SERD and potential new medicine camizestrant. AstraZeneca is also collaborating with Daiichi Sankyo to explore the potential of TROP2-directed ADC, datopotamab deruxtecan, in this setting..

在HR阳性乳腺癌中，阿斯利康继续使用基础药物Faslodex和Zoladex（戈舍瑞林）改善预后，旨在用一流的AKT抑制剂Truqap和下一代SERD以及潜在的新药卡米西坦重塑HR阳性空间。阿斯利康还与第一三共合作，在这种情况下探索TROP2指导的ADC datopotamab deruxtecan的潜力。。

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（olaparib）是一种靶向治疗选择，已在具有遗传性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林帕扎，并探索其在早期疾病中的潜力。。

To bring much-needed treatment options to patients with triple-negative breast cancer, an aggressive form of breast cancer, AstraZeneca is evaluating the potential of datopotamab deruxtecan alone and in combination with immunotherapy Imfinzi (durvalumab), and Imfinzi in combination with other oncology medicines, including Lynparza and Enhertu..

为了给三阴性乳腺癌（一种侵袭性乳腺癌）患者带来急需的治疗选择，阿斯利康正在评估达托单抗-德鲁替康单独以及与免疫疗法Imfinzi（durvalumab）和Imfinzi联合其他肿瘤药物（包括Lynparza和Enhertu）的潜力。。

AstraZeneca in oncology

阿斯利康肿瘤学

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（AstraZeneca）正在领导一场肿瘤学革命，致力于为各种形式的癌症提供治疗，遵循科学理解癌症及其复杂性，发现、开发并向患者提供改变生命的药物。

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.

。正是通过不断的创新，阿斯利康建立了行业内最多样化的投资组合和渠道之一，有可能促进医学实践的变化并改变患者的体验。

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

阿斯利康的愿景是重新定义癌症护理，并有一天消除癌症作为死亡原因。

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）是一家全球科学领先的生物制药公司，专注于肿瘤学，罕见病和生物制药（包括心血管，肾脏和代谢以及呼吸和免疫学）处方药的发现，开发和商业化。

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.

阿斯利康的创新药物总部位于英国剑桥，在125多个国家销售，全球数百万患者使用。请访问astrazeneca.com并在社交媒体@astrazeneca上关注该公司。