Truqap + Faslodex在欧盟批准用于晚期er阳性乳腺癌患者

首个也是唯一一个在欧盟批准用于具有特异性生物标志物改变(PIK3CA)的乳腺癌患者的AKT抑制剂, AKT1 or PTEN)

批准基于CAPItello-291的结果，该结果显示该联合治疗将疾病进展或死亡风险降低了50%. Faslodex alone in a biomarker-altered population
 

AstraZeneca’s Truqap (capivasertib) in combination with Faslodex (fulvestrant)已被欧盟(EU)批准用于治疗雌激素受体(ER)阳性的成人患者, HER2阴性的局部晚期或转移性乳腺癌伴一种或多种PIK3CA, AKT1, 或pten在内分泌基础疗法复发或进展后的改变.

The approval by the European Commission follows the positive opinion 人用医药产品委员会的报告，并基于 CAPItello-291 Phase III trial published in The New England Journal of Medicine.1

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

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 激素受体(HR)阳性乳腺癌(表达雌激素或孕激素受体), or both), 是最常见的乳腺癌亚型，70%的肿瘤被认为是hr阳性和her2阴性.3 More than 97% of HR-positive breast cancer tumours are ER-positive.4,5 Collectively, mutations in PIK3CA, AKT1 and alterations in PTEN 经常发生，约50%的晚期hr阳性乳腺癌患者受到影响.6-8

Mafalda Oliveira, MD, PhD, Vall d’Hebron University Hospital, 巴塞罗那Vall d’hebron肿瘤研究所乳腺癌组的高级临床研究员, Spain, 她说:“晚期er阳性乳腺癌患者通常会经历肿瘤进展或对广泛使用的内分泌治疗方案产生耐药性, 迫切需要为他们提供更多的时间，使他们的疾病得到控制. 今天的批准对欧洲大约一半的er阳性乳腺癌患者来说是一个好消息，这些患者的肿瘤中含有这些生物标志物, 对于临床医生来说，测试和识别可能从这种组合中受益的合格患者是很重要的.”

立博平台肿瘤事业部执行副总裁Dave Fredrickson表示:“Truqap 现在是欧盟批准的第一个也是唯一一个用于er阳性乳腺癌患者的AKT抑制剂，这些患者的肿瘤中含有这些特定的生物标志物. 在欧洲，乳腺癌仍然是癌症相关死亡的主要原因, 今天的消息代表着在为需要新治疗的患者提供重要的新治疗选择方面迈出了重要的一步, innovative therapies.”

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

中国和其他几个国家的监管申请目前正在审查中. 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.

Financial considerations
Following this approval in the EU, Astex Therapeutics有资格从立博平台获得该药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，未来销售的特许权使用费.

Notes

HR-positive breast cancer
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驱动疾病的内分泌治疗被广泛用作晚期环境的一线治疗, and often paired with CDK4/6 inhibitors.9-11 However, 对CDK4/6抑制剂和当前内分泌疗法的耐药性在许多晚期疾病患者中出现.10 Once this occurs, treatment options are limited 化疗是目前的标准治疗，而且生存率很低，大约35%的患者预计在诊断后能活到5年以上.3,10,12

内分泌治疗的优化和克服阻力，使患者继续受益于这些治疗, as well as identifying new therapies for those who are less likely to benefit, are active areas of focus for breast cancer research.

CAPItello-291
CAPItello-291是一项III期、双盲、随机试验，评估了该药物的疗效 Truqap in combination with Faslodex versus placebo plus Faslodex 用于治疗局部晚期(不能手术)或转移性hr阳性(er阳性和er阳性), progesterone receptor-positive), HER2-low or negative (immunohistochemistry (IHC) 0 or 1+, or IHC 2+/in-situ hybridisation (ISH)-negative) breast cancer.

这项全球试验招募了708名组织学证实为hr阳性的成年患者, 在芳香酶抑制剂治疗期间或之后复发或进展的her2低或阴性乳腺癌, with or without a CDK4/6 inhibitor, and up to one line of chemotherapy for advanced disease. 该试验在总体患者群体和PI3K/AKT通路(PIK3CA)具有合格改变的肿瘤患者群体中具有PFS的双重主要终点, AKT1 or PTEN genes). In the trial, 大约40%的肿瘤有这些改变，大约70%的患者先前接受过CDK4/6抑制剂.

Truqap
Truqap is a first-in-class, potent, 三磷酸腺苷(ATP)-三种AKT亚型的竞争性抑制剂(AKT1/2/3). Truqap 400mg每日两次，间歇给药4天，休息3天. 这是在早期试验中根据耐受性和目标抑制程度选择的.

Truqap is approved in the US, EU, 日本和其他几个国家用于治疗成人hr阳性(或er阳性)患者, her2阴性的局部晚期或转移性乳腺癌伴一种或多种生物标志物改变(PIK3CA), 根据CAPItello-291试验的结果，AKT1或PTEN)在基于内分泌的方案中或之后复发或进展. Truqap 在澳大利亚也被批准用于治疗成人hr阳性患者, her2阴性的局部晚期或转移性乳腺癌，在基于这些试验结果的内分泌治疗方案中或之后复发或进展.

Truqap 目前正在III期临床试验中进行评估，以联合已有的治疗方法治疗乳腺癌(CAPItello-292)和前列腺癌(CAPItello-280和CAPItello-281).

Truqap 是立博平台在与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
Faslodex is an endocrine therapy indicated for the treatment of ER-positive, 绝经后未接受内分泌治疗的局部晚期或转移性乳腺癌, or with disease relapse on or after adjuvant anti-estrogen therapy, or disease progression on anti-estrogen therapy.

In the US, EU and Japan, Faslodex 也被批准与CDK4/6抑制剂联合用于治疗女性hr阳性, HER2-negative advanced or metastatic breast cancer, whose cancer has progressed after endocrine medicine. 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 被批准作为单一疗法或与包括CDK4/6在内的各种药物类别的药物联合使用, PI3K和AKT抑制剂用于hr阳性晚期乳腺癌患者的治疗，并正在与其他药物类别的药物联合进行评估.

AstraZeneca in breast cancer
Driven by a growing understanding of breast cancer biology, AstraZeneca is starting to challenge, and redefine, 目前的临床模式是如何对乳腺癌进行分类和治疗，以便为有需要的患者提供更有效的治疗，并怀着有朝一日消除乳腺癌这一致死原因的大胆雄心.

立博平台拥有全面的已批准和有前景的化合物组合，利用不同的作用机制来解决生物多样性的乳腺癌肿瘤环境.

With Enhertu (trastuzumab deruxtecan), a HER2-directed antibody drug conjugate (ADC), 立博平台和Daiichi Sankyo的目标是改善先前治疗的her2阳性和her2低转移性乳腺癌的预后，并正在探索其在早期治疗线和新发乳腺癌中的潜力..

在hr阳性乳腺癌中，立博平台继续通过基础药物改善预后 Faslodex and Zoladex (goserelin)，旨在用一流的AKT抑制剂重塑hr阳性空间， Truqap, and next-generation SERD and potential new medicine camizestrant. 立博平台还与Daiichi Sankyo合作，探索trop2导向ADC的潜力, datopotamab deruxtecan, in this setting.

PARP inhibitor Lynparza 奥拉帕尼(olaparib)是一种靶向治疗方案，已经在具有遗传性BRCA突变的早期和转移性乳腺癌患者中进行了研究. 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.

为三阴性乳腺癌患者提供急需的治疗选择, an aggressive form of breast cancer, 立博平台正在评估datopotamab deruxtecan单独和联合免疫疗法的潜力 Imfinzi (durvalumab), and Imfinzi in combination with other oncology medicines, including Lynparza and Enhertu.

AstraZeneca in oncology
立博平台正在引领肿瘤学领域的一场革命，致力于为各种形式的癌症提供治疗, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.

The Company's focus is on some of the most challenging cancers. 正是通过持续的创新，立博平台建立了行业中最多样化的产品组合和管道之一, 有可能催化医学实践的变化，改变病人的体验.

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

AstraZeneca
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. Based in Cambridge, UK, 立博平台的创新药物在超过125个国家销售，并被全球数百万患者使用. Please visit nxperfect.com and follow the Company on social media @AstraZeneca

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References

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tags

  • Oncology
  • Corporate and financial