日本首个也是唯一一个批准用于具有特异性生物标志物改变(PIK3CA)乳腺癌患者的AKT抑制剂, AKT1 or PTEN)
基于CAPItello-291的批准结果显示，Truqap和Faslodex相比，将疾病进展或死亡风险降低了50%. 在生物标志物改变的人群中单独使用Faslodex
AstraZeneca’s Truqap 结合;结合 Faslodex (fulvestrant) has been approved in Japan for the treatment of adult patients with unresectable or recurrent PIK3CA, AKT1, 或pten改变的激素受体(HR)阳性, HER2-negative breast cancer following progression after treatment with endocrine therapy.
经日本厚生劳动省批准, Labour, 和福利(MHLW)的结果是基于 CAPItello-291 III期试验发表于 新英格兰医学杂志.1 In the trial, Truqap in combination with Faslodex 疾病进展或死亡的风险降低了50% Faslodex alone in patients with tumours harbouring PI3K/AKT pathway biomarker alterations (based on hazard ratio of 0.50, 95%置信区间0.38-0.65; p=<0.001; median progression-free survival (PFS) 7.3 versus 3.1 months).1
In Japan, more than 90,2022年，有1000名女性被诊断出患有乳腺癌, and more than 17,同年有000名病人死于这种疾病.2 Globally, hr阳性乳腺癌(表达雌激素或孕激素受体), or both), 最常见的乳腺癌亚型是什么, with more than 65% of tumours considered HR-positive and HER2-low or HER2-negative.3 总的来说，PIK3CA、AKT1的突变和PTEN的改变 occur frequently, affecting approximately 50% of patients with advanced HR-positive breast cancer.4-6 在这种情况下，内分泌疗法被广泛使用, 通常与周期蛋白依赖性激酶(CDK) 4/6抑制剂联合使用, 但是一些肿瘤对这些疗法产生了耐药性, 强调需要额外的联合方法与内分泌治疗，以延长化疗开始前的时间.7
Masakazu Toi, MD, PHD, 东京都癌症和传染病中心主任, Komagome Hospital, 日本方面表示:“capivasertib和fulvestrant的批准标志着日本晚期激素受体阳性乳腺癌治疗的新时代, 为大约一半患有PIK3CA突变肿瘤的患者提供了急需的新治疗选择, AKT1 or alterations in PTEN. It is important for us to detect these specific tumour biomarker alterations in each patient we see, 因此，他们有可能从这种重要的结合中受益，以延长内分泌治疗的有效性，并延缓疾病的进展.”
Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said:
“乳腺癌是日本女性中最常见的癌症, and innovative, 迫切需要新的治疗方案. Today’s approval of Truqap, 一种一流的akt抑制剂, 代表了hr阳性乳腺癌治疗向前迈出的重要一步，并为大约50%患有这些特定突变或改变的肿瘤患者提供了重要的新选择.”
在CAPItello-291试验中 Truqap plus Faslodex 是否与之前评估联合用药的试验中观察到的结果相似.1
The MHLW have also approved a companion diagnostic test to detect the relevant alterations (PIK3CA, AKT1 and PTEN).
中国的监管申请目前正在审查中, the European Union, and several other countries, and this indication for Truqap in combination with Faslodex is already approved in the US and several other countries based on results from the CAPItello-291 trial.
Financial considerations
在日本获得批准后, Astex Therapeutics有资格从澳门在线赌城娱乐获得该药在日本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
Breast cancer is the second most common cancer and one of the leading causes of cancer-related death worldwide.8 2022年，超过200万名患者被诊断出患有乳腺癌, with more than 665,000 deaths globally.8
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，超过65%的肿瘤被认为是hr阳性和her2低或her2阴性.3
The growth of HR-positive breast cancer cells is often driven by estrogen receptors (ER), and endocrine therapies that target ER-driven disease are widely used as 1st-line treatment in the advanced setting, 并且经常与CDK4/6抑制剂配对.7,9,10 However, resistance to CDK4/6 inhibitors and current endocrine therapies develops in many patients with advanced disease.9 一旦出现这种情况，治疗选择就有限了 化疗是目前的标准治疗方法，生存率很低，约30%的患者预计在诊断后能活5年以上.3,9,11
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, 乳腺癌研究的活跃领域是什么.
CAPItello-291
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, her2低或阴性(免疫组化)0或1+, 或IHC 2+/原位杂交(ISH)阴性)乳腺癌.
The global trial enrolled 708 adult patients with histologically confirmed HR-positive, 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, 有或没有CDK4/6抑制剂, 对于晚期疾病，最多可以进行一次化疗. 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, 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 in combination with Faslodex is approved in the US, Japan and several other countries for the treatment of adult patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer with one or more biomarker alterations (PIK3CA, AKT1或PTEN)基于CAPItello-291试验的结果. 符合条件的患者将至少在一种基于内分泌的转移性治疗方案中取得进展，或在完成辅助治疗后12个月内复发.
Truqap 目前正在III期试验中进行评估，用于治疗多种亚型乳腺癌和其他肿瘤类型，并与现有治疗方法相结合. The ongoing clinical research programme is focused on tumours reliant on signalling via the PI3K/AKT pathway, 在肿瘤中，这一途径的生物标志物发生了改变.
Truqap 是澳门在线赌城娱乐在与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 estrogen receptor-positive, 绝经后未接受内分泌治疗的局部晚期或转移性乳腺癌, 或在辅助抗雌激素治疗期间或之后疾病复发, 或者抗雌激素治疗的疾病进展.
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阴性的晚期或转移性乳腺癌, 谁的癌症在接受内分泌治疗后进展了. 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.
澳门在线赌城娱乐治疗乳腺癌
由于对乳腺癌生物学的了解越来越深入, 澳门在线赌城娱乐开始挑战, 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.
澳门在线赌城娱乐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), her2导向抗体药物偶联物(ADC), 澳门在线赌城娱乐和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.
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，以及下一代SERD和潜在新药卡米司腾. AstraZeneca is also collaborating with Daiichi Sankyo to explore the potential of TROP2-directed ADC, 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. 澳门在线赌城娱乐与默沙东 & Co., Inc. 在美国和加拿大)继续研究 Lynparza 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, 一种侵袭性乳腺癌, AstraZeneca is evaluating the potential of datopotamab deruxtecan alone and in combination with immunotherapy Imfinzi (durvalumab), Truqap 结合化疗，和 Imfinzi 与其他肿瘤药物联合使用，包括 Lynparza and Enhertu.
AstraZeneca in oncology
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, 开发并向患者提供改变生活的药物.
该公司专注于一些最具挑战性的癌症. 正是通过持续的创新，澳门在线赌城娱乐建立了行业中最多样化的产品组合和管道之一, with the potential to catalyse changes in the practice of medicine and transform the patient experience.
澳门在线赌城娱乐的愿景是重新定义癌症治疗和, one day, 消除癌症作为死亡原因.
AstraZeneca
澳门在线赌城娱乐(LSE/STO/Nasdaq: AZN)是一家全球性制药公司, 以科学为主导的澳门第一赌城在线娱乐公司，专注于发现, development, 以及肿瘤学处方药的商业化, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & 新陈代谢和呼吸 & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit hebhgkq.com 并在社交媒体上关注公司 @AstraZeneca.
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References
1. Turner N, et al. Capivasertib治疗激素受体阳性晚期乳腺癌. NEJM. 2023; 388:2058–70.
2. World Health Organization. GLOBOCAN Japan Fact Sheet. Available at: http://gco.iarc.who.int/media/globocan/factsheets/populations/392-japan-fact-sheet.pdf. Accessed March 2024.
3. National Cancer Institute. 监测，流行病学和最终结果方案. Available at: http://seer.cancer.gov/statfacts/html/breast-subtypes.html. Accessed March 2024.
4. Howell S J, et al. Fulvestrant plus capivasertib versus placebo after relapse or progression on an aromatase inhibitor in metastatic, 雌激素受体阳性, her2阴性乳腺癌(FAKTION). J Clin Oncol. 2022; 23:851-64.
5. Hortobagyi G N, et al. Correlative Analysis of Genetic Alterations and Everolimus Benefit in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Results From BOLERO-2. J Clin Oncol. 2016; 34:419-26.
6. Millis S Z, et al. Landscape of phosphatidylinositol-3-kinase pathway alterations across 19784 diverse solid tumors. JAMA Oncol. 2016;2(12):1565-73.
7. Lin M, et al. Comparative Overall Survival of CDK4/6 Inhibitors Plus Endocrine Therapy vs. Endocrine Therapy Alone for Hormone receptor-positive, HER2-negative metastatic breast cancer. J Cancer. 2020; 10.7150/jca.48944.
8. World Health Organization. GLOBOCAN Breast Fact Sheet. Available at: http://gco.iarc.who.int/media/globocan/factsheets/cancers/20-breast-fact-sheet.pdf. Accessed March 2024.
9. Lloyd M R, et al. Mechanisms of Resistance to CDK4/6 Blockade in Advanced Hormone Receptor–positive, her2阴性乳腺癌和新兴的治疗机会. Clin Cancer Res. 2022; 28(5):821-30.
10. Scabia V, et al. 雌激素受体阳性乳腺癌具有患者特异性的激素敏感性，依赖于孕激素受体. Nat Commun. 2022; 10.1038/s41467-022-30898-0.
11. 全国癌症综合网络. 肿瘤临床实践指南(NCCN指南). Available at: http://www.nccn.org/guidelines/guidelines-detail?category=1&id=1419. Accessed March 2024.