澳门在线赌城娱乐和Daiichi Sankyo的Enhertu也证明了临床疗效
有意义的无进展生存改善
her2超低表达患者
DESTINY-Breast06 III期临床试验的高水平阳性结果表明 Enhertu 在hr阳性患者的主要试验人群中，与标准治疗化疗相比，曲妥珠单抗(trastuzumab deruxtecan)在无进展生存期(PFS)方面表现出具有统计学意义和临床意义的改善, HER2-low (IHC 1+ or 2+/ISH-) metastatic breast cancer following one or more lines of endocrine therapy.
A statistically significant and clinically meaningful improvement in PFS was also observed in the overall trial population (patients with HER2-low and HER2-ultralow [defined as IHC 0 with membrane staining; IHC >0<1+] metastatic breast cancer). A prespecified subgroup analysis showed the clinically meaningful improvement was consistent between patients with HER2-low and HER2-ultralow expression.
Overall survival (OS) data were not mature at the time of the analysis; however, Enhertu 在her2低转移性乳腺癌患者和整个试验人群中，与标准治疗化疗相比，显示出早期OS改善的趋势. 该试验将按计划继续进行，进一步评估OS和其他次要终点.
Susan Galbraith，肿瘤学研究中心执行副总裁&澳门在线赌城娱乐公司的博士说:“DESTINY-Breast06表明了这一点 Enhertu 是否可以成为her2低和her2超低转移性乳腺癌患者在接受一种或多种内分泌治疗后的新的护理标准. 这些数据强调了治疗的潜力 Enhertu 在hr阳性乳腺癌的范围内, 进一步重新定义转移性乳腺癌的治疗方法.”
Ken Takeshita, Global Head, R&D, Daiichi Sankyo, DESTINY-Breast06的主要结果强调了继续挑战当前治疗模式和既定乳腺癌分类的重要性，以发展澳门第一赌城在线娱乐如何治疗hr阳性患者, 表达her2的转移性乳腺癌. 基于《澳门第一赌城在线娱乐》中改变实践的数据, 这些结果加强了使用 Enhertu 在早期的治疗领域和更广泛的患者群体中.”
Enhertu 是由Daiichi Sankyo公司发现并由AstraZeneca和Daiichi Sankyo公司联合开发和商业化的一种专门设计的her2导向的DXd抗体药物偶联物(ADC)吗.
据估计，约60-65%的hr呈阳性, HER2-negative breast cancers are HER2-low and potentially an additional 25% may be HER2-ultralow.1,2 Endocrine therapies are widely used in the early lines of treatment for HR-positive metastatic breast cancer; however after two lines of treatment, 内分泌治疗的进一步疗效往往有限.3 目前内分泌治疗后的护理标准是化疗, 哪个与不良反应率和结果相关.3-6
The safety profile of Enhertu was consistent with previous breast cancer clinical trials with no new safety signals identified.
The data will be presented at a forthcoming medical meeting and shared with global regulatory authorities.
Notes
DESTINY-Breast06
DESTINY-Breast06 is a global, randomised, open-label, III期临床试验评估的有效性和安全性 Enhertu (5.4 mg/kg)与研究者选择的化疗(卡培他滨), 紫杉醇或nab-紫杉醇), HER2-low (IHC 1+ or 2+/ISH-) or HER2-ultralow (defined as IHC 0 with membrane staining; IHC >0<1+) advanced or metastatic breast cancer. 该试验中的患者之前没有因晚期或转移性疾病而接受化疗，并且在开始使用内分泌治疗联合CDK4/6抑制剂的一线治疗后6个月内经历了疾病进展，或者在转移性环境中接受了至少两种先前的内分泌治疗.
主要终点是hr阳性患者的PFS, 通过盲法独立中心评价(BICR)测量的her2低患者群体. 关键次要终点包括her2低表达患者的OS和总体试验人群(her2低和her2超低)中BICR和OS的PFS。. 其他次要终点包括客观有效率, duration of response, 到第一次后续治疗或死亡的时间, 时间到第二次后续治疗或死亡与安全. Analysis of the HER2-ultralow subgroup was not powered to demonstrate statistical significance.
DESTINY-Breast06 enrolled 866 patients (n=713 for HER2-low and n=153 for HER2-ultralow) at multiple sites in Asia, Europe, North America and South America. 有关该试验的更多信息，请访问 ClinicalTrials.gov.
Breast cancer and HER2 expression
Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide.7 2022年确诊的乳腺癌病例超过200万例，其中超过665例,000 deaths globally.7 而那些被诊断为早期乳腺癌的患者的存活率很高, 只有大约30%被诊断为转移性疾病或进展为转移性疾病的患者在诊断后预计能活5年.8
HR-positive, her2阴性是最常见的乳腺癌亚型, 约占所有乳腺癌的70%.8 HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumours, including breast cancer.9 Patients with high levels of HER2 expression (IHC 3+ or 2+/ISH+) are classified as HER2-positive and treated with HER2-targeted therapies, 约占所有乳腺癌的15-20%.10 Historically, tumours that were not classified as HER2-positive were classified as HER2-negative; however, 许多这些肿瘤仍然携带一定程度的HER2表达.11 据估计，约60-65%的hr呈阳性, HER2-negative breast cancers are HER2-low and potentially an additional 25% may be HER2-ultralow.1,2
Prior to the approval of Enhertu 基于destiny - breast - 04试验的her2低转移性乳腺癌化疗后的预后, there were no targeted therapies approved specifically for patients with HER2-low expression.12 There are no targeted therapies specifically approved for patients with HER2-ultralow expression.
Enhertu
Enhertu is a HER2-directed ADC. 采用Daiichi Sankyo专有的DXd ADC技术设计， 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)通过基于四肽的可切割连接体.
Enhertu (5.4mg /kg)已被60多个国家批准用于治疗既往接受过(或一种或多种)基于her2的抗治疗方案的不可切除或转移性her2阳性(IHC 3+或2+/ISH+)乳腺癌的成人患者, 无论是在转移性情况下还是在新辅助或辅助情况下, 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)在60多个国家被批准用于治疗不可切除或转移性her2低(IHC 1+或2+/ISH-)乳腺癌的成人患者，这些患者先前在转移性环境中接受过全身治疗，或在完成辅助化疗期间或6个月内出现疾病复发 DESTINY-Breast04 trial.
Enhertu (5.4mg /kg)已被超过35个国家批准用于治疗肿瘤具有活化性的不可切除或转移性NSCLC成年患者 HER2 (ERBB2) mutations, 由当地或地区认可的测试检测到的, 以及之前接受过系统治疗的患者基于 DESTINY-Lung02 trial. 该适应症在美国的持续批准可能取决于验证性试验中临床获益的验证和描述.
Enhertu (6.4mg /kg)已在40多个国家被批准用于治疗局部晚期或转移性her2阳性(IHC 3+或2+/ISH+)胃或胃食管交界处(GEJ)腺癌的成年患者，这些患者先前接受过基于曲妥珠单抗的方案 DESTINY-Gastric01 and/or DESTINY-Gastric02 trials.
Enhertu (5.4mg /kg)在美国被批准用于治疗既往接受过全身治疗且根据试验结果没有令人满意的替代治疗方案的不可切除或转移性her2阳性(IHC 3+)实体瘤的成人患者 DESTINY-PanTumor02, DESTINY-Lung01 and DESTINY-CRC02 trials.
Enhertu development programme
A comprehensive global clinical development programme is underway evaluating the efficacy and safety of Enhertu 单药治疗多种her2靶向癌症. Trials in combination with other anti-cancer treatments, such as immunotherapy, also are underway.
Daiichi Sankyo collaboration
AstraZeneca and Daiichi Sankyo entered into a global collaboration to jointly develop and commercialise Enhertu in March 2019 and datopotamab deruxtecan in July 2020在日本，第一三共维持每个ADC的专有权. Daiichi Sankyo负责生产和供应 Enhertu and datopotamab deruxtecan.
AstraZeneca in breast cancer
由于对乳腺癌生物学的了解越来越深入, 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.
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)，旨在用一流的AKT抑制剂重塑hr阳性空间， 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 (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. 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.
为三阴性乳腺癌患者提供急需的治疗选择, an aggressive form of breast cancer, AstraZeneca is evaluating the potential of datopotamab deruxtecan alone and in combination with immunotherapy Imfinzi (durvalumab), Truqap in combination with chemotherapy, and 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, 跟随科学去了解癌症及其所有的复杂性, 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. 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.
澳门在线赌城娱乐的愿景是重新定义癌症治疗和, one day, eliminate cancer as a cause of death.
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 & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit sh-fyz.com 并在社交媒体上关注公司 @AstraZeneca.
Contacts
References
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12. Modi S, et al. 曲妥珠单抗Deruxtecan治疗先前治疗过的her2低晚期乳腺癌. N Engl J Med. 2022;387:9-20.
Adrian Kemp
Company Secretary
AstraZeneca PLC