2020年11月5日07:15 GMT
接受Lynparza和bevacizumab治疗的患者无疾病进展的中位生存期为37年.2 months vs. 17.单独使用贝伐单抗7个月
每两个患有晚期卵巢癌的女性中就有一个患有hrd阳性肿瘤
澳门在线赌城娱乐和默沙东 Lynparza (olaparib) has been approved in the European Union (EU) for the 1st-line maintenance treatment with bevacizumab of patients with homologous recombination deficient (HRD)-positive advanced ovarian cancer.
Ovarian cancer is the fifth most common cause of cancer death in the EU and the five-year survival rate is approximately 45%, 部分原因是女性通常被诊断为疾病晚期(III期或IV期).1-3
The approval by the European Commission was based on a biomarker subgroup analysis of the PAOLA-1 Phase III trial which showed Lynparza, 联合贝伐单抗维持治疗, demonstrated a substantial progression-free survival (PFS) improvement versus bevacizumab alone for patients with HRD-positive advanced ovarian cancer. It follows the 建议批准 由欧洲药品管理局人用药品委员会于2020年9月提交.
伊莎贝尔Ray-Coquard, PAOLA-1 III期试验的首席研究员和医学肿瘤学家, 中心lsamon bsamrard和GINECO集团主席, Paris, France, 她说:“对于患有晚期卵巢癌的女性来说, the goal of 1st-line treatment is to delay disease progression for as long as possible with the intent of achieving long-term remission. 不幸的是，从历史上看，一旦患者的癌症复发，就无法治愈. Lynparza together with bevacizumab has demonstrated an impressive median progression-free survival benefit of more than three years and is poised to become the standard of care for eligible patients with HRD-positive tumours in the EU.”
戴夫Fredrickson, 执行副总裁, 肿瘤事业部, 他说:“在所有新诊断的晚期卵巢癌患者中，有一半患有hrd阳性肿瘤. 接受治疗的妇女 Lynparza in combination with bevacizumab in the PAOLA-1 Phase III trial lived progression free for a median of more than three years, 表明HRD检测应成为临床诊断的重要组成部分. HRD status can help physicians select a personalised 1st-line treatment regimen for patients to substantially delay relapse in this devastating disease.”
Roy Baynes, 高级副总裁兼全球临床开发主管, 首席医疗官, MSD研究实验室, said: “Biomarker testing has rapidly enhanced our understanding of how PARP inhibition can help target this disease. The EU approval reinforces that HRD-positive tumours represent a distinct subset of advanced ovarian cancer and HRD testing is critical for women in this setting.”
PAOLA-1 III期试验表明 Lynparza, 联合贝伐单抗维持治疗, 将疾病进展或死亡风险降低67%(基于风险比为0.33; 95% confidence interval 0.25-0.45). The addition of Lynparza PFS中位数提高到37.2个月对17个月.7例hrd阳性晚期卵巢癌患者单独使用贝伐单抗. PAOLA-1试验的数据发表于 新英格兰医学杂志 in 2019.
Further results recently presented at the European Society for Medical Oncology Virtual Congress 2020 showed a statistically significant improvement in the key secondary endpoint of the time to second disease progression (PFS2). Lynparza 贝伐单抗提供了超越首次疾病进展的益处，将PFS2改善至中位数50.3个月vs 35个月.3例单独使用贝伐单抗.
欧盟的全部指示是赞成 Lynparza in combination with bevacizumab for the maintenance treatment of adult patients with advanced (FIGO Stages III and IV) high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer who are in response (complete or partial) following completion of 1st-line platinum-based chemotherapy in combination with bevacizumab and whose cancer is associated with HRD positive status defined by either a breast cancer susceptibility gene 1/2 (BRCA1/2) mutation and/or genomic instability.
Lynparza 联合贝伐单抗是 在美国获得批准 and in several other countries as a 1st-line maintenance treatment for patients with HRD-positive advanced ovarian cancer and is currently under regulatory review in other countries around the world.
金融方面的考虑
在获得批准后 Lynparza in the EU, 澳门在线赌城娱乐将从默沙东获得2500万美元的监管里程碑付款, 预计将在2020年第四季度作为合作收入入账.
Ovarian cancer
In 2018, 有将近68个,在欧盟诊断出的卵巢癌新病例有5000例，大约有45例,000 deaths.3 大约50%的卵巢癌是hrd阳性，包括BRCA1/2突变.4,5 大约15%的卵巢癌有BRCA1/2突变.6 The primary aim of 1st-line treatment is to delay disease progression for as long as possible with the intent to achieve long-term remission.7-9
同源重组缺陷
HRD, 卵巢癌亚组的定义是什么, 包括广泛的基因异常, 包括BRCA突变等. 就像BRCA基因突变一样, HRD干扰正常细胞DNA修复机制，并赋予PARP抑制剂敏感性，包括 Lynparza.10
PAOLA-1
PAOLA-1是一项双盲III期临床试验，用于检测抗肿瘤药物的有效性和安全性 Lynparza 添加到标准护理贝伐单抗与单独贝伐单抗, as a 1st-line maintenance treatment for newly diagnosed advanced FIGO Stage III-IV high-grade serous or endometroid ovarian, fallopian tube, or peritoneal cancer patients who had a complete or partial response to 1st-line treatment with platinum-based chemotherapy and bevacizumab. 澳门在线赌城娱乐和默沙东 2019年8月宣布 该试验在总体试验人群中达到了PFS的主要终点.
Lynparza
Lynparza (olaparib) is a first-in-class PARP inhibitor and the first targeted treatment to block DNA damage response (DDR) in cells/tumours harbouring a deficiency in homologous recombination repair (HRR), 比如BRCA1和/或BRCA2的突变. 对PARP的抑制作用 Lynparza 导致捕获与DNA单链断裂结合的PARP, 复制分叉停止, 它们的崩溃，DNA双链断裂和癌细胞死亡. Lynparza 正在一系列parp依赖性肿瘤类型中进行测试，这些肿瘤类型在DDR通路中存在缺陷和依赖性.
Lynparza 目前是否在一些国家获得批准, 包括欧盟国家, 用于铂敏感复发卵巢癌的维持治疗. 它已在美国获得批准, the EU, Japan, China, and several other countries as 1st-line maintenance treatment of BRCA-mutated advanced ovarian cancer following response to platinum-based chemotherapy. 它在美国也获得了批准 as a 1st-line maintenance treatment with bevacizumab for patients with HRD-positive advanced ovarian cancer (BRCAm and/or genomic instability). Lynparza 在美国被批准了吗, Japan, 以及其他一些国家的brca基因突变, HER2-negative, 转移性乳腺癌, previously treated with chemotherapy; in the EU, 这包括局部晚期乳腺癌. 它在美国也获得了批准, 用于治疗种系BRCAm转移性胰腺癌. Lynparza 在美国被批准了吗 for homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (BRCAm and other HRR gene mutations). 一些国家正在对卵巢癌进行监管审查, breast, 胰腺癌和前列腺癌.
Lynparza, 由澳门在线赌城娱乐和默沙东联合开发并商业化的药物, 已经被用来治疗30岁以上了吗,全球有5000名患者. Lynparza 是否拥有所有PARP抑制剂中最广泛和最先进的临床试验开发计划, and 澳门在线赌城娱乐和默沙东 are working together to understand how it may affect multiple PARP-dependent tumours as a monotherapy and in combination across multiple cancer types. Lynparza is the foundation of AstraZeneca's industry-leading portfolio of potential new medicines targeting DDR mechanisms in cancer cells.
澳门在线赌城娱乐和默沙东战略肿瘤学合作
2017年7月，澳门在线赌城娱乐和默克 & Co., Inc., Kenilworth, NJ, US, 在美国和加拿大以外被称为MSD, 宣布全球肿瘤学战略合作，共同开发和共同商业化 Lynparza，世界上第一个PARP抑制剂，以及 Koselugo selumetinib是一种丝裂原活化蛋白激酶(MEK)抑制剂，用于多种癌症类型. 携手合作，公司将会发展 Lynparza and Koselugo 与其他潜在的新药联合使用或作为单一疗法. 这些公司将独立发展 Lynparza and Koselugo 联合各自的PD-L1和PD-1药物.
澳门在线赌城娱乐在肿瘤学
澳门在线赌城娱乐在肿瘤学领域有着深厚的传统，并提供快速增长的药物组合 有可能改变患者生活和公司未来的新药. 2014年至2020年期间有7种新药上市，并且有广泛的研发渠道 开发中的小分子和生物制剂, 公司致力于将肿瘤作为澳门在线赌城娱乐专注于肺部的关键增长动力, ovarian, 乳腺癌和血癌.
通过利用四个科学平台的力量——免疫肿瘤学, 肿瘤驱动因素和耐药性, DNA Damage Response and Antibody Drug Conjugates – and by championing the development of personalised combinations, 澳门在线赌城娱乐的愿景是重新定义癌症治疗, 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, 处方药的开发和商业化, 主要用于治疗肿瘤等三个治疗领域的疾病, Cardiovascular, Renal & 新陈代谢和呼吸 & Immunology. 总部设在剑桥, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit sjunjek.com 并在Twitter上关注公司 @AstraZeneca.
Contacts
References
1. EuroHealth. (2018). 卵巢癌:沉默的杀手. Available at: http://eurohealth.ie/policy-brief-women-and-ovarian-cancer-in-the-eu-2018/ [2020年10月生效].
2. ECIS. (2020).2020年所有癌症部位的癌症发病率和死亡率估计数. Available here [2020年10月生效].
3. 世界卫生组织. IARC. Globocan. (2018). Available at: http://gco.iarc.fr/ [2020年10月生效].
4. Moschetta et al. (2016). 浆液性卵巢癌的BRCA体细胞突变和表观遗传修饰. 肿瘤学年鉴，27(8)，页.1449-1455.
5. Bonadio et al. (2018). 卵巢癌同源重组缺乏症的流行病学及治疗进展. 临床，73(增刊1):450.
6. Ramus. (2009). BRCA1和BRCA2在卵巢癌中的作用. 分子肿瘤学，3(2)，pp.138–150.
7. Raja et al. (2012). 卵巢癌的最佳一线治疗. 肿瘤学年鉴. 23增刊10,x118-127.
8. NHS选择，卵巢癌可在: http://www.nhs.uk/conditions/ovarian-cancer/treatment/ [2020年10月生效].
9. Ledermann et al. (2013). 新诊断和复发的上皮性卵巢癌:ESMO临床实践诊断指南, 治疗及随访. 《澳门第一赌城在线娱乐》，24页.vi24-vi32.
10. Moore, K. (2018). 奥拉帕尼在新诊断晚期卵巢癌患者中的维持作用. 新英格兰医学杂志，379(26)，页.2495-2505.
Adrian Kemp
公司秘书
AstraZeneca PLC