5 November 2020 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. 17.7 months with bevacizumab alone
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
AstraZeneca and MSD’s 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, in combination with bevacizumab maintenance treatment, demonstrated a substantial progression-free survival (PFS) improvement versus bevacizumab alone for patients with HRD-positive advanced ovarian cancer. It follows the recommendation for approval 由欧洲药品管理局人用药品委员会于2020年9月提交.
Isabelle Ray-Coquard, PAOLA-1 III期试验的首席研究员和医学肿瘤学家, Centre Léon Bérard and President of the GINECO group, Paris, France, said: “For women with advanced ovarian cancer, 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.”
Dave Fredrickson, Executive Vice President, Oncology Business Unit, 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. Women treated with 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, Chief Medical Officer, MSD Research Laboratories, 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.”
The PAOLA-1 Phase III trial showed that Lynparza, in combination with bevacizumab maintenance treatment, 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 improved PFS to a median of 37.2 months versus 17.7例hrd阳性晚期卵巢癌患者单独使用贝伐单抗. The data from the PAOLA-1 trial was published in The New England Journal of Medicine 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 months versus 35.3 with bevacizumab alone.
The full EU indication is for 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 in combination with bevacizumab is approved in the US 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.
Financial considerations
Following this approval for 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, there were nearly 68,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
Homologous recombination deficiency
HRD, which defines a subgroup of ovarian cancer, encompasses a wide range of genetic abnormalities, including BRCA mutations and beyond. As with BRCA gene mutations, 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. AstraZeneca and MSD announced in August 2019 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), such as mutations in BRCA1 and/or BRCA2. Inhibition of PARP with Lynparza 导致捕获与DNA单链断裂结合的PARP, stalling of replication forks, 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 is currently approved in a number of countries, including those in the EU, 用于铂敏感复发卵巢癌的维持治疗. It is approved in the US, 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. It is also approved in the US as a 1st-line maintenance treatment with bevacizumab for patients with HRD-positive advanced ovarian cancer (BRCAm and/or genomic instability). Lynparza is approved in the US, Japan, and a number of other countries for germline BRCA-mutated, HER2-negative, metastatic breast cancer, previously treated with chemotherapy; in the EU, this includes locally advanced breast cancer. It is also approved in the US, 用于治疗种系BRCAm转移性胰腺癌. Lynparza is approved in the US 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, pancreatic and prostate cancers.
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, has been used to treat over 30,000 patients worldwide. 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 AstraZeneca and MSD 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.
The AstraZeneca and MSD strategic oncology collaboration
In July 2017, AstraZeneca and Merck & Co., Inc., Kenilworth, NJ, US, known as MSD outside the US and Canada, 宣布全球肿瘤学战略合作，共同开发和共同商业化 Lynparza, the world’s first PARP inhibitor, and 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. Working together, the companies will develop Lynparza and Koselugo 与其他潜在的新药联合使用或作为单一疗法. Independently, the companies will develop Lynparza and Koselugo 联合各自的PD-L1和PD-1药物.
AstraZeneca in oncology
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 of small molecules and biologics in development, 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, breast and blood cancers.
通过利用四个科学平台的力量——免疫肿瘤学, Tumour Drivers and Resistance, 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, eliminate cancer as a cause of death.
AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, 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 & 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 ulzb.net and follow the Company on Twitter @AstraZeneca.
Contacts
References
1. EuroHealth. (2018). Ovarian Cancer: The Silent Killer. Available at: http://eurohealth.ie/policy-brief-women-and-ovarian-cancer-in-the-eu-2018/ [Accessed October 2020].
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 [Accessed October 2020].
3. The World Health Organization. IARC. Globocan. (2018). Available at: http://gco.iarc.fr/ [Accessed October 2020].
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. Annals of Oncology, 27(8), pp.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. Clinics, 73(Suppl 1): e450s.
6. Ramus. (2009). The Contribution of BRCA1 and BRCA2 to Ovarian Cancer. Molecular Oncology, 3(2), pp.138–150.
7. Raja et al. (2012). Optimal first-line treatment in ovarian cancer. Annals on Oncology. 23 Suppl 10, x118-127.
8. NHS Choices, Ovarian Cancer Available at: http://www.nhs.uk/conditions/ovarian-cancer/treatment/ [Accessed October 2020].
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, treatment and follow-up. Annals of Oncology, 24, pp.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. New England Journal of Medicine, 379(26), pp.2495-2505.
Adrian Kemp
Company Secretary
AstraZeneca PLC