2020年11月5日07:15 GMT
Patients treated with Lynparza and bevacizumab lived without disease progression for a median of 37.2 months vs. 17.单独使用贝伐单抗7个月
One in two women with advanced ovarian cancer has an HRD-positive tumour
澳门在线赌城娱乐和默沙东 Lynparza (olaparib)已在欧盟(EU)批准用于同源重组缺陷(HRD)阳性晚期卵巢癌患者的贝伐单抗一线维持治疗.
卵巢癌是欧盟癌症死亡的第五大常见原因，五年生存率约为45%, due partly because women are often diagnosed with advanced disease (Stage III or IV).1-3
欧盟委员会的批准是基于PAOLA-1 III期临床试验的生物标志物亚组分析 Lynparza, 联合贝伐单抗维持治疗, 与单独使用贝伐单抗相比，hrd阳性晚期卵巢癌患者的无进展生存期(PFS)显著改善. 它遵循 建议批准 by the Committee for Medicinal Products for Human Use of the European Medicines Agency in September 2020.
伊莎贝尔Ray-Coquard, principal investigator of the PAOLA-1 Phase III trial and medical oncologist, 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, 一线治疗的目标是尽可能延缓疾病进展，以达到长期缓解的目的. Unfortunately, once a patient’s cancer recurs, it historically has been incurable. Lynparza 贝伐单抗联合贝伐单抗已显示出令人印象深刻的中位无进展生存期超过3年，并有望成为欧盟符合条件的hrd阳性肿瘤患者的标准治疗.”
戴夫Fredrickson, 执行副总裁, 肿瘤事业部, said: “Half of all newly diagnosed patients with advanced ovarian cancer have HRD-positive tumours. 接受治疗的妇女 Lynparza 在PAOLA-1 III期临床试验中，联合贝伐单抗的患者无进展生存期中位数超过3年, showing that HRD testing should be an essential component of clinical diagnosis. HRD状态可以帮助医生为患者选择个性化的一线治疗方案，从而大大延缓这种毁灭性疾病的复发.”
Roy Baynes, Senior Vice President and Head of Global Clinical Development, 首席医疗官, MSD研究实验室, 他说:“生物标志物测试迅速增强了澳门第一赌城在线娱乐对PARP抑制如何帮助靶向这种疾病的理解. 欧盟的批准强化了HRD阳性肿瘤代表晚期卵巢癌的一个独特子集，HRD检测对这种情况下的女性至关重要.”
PAOLA-1 III期试验表明 Lynparza, 联合贝伐单抗维持治疗, reduced the risk of disease progression or death by 67% (based on a hazard ratio of 0.33; 95% confidence interval 0.25-0.45). 的加入 Lynparza PFS中位数提高到37.2个月对17个月.7 with bevacizumab alone in patients with HRD-positive advanced ovarian cancer. PAOLA-1试验的数据发表于 新英格兰医学杂志 in 2019.
最近在2020年欧洲肿瘤医学学会虚拟会议上公布的进一步结果显示，关键次要终点到第二次疾病进展的时间(PFS2)在统计学上有显着改善。. Lynparza with bevacizumab provided benefit beyond first disease progression, improving PFS2 to a median of 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 与贝伐单抗联合用于晚期(FIGO III期和IV期)高级别上皮性卵巢成年患者的维持治疗, 输卵管癌或原发性腹膜癌，在完成一线铂基化疗联合贝伐单抗后(完全或部分)有反应，并且其癌症与HRD阳性状态相关，该状态由乳腺癌易感基因1/2 (BRCA1/2)突变和/或基因组不稳定性定义.
Lynparza 联合贝伐单抗是 在美国获得批准 并在其他几个国家作为hrd阳性晚期卵巢癌患者的一线维持治疗，目前正在世界其他国家接受监管审查.
金融方面的考虑
在获得批准后 Lynparza in the EU, AstraZeneca will receive a regulatory milestone payment from MSD of $25m, anticipated to be booked as collaboration revenue during the fourth quarter of 2020.
卵巢癌
In 2018, 有将近68个,000 new cases of ovarian cancer diagnosed in the EU and around 45,000 deaths.3 Approximately 50% of ovarian cancers are HRD-positive including BRCA1/2 mutation.4,5 Approximately 15% of ovarian cancers have a BRCA1/2 mutation.6 一线治疗的主要目的是尽可能延缓疾病进展，以达到长期缓解的目的.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 interferes with normal cell DNA repair mechanisms and confers sensitivity to PARP inhibitors including Lynparza.10
PAOLA-1
PAOLA-1 is a double-blinded Phase III trial testing the efficacy and safety of Lynparza added to standard-of-care bevacizumab versus bevacizumab alone, 作为新诊断的晚期FIGO III-IV期高级别浆液性或子宫内膜样卵巢的一线维持治疗, 输卵管, 或对铂基化疗和贝伐单抗一线治疗有完全或部分反应的腹膜癌患者. 澳门在线赌城娱乐和默沙东 2019年8月宣布 that the trial met its primary endpoint of PFS in the overall trial population.
Lynparza
Lynparza (olaparib)是一种一流的PARP抑制剂，也是第一个靶向治疗，用于阻断同源重组修复(HRR)缺陷的细胞/肿瘤中的DNA损伤反应(DDR)。, 比如BRCA1和/或BRCA2的突变. 对PARP的抑制作用 Lynparza leads to the trapping of PARP bound to DNA single-strand breaks, 复制分叉停止, their collapse and the generation of DNA double-strand breaks and cancer cell death. Lynparza is being tested in a range of PARP-dependent tumour types with defects and dependencies in the DDR pathway.
Lynparza 目前是否在一些国家获得批准, 包括欧盟国家, for the maintenance treatment of platinum-sensitive relapsed ovarian cancer. 它已在美国获得批准, the EU, Japan, China, 和其他几个国家作为brca突变的晚期卵巢癌在铂类化疗后的一线维持治疗. 在美国，它也被批准作为贝伐单抗治疗hrd阳性晚期卵巢癌(BRCAm和/或基因组不稳定)患者的一线维持治疗。. 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阴性, 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, the EU and several other countries for the treatment of germline BRCAm metastatic pancreatic cancer. Lynparza 在美国被批准用于同源重组修复(HRR)基因突变的转移性去势抵抗性前列腺癌(BRCAm和其他HRR基因突变). Regulatory reviews are underway in several countries for ovarian, breast, 胰腺癌和前列腺癌.
Lynparza, which is being jointly developed and commercialised by 澳门在线赌城娱乐和默沙东, 已经被用来治疗30岁以上了吗,全球有5000名患者. Lynparza has the broadest and most advanced clinical trial development programme of any PARP inhibitor, 澳门在线赌城娱乐和默沙东正在合作，以了解它如何作为单一疗法影响多种parp依赖性肿瘤，以及在多种癌症类型中联合使用. Lynparza 澳门在线赌城娱乐行业领先的靶向癌细胞DDR机制的潜在新药组合的基础是什么.
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, announced a global strategic oncology collaboration to co-develop and co-commercialise Lynparza，世界上第一个PARP抑制剂，以及 Koselugo (selumetinib), a mitogen-activated protein kinase (MEK) inhibitor, for multiple cancer types. 携手合作，公司将会发展 Lynparza and Koselugo in combination with other potential new medicines and as monotherapies. 这些公司将独立发展 Lynparza and Koselugo in combination with their respective PD-L1 and PD-1 medicines.
澳门在线赌城娱乐在肿瘤学
AstraZeneca has a deep-rooted heritage in oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With seven new medicines launched between 2014 and 2020, and a broad pipeline 开发中的小分子和生物制剂, the Company is committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, 乳腺癌和血癌.
By harnessing the power of four scientific platforms – Immuno-Oncology, 肿瘤驱动因素和耐药性, DNA损伤反应和抗体药物偶联物-并通过倡导个性化组合的发展, AstraZeneca has the vision to redefine cancer treatment and, 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, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, 心血管, Renal & 新陈代谢和呼吸 & Immunology. 总部设在剑桥, UK, 澳门在线赌城娱乐在100多个国家开展业务，其创新药物被全球数百万患者使用. 请访问 jiasenyuan.com 并在Twitter上关注公司 @AstraZeneca.
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References
1. EuroHealth. (2018). 卵巢癌:沉默的杀手. 可以在: http://eurohealth.ie /政策——短暂-女性-和-Ovarian cancer症- - -欧盟- 2018 / [2020年10月生效].
2. ECIS. (2020).Estimates of cancer incidence and mortality in 2020, for all cancer sites. Available here [2020年10月生效].
3. 世界卫生组织. IARC. Globocan. (2018). 可以在: http://gco.iarc.fr/ [2020年10月生效].
4. Moschetta等人. (2016). BRCA somatic mutations and epigenetic BRCA modifications in serous ovarian cancer. 肿瘤学年鉴，27(8)，页.1449-1455.
5. Bonadio等人. (2018). 同源重组缺陷 in ovarian cancer: a review of its epidemiology and management. 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./英国/条件/Ovarian cancer/治疗 [2020年10月生效].
9. Ledermann等. (2013). Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO Clinical Practice Guidelines for diagnosis, 治疗及随访. 《澳门在线赌城娱乐》，24页.vi24-vi32.
10. Moore, K. (2018). Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. 新英格兰医学杂志，379(26)，页.2495-2505.
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