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2020年9月20日17:30英国夏令时
Lynparza是唯一的PARP抑制剂
转移性去势抵抗性前列腺癌的生存率
Final results from the 深刻的 Phase III trial showed 澳门在线赌城娱乐 和 MSD’s Lynparza (olaparib) demonstrated a statistically significant 和 clinically meaningful improvement in overall survival (OS) versus enzalutamide or abiraterone in men with metastatic castration-resistant prostate 癌症 (mCRPC) with BRCA1/2 or 自动取款机 gene mutations, a subpopulation of homologous recombination repair (HRR) gene mutations.
Patients had progressed on prior treatment with new hormonal agent (NHA) treatments (i.e. 恩杂鲁胺和阿比特龙). Prostate 癌症 is the second-most common type of 癌症 in men, with an estimated 1.2018年全球新增确诊患者300万例.1 Approximately 20-30% of men with mCRPC have an HRR gene mutation.2
在OS的关键次要端点， Lynparza reduced the risk of death by 31% versus enzalutamide or abiraterone (based on a hazard ratio [HR] of 0.69; 95% confidence interval [CI] 0.50-0.97; p=0.0175). 中位OS为19.1个月 Lynparza 和14.恩杂鲁胺或阿比特龙治疗7个月, despite 66% of men on NHA treatments had crossed over to receive treatment with Lynparza 随着疾病进展.
An exploratory analysis also showed a non-statistically significant improvement in OS in the overall trial population of men with HRR基因突变 (BRCA1/2, 自动取款机, CDK12和其他11个HRRm基因), 降低21%的死亡风险 Lynparza 相对于恩杂鲁胺或阿比特龙(基于HR为0).79; 95% CI 0.61-1.03). 中位OS为17.3个月vs 14个月.恩杂鲁胺或阿比特龙治疗0个月.
约翰·德·波诺, one of the principal investigators of the 深刻的 Phase III trial, Head of Drug 发展 at The Institute for 癌症 研究 和 The Royal Marsden NHS Foundation Trust, 他说:“Lynparza has demonstrated significant clinical benefit across key endpoints in 深刻的 和 the final overall survival results reinforce its potential to change the treatment st和ard for men with metastatic castration-resistant prostate 癌症. 深刻的试验表明 Lynparza can play an important role in this new era of precision medicine in prostate 癌症, bringing a targeted therapy at a molecular level to patients with a historically poor prognosis 和 few treatment options.”
josore Baselga，肿瘤学研究执行副总裁&D, 他说:“These results help to transform the treatment l和scape for certain men with metastatic castration-resistant prostate 癌症, 在那些整体生存很难实现的地方. Lynparza is the only PARP inhibitor to demonstrate overall survival versus enzalutamide or abiraterone for men with BRCA or 自动取款机 mutations. 澳门第一赌城在线娱乐期待着继续带来 Lynparza 献给世界各地的病人.”
罗伊Baynes, Senior Vice President 和 Head of Global Clinical 发展, 首席医疗官, MSD研究实验室, 他说:“The 深刻的 trial is the first positive Phase III trial using molecular biomarker testing to help identify treatment options for certain men with metastatic castration-resistant prostate 癌症. These results further underpin the importance of genomic testing for HRR基因突变 to identify this at-risk patient population 和 help physicians make treatment decisions. 这些结果表明的潜力 Lynparza for metastatic castration-resistant prostate 癌症 patients with certain HRR mutations.”
Final OS results from the 深刻的 Phase III trial were presented on Sunday 20 September during the Presidential Symposium at the 2020 European Society of Medical 肿瘤学 virtual congress, 同时发表于 新英格兰医学杂志.
OS结果总结
OS数据截止日期为2020年3月20日
The most common adverse events (AEs) ≥20% were anaemia (50%), 恶心(43%), 疲劳/无力(42%), 食欲下降(31%), 腹泻(21%)和呕吐(20%). 最常见的≥3级ae是贫血(23%)。, 恶心(2%), 疲劳/无力(3%), 食欲减退(2%), 腹泻(1%). 20%的病人接受治疗 Lynparza 因不良反应而停止治疗.
深刻的 III期临床试验 在2019年8月达到了主要终点,显示 Lynparza significantly improved radiographic progression-free survival (rPFS) in men with BRCA1/2 or 自动取款机 genes, 和 met a key secondary endpoint of rPFS in the overall HRRm population, 是什么构成了 2020年5月获得美国批准. Regulatory reviews are ongoing in 欧盟 和 other countries.
澳门在线赌城娱乐 和 MSD are exploring additional trials in metastatic prostate 癌症 including the ongoing PROpel Phase III trial testing Lynparza as a 1st-line medicine for patients with mCRPC in combination with abiraterone versus abiraterone alone. 预计数据将于2021年发布.
转移性去势抵抗性前列腺癌(mCRPC)
Prostate 癌症 is associated with a significant mortality rate.1 发展 of prostate 癌症 is often driven by male sex hormones called 和rogens, 包括睾丸素.3 在mCRPC患者中, their prostate 癌症 grows 和 spreads to other parts of the body despite the use of 和rogen-deprivation therapy to block the action of male sex hormones.3 Approximately 10-20% of men with advanced prostate 癌症 will develop CRPC within five years, 和 at least 84% of these men will have metastases at the time of CRPC diagnosis.4 Of men with no metastases at CRPC diagnosis, 33% are likely to develop metastases within two years.4 尽管对男性mccrpc的治疗取得了进展, five-year survival is low 和 extending survival remains a key treatment goal.4
HRR基因突变
HRR genes allow for accurate repair of damaged DNA in normal cells.5,6 HRR deficiency (HRD) means the DNA damage cannot be repaired, 和 can result in normal cell death.6 这在癌细胞中是不同的, where a mutation in HRR pathways leads to abnormal cell growth 和 therefore 癌症.6 HRD is a well-documented target for PARP inhibitors, such as Lynparza. PARP inhibitors block a rescue DNA damage repair mechanism by trapping PARP bound to DNA single-str和 breaks which leads to replication fork stalling causing their collapse 和 the generation of DNA double-str和 breaks, 进而导致癌细胞死亡.6
深刻的
深刻是一种前景, 多中心, 随机, 非盲, III期临床试验测试的有效性和安全性 Lynparza versus enzalutamide or abiraterone in patients with mCRPC who have progressed on prior treatment with NHA treatments (abiraterone or enzalutamide) 和 have a qualifying tumour mutation in BRCA1/2, 自动取款机或其他12个参与HRR途径的基因之一.
The trial was designed to analyse patients with HRRm genes in two cohorts: the primary endpoint was rPFS in those with mutations in BRCA1/2 or 自动取款机 genes 和 then, if Lynparza 显示出临床益处, a formal analysis was performed of the overall trial population of patients with HRRm genes (BRCA1/2, 自动取款机, CDK12 和 11 other HRRm genes; a key secondary endpoint).
Lynparza
Lynparza (olaparib) is a first-in-class PARP inhibitor 和 the first targeted treatment to block DNA damage response (DDR) in cells/tumours harbouring a deficiency in HRR, 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-str和 breaks, 复制分叉停止, their collapse 和 the generation of DNA double-str和 breaks 和 癌症 cell death. Lynparza is being tested in a range of PARP-dependent tumour types with defects 和 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 卵巢 癌症. 它已在美国获得批准, 欧盟, 日本, 中国, 和 several other countries as 1st-line maintenance treatment of BRCA-mutated advanced 卵巢 癌症 following response to platinum-based chemotherapy. It is also approved in the US as a 1st-line maintenance treatment with bevacizumab for patients with homologous recombination deficiency (HRD)-positive advanced 卵巢 癌症. Lynparza 在美国被批准了吗, 日本, 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 欧盟, 这包括局部晚期乳腺癌. It is also approved in the US 和 several other countries for the treatment of germline BRCA-mutated metastatic pancreatic 癌症. Lynparza 在美国被批准了吗 for HRR gene-mutated metastatic castration-resistant prostate 癌症. Regulatory reviews are underway in several countries for 卵巢, 乳房, 胰腺癌和前列腺癌.
Lynparza, which is being jointly developed 和 commercialised by 澳门在线赌城娱乐 和 MSD, 已经被用来治疗30岁以上了吗,全球有5000名患者. Lynparza has the broadest 和 most advanced clinical trial development programme of any PARP inhibitor, 和 澳门在线赌城娱乐 和 MSD are working together to underst和 how it may affect multiple PARP-dependent tumours as a monotherapy 和 in combination across multiple 癌症 types. Lynparza is the foundation of 澳门在线赌城娱乐’s industry-leading portfolio of potential new medicines targeting DDR mechanisms in 癌症 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.公司., 进军, NJ, US, 在美国和加拿大以外被称为MSD, announced a global strategic oncology collaboration to co-develop 和 co-commercialise Lynparza，世界上第一个PARP抑制剂，以及 Koselugo selumetinib是一种MEK抑制剂，用于多种癌症类型. 携手合作，公司将会发展 Lynparza 和 Koselugo in combination with other potential new medicines 和 as monotherapies. 这些公司将独立发展 Lynparza 和 Koselugo in combination with their respective PD-L1 和 PD-1 medicines.
澳门在线赌城娱乐在肿瘤学
澳门在线赌城娱乐 has a deep-rooted heritage in oncology 和 offers a quickly growing portfolio of new medicines that has the potential to transform patients’ lives 和 the Company’s future. With seven new medicines launched between 2014 和 2020, 和 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 澳门在线赌城娱乐 focused on lung, 卵巢, 乳腺癌和血癌.
By harnessing the power of four scientific platforms – Immuno-肿瘤学, 肿瘤驱动因素和耐药性, DNA Damage Response 和 Antibody Drug Conjugates – 和 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, 有一天,, 消除癌症作为死亡原因.
澳门在线赌城娱乐
澳门在线赌城娱乐(LSE/STO/NYSE: AZN)是一家全球性制药公司, science-led biopharmaceutical company that focuses on the discovery, 处方药的开发和商业化, primarily for the treatment of diseases in three therapy areas - 肿瘤学, 心血管, 肾 & 新陈代谢和呼吸 & 免疫学. 总部设在剑桥, UK, 澳门在线赌城娱乐 operates in over 100 countries 和 its innovative medicines are used by millions of patients worldwide. 请访问 澳门在线赌城娱乐.com 并在推特上关注公司 @澳门在线赌城娱乐.
参考文献
1. 布雷等人. (2018). Global 癌症 statistics 2018: GLOBOCAN estimates of incidence 和 mortality worldwide for 36 癌症s in 185 countries. CA:临床医生的癌症杂志, 68(6), pp.394-424.
2. 马特奥，J，等(2015). DNA-repair defects 和 olaparib in metastatic prostate 癌症. 新英格兰医学杂志, 373(18), pp.1697 - 1708.
3. 癌症.网. (2019). Treatment of metastatic castration-resistant prostate 癌症.
www.癌症.net/research-和-advocacy/asco-care-和-treatment-recommendations-patients/treatment-metastatic-castration-resistant-prostate-癌症 [最后访问日期:2020年9月].
4. 科比,M. (2011). Characterising the castration-resistant prostate 癌症 population: a systematic review. 国际临床实践杂志, 65(11), pp.1180-1192.
5. Li等人. (2008). Homologous recombination in DNA repair 和 DNA damage tolerance. 细胞研究, 18(1), pp.99-113.
6. Ledermann等. (2016). 同源重组缺乏症与卵巢癌. 欧洲癌症杂志， 60, pp.49-58.