Imfinzi也推荐用于错配修复缺陷疾病的患者
推荐基于两种方案的DUO-E III期结果
表现出统计学意义和临床意义的改善
无进展生存期vs. 单独化疗
澳门葡京网赌游戏公司 Imfinzi (durvalumab)和 Lynparza (olaparib)已被推荐在欧盟(EU)批准用于某些原发性晚期或复发性子宫内膜癌患者的治疗. Imfinzi 加上化疗作为一线治疗，然后是 Lynparza and Imfinzi 是否推荐错配修复熟练(pMMR)患者使用. Imfinzi 加上化疗之后 Imfinzi alone has been recommended for patients with mismatch repair deficient (dMMR) disease.
欧洲药品管理局(EMA)人用药品委员会(CHMP)基于预先指定的基于错配修复(MMR)状态的探索性亚组分析的积极意见 双e期第三期 发表在 临床肿瘤学杂志 2023年10月.
This analysis showed a reduction in the risk of disease progression or death for pMMR patients in the Lynparza and Imfinzi 手臂减少43%(中位数15.0个月vs . 9个月.7个月，风险比[HR] 0.57; 95% confidence interval [CI] 0.44-0.73)相对于控制臂.1 Results for dMMR patients showed a reduction in the risk of disease progression or death in the Imfinzi 手臂减少58%(中位数未到达vs . 7%).0个月，HR 0.42; 95% CI 0.22-0.80)相对于控制臂.1
In Europe, 子宫内膜癌是女性中第四大常见癌症, 近125人,000例诊断，超过30例,2022年将有1000人死亡.2,3 Patients diagnosed at an early stage of disease have a five-year survival rate of approximately 80-90%, 但对于晚期疾病患者，这一比例降至不到20%.4,5 迫切需要新的治疗方案, 尤其是70-80%的pMMR患者.5,6 这一建议强调了在诊断时进行MMR检测的重要性, 哪一种已经建立并广泛使用.7,8
埃尔斯·范nieuwenhuysen, 鲁汶大学妇科肿瘤学家, 比利时和试验研究者, said: “Patients with advanced or recurrent endometrial cancer currently have a very poor prognosis, 尤其是错配修复熟练症患者. 这一建议强调了durvalumab以及奥拉帕尼和durvalumab联合治疗错配修复缺陷和错配修复精通状态患者的显著益处. This marks an important step toward improving outcomes for these patients in Europe.”
Susan Galbraith，肿瘤学研究中心执行副总裁&D, AstraZeneca, said: “Today's recommendation for approval in the EU recognises the potential of the Lynparza and Imfinzi 联合用药为子宫内膜癌患者提供临床获益, especially for those with mismatch repair proficient disease who have few available treatments today. If approved, 欧洲的患者将有一种新的联合治疗选择，为免疫治疗带来PARP抑制的额外好处.”
两种实验方案的安全性都是可控的, well-tolerated and broadly consistent with the known profiles of the individual agents.1,9,10
规管意见书 Imfinzi and Lynparza are currently under review in Japan and several other countries based on the DUO-E trial. Imfinzi plus chemotherapy was recently approved for dMMR patients with primary advanced or recurrent endometrial cancer in the US.11
Notes
子宫内膜癌
子宫内膜癌是一种高度异质性的疾病，起源于子宫内膜组织，在已经绝经的妇女中最常见, 平均诊断年龄超过60岁.12-15
The majority of patients with endometrial cancer are diagnosed at an early stage of disease, 癌症局限于子宫的地方.16 他们通常通过手术和/或放射治疗, 5年生存率高(约80-90%).17 晚期患者(III-IV期)通常预后较差, 五年存活率下降到不到20%.4 Immunotherapy combined with chemotherapy is emerging as a new standard of care for advanced endometrial cancer, 特别是对于患有dMMR疾病的患者, 他们占所有患者的20-30%.11,17-20 There remains a high unmet need for treatments for the remaining 70-80% of endometrial cancer patients with pMMR disease.5,6
DUO-E
DUO-E试验(GOG 3041/ENGOT-EN10)是一个三臂试验, randomised, 双盲, 安慰剂对照, 一线多中心III期临床试验 Imfinzi (durvalumab) 加铂类化疗(卡铂和紫杉醇) 后面是 Imfinzi 单一疗法或 Imfinzi plus Lynparza (olaparib) 新诊断的晚期或复发子宫内膜癌患者的维持治疗与单纯铂基化疗的比较.
DUO-E试验将699名新诊断为晚期或复发性上皮性子宫内膜癌的患者随机分为两组 Imfinzi (1120mg)或安慰剂, 除了标准治疗铂类化疗外，每三周给予一次. After 4-6 cycles of chemotherapy, patients (whose disease had not progressed) then received either Imfinzi (1500mg)或安慰剂作为维持，每四周加300mg Lynparza (300mg BID [2x150mg片剂，每日两次])或安慰剂，直至疾病进展.
The dual primary endpoint was progression-free survival (PFS) of each treatment arm versus standard of care. 关键次要终点包括总生存期(OS)、安全性和耐受性. 试验继续评估这两种方法的操作系统 Imfinzi 单药治疗, Imfinzi plus Lynparza 作为整个试验人群的维持治疗. Mismatch repair (MMR) status, recurrence status and geographic location were stratification factors. The trial was sponsored independently by AstraZeneca and conducted in 253 study locations across 22 countries including the US, Europe, 南美洲和亚洲.
有关试验的更多信息，请访问 临床试验.gov.
Imfinzi
Imfinzi (durvalumab)是一种人单克隆抗体，结合PD-L1蛋白并阻断PD-L1与PD-1和CD80蛋白的相互作用, countering the tumour’s immune-evading tactics and releasing the inhibition of immune responses.
Imfinzi is the only approved immunotherapy and the global standard of care in the curative-intent setting of unresectable, Stage III non-small cell lung cancer (NSCLC) in patients whose disease has not progressed after chemoradiation therapy. Imfinzi is also approved for the treatment of extensive-stage small cell lung cancer (SCLC) and in combination with a short course of Imjudo (tremelimumab)和化疗治疗转移性NSCLC.
除了对肺癌的适应症， Imfinzi 被批准与化疗(吉西他滨加顺铂)联合治疗局部晚期或转移性胆道癌，并与 Imjudo 不可切除的肝细胞癌(HCC). Imfinzi 在日本和欧盟也被批准作为不可切除HCC的单药治疗.
Since the first approval in May 2017, more than 220,000 patients have been treated with Imfinzi. 作为广泛发展计划的一部分， Imfinzi is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with SCLC, NSCLC, 膀胱癌, 乳腺癌, 一些胃肠道癌症和其他实体肿瘤.
Lynparza
Lynparza 是一种一流的PARP抑制剂，也是首个阻断同源重组相关(HRR)基因缺乏的细胞/肿瘤中的DNA损伤反应(DDR)的靶向治疗方法, 比如那些BRCA1和/或BRCA2突变的人, or those where deficiency is induced by other agents (such as new hormonal agents [NHAs]).
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, their collapse and the generation of DNA double-strand breaks and cancer cell death. Lynparza may also help enhance immunogenicity and increase the impact of anti-tumour immune responses.
Lynparza 目前在多个国家被批准治疗多种肿瘤类型, 包括铂敏感复发卵巢癌的维持治疗，以及brca突变(BRCAm)和同源重组修复缺陷(HRD)阳性晚期卵巢癌的单药治疗和联合贝伐单抗一线维持治疗, respectively; for germline BRCA mutation (gBRCAm), her2阴性转移性乳腺癌(在欧盟和日本), this includes locally advanced 乳腺癌); for gBRCAm, her2阴性的高危早期乳腺癌(日本), this includes all BRCAm HER2-negative high-risk early 乳腺癌); for gBRCAm metastatic pancreatic cancer; in combination with abiraterone for the treatment of metastatic castration-resistant prostate cancer (mCRPC) when chemotherapy is not clinically indicated (EU only) and for BRCAm mCRPC (US and Japan); and as monotherapy for HRR gene-mutated mCRPC in patients who have progressed on prior NHA treatment (BRCAm only in the EU and Japan). In China, Lynparza 被批准用于治疗brca突变的mCRPC以及贝伐单抗一线维持治疗hrd阳性晚期卵巢癌.
Lynparza 是由澳门葡京网赌游戏和默沙东联合开发和商业化的, 既可作为单一疗法，也可与其他潜在药物联合使用. 这些公司正在独立发展，并将商业化 Lynparza 结合各自的PD-L1和PD-1药物， Imfinzi (durvalumab)和 Keytruda (pembrolizumab). Lynparza 已用于治疗全球约14万名患者. Lynparza 是否有广泛的临床试验开发计划, 澳门葡京网赌游戏和默沙东正在合作，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 is the foundation of 澳门葡京网赌游戏公司 industry-leading portfolio of potential new medicines targeting DDR mechanisms in cancer cells.
澳门葡京网赌游戏在免疫肿瘤学(IO)中的应用
AstraZeneca is a pioneer in introducing the concept of immunotherapy into dedicated clinical areas of high unmet medical need. 该公司拥有全面和多样化的IO产品组合和管道，以免疫疗法为基础，旨在克服抗肿瘤免疫反应的逃避，并刺激人体免疫系统攻击肿瘤.
AstraZeneca aims to reimagine cancer care and help transform outcomes for patients with Imfinzi 作为单一疗法和联合疗法 Imjudo 以及其他新的免疫疗法和模式. 该公司还在探索下一代免疫疗法，如双特异性抗体和利用免疫的不同方面来靶向癌症的疗法.
澳门葡京网赌游戏正在大胆地追求一种创新的临床策略，将基于io的治疗方法引入到各种癌症类型的新环境中，以实现长期生存. 有广泛的临床项目, 该公司还支持在早期疾病阶段使用IO治疗, 哪里有最大的治愈潜力.
澳门葡京网赌游戏在肿瘤学
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.
澳门葡京网赌游戏的愿景是重新定义癌症治疗和, one day, 消除癌症作为死亡原因.
AstraZeneca
澳门葡京网赌游戏(LSE/STO/Nasdaq: AZN)是一家全球性制药公司, 以科学为主导的澳门葡京赌博游戏公司，专注于发现, development, 以及肿瘤学处方药的商业化, 罕见疾病, 和澳门葡京赌博游戏, 包括心血管, Renal & 新陈代谢和呼吸 & Immunology. 总部设在剑桥, UK, AstraZeneca's innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit jnjsp.com 并在社交媒体上关注公司 @AstraZeneca.
References
1. Westin SN, et al. Durvalumab联合卡铂/紫杉醇，随后维持Durvalumab联合或不联合奥拉帕尼作为晚期子宫内膜癌的一线治疗:III期DUO-E试验. 临床肿瘤学杂志. 2023;42(3):283-299.
2. 世界卫生组织. IARC. 绝对数字，发病率，女性，2022年. Europe. 可以在: http://gco.iarc.fr /今天/ en / dataviz /派?mode=cancer&cancers=24&sexes=2&group_populations = 1&数量= 908. 2024年6月发布.
3. 世界卫生组织. IARC. 从2022年到2050年的估计数量，女性，年龄[0-85+]. Europe. 可以在: http://gco.iarc.fr /明天/ en / dataviz /趋势?types=0_1&sexes=2&mode=cancer&group_populations = 0&multiple_populations = 0&multiple_cancers = 1&cancers=24&数量= 908. 2024年6月发布.
4. Cao SY, et al. III期子宫内膜癌患者根治性手术后辅助化疗或放化疗的复发和生存:一项系统回顾和荟萃分析. BMC Cancer. 2023;23:31.
5. Kelkar SS, et al. 美国晚期子宫内膜癌非微卫星不稳定性高(Non-MSI-high)或错配修复熟练(pMMR)患者的治疗模式和现实世界的临床结果. 妇科肿瘤学报告. 2022;42:101026.
6. Yang Y, et al. Molecular subtypes of endometrial cancer: Implications for adjuvent treatment strategies. 国际妇科杂志 & Obstetrics. 2024;164:436-459.
7. Abu-Rustum N, et al. 子宫肿瘤，版本1.2023年，肿瘤学NCCN临床实践指南. 国家综合癌症网络杂志. 2023;21(2):181-209.
8. Stelloo E, et al. 子宫内膜癌错配修复缺陷检测的实用指南. 肿瘤学年鉴. 2017;28(1):96-102.
9. Lynparza SmPC. 可以在: http://www.ema.europa.eu/en/documents/product-information/lynparza-epar-product-information_en.pdf. 2024年6月发布.
10. Imfinzi SmPC. 可以在: http://www.ema.europa.eu/en/documents/product-information/imfinzi-epar-product-information_en.pdf. 2024年6月发布.
11. FDA. FDA approves durvalumab with chemotherapy for mismatch repair deficient primary advanced or recurrent endometrial cancer. 可以在: http://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-durvalumab-chemotherapy-mismatch-repair-deficient-primary-advanced-or-recurrent. 2024年6月发布.
12. Dork T, et al. 子宫内膜癌的遗传易感性:危险因素和临床管理. Cancers. 2020;12(9):2407.
13. Oakin A, et al. 子宫内膜癌: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. 肿瘤学年鉴. 2022;33(9):860-877.
14. 美国癌症协会. 什么是子宫内膜癌? 可以在 http://www.cancer.org/cancer/endometrial-cancer/about/what-is-endometrial-cancer.html. 2024年6月发布.
15. 美国癌症协会. 子宫内膜癌的关键统计数据. 可以在: http://www.cancer.org/cancer/types/endometrial-cancer/about/key-statistics.html. 2024年6月发布.
16. 国家癌症研究所. SEER. 癌症统计事实:子宫癌. 可以在: http://seer.cancer.gov/statfacts/html/corp.html. 2024年6月发布.
17. Hamoud BH, et al. 子宫癌免疫治疗的发展前景:一个全面的回顾. Life. 2023;13:1502.
18. Corr B, et al. 子宫内膜癌:分子分类和未来治疗. BMJ医学. 2022;1(1):e000152.
19. FDA. FDA approves pembrolizumab with chemotherapy for primary advanced or recurrent endometrial carcinoma. 可以在: http://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-chemotherapy-primary-advanced-or-recurrent-endometrial-carcinoma. 2024年6月发布.
20. Gov.uk. MHRA批准单克隆抗体治疗, Jemperli, 用于子宫内膜癌的化疗. 可以在 http://www.gov.uk/government/news/mhra-authorises-monoclonal-antibody-treatment-jemperli-to-be-used-with-chemotherapy-for-endometrial-cancer. 2024年6月发布.
Adrian Kemp
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