Durvalumab

点击蓝字 关注我们 本 期 看 点 三阴性乳腺癌(TNBC)在乳腺癌中的占比为15%，却是整个乳腺癌各种类型中最难治疗的类型。随着免疫检查点抑制剂和ADC等创新型药物的研发进展，在深刻改变其他实体瘤治疗格局之际，TNBC领域也迎来突破： 阿斯利康（AstraZeneca）与第一三共（Daiichi Sankyo）联合开发的抗体偶联药物（ADC）Datroway（datopotamab deruxtecan）在III期TROPION-Breast02临床试验中取得积极结果，成为首个在侵袭性三阴性乳腺癌（TNBC）治疗中与化疗相比能显著提高总生存期（OS）的肿瘤药物。 该试验针对不适合免疫治疗的局部复发不可手术或转移性三阴性乳腺癌患者，评估Datroway作为一线治疗的疗效。结果显示，与研究者选择的化疗方案相比，Datroway在总生存期（OS）和无进展生存期（PFS）这两个主要终点上均显示出统计学显著且临床意义的改善。 对于预后最差的乳腺癌患者而言，今天的结果标志着治疗转折点。 本期内容 01 乳腺癌流行病学及治疗现状 02 Datroway的作用机制与开发背景 03 未来发展与监管进程 04 总结与展望 【01 乳腺癌流行病学及治疗现状】 乳腺癌常被称为“粉红杀手”，发病率高居女性恶性肿瘤首位，且男性乳腺癌患者也存在(0.5%-1%)。 2022年新诊断女性乳腺癌230万，约占女性癌症病例的四分之一；其中，中国女性新发乳腺癌患者约35.72万，占世界乳腺癌患者新发病例的15.5%，死亡患者7.5万，占世界乳腺癌死亡人数的11.3%。 在整个乳腺癌中，最为难治疗的是三阴性乳腺癌(Triple-Negative Breast Cancer, TNBC)，其特点是在免疫组化检测中，雌激素受体(ER)、孕激素受体(PR)以及人表皮生长因子受体2 (HER2)均为阴性，是临床上难治性癌种。 2011年，St.Gallen国际乳腺癌治疗专家共识的提出，基于对乳腺癌生物学亚型认识的深入，采用了按照乳腺癌分类来进行治疗决策的新方法，这也标志着乳腺癌个体化治疗时代的到来。 近年来，免疫治疗已经在TNBC领域获得诸多突破，就TNBC免疫重要治疗III期临床研究汇总如下： TROPION-Breast02研究是一项全球性、多中心、随机、开放标签的III期试验，在非洲、亚洲、欧洲、北美和南美洲招募了644名患者。 这些患者均为不适合免疫治疗的局部复发、无法手术或转移性TNBC患者，试验比较了Datroway与研究者选择的化疗（包括紫杉醇、纳米紫杉醇、卡培他滨、卡铂或艾日布林）的疗效和安全性。 02 Datroway的作用机制与开发背景 Datroway是一种靶向TROP2的抗体药物偶联物（ADC），采用第一三共专有的DXd ADC技术设计。 来源：https://datrowayhcp.com/mechanism-of-action 该药物由以下部分组成：人源化抗TROP2 IgG1单克隆抗体；通过可切割四肽连接子偶联拓扑异构酶I抑制剂负载物（DXd） TROP2是一种在多种实体瘤（包括TNBC）中广泛表达的蛋白质，与肿瘤进展和不良生存率相关。 阿斯利康和第一三共于2020年达成协议，共同开发和商业化Datroway，旨在延续双方在HER2靶向ADC药物Enhertu方面的成功。 【03 未来发展与监管进程】 阿斯利康和第一三共正在积极推进Datroway在不同乳腺癌适应症中的开发： TROPION-Breast03：评估Datroway联合或不联合Imfinzi用于新辅助治疗后存在残留侵袭性疾病的I-III期TNBC患者 TROPION-Breast04：评估新辅助Datroway联合Imfinzi用于II-III期三阴性或HR低表达、HER2低表达或阴性乳腺癌患者 TROPION-Breast05：评估一线Datroway联合或不联合Imfinzi用于肿瘤表达PD-L1的转移性TNBC患者 公司计划将TROPION-Breast02试验的完整数据提交给即将召开的医学会议，并与全球监管机构分享这些结果，以期尽快将这种治疗选择带给患者。 04 总结与展望 Datroway已在全球超过35个国家获批用于治疗既往接受过内分泌疗法和化疗的HR阳性、HER2阴性转移性乳腺癌患者。此次在三阴性乳腺癌治疗领域的突破，标志着ADC药物在解决难治性乳腺癌方面迈出了重要一步，为预后最差的患者群体带来了新的希望。 如何索取幻灯及其他福利 在这个瞬息万变的医药时代，每一位专业人士都在追求卓越，力求在肿瘤治疗、研究设计、行业洞察等领域不断突破。作为聚焦医药行业的第三方专业医学服务商，我们始终致力于为每一位伙伴提供最前沿、最实用的医学知识与服务，助力您的职业成长与学术探索。 过去，我们携手走过了一段段充实而精彩的旅程，从肿瘤基础类幻灯到研究进展类幻灯，从研究设计小课堂到行业研究类幻灯，每一份资料都凝聚着我们的专业与用心，也见证了您的成长与进步。如今，2025年已至7月，我们带着全新的会员福利计划，再次向您发出诚挚的邀请，开启一段新的赋能之旅。 不定期还有会员福利惊喜赠送或享限时优惠价格哦！早购买，早获益，意愿者请联系如下。 ★

Positive high-level results from the TROPION-Breast02 Phase III trial showed Datroway (datopotamab deruxtecan) demonstrated a statistically significant and clinically meaningful improvement for the dual primary endpoints of overall survival (OS) and progression-free survival (PFS) compared to investigator's choice of chemotherapy as 1st-line treatment for patients with locally recurrent inoperable or metastatic triple-negative breast cancer (TNBC) for whom immunotherapy was not an option. Approximately 70% of patients with metastatic TNBC are not candidates for immunotherapy, including all patients whose tumours do not express PD-L1 as well as patients with PD-L1 expressing tumours who cannot receive immunotherapy due to other factors.1 Chemotherapy remains the 1st-line standard of care for these patients.2 Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: “TROPION-Breast02 is the only trial ever to show an overall survival benefit in the first-line treatment of patients with metastatic triple-negative breast cancer for whom immunotherapy is not an option. We expect today’s results will mark an inflection point in the treatment of these patients who have the poorest prognosis of any type of breast cancer and urgently need better options.” Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said: “Datroway is the first antibody drug conjugate and the only therapy to significantly improve overall survival compared to chemotherapy in patients with metastatic triple-negative breast cancer for whom immunotherapy is not an option. These landmark results from TROPION-Breast02 strengthen our confidence in our ongoing clinical development programme for Datroway in triple-negative breast cancer and other tumour types. We look forward to discussing these data with global regulatory authorities and to bringing Datroway to patients with triple-negative breast cancer as soon as possible.” The safety profile of Datroway was consistent with previous clinical trials of Datroway in breast cancer. These data will be presented at an upcoming medical meeting and shared with regulatory authorities. Datroway is a specifically engineered TROP2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo. AstraZeneca and Daiichi Sankyo are evaluating Datroway across stages and treatment settings of TNBC in three additional Phase III trials. TROPION-Breast03 is evaluating Datroway with or without Imfinzi (durvalumab) in patients with Stage I-III TNBC with residual invasive disease after neoadjuvant systemic therapy. TROPION-Breast04 is evaluating neoadjuvant Datroway plus Imfinzi in patients with Stage II-III triple-negative or hormone receptor (HR)-low, HER2-low or -negative breast cancer. TROPION-Breast05 is evaluating 1st-line Datroway with or without Imfinzi in patients with metastatic TNBC whose tumours express PD-L1. Notes Triple-negative breast cancer TNBC accounts for approximately 15% of all breast cancer cases, with an estimated 345,000 diagnoses globally each year.3,4 TNBC is diagnosed more frequently in younger and premenopausal women, and is more prevalent in Black and Hispanic women.5-7 Metastatic TNBC is the most aggressive type of breast cancer and has the worst prognosis, with median overall survival of just 12 to 18 months and only about 14% of patients living five years following diagnosis.5,8,9 While some breast cancers may test positive for oestrogen receptors, progesterone receptors or overexpression of HER2, TNBC tests negative for all three.5 Due to its aggressive nature and absence of common breast cancer receptors, TNBC is characteristically difficult to treat.5 For patients with metastatic disease with PD-L1 expressing tumours, the addition of immunotherapy to chemotherapy has improved outcomes in the 1st-line setting.10,11 However, for the approximately 70% of patients with metastatic TNBC who are not candidates for immunotherapy, chemotherapy remains the 1st-line standard of care.1,2 TROP2 is a protein broadly expressed in several solid tumours including TNBC.12 TROP2 is associated with increased tumour progression and poor survival in patients with breast cancer.13,14 TROPION-Breast02 TROPION-Breast02 is a global, multicentre, randomised, open-label Phase III trial evaluating the efficacy and safety of Datroway versus investigator’s choice of chemotherapy (paclitaxel, nab-paclitaxel, capecitabine, carboplatin or eribulin) in patients with previously untreated locally recurrent inoperable or metastatic TNBC for whom immunotherapy was not an option. This included patients whose tumours did not express PD-L1 as well as patients with PD-L1 expressing tumours who could not receive immunotherapy due to prior exposure in early-stage disease, comorbidities or immunotherapy not being accessible in their geography. Enrolment included patients with de novo or recurrent disease, regardless of disease-free interval, and those with poor prognostic factors such as brain metastases. The dual primary endpoints of TROPION-Breast02 are PFS as assessed by blinded independent central review and OS. Key secondary endpoints include PFS as assessed by investigator, objective response rate, duration of response, disease control rate, pharmacokinetics and safety. TROPION-Breast02 enrolled 644 patients at sites in Africa, Asia, Europe, North America and South America. For more information, visit ClinicalTrials.gov. Datroway Datroway (datopotamab deruxtecan; datopotamab deruxtecan-dlnk in the US only) is a TROP2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, Datroway is one of six DXd ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programmes in AstraZeneca’s ADC scientific platform. Datroway is comprised of a humanised anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. Datroway is approved in more than 35 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HR-positive, HER2-negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease based on results from the TROPION-Breast01 trial. Datroway is available in the US under accelerated approval for the treatment of adult patients with locally advanced or metastatic EGFR-mutated non-small cell lung cancer (NSCLC) who have received prior EGFR-directed therapy and platinum-based chemotherapy based on results from the TROPION-Lung05 and TROPION-Lung01 trials. Continued approval for this indication in the US may be contingent upon verification and description of clinical benefit in a confirmatory trial. Datroway is approved in Russia for the same population. Datroway clinical development programme A comprehensive global clinical development programme is underway with more than 20 trials evaluating the efficacy and safety of Datroway across multiple cancers, including NSCLC, TNBC and urothelial cancer. The programme includes eight Phase III trials in lung cancer and five Phase III trials in breast cancer evaluating Datroway as a monotherapy and in combination with other anticancer treatments in various settings. Daiichi Sankyo collaboration AstraZeneca and Daiichi Sankyo entered into a global collaboration to jointly develop and commercialise Enhertu in March 2019 and Datroway in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of Enhertu and Datroway. AstraZeneca in breast cancer Driven by a growing understanding of breast cancer biology, AstraZeneca is challenging, and redefining, the current clinical paradigm for how breast cancer is classified and treated to deliver even more effective treatments to patients in need – with the bold ambition to one day eliminate breast cancer as a cause of death. AstraZeneca has a comprehensive portfolio of approved and promising compounds in development that leverage different mechanisms of action to address the biologically diverse breast cancer tumour environment. With Enhertu, AstraZeneca and Daiichi Sankyo are aiming to improve outcomes in previously treated HER2-positive, HER2-low and HER2-ultralow metastatic breast cancer, and are exploring its potential in earlier lines of treatment and in new breast cancer settings. In HR-positive breast cancer, AstraZeneca continues to improve outcomes with foundational medicines Faslodex (fulvestrant) and Zoladex (goserelin) and aims to reshape the HR-positive space with first-in-class AKT inhibitor, Truqap (capivasertib), the TROP2-directed ADC, Datroway, and next-generation oral SERD and potential new medicine camizestrant. PARP inhibitor Lynparza (olaparib) is a targeted treatment option that has been studied in early and metastatic breast cancer patients with an inherited BRCA mutation. AstraZeneca with MSD (Merck & Co., Inc. in the US and Canada) continue to research Lynparza in these settings. AstraZeneca is also exploring the potential of saruparib, a potent and selective inhibitor of PARP1, in combination with camizestrant in BRCA-mutated, HR-positive, HER2-negative advanced breast cancer. To bring much-needed treatment options to patients with triple-negative breast cancer, an aggressive form of breast cancer, AstraZeneca is collaborating with Daiichi Sankyo to evaluate the potential of Datroway alone and in combination with immunotherapy Imfinzi.  AstraZeneca in oncology AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients. The Company’s focus is on some of the most challenging cancers. 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. AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death. AstraZeneca AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca’s innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on social media @AstraZeneca. Contacts For details on how to contact the Investor Relations Team, please click here. For Media contacts, click here. References Matthew Bowden Company Secretary AstraZeneca PLC Oncology Corporate and financial