Fam-trastuzumab deruxtecan-NXKI

点击蓝字 关注我们 本 期 看 点 2025年欧洲肿瘤内科学会（ESMO 2025）将于10月17-21日在德国柏林举行。作为全球肿瘤学领域的顶尖盛会，多项即将改变临床实践的重磅研究将在本届大会发布。目前，大会“突破性摘要”（LBA）的标题已经公布。 在全球肿瘤治疗格局中，乳腺癌无疑是创新药物竞争最为密集的领域之一。从 HER2 靶向到 TNBC（Triple Negative Breast Cancer）再到 HR+/HER2− 通路，治疗模式正在迭代出新。 2025  ESMO 多项Ⅲ期临床试验的数据更新或将直接影响乳腺癌未来临床指南的修订，尤其是以下四项： DESTINY-Breast11：T-DXd（Enhertu）新辅助阶段的关键验证。 ASCENT-03：Trodelvy 挑战 TNBC 一线治疗。 monarchE：阿贝西利（Abemaciclib）辅助治疗的长期生存结果。 VIKTORIA-1：Gedatolisib 打开 PI3K 通路耐药后的新方向。 本期内容 01 四大重磅研究全景速览 02 DESTINY-Breast11：T-DXd新辅助 03 ASCENT-03：Trodelvy  TNBC 1L 04 HR+/HER2− 乳腺癌 【01 四大重磅研究全景速览】 291O: DESTINY-Breast11 研究  标题： Neoadjuvant trastuzumab deruxtecan alone (T-DXd) or followed by paclitaxel + trastuzumab + pertuzumab (T-DXd-THP) vs SOC for high-risk HER2+ early breast cancer (eBC) 新辅助德曲妥珠单抗单药（T-DXd）或序贯紫杉醇+曲妥珠单抗+帕妥珠单抗（T-DXd-THP）对比标准治疗（SOC）用于高危HER2阳性早期乳腺癌（eBC） 研究显示，新辅助 T-DXd + THP 显著提升 pCR，较标准方案（AC→THP）有统计学与临床意义的改善。 LBA20: ASCENT-03 研究 标题： A randomized phase 3 study of sacituzumab govitecan (SG) vs chemotherapy (chemo) in patients (pts) with previously untreated advanced triple-negative breast cancer (TNBC) who are unable to receive PD-(L)1 inhibitors (PD-[L]1i) 一项随机Ⅲ期研究：在无法接受PD-(L)1抑制剂（PD-[L]1i）的初治晚期三阴性乳腺癌（TNBC）患者中，比较戈沙妥珠单抗-戈维替康（SG）与化疗（chemo）的疗效 LBA13：monarchE 研究 标题： monarchE: primary overall survival (OS) results of adjuvant abemaciclib + endocrine therapy (ET) for HR+, HER2-, high-risk early breast cancer (EBC). monarchE：阿贝西利联合内分泌治疗（ET）用于 HR 阳性、HER2 阴性、高风险早期乳腺癌的辅助治疗——主要总体生存（OS）结果 LBA17: VIKTORIA-1研究 标题： Gedatolisib (geda) + fulvestrant ± palbociclib (palbo) vs fulvestrant in patients (pts) with HR+/HER2-/PIK3CA wild-type (WT) advanced breast cancer (ABC): first results from VIKTORIA-1 Gedatolisib（geda）联合氟维司群（fulvestrant）±帕博西尼（palbociclib）对比氟维司群单药治疗 HR+/HER2−/PIK3CA 野生型（WT）晚期乳腺癌（ABC）患者：VIKTORIA-1 研究首次结果 【02 DESTINY-Breast11：T-DXd新辅助】 2025年5月7日，阿斯利康宣布：与第一三共联合开发的 HER2 ADC 药物德曲妥珠单抗（trastuzumab deruxtecan，DS-8201，Enhertu，T-DXd）在Ⅲ期研究 DESTINY-Breast11 中取得积极结果。 人群：高危、局部进展期或炎性 HER2 阳性早期乳腺癌，高危定义包括淋巴结阳性（N1–3）或原发肿瘤 T3–4。 主要发现：与标准治疗 ddAC→THP 相比，T-DXd→THP 的新辅助方案显著提高 病理完全缓解率（pCR），且具统计学与临床意义；EFS 尚未成熟，但早期趋势有利于 T-DXd→THP。 研究设计 类型：全球、多中心、随机、开放标签、Ⅲ期试验（1:1:1 随机）。 对照/方案（均为新辅助，周期均为3周一周期的标准设置，文内用“周期”表示疗程数）： T-DXd 单药：共 8 个周期 T-DXd； T-DXd→THP：4 个周期 T-DXd 后序贯 4 个周期 THP（紫杉醇 + 曲妥珠单抗 Herceptin + 帕妥珠单抗 Perjeta）； 标准治疗 ddAC→THP：4 个周期 ddAC（多柔比星 + 环磷酰胺）后序贯 4 个周期 THP。 终点设置 主要终点：由盲法独立中央复审（BICR）评估的 pCR（乳腺及腋窝淋巴结无浸润性癌）。 次要终点：无事件生存期（EFS）、无侵袭性疾病生存期（IDFS）、总生存期（OS）、药代动力学、免疫原性与安全性。 主要结果（高层次公布） 疗效：与标准方案 ddAC→THP 相比，T-DXd→THP 在主要终点 pCR 上实现显著提高，具统计学与临床意义。 pCR 定义：手术切除标本中乳腺与淋巴结均未发现浸润性癌细胞。 EFS：期中分析时尚未成熟，但早期趋势显示 T-DXd→THP 优于标准方案。 安全性 总体耐受性：与 ddAC→THP 相比，T-DXd→THP 的安全性整体更优，未见新的安全性信号。 间质性肺疾病（ILD）：由独立评审委员会评估，T-DXd→THP 与 ddAC→THP 的 ILD 发生率相近；研究中对 ILD 的监测与管理按既定流程执行。 结论与临床启示 DESTINY-Breast11 显示 T-DXd 在新辅助阶段具备显著提高 pCR的能力，并呈现早期 EFS 获益趋势及更可控的安全性概况。结果支持 HER2 阳性早期乳腺癌治疗策略从传统 蒽环类→双抗+紫杉醇向ADC 前移并序贯双抗化疗的路径演进；随着中长期随访推进，EFS/IDFS/OS 的成熟数据有望进一步验证其治愈意图人群中的长期获益。 03 ASCENT-03：Trodelvy  TNBC 1L ASCENT-03：一线转移性TNBC中，Trodelvy 显著延长PFS并达到主要终点 研究概述 试验名称/分期：ASCENT-03，Ⅲ期、开放标签、随机对照（NCT05382299） 入组人群：既往未接受系统治疗的局部晚期不可手术或转移性TNBC；需为PD-(L)1 抑制剂不适用或PD-L1阴性人群；ECOG 0–1，器官功能充足。 样本量与中心：约 540 例，全球516个中心。 研究设计与治疗方案 随机分组（1:1）： 紫杉醇 90 mg/m²（q28d 的第1、8、15天），或 白蛋白紫杉醇 100 mg/m²（q28d 的第1、8、15天），或吉西他滨 1000 mg/m² + 卡铂 AUC 2（q21d 的第1、8天）。 试验组：Sacituzumab govitecan（SG, Trodelvy） 10 mg/kg，q21d 的第1、8天给药；对照组（医师选择化疗）： 终点设置 主要终点：无进展生存期（PFS）；关键次要终点：总生存期（OS）；其他次要终点：客观缓解率（ORR）、缓解持续时间（DoR）、起效时间（TTR）、治疗相关不良事件发生率、实验室异常发生率、生活质量基线变化等。 主要结果（公司5月更新） 主要终点达成：与化疗相比，SG 显著、具有临床意义地延长 PFS； 安全性：不良反应谱与既往研究一致，未见新的安全性问题； OS：本次分析时 尚未成熟，未观察到 OS 劣势。 意义：该结果被研究方评价为20余年来该人群首个具有临床意义的进展（相较传统化疗）。 专家与后续计划 研究者指出，约有近半数转移性TNBC患者无法进入二线治疗，凸显在一线阶段更有效且可及的创新治疗之迫切需求。 完整数据将于即将召开的医学会议披露，并提交监管机构。 实践启示：在TNBC一线治疗决策中，SG 单药相对医师选择化疗具有优先考虑价值；后续需关注OS成熟与安全性长期随访。 04 HR+/HER2− 乳腺癌 在 ESMO 2025 公布的两项 HR+/HER2− 乳腺癌研究中，monarchE 与 VIKTORIA-1 分别聚焦于辅助与晚期阶段的关键治疗策略。 Ⅲ期全球性 monarchE 研究（LBA13）评估了 阿贝西利（Abemaciclib）联合内分泌治疗（ET） 在 HR 阳性、HER2 阴性、高危早期乳腺癌患者中的辅助疗效。共纳入 5637 例患者，随机分配接受阿贝西利（150 mg bid）联合 ET 或单纯 ET。预设的中期分析结果显示，在 ≥4 年随访后，联合组在降低侵袭性无病生存事件方面表现出显著获益（HR = 0.68，95% CI 0.60–0.77，P < 0.001），约 80% 的患者获得临床受益。总体生存（OS）数据尚未成熟，但趋势积极。与此同时，Ⅲ期 VIKTORIA-1 研究（LBA17）则验证了 Gedatolisib + Fulvestrant ± Palbociclib 在 HR+/HER2−、PIK3CA 野生型晚期乳腺癌中的疗效。该开放标签全球研究将患者按 1:1:1 分为三组：A 组（Gedatolisib + Palbociclib + Fulvestrant）、B 组（Gedatolisib + Fulvestrant）及 C 组（Fulvestrant 单药）。结果显示，A 组中位 PFS 为 9.3 个月（HR = 0.24，P < 0.0001），B 组为 7.4 个月（HR = 0.33，P < 0.0001），均显著优于对照组的 2.0 个月。两项研究共同勾勒出 HR+/HER2− 人群从早期到晚期的连续治疗图景：阿贝西利在辅助阶段巩固了 CDK4/6 抑制剂的标准地位，而 Gedatolisib 的出现则为晚期耐药后的精准联合治疗提供了新的路径。 ★

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