摘要：2025年9月10日-14日，第28届中国临床肿瘤学会（CSCO）年会在山东济南盛大召开。会议以“规范诊疗，创新引领”为主题，吸引了海内外学者共襄盛举。会上，日本福岛医科大学医院Shigehira Saji（佐治 重衡）教授分享了靶向滋养层细胞表面抗原2（Tr
编者按：2025年9月10日-14日，第28届中国临床肿瘤学会（CSCO）年会在山东济南盛大召开。会议以“规范诊疗，创新引领”为主题，吸引了海内外学者共襄盛举。会上，日本福岛医科大学医院Shigehira Saji（佐治 重衡）教授分享了靶向滋养层细胞表面抗原2（Trop-2）抗体偶联药物（ADC）在激素受体阳性（HR+）乳腺癌的治疗前景，引发了与会专家的展望与思考。此前于8月22日，中国国家药品监督管理局(NMPA)正式批准了新型Trop-2 ADC 德达博妥单抗(Dato-DXd)上市，用于治疗既往接受过内分泌治疗且在晚期疾病阶段接受过至少一线化疗的不可切除或转移性激素受体(HR)阳性、人表皮生长因子受体2(HER2)阴性(定义为IHC 0、IHC 1+ 或 IHC 2+/ISH-)的乳腺癌成人患者。在此背景下，CSCO候任理事长、中国人民解放军总医院江泽飞教授对话Shigehira Saji教授，分享中日HR+乳腺癌治疗现状，解析Dato-DXd临床应用疗效及安全性管理要点，展望未来Trop-2 ADC广阔前景，为全球乳腺癌诊疗奉上亚洲智慧。
01
《肿瘤瞭望》：此次大会上，Shigehira Saji教授介绍了HR阳性晚期乳腺癌中Trop-2 ADC的应用前景。请两位专家谈谈后CDK4/6i时代，HR+晚期乳腺癌的治疗现状是怎样的？Trop-2 ADC处于何种地位？
Oncology Frontier: At 2025 Annual Meeting of CSCO, Professor Shigehira Saji introduced the application prospects of Trop-2 ADC in HR-positive advanced breast cancer. Could you discuss the current treatment status of HR+ advanced breast cancer in the post-CDK4/6i era? What is the position of Trop-2 ADC in this context?
Shigehira Saji 教授：对于HR+晚期乳腺癌CDK4/6i及内分泌治疗耐药的治疗探索已成为极具前沿性的热门话题。过去，在内分泌治疗耐药后我们只能选择化疗，而如今ADC已成为新的选择，包括德曲妥珠单抗（T-DXd）、Dato-DXd、戈沙妥珠单抗（SG）等。Trop-2靶点在多个癌种中存在高表达，在临床实践中占据了极为重要的地位，临床应用相当广泛[1]。在使用Trop-2 ADC时，无需检测Trop-2的具体表达水平。
日本在8月25日已经批准T-DXd用于HR+，且伴有HER2低表达和超低表达晚期乳腺癌患者，意味着其将成为内分泌耐药后的一线治疗方案[2]。而在二线及其后或对于HER2零表达患者，则可选择Dato-DXd或SG，但因SG获批较晚，尚未在日本真正投入使用，故我们仍以Dato-DXd为主。
Prof. Shigehira Saji : The exploration of treatment strategies for HR+ advanced breast cancer resistant to CDK4/6 inhibitors and endocrine therapy has emerged as a cutting-edge and highly prominent topic. In the past, chemotherapy was the only option following endocrine resistance; however, (ADCs) have now become a new standard of care, including trastuzumab deruxtecan (T-DXd), datopotamab deruxtecan (Dato-DXd), and sacituzumab govitecan (SG). The Trop-2 target is highly expressed across multiple cancer types and holds a very important position in clinical practice, with broad applications. When using Trop-2 ADCs, there is no need to measure the Trop-2 expression.
Japan approved T-DXd on August 25 for patients with HR+ advanced breast cancer with HER2-low and HER2-ultralow expression, signifying its new role as a first-line treatment option after endocrine resistance. For second-line or subsequent therapies or patients with HER2-zero disease, Dato-DXd or SG may be selected. However, due to SG's relatively late approval and is not yet widely available in Japan, Dato-DXd remains the predominant choice in practice .
江泽飞 教授：非常有幸能与日本学者合作，共同在HR+乳腺癌领域开展交流，在国际舞台中展现亚洲的形象和声音。HR+乳腺癌的治疗从最早单一内分泌治疗逐步走向了联合治疗、走向了ADC治疗。非常荣幸能够在早年间与国内外学者在乳腺癌、肺癌等领域就Dato-DXd展开合作，也非常欣喜地看到其获得了国家药物监督管理局（NMPA）的批准，期待Dato-DXd能够让更多患者从中获益。
Prof. Zefei Jiang : We are also very honored to have such cooperation with Japanese scholars in the field of HR+ breast cancer, working together to present Asian perspectives and contributions on the global academic stage. The treatment landscape for HR+ breast cancer has evolved significantly—from single-agent endocrine therapy, to combination regimens, and now to ADCs. I am Particularly privileged to have collaborated with international colleagues across disciplines, including breast and lung cancers, in the early exploration of Dato-DXd. It is immensely gratifying to witness its approval by the National Medical Products Administration (NMPA). We anticipate that Dato-DXd will bring meaningful clinical benefits to a broader population of patients.
02
《肿瘤瞭望》：8月22日，中国NMPA正式批准了新型Trop-2 ADC Dato-DXd上市，请谈谈其具体表现如何？
Oncology Frontier: On August 22, China's NMPA officially approved the marketing of the novel Trop-2 ADC Dato-DXd. Could you please comment on its clinical performance?
江泽飞 教授：ADC已经应用到了乳腺癌的不同领域，比如抗HER2 ADC已经覆盖了HER2阳性、低表达和超低表达。对于HER2阴性乳腺癌患者，ADC的探索也在持续进行。此次Dato-DXd获批的适应证主要针对HR+乳腺癌患者。众所周知，当前CDK4/6i已经成为HR+乳腺癌晚期一线乃至早期辅助治疗阶段的常用方案，晚期患者存在大量原发或继发耐药状况。在此背景下，新型ADC将为患者带来更多的治疗机会。因此，今年《中国临床肿瘤学会（CSCO）乳腺癌诊疗指南》也将Dato-DXd作为HR+、HER2低表达晚期乳腺癌的重要推荐[3]。随着今年8月份Dato-DXd的获批，未来将会积累更多经验和数据。希望它能早日被纳入医保，让更多患者能够用得上、用得起。
Prof. Zefei Jiang : ADCs have been applied across various domains of breast cancer treatment. For instance, anti-HER2 ADCs now cover HER2-positive, low-expression, and ultra-low expression populations. Explorations of ADCs for HER2-negative breast cancer patients are also ongoing. The recently approved indication for Dato-DXd primarily targets HR-positive breast cancer patients. As is well known, CDK4/6 inhibitors have become a standard regimen for first-line and adjuvant therapy in HR-positive breast cancer. However, a significant number of advanced patients experience primary or secondary resistance. In this context, novel ADCs like Dato-DXd provide additional therapeutic opportunities for these patients. Consequently, 《Chinese Society of Clinical Oncology (CSCO) Breast Cancer Guidelines 2025》have included Dato-DXd as an important recommendation for HR-positive, HER2-low advanced breast cancer. With Dato-DXd's approval in August this year, more real-world experience and data are expected to accumulate. It is hoped that it will soon be included in the national medical insurance reimbursement list to improve accessibility and affordability for more patients.
03
《肿瘤瞭望》：在安全性方面，Dato-DXd的表现如何，与其他Trop-2 ADC有哪些区别？
Oncology Frontier: Regarding safety, how does Dato-DXd perform, and what are the differences compared to other Trop-2 ADCs?
Shigehira Saji 教授：我们在T-DXd、Dato-DXd的临床应用方面积累了丰富经验。对于Dato-DXd而言，临床实践中需要主要关注的不良反应是眼毒性和口腔黏膜炎[4]。在临床试验阶段，我们对其处理已有了充足经验，可在用药前指导患者使用人工泪液或预防口腔黏膜炎的药物，即可有效防止眼毒性和口腔黏膜炎的发生。总之，在Dato-DXd的安全性管理方面，我认为预防更为重要。
Prof. Shigehira Saji : We have accumulated substantial experience in the clinical application of both T-DXd and Dato-DXd. For Dato-DXd, the adverse events requiring primary attention in clinical practice are ocular toxicity and oral mucositis. Through our experience in clinical trials, we have developed robust strategies to mitigate these risks—prophylactic use of artificial tears and oral mucositis-preventive agents prior to treatment initiation has proven effective in reducing the incidence of these adverse events. In summary, regarding the safety management of Dato-DXd, I believe prevention holds greater importance.
江泽飞 教授：不同ADC之间可能存在共同的设计理念、相似的设计结构、相对一致的靶点，但在连接子、细胞毒载荷等分子结构层面存在不同，应用剂量和毒性表现也不一致，在不同瘤种、不同疾病阶段、不同既往治疗措施对应的管理方式也不尽相同。若患者既往对治疗较为敏感或累积毒性较多，或从一种ADC切换为另一中ADC，则需注意加强安全性管理。
如今，晚期HR+乳腺癌的治疗有了内分泌治疗、化疗、ADC等手段，在不同药品间的衔接时，还应注意避免选用机制一致的药物，以避免不良反应谱重叠。比如患者在前期治疗时的不良事件主要为骨髓毒性，则后续药物选择时应尽可能避免此类状况，并注意给予合理的用药剂量。在系统治疗的全过程中，我们应关注患者的临床获益和耐受性。同一个患者对不同药物的耐受性可能有一致的趋势，提醒临床医生需要清楚地了解患者既往治疗时对药品或方案的耐受性，从而为新药的应用和管理提供一定的参考。
新药上市后的临床应用还有一点需要注意，即临床实践中患者可能已经接受过多种传统治疗，与临床研究设计的入组遴选标准并不一致。因此，希望同道们可以很好地了解药品的作用机制、不良反应谱和安全管理措施，让更多患者能够在合适的时机、合理的剂量下，实现新药更好地应用。
Prof. Zefei Jiang : While different ADCs may share common design philosophies, similar structural frameworks, and relatively consistent target antigens, they often diverge in molecular architecture—particularly in linkers and cytotoxic payloads—leading to variations in dosage regimens and toxicity profiles. Accordingly, management strategies must be tailored to specific tumor types, disease stages, and prior treatments. Particular attention should be paid to safety monitoring when switching between ADCs, especially for patients with heightened treatment sensitivity or accumulated toxicity from previous therapies.
The treatment landscape for advanced HR+ breast cancer now includes endocrine therapy, chemotherapy, and ADCs. When sequencing these agents, it is critical to avoid overlapping mechanisms of action to prevent cumulative toxicity. For instance, if a patient experienced significant myelosuppression with prior treatment, subsequent therapy should avoid agents with similar hematological toxicity, and drug dosing must be carefully calibrated. Throughout systemic treatment, both clinical efficacy and patient tolerance should be closely monitored. An individual’s tolerance to one drug may predict responses to others, underscoring the need for clinicians to thoroughly understand the patient’s prior treatment history to inform safer and more effective use of new agents.
Another practical consideration in the post-approval use of novel ADCs is that real-world patients often have more complex treatment histories compared to those in clinical trials. It is therefore essential for clinicians to fully comprehend each drug’s mechanism of action, adverse event spectrum, and corresponding management strategies. This knowledge ensures that more patients can benefit from these advanced therapies at appropriate doses and optimal times.
04
《肿瘤瞭望》：对于TROP2 ADC Dato-DXd的未来表现，您有何期待?
Oncology Frontier: Please share your expectations for the future performance of the Trop-2 ADC Dato-DXd?
Shigehira Saji 教授：Dato-DXd已在HR+晚期乳腺癌的二线及后续治疗中发挥了重要作用，未来有望成为TNBC一线乃至围术期新辅助或辅助治疗药物。我们对其在乳腺癌各个疾病阶段发挥更广泛的作用充满期待。
Prof. Shigehira Saji : Dato-DXd has established a significant role in the second-line and later treatment of HR+ advanced breast cancer. Looking ahead, it holds promise as a potential therapeutic option for first-line treatment of TNBC, as well as in the perioperative setting, including both neoadjuvant and adjuvant therapy. We anticipate its broader application across various stages of breast cancer management, expecting it to deliver more comprehensive benefits.
江泽飞 教授：基于Dato-DXd独特的机制和良好的疗效，未来我们特别希望此类新型产品能在TNBC的治疗中有所突破。另外，ADC联合免疫治疗、单抗、双抗以及其他新作用机制药物的治疗策略已成为未来的发展方向，已有多项国内外研究在此方面展开探索。总之，希望此类好的产品可以更好地、更早地应用于临床，探索更多合理的联合应用策略，以期提升疗效和安全性，让更多患者从中获益，乃至走向治愈。
Prof. Zefei Jiang : Based on the unique mechanism and favorable efficacy profile of Dato-DXd, we are particularly hopeful that this novel agent will achieve breakthroughs in the treatment of TNBC in the future. Furthermore, therapeutic strategies involving ADC-based combinations—such as with immunotherapy, monoclonal antibodies, bispecific antibodies, and agents featuring novel mechanisms of action—represent a major direction for future development. Multiple domestic and international studies have already initiated exploration in this area. In summary, we anticipate that such promising agents can be applied in clinical practice earlier and more broadly, with further investigation into rational combination strategies. These efforts are expected to enhance both efficacy and safety, ultimately benefiting more patients and potentially moving towards a cure.
▌参考文献：
[1] Guerra E, Trerotola M, Alberti S. Targeting Trop-2 as a Cancer Driver. J Clin Oncol. 2023;41(29):4688-4692. doi:10.1200/JCO.23.01207
[2] ENHERTU® Approved in Japan as First HER2 Directed Medicine for Patients with HER2 Low or HER2 Ultralow Metastatic Breast Cancer Following at Least One Endocrine Therapy. Available at [2025.09.17] : https://www.daiichisankyo.com/files/news/pressrelease/pdf/202508/20250825_E2.pdf
[3] 中国临床肿瘤学会指南工作委员会. 中国临床肿瘤学会（CSCO）乳腺癌诊疗指南 2025.-北京:人民卫生出版社. 2025.04
[4] Bardia A, Jhaveri K, Im SA, et al. Datopotamab Deruxtecan Versus Chemotherapy in Previously Treated Inoperable/Metastatic Hormone Receptor-Positive Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer: Primary Results From TROPION-Breast01. J Clin Oncol. Published online September 12, 2024. doi:10.1200/JCO.24.00920
来源：肿瘤瞭望