Randomized Phase III Trial of Multimodality Therapy Versus Standard of Care Systemic Therapy in HER2 Positive (HER2+) De Novo (AJCC Stage IV) Oligometastatic Breast Cancer With Response to Initial Chemotherapy

This phase III trial evaluates the effect of adding locoregional therapy (surgery and radiation) and metastasis-directed stereotactic body radiation therapy (SBRT) to standard systemic therapy following standard HER2-targeted systemic therapy, compared to standard systemic therapy alone, in treating patients with HER2-positive stage IV breast cancer that has spread from where it first started (primary site) to other places in the body (metastatic) or to a limited number of sites (oligometastatic). The usual approach for patients with (oligo)metastatic HER2-positive breast cancer is systemic drug treatment, which means medicines that travel through the whole body to treat both the breast and any areas where the cancer has spread. There are a number of approved HER2-targeted systemic therapy regimens available to patients. These typically include immunotherapy and/or chemotherapy. Immunotherapy drugs may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Unlike systemic therapy, locoregional therapies like surgery and radiation are focused treatments at the site of disease, delivered with the intent of sparing healthy tissues. Breast surgeries such as breast conserving therapy or total mastectomy are procedures in which the cancerous breast tissue (and healthy breast tissue in the case of total mastectomy) are surgically removed from the body. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. SBRT is a type of external radiation therapy that uses special equipment to position a patient and precisely deliver radiation to tumors in the body (except the brain). The total dose of radiation is divided into smaller doses given over several days. This type of radiation therapy helps spare normal tissue. Adding locoregional therapy, as well as metastasis-directed SBRT, to standard systemic therapy may help patients with (oligo)metastatic, HER2-positive stage IV breast cancer live longer overall or before their cancer progresses, and may help more patients achieve no evidence of disease, when compared to standard systemic therapy alone.

开始日期2027-03-09

申办/合作机构

SWOG

[+1]

NCT07126561

/ Not yet recruiting临床2期IIT

Phase II Open Label Trial of Trastuzumab Deruxtecan (Enhertu, DS-8210) in HER2 Positive Newly Diagnosed Metastatic Esophageal, Gastric, GEJ Cancer Patients With an ECOG Performance Status of 2

Purpose: This clinical trial is designed to evaluate the safety and effectiveness of Trastuzumab Deruxtecan for patients with HER2 Positive Newly Diagnosed Metastatic Esophageal, Gastric, GEJ Cancer. The goal is to determine how well this treatment works and to identify any potential side effects.
Who Can Participate: We are looking for Participants with histologically confirmed HER2 positive locally advanced unresectable and/or metastatic esophageal, gastric or GEJ adenocarcinoma with an ECOG PS of 2 and measurable disease according to RECIST 1.1 within 42 days prior to registration. Participants will be carefully screened to ensure they meet the study requirements.
What to Expect: Participants will undergo 6.4mg/kg, IV infusion of Trastuzumab deruxtucan over the course of the study. They will receive detailed information about the study and will have the opportunity to ask questions before deciding to participate. Informed consent will be obtained to ensure that participants understand the study's purpose, procedures, risks, and benefits.
Safety Monitoring: The health and safety of participants are our top priority. An Independent Data and Safety Monitoring Committee (DSMC) will regularly review the study data to ensure participant safety and to monitor for any adverse events. Any serious side effects will be reported and addressed promptly.
Benefits and Risks: While the study aims to provide potential benefits, such as improved treatment options for HER2 Positive Newly Diagnosed Metastatic Esophageal, Gastric, GEJ Cancer there may also be risks involved. Participants will be informed of all possible risks before enrolling in the study.
Confidentiality: All personal information will be kept confidential, and data will be used only for research purposes.
Contact Information: For more information about this study, please contact PhaseIICRA@medicine.bsd.uchicago.edu

开始日期2026-11-01

申办/合作机构

The University of Chicago

NCT07137416

/ Recruiting临床1期IIT

Phase 1b Study of Pidnarulex and Trastuzumab Deruxtecan in Patients With HER2 Expressing Solid Tumors

This phase I trial tests the safety, side effects, and best dose of pidnarulex in combination with trastuzumab deruxtecan in treating patients with breast cancer and other solid tumors that express varying levels of a protein called HER2 and that has spread from where it first started (primary site) to other places in the body (metastatic), that cannot be removed by surgery (unresectable), or that has spread to nearby tissue or lymph nodes (locally advanced). Pidnarulex is an enzyme inhibitor that causes cell death and prevents tumor cell growth. Trastuzumab deruxtecan is in a class of medications called antibody-drug conjugates. It is composed of a monoclonal antibody, called trastuzumab, linked to a chemotherapy drug, called deruxtecan. Trastuzumab attaches to HER2 positive tumor cells in a targeted way and delivers deruxtecan to kill them. Giving pidnarulex in combination with trastuzumab deruxtecan may be safe, tolerable and/or effective in treating patients with metastatic, unresectable, or locally advanced HER2-expressing breast cancer or other solid tumors.

开始日期2026-10-05

申办/合作机构

National Cancer Institute

100 项与德曲妥珠单抗相关的临床结果

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100 项与德曲妥珠单抗相关的转化医学

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100 项与德曲妥珠单抗相关的专利（医药）

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1,065

项与德曲妥珠单抗相关的文献（医药）

2026-07-01·Value in Health Regional Issues

Budget Impact Analysis of Fam-Trastuzumab-Deruxtecan as a Second Line in Patients With HER2-Positive Metastatic Breast Cancer in Oman

Article

作者: Aljaber, Rana ; Al Froukh, Rawan F ; Al Hashar, Amna

OBJECTIVES:

Despite advancements, breast cancer remains a major global health and financial challenge. Trastuzumab-based therapies, particularly Fam-Trastuzumab-Deruxtecan (T-DXd), have shown superior outcomes, leading to its recommendation as a preferred second-line treatment. However, its high cost necessitates a budget impact analysis (BIA) to evaluate financial feasibility. This study assesses the 1-year budget impact of replacing Trastuzumab Emtansine (TDM1) with T-DXd for HER2+ metastatic breast cancer in an Omani cancer center.

METHODS:

A static BIA model was built based on National Institute for Health and Care Excellence template with adaptation as required. The model time horizon was 1 year then projected over another 2 years, using 2022 as the baseline year, adopting Omani healthcare-payer perspective. The analysis considered 2 scenarios: (1) TDM1 as the current formulary drug and (2) T-DXd is introduced instead of TDM1, assuming that treatment share would be 100%. One-way sensitivity analysis is performed to assess the model's robustness.

RESULTS:

The BIA demonstrated that replacing TDM1 with T-DXd for the eligible patients would lead to increase in the budget expenditure. Over a 3-year period, considering the provided assumptions and input data, the cumulative excess amount to €5 909 481.67. The primary contributing factors are the drug acquisition cost and the median treatment duration. The sensitivity analysis results suggest the model is robust to changes in adverse drug reaction costs, unlike changes in treatment duration and drug cost.

CONCLUSIONS:

Although T-DXd improves clinical outcomes, its adoption as a second-line treatment in Oman poses a substantial financial burden, necessitating careful budget planning to ensure long-term affordability.

2026-06-01·BREAST

Antibody–drug conjugate sequencing in HER2-positive metastatic breast cancer: Real-world outcomes of trastuzumab deruxtecan with and without prior T-DM1 exposure

Article

作者: Bayram, Ertuğrul ; Deliktaş Onur, İlknur ; Yeşil Çınkır, Havva ; Majidova, Nargiz ; Gündüz, Şeyda ; Erdem, Dilek ; Karadurmuş, Nuri ; Er, Özlem ; Selçukbiricik, Fatih ; Başaran, Gül ; Güney, Bünyamin ; Kalem, Ali ; Gürsu, Rıza Umar ; Oruç, Ahmet ; Seyyar, Mustafa ; Tünbekici, Salih ; Güren, Ali Kaan ; Ateş, Öztürk ; Köylü, Bahadır ; Yazıcı, Melike ; Güney, Gizem ; Akdoğan, Orhun ; Türker, Sema ; Araz, Murat ; Göker, Erdem ; Kaban, Kerim ; Yılmaz, Mesut ; Aykan, Musa Barış ; Demir, Nazan ; Yıldız, İbrahim ; Molinas Mandel, Nil ; Kıkılı, Cevat İlteriş ; Biter, Sedat ; Korkmaz, Taner ; Tunalı, Didem ; Çabuk, Devrim ; Laçin, Şahin ; Bilici, Ahmet ; Sezer, Ahmet ; Altunok, Oğuz ; Şahin, Taha Koray ; Çelik, Emir ; Bayoğlu, İbrahim Vedat ; Aksoy, Sercan ; Açıkel Yüksel, Sakine Damla ; Ekinci, Ömer Burak ; Kemik, Fatih ; Özçelik, Hakan ; Güven, Deniz Can ; Yazıcı, Ozan ; Tural, Deniz

BACKGROUND:

Optimal sequencing of trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd) in HER2 positive metastatic breast cancer (mBC) remains uncertain, and real-world evidence on the impact of prior T-DM1 exposure on subsequent T-DXd outcomes is limited.

METHODS:

We conducted a multicenter, retrospective cohort study across 21 oncology centers in Türkiye including consecutive adults with HER2 positive mBC who received at least one cycle of T-DXd between 2020 and 2025. Patients were classified as T-DM1 pretreated or T-DM1 naive at T-DXd initiation. The primary endpoint was progression free survival (PFS); secondary endpoints included objective response rate (ORR), duration of response (DOR), and overall survival (OS). To address confounding by indication, we applied stabilized inverse probability of treatment weighting (IPTW) based on prespecified clinical covariates and assessed covariate balance using standardized mean differences.

RESULTS:

Among 218 patients treated with T-DXd, 137 (62.8%) had received prior T-DM1 and 81 (37.2%) were T-DM1 naive. The ORR was 71.9%, including 15.2% complete and 56.7% partial responses. Median DOR in the overall cohort was 20.96 months (95% CI, 15.71-26.22). In the IPTW-weighted analysis, prior T-DM1 exposure was associated with significantly shorter PFS: 12.1 months (95% CI, 10.3-20.5) versus 26.0 months (95% CI, 18.9 - not reached) in T-DM1 naive patients (IPTW-weighted log-rank p = 0.006). Prior T-DM1 remained independently associated with higher progression risk (HR 1.99, 95% CI 1.09 - 3.62; p = 0.02). Median OS was 18.9 months (95% CI, 17.2-not reached) in T-DM1 pretreated patients and not reached in T-DM1 naive patients; the IPTW-weighted OS hazard ratio did not reach statistical significance (HR 1.80, 95% CI 0.86-3.79; p = 0.12).

CONCLUSIONS:

Trastuzumab deruxtecan demonstrated substantial real-world activity after prior T-DM1 exposure, but PFS was significantly shorter compared with T-DM1 naive patients, even after rigorous adjustment for measured confounding. These findings highlight the clinical relevance of antibody drug conjugate sequencing and support prospective studies to define the optimal positioning of T-DXd in HER2 positive mBC treatment algorithms.

2026-06-01·DRUGS

Sequential Use of Trastuzumab Deruxtecan and Sacituzumab Govitecan in Patients with Breast Cancer: A Pharmacological Approach to Support the Clinical Rationale

Review

作者: Mathijssen, Ron H J ; Bria, Emilio ; Curigliano, Giuseppe ; Danesi, Romano ; Inglese, Elvira ; Del Re, Marzia ; Blok, Erik J

Antibody-drug conjugates (ADCs) represent a major advance in breast cancer therapy, with trastuzumab deruxtecan and sacituzumab govitecan emerging as leading agents targeting distinct tumor antigens and employing different linker-payload designs. Trastuzumab deruxtecan is a second-generation HER2-directed ADC composed of trastuzumab linked via a cleavable tetrapeptide linker to the camptothecin derivative exatecan, a highly potent topoisomerase I inhibitor. Its high drug-to-antibody ratio (DAR 8:1), membrane-permeable payload, and efficient lysosomal release confer strong antitumor activity, including a robust bystander effect in HER2-low tumors. By contrast, sacituzumab govitecan is a TROP-2-targeted ADC conjugated through a hydrolysable CL2A linker to SN-38, the active metabolite of irinotecan. Sacituzumab govitecan features a high DAR (7.6:1) and allows extracellular as well as intracellular release of SN-38, enhancing bystander killing in tumors with heterogeneous TROP-2 expression, while maintaining a favorable toxicity profile due to the lower intrinsic potency of SN-38 relative to exatecan. Since both these ADCs are conjugated to topoisomerase I inhibitors, concerns about potential cross-resistance regarding their sequencing in clinical practice are being raised, and currently there is a lack of predictive biomarkers providing a rational basis for their sequential administration. Resistance mechanisms exhibit significant heterogeneity: resistance to trastuzumab deruxtecan has been associated with mutations in TOPO I and SLX4, impaired lysosomal function, and efflux via ABC transporters. In contrast, resistance to sacituzumab govitecan is linked to overexpression of multidrug resistance proteins, particularly BCRP-mediated efflux. Clinically, trastuzumab deruxtecan has shown substantial efficacy in both HER2-positive and HER2-low breast cancer, whereas sacituzumab govitecan has demonstrated efficacy across triple-negative and hormone receptor-positive/HER2-negative breast cancers. Collectively, these agents highlight how variations in target antigen, linker chemistry, and payload potency impact ADC activity, therapeutic index, and potential strategies for sequential treatment in advanced breast cancer.

6,078

项与德曲妥珠单抗相关的新闻（医药）

2026-05-26

·癌度

《癌度快报》2026年5月26日：从肺癌到罕见肿瘤，美国MD安德森在2026年ASCO公布多项精准治疗进展！

临床试验病友交流群（点击）一、新药快讯 1、2026年ASCO大会披露三特异性抗体CS2009治疗实体肿瘤的临床数据！基石药业的PD-1、VEGF和CTLA-4三抗CS2009亮相ASCO 2026，I期临床试验数据显示其在多线经治晚期实体瘤中展现初步疗效：无驱动基因非小细胞肺癌（27例）治疗应答率ORR为18.5%，软组织肉瘤（9例）ORR为33.3%，非透明细胞肾癌（5例）ORR为20%，三阴性乳腺癌（6例）ORR为16.7%，疾病控制率DCR最高达74.1%。≥2线非小细胞肺癌（30例可评估）ORR约20%（30mg/kg亚组25%）。安全性良好，无DLT及死亡，≥3级TRAE约20%。该药通过肿瘤局部激活CTLA-4降低外周毒性，目前处于早期临床，未获批上市，符合条件者可咨询正规临床试验入组。 2、靶向HER2的前沿药BL‑M07D1启动治疗胆管癌的三期临床试验！ 2026年5月26日，靶向HER2 表达的ADC药物BL‑M07D1新登III期临床试验（CTR20261975）：面向HER2表达、含铂化疗失败的局部晚期/转移性胆道癌，随机对照BL‑M07D1 vs 医生选择化疗（TPC），国内拟入组398例，主要终点为总生存期（OS）。全球目前尚无HER2的ADC获批胆道癌适应症，这也是首个进入胆道癌III期的国产HER2 ADC（同赛道第一三共/阿斯利康的德曲妥珠单抗仍在推进联合一线III期）。⚠️该适应症未获批，多线失败后若检测HER2阳性（IHC/ISH需规范复核），可咨询癌度申请临床试验和入组。 3、免疫组合疗法治疗肝癌获得积极临床试验结果！难治性/既往免疫（PD‑1/PD‑L1）失败又没好选项的晚期肝癌患者，目前有了一个新的治疗机会，近日公布的数据表明：botensilimab（CTLA‑4多功能抗体）联合 balstilimab（PD‑1单抗）的 1b期扩展队列（共19例入组、18例可评估，近半数还是ALBI 2级/肝储备更差人群）使用这一药物组合的客观缓解率ORR达到了17%（1例完全缓解+2例部分缓解），18周临床获益率CBR 50%，中位无进展生存期约4.4个月，中位总生存期约12.3个月；而这类人群历史后线ORR多在6–14%、中位总生存期mOS常≤10.5个月，所以这算是一个“往前挪一小步”的希望点。但必须泼冷水：样本极小、属于早期机制探索数据，远没到改写标准治疗。二、抗癌前沿 1、从肺癌到罕见肿瘤，美国MD安德森在2026年ASCO公布多项精准治疗进展！ ①KRAS基因G12C突变晚期非小细胞肺癌一线：新一代KRAS基因G12C抑制剂 divarasib + PD‑1（帕博利珠单抗）的1b/2期（Krascendo 170）在PD‑L1阳性人群客观应答率ORR约73%，中位无进展生存期约19.3个月，PD‑L1阴性也看到应答苗头，不良反应可控——但它仍是在研联合方案、未获批此用法，别自行拼药；②复发性小细胞肺癌：靶向SEZ6的ADCABBV‑706在后线人群中“过半肿瘤缩小”，推荐剂量/二线时点更突出（文中称“超80%缩小、部分持续≥6个月”），同样未上市此适应症；③罕见腺样囊性癌ACC：首创RNA靶向/降解思路药物REM‑422（ARIA研究）1/2期看到肿瘤缩小比例约43%、疾病控制且部分持续超1年、近2年仍在用，机制新但证据仍早；④极罕见侵袭性肾髓样癌RMC（多与镰状细胞特征相关）：老药新用——EGFR单抗帕尼单抗多线后治疗应答率ORR约53.9%（完全缓解率约15.4%）、中位总生存期近10个月，也好于历史化疗印象。 “吉爱3000”惠民检项目，最低2000+可及的基因检测专属福利，全球新药临床试验免费用药、基因检测报告解读，详情微信“长按”下图扫码联系癌度王博进行咨询。另外，由于微信公众平台的机制调整，恳请各位粉丝朋友花一两秒钟帮我们点亮文章下方的【小手】和【爱心】，这对我们至关重要。谢谢大家！点亮小手爱心，送来温暖鼓励

ASCO会议临床3期临床结果抗体药物偶联物

2026-05-26

·ioncology

第十六届浙江大学大肠癌学术论坛丨朱梁军教授解读HER2阳性结直肠癌的精准治疗策略与挑战

点击蓝字关注我们 2026年5月15日至17日，第十六届浙江大学大肠癌学术会议（ZUCCS'16）期间，《肿瘤瞭望》对江苏省肿瘤医院朱梁军教授进行了专访，朱教授主要对HER2阳性结直肠癌的治疗模型进行了分享。HER2阳性结直肠癌是一类恶性程度高、预后差的特殊类型结直肠癌，随着精准医疗理念的深入，其治疗格局正在发生转变。访谈期间，朱教授围绕HER2阳性结直肠癌的治疗现状进行了深入剖析，重点探讨了ADC类新型药物带来的生存曙光，以及在复杂突变背景下如何权衡治疗靶点的核心策略，为临床诊疗提供了新的思考方向。 ✓ 《肿瘤瞭望》请您简单介绍一下现阶段HER2阳性结直肠癌治疗，还存在哪些临床未被满足的治疗需求？朱梁军教授目前，晚期结直肠癌的治疗已全面迈入精准靶向与免疫治疗时代。其中，HER2阳性结直肠癌作为一种特殊亚型，正逐渐被大家所认识。这类结直肠癌患者虽然发病率较低，约3%~5%，但其恶性程度非常高，对常规化疗、免疫治疗及靶向治疗的应答率均不理想，患者的生存期极短。但现在，一些针对HER2过表达或扩增的晚期结直肠癌的新型药物的临床应用，取得了较好的疗效。无论是大分子类药物，如抗体偶联药物（ADC），或是小分子的酪氨酸激酶抑制剂（如图卡替尼、吡罗替尼等），在单药或联合治疗模式下均展现出良好的疗效。当然，最关键的是，精准治疗的前提在于精准检测。当前，对于HER2扩增的检测标准，我们国家也在开展专家讨论论证，以确定统一判断标准。核心争议在于，是以超过50%还是以超过10%的肿瘤细胞数IHC3+或IHC2+/FISH阳性为标准，仍需进一步明确。 ✓ 《肿瘤瞭望》您本次演讲聚焦HER2阳性结直肠癌治疗新模式，相比传统化疗和常规靶向方案，当前HER2阳性结直肠癌涌现的治疗新模式，核心突破主要体现在哪些方面？朱梁军教授对于HER2阳性结直肠癌患者，新的治疗方向主要是靶向治疗从后线向前线推进的趋势。正如BRAF突变患者，基于BREAKWATER研究确立了“双靶联合化疗”的一线标准，那么HER2阳性患者是否也能沿用同样理念。现有的DS8201（德曲妥珠单抗）研究数据显示，其在后线治疗中客观缓解率可达45%左右，如果将其与双靶、化疗甚至免疫治疗联合，用于HER2阳性结直肠癌患者一线治疗，是否能取得更好的疗效，这也是非常值得期待的研究方向。 ✓ 《肿瘤瞭望》临床中部分HER2阳性患者合并其他突变，诊疗更为复杂，针对这类人群，该如何个体化选择治疗新模式？朱梁军教授确实，在晚期结直肠癌患者中，临床中会存在多靶点共存的复杂局面。例如，通过基因检测发现，部分HER2阳性患者可能同时伴有BRAF突变、RAS突变或存在微卫星高度不稳定（MSI-H）状态，针对此类患者，到底应以哪一靶点为主进行治疗。现有研究证据表明，对于HER2阳性且RAS野生型的患者，抗HER2治疗的疗效相对更佳（后线治疗有效率约40%）；反之，若合并BRAF突变，抗HER2疗效则显著下降（有效率仅约10%）。这提示我们在为这类患者制定治疗方案时要仔细评估，应该以哪一个治疗靶点为主。对于BRAF突变合并MSI-H状态的患者，鉴于免疫治疗在该人群中良好的疗效，应优先以免疫治疗为主。总体而言，针对合并其他突变的HER2阳性的结直肠癌患者，哪种靶点或者说哪种治疗策略疗效更好的话，就应该将其作为主要治疗方向。 ✓ 《肿瘤瞭望》针对HER2低表达患者，目前临床治疗策略是否需要重新界定、进行分层调整？这类患者是否也能从新型HER2治疗方案中获得潜在获益？朱梁军教授对于HER2阳性结直肠癌患者，随着ADC药物的横空出世，其在胃癌、乳腺癌乃至泌尿肿瘤中，即便是在HER2低表达（IHC1+或2+）人群中亦显示出显著获益，这为我们提供了重要启示。针对HER2阳性结直肠癌，目前临床上面临的主要困惑主要有两点。一是检测标准，到底是以50%的肿瘤细胞过表达为标准，还是以10%为宜，目前仍未形成统一意见。二是对于HER2低表达患者，能否借鉴胃癌领域中ADC治疗的成功经验，虽然这一点目前尚未开展相关临床研究。但我相信，未来必将涌现出更多的探索性研究，期待相关研究结果的公布，以更好的指导临床治疗。专家简介朱梁军教授江苏省肿瘤医院江苏省肿瘤医院主任医师；中国医药教育协会腹部肿瘤结直肠癌分会委员；中国医药教育协会疑难肿瘤专委会第二届常务委员；中国医药教育协会肿瘤药物临床研究专业委员会委员；中国临床肿瘤学会（CSCO）结直肠癌专家委员会常务委员；中国临床肿瘤学会（CSCO）肝癌、神经内分泌肿瘤、临床研究专家委员会委员；中国医师协会结直肠肿瘤专委会第二届委员会结直肠肝转移学组、内科学组组员；中华结直肠癌MDT联盟江苏分盟主任委员；江苏省肿瘤防治联盟大肠癌专家委员会副主任委员；江苏省医师协会结直肠肿瘤专委会第二届委员会委员；江苏省医师协会结直肠肿瘤专委会第二届委员会内科学组副组长；国家抗肿瘤药物临床应用监测专家委员会结直肠癌组专家；长期从事消化道领域肿瘤的多学科联合治疗，近二年以通讯作者在 eClinicalMedicine和 Signal Transduction and Targeted Therapy发表IIT研究论文两篇。（来源：肿瘤瞭望消化时讯）声明凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。

抗体药物偶联物免疫疗法多肽偶联药物

2026-05-26

·医脉通

TROPION-Breast01研究最终生存分析

前言激素受体（HR）阳性、人表皮生长因子受体2（HER2）阴性乳腺癌作为最常见的亚型，内分泌治疗联合CDK4/6抑制剂是其标准治疗手段。然而，对于内分泌治疗耐药或不适合内分泌治疗的患者，首选方案仍是化疗，但该方法并不总能带来总生存期（OS）的改善，且伴随严重的不良反应。近年来，抗体药物偶联物（ADC）的问世为这类患者提供了新的治疗选择，其中Trop-2靶向ADC药物德达博妥单抗（Dato-DXd）已在TROPION-Breast01研究中展现出显著的无进展生存期（PFS）改善和可控的安全性。本文将结合TROPION-Breast01Ⅲ期临床试验的最终OS分析[1]数据，对Dato-DXd在既往经治的不可切除/转移性HR+/HER2-乳腺癌中的长期疗效与安全性进行解读。研究背景 TROPION-Breast01研究（NCT05104866）是一项全球多中心、随机、开放标签的Ⅲ期临床试验，截至2023年7月，经盲法独立中心评审（BICR）证实，与研究者选择的化疗（ICC；艾瑞布林、卡培他滨、长春瑞滨或吉西他滨）相比，Dato-DXd在双主要终点之一的PFS方面显示出具有统计学显著性和临床意义的改善（HR 0.63，P<0.0001）。与此同时，Dato-DXd还显示出良好且可管理的安全性，其≥3级治疗相关不良事件（TRAEs）的发生率不到ICC组的一半（20.8% vs 44.7%），且Dato-DXd组因TRAEs导致剂量减低和治疗中断的患者比例均低于ICC组。基于TROPION-Breast01研究的阳性结果，Dato-DXd目前已获批用于转移性HR+/HER2-乳腺癌患者的治疗。然而，在进行PFS分析时，其另一双重主要终点OS数据尚未成熟，在本次更新的数据中，研究者通过延长随访时间并进行最终OS分析，旨在明确Dato-DXd相较于ICC的长期生存获益，并补充长期随访后的安全性数据，以期为临床治疗决策提供更充分的依据。研究方法 TROPION-Breast01研究共纳入732例不可手术或转移性HR+/HER2-乳腺癌患者，所有入组患者均对内分泌治疗耐药且经研究者评估不适合继续接受内分泌治疗，并在晚期阶段接受过一至二线化疗。入组患者按1:1比例随机分配至Dato-DXd组（6mg/kg，Q3W）或ICC组。双重主要终点为BICR评估的PFS和OS。次要疗效终点包括客观缓解率（ORR）、缓解持续时间（DoR）和12周疾病控制率（DCR）（均由BICR和研究者评估）、研究者评估的PFS、至首次后续治疗或死亡时间（TFST）、至第二次后续治疗或死亡时间（TSST）以及至第二次进展或死亡时间（PFS2），以及安全性和耐受性。研究结果主要终点最终OS分析（数据截止2024年7月24日）：中位随访时间为22.8个月，OS事件在Dato-DXd组发生223例（61.1%），在ICC组发生213例（58.0%）。结果显示，Dato-DXd组和ICC组的中位OS分别为18.6个月和18.3个月，风险比（HR）为1.01（95%CI 0.83-1.22，P=0.9445）。图1 TROPION-Breast01研究OS数据[1] 值得关注的是，在停止研究药物治疗后，患者后续抗肿瘤治疗方案的应用对最终的OS结果解读产生了影响。数据显示，在ICC治疗组中，有24.0%的患者（n=88）后续接受了ADC（T-DXd或SG）治疗，而在Dato-DXd组中，这一比例仅为12.3%（n=45），而这一差异可能在一定程度上缩小了Dato-DXd带来的潜在OS优势。为了校正这一干扰，研究者采用逆概率删失加权法（IPCW）进行了敏感性分析，结果显示，Dato-DXd组的中位OS为19.1个月，而ICC组为17.5个月；调整后的OS HR为0.86（95%CI 0.70-1.06），呈现出有利于Dato-DXd的趋势。以上数据提示，若无后线ADC治疗的交叉影响，Dato-DXd在OS上的获益可能更为明确。图2 采用IPCW法校正后的OS数据[1] 次要疗效终点尽管在OS方面未显示出统计学意义，在所有次要疗效终点上，分析结果均证实Dato-DXd在疾病控制上的临床优势：研究者评估的PFS HR为0.64（95%CI 0.55-0.76），与此前报告的BICR评估的PFS数据显示出高度的一致性。与此同时，Dato-DXd组与ICC组相比，研究者评估的确认ORR分别为36.7%和22.1%，中位DoR分别为7.2个月和6.0个月，12周DCR分别为80.8%和66.8%；且Dato-DXd组的PFS2、TFST和TSST相较于ICC组也实现了有效延长（中位PFS2：11.7个月 vs 10.4个月，HR 0.76；中位TFST：8.0个月 vs 5.2个月，HR 0.58；中位TSST：13.7个月 vs 12.3个月，HR 0.83）。图3 TROPION-Breast01研究PFS2数据[1] 亚组分析预设亚组分析显示，基线脑转移患者亚组（Dato-DXd组35例，ICC组23例）观察到了OS获益趋势（HR=0.55），但因样本量较小，无法得出明确结论。根据HER2 IHC状态进行的探索性OS分析中，对于HER2 IHC 0患者，Dato-DXd组和ICC组的中位OS分别为17.8个月和14.3个月（HR=0.89）；对于HER2 IHC 1+/2+且FISH-患者，两组中位OS分别为19.0个月和18.7个月（HR=1.06，95%CI 0.79-1.43），提示Dato-DXd在各HER2 IHC亚型中均有临床获益潜力。安全性安全性方面，尽管Dato-DXd组中位治疗持续时间更长（6.8个月 vs 4.1个月），但其≥3级TRAEs发生率仅为化疗组的一半（22.2% vs 45.6%），且Dato-DXd组因不良事件导致剂量调整或治疗中断比例亦低于化疗组。值得注意的是，Dato-DXd组与化疗组在不良反应谱上显示出明显差异。其中，Dato-DXd组最常见的TRAEs包括恶心（51.9%）、口腔炎（51.4%）、脱发（36.4%）和疲劳（25.0%）；治疗相关特殊关注不良事件（AESI）主要表现为低级别口腔黏膜炎/口腔炎，眼表事件和间质性肺病（ILD）。而化疗组的安全性特征则仍以血液学毒性为主，包括贫血（所有级别：19.9%；≥3级：2.6%）、白细胞减少（所有级别：17.4%；≥3级：7.4%）和中性粒细胞减少（所有级别：43.3%；≥3级：31.1%）。表1 TROPION-Breast01研究安全性数据[1] 讨论 TROPION-Breast01研究的最终OS分析显示，尽管Dato-DXd与ICC相比未能获得具有统计学意义的OS改善，但该结果可能受到后续治疗不均衡的影响——对照组后续接受ADC治疗的比例显著高于试验组，而ADC类药物的良好疗效可能抵消了试验组的生存优势。事后敏感性分析显示，在调整后续ADC治疗产生的偏倚后，Dato-DXd组观察到OS数值改善，进一步支持其潜在的长期生存获益。值得强调的是，研究已达到双主要终点之一的PFS，且所有次要疗效终点均持续倾向于Dato-DXd，包括ORR、DoR、DCR、PFS2等，提示Dato-DXd可有效控制肿瘤进展、延长患者无治疗失败时间，为患者带来临床获益。此外，Dato-DXd在HER2 IHC 0型患者中展现出良好的疗效，为这一亚组患者提供了新的治疗选择；基线脑转移患者亚组的初步数据也提示Dato-DXd可能具有颅内抗肿瘤活性，但需更大样本量研究验证。安全性方面，Dato-DXd的≥3级TRAEs发生率不足ICC的一半，且不良事件多为可管理的1-2级，无新的迟发毒性出现，加之其给药方案更为便捷，显著提升了患者的治疗耐受性和依从性。综合疗效和安全性数据，支持Dato-DXd作为既往经治的不可手术/转移性HR阳性/HER2阴性乳腺癌患者的一种治疗选择。结论在Tropion-Breast01试验中，其双重主要终点之一——BICR评估的PFS显示出具有统计学显著性和临床意义的改善，尽管另一双主要终点OS未观察到统计学意义，但这可能与两组患者在出组后的ADC治疗选择差异有关。综合Dato-DXd组在次要疗效终点和整体安全性上的优势，此次最终分析的结果表明，Dato-DXd可作为既往经治的不可手术/转移性HR+/HER2-乳腺癌患者的治疗选择。参考文献： [1] Pistilli B, Jhaveri K, et al. Datopotamab deruxtecan versus chemotherapy in previously treated inoperable/metastatic hormone receptor-positive, HER2-negative breast cancer: final overall survival analysis of the phase III TROPION-Breast01 study. Ann Oncol. 2026 May;37(5):663-674. 审批编号：CN-183865 有效期至：2027-05-20 本材料由阿斯利康提供，仅供医疗卫生专业人士参考，不用于推广目的。若涉及具体药物使用，请参考相关药物说明书，阿斯利康不建议您将产品超说明书使用。撰写：Penny 审校：River 排版：Zelda 执行：Zelda 本平台旨在为医疗卫生专业人士传递更多医学信息。本平台发布的内容，不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议。如该等信息被用于了解医学信息以外的目的，本平台不承担相关责任。本平台对发布的内容，并不代表同意其描述和观点。若涉及版权问题，烦请权利人与我们联系，我们将尽快处理。

100 项与德曲妥珠单抗相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	德曲妥珠单抗	L01XC	DB14962

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
HER2阳性转移性乳腺癌	美国	Daiichi Sankyo, Inc.	2026-05-15
胃癌	印度	AstraZeneca PLC	2025-10-07
HER2阳性实体瘤	英国	Daiichi Sankyo UK Ltd.	2025-04-09
HR阳性/HER2低表达乳腺癌	美国	Daiichi Sankyo Co., Ltd.	2025-01-28
HR阳性/HER2阳性乳腺癌	韩国	Daiichi Sankyo Co., Ltd.	2022-09-19
HER2突变型非小细胞肺癌	美国	Daiichi Sankyo, Inc.	2022-08-11
HER2阳性胃腺癌	澳大利亚	AstraZeneca Pty Ltd.	2021-10-08
HER2低表达乳腺癌	澳大利亚	AstraZeneca Pty Ltd.	2021-10-08
转移性乳腺癌	加拿大	AstraZeneca Canada, Inc.	2021-04-15
HER2阳性胃食管结合部腺癌	美国	Daiichi Sankyo, Inc.	2021-01-15
HER2阳性胃癌	日本	Daiichi Sankyo Co., Ltd.	2020-09-25
HER2阳性乳腺癌	美国	Daiichi Sankyo, Inc.	2019-12-20

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
实体瘤	临床3期	美国	Daiichi Sankyo, Inc.	2025-12-23
实体瘤	临床3期	中国	Daiichi Sankyo, Inc.	2025-12-23
实体瘤	临床3期	日本	Daiichi Sankyo, Inc.	2025-12-23
实体瘤	临床3期	澳大利亚	Daiichi Sankyo, Inc.	2025-12-23
实体瘤	临床3期	巴西	Daiichi Sankyo, Inc.	2025-12-23
实体瘤	临床3期	法国	Daiichi Sankyo, Inc.	2025-12-23
实体瘤	临床3期	以色列	Daiichi Sankyo, Inc.	2025-12-23
实体瘤	临床3期	意大利	Daiichi Sankyo, Inc.	2025-12-23
实体瘤	临床3期	韩国	Daiichi Sankyo, Inc.	2025-12-23
实体瘤	临床3期	西班牙	Daiichi Sankyo, Inc.	2025-12-23

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适应症

分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04379596 (DESTINY-Gastric03, AACR2026)	临床1/2期	食管腺癌 \| HER2阳性胃癌 \| 胃食管交界处腺癌一线 HER2-positive	30	trastuzumab deruxtecan + rilvegostomig + fluoropyrimidine (HER2-positive gastric cancer, gastroesophageal junction adenocarcinoma, or esophageal adenocarcinoma)	鹽鑰廠襯鏇選觸齋範範(遞鹹襯餘餘糧選醖餘獵) = 艱鏇鏇繭構廠網蓋構夢醖鹽窪網顧遞餘窪觸簾 (鹽衊醖積繭鹽願鑰觸衊 ) 更多	积极	2026-04-21
NCT07151586 (ALTER, AACR2026)	临床2期	三阴性乳腺癌 HER2-low	260	Alternating sacituzumab-govitecan and trastuzumab-deruxtecan	簾製壓襯蓋鑰鑰窪壓襯(膚衊繭製蓋衊鏇顧醖積) = 醖構獵醖艱廠遞蓋獵襯糧築夢淵觸鹹餘夢鬱鏇 (膚積顧齋艱顧壓鹽壓鏇 ) 更多	积极	2026-04-21
				Sacituzumab-govitecan	簾製壓襯蓋鑰鑰窪壓襯(膚衊繭製蓋衊鏇顧醖積) = 鑰淵網繭鹽顧願願襯鑰糧築夢淵觸鹹餘夢鬱鏇 (膚積顧齋艱顧壓鹽壓鏇 ) 更多
AACR2026	N/A	HER2阳性卵巢癌 \| HER2表达子宫内膜癌 HER2 expressing	33	Trastuzumab deruxtecan	鏇蓋鑰壓窪遞鏇願衊獵(觸鬱廠醖範選鏇鬱衊願) = 築網選選選願鬱憲構願積顧簾憲繭鹹選遞構鬱 (觸餘鏇糧蓋衊窪夢鬱艱 ) 更多	积极	2026-04-20
				Trastuzumab deruxtecan (Ovarian cancer)	鏇蓋鑰壓窪遞鏇願衊獵(觸鬱廠醖範選鏇鬱衊願) = 糧簾壓醖襯築範顧憲艱積顧簾憲繭鹹選遞構鬱 (觸餘鏇糧蓋衊窪夢鬱艱 ) 更多
AACR2026	N/A	转移性结直肠癌二线 HER2-amplified \| MSS	3,734	trastuzumab deruxtecan	鏇構艱餘壓鹽構鹽範願(淵淵齋壓齋醖夢築淵衊): HR = 1.14 (95.0% CI, 1.05 ~ 1.24), P-Value = 0.0024 更多	积极	2026-04-19
				Standard Chemotherapy
ESMO_ELCC2026	N/A	转移性非小细胞肺癌二线 ERBB2 altered	5	Trastuzumab deruxtecan	範積齋網網製選鹹壓構(觸夢鹹襯選衊鑰顧顧夢) = No ILD/pneumonitis 願糧顧遞醖構憲憲製製 (鹽夢衊艱積鏇淵範範蓋 ) 更多	积极	2026-03-25
ESMO_TAT2026	N/A	HER2-positive \| ERBB2-mutated	61	Trastuzumab deruxtecan (ERBB2 mutations)	膚壓願廠遞襯衊網獵積(鏇築衊夢壓築醖廠網獵) = 廠觸製遞蓋繭餘衊艱鏇築窪遞衊齋艱壓齋廠窪 (夢餘窪簾夢膚選積鑰積 ) 更多	积极	2026-03-16
				Trastuzumab deruxtecan (HER2 IHC 3+)	膚壓願廠遞襯衊網獵積(鏇築衊夢壓築醖廠網獵) = 遞糧選膚顧淵遞憲壓選築窪遞衊齋艱壓齋廠窪 (夢餘窪簾夢膚選積鑰積 ) 更多
NCT05744375 (TRANSCENDER, CTgov)	临床2期	局部晚期乳腺癌 \| HER2阳性转移性乳腺癌	2	Trastuzumab deruxtecan	構簾製襯鏇願憲顧憲鹽 = 壓衊膚淵蓋廠鹽齋鏇範獵觸構積壓夢獵窪顧獵 (鹽淵鹽餘衊醖鹽壓製鹽, 齋廠廠憲餘醖襯製廠齋 ~ 夢鬱淵膚窪選襯鬱鬱糧) 更多	-	2026-03-12
ESMO_SRC2026	N/A	实体瘤	9	Trastuzumab deruxtecan	鹹夢構範壓廠構憲積選(鏇觸廠艱願鹹簾醖淵製) = 窪鹹願網範窪積簾鹽淵衊襯鬱構鏇鹽醖鹽衊遞 (製觸鹽繭簾遞蓋繭鑰範 )	积极	2026-03-09
NCT06989112 (DESTINY-Endometrial01, ESGO2026)	临床3期	复发性子宫内膜癌一线 HER2-expressing \| mismatch repair-proficient (pMMR)	600	trastuzumab deruxtecan + rilvegostomig	鑰夢蓋鹹夢蓋願鑰鹹淵(鹽築鏇鬱範繭壓憲鹽鏇) = 繭範網壓積夢製顧構製齋淵醖醖艱獵築鬱襯遞 (選願艱艱壓衊觸糧夢衊, 24.9 ~ NR) 更多	积极	2026-02-28
				trastuzumab deruxtecan + pembrolizumab	網觸鹹窪鹽積範襯廠製(衊餘廠膚壓願窪構艱餘) = 夢齋蓋膚餘鹹製遞簾願糧鬱窪淵艱淵壓製構鬱 (選築願構鹹選膚衊構構, 8.3 ~ 16.5) 更多
NCT04622319 (DESTINY-Breast05, Pubmed \| N Engl J Med)	临床3期	HER2阳性乳腺癌新辅助 HER2-positive	1,635	Trastuzumab Deruxtecan	窪網糧選願衊選範鹹選(網鏇醖艱鏇窪膚願膚鹹) = 觸築鹽製鏇憲鏇餘衊製糧遞製鑰獵醖遞積範壓 (願簾繭簾鏇淵繭壓窪簾 ) 更多	积极	2026-02-26
				Trastuzumab emtansine (T-DM1)	窪網糧選願衊選範鹹選(網鏇醖艱鏇窪膚願膚鹹) = 鬱鏇遞窪鏇鏇簾廠鑰選糧遞製鑰獵醖遞積範壓 (願簾繭簾鏇淵繭壓窪簾 ) 更多