Multigene Risk Score Combined With Ki-67 Dynamic Assessment in Stratified Neoadjuvant Endocrine Therapy Treatment With or Without CDK4/6 Inhibitors in HR+/HER2- Breast Cancer: a Randomize-controlled Study

This is a prospective, single-center, randomize-controlled study. The purpose of this study is to evaluate the efficacy of neoadjuvant CDK4/6 inhibitors in patients with high-risk EPclin multigene risk analysis and non-response to Ki-67 2W, and to explore predictive biomarkers for sensitivity to CDK4/6 inhibitor therapy.

开始日期2024-11-15

申办/合作机构

北京大学

NCT06684600 / Recruiting临床2期IIT

A Single-arm, Phase II Clinical Trial of Dalpiciclib Combined with Pyrotinib As Second-line Treatment of Advanced Esophageal Squamous Cell Carcinoma

The purpose of this study is to observe and evaluate the efficacy and safety of dalpiciclib combined with pyrotinib as second-line therapy in patients with advanced esophageal squamous cell carcinoma.

开始日期2024-11-01

申办/合作机构

北京大学

NCT06605690 / Not yet recruitingN/AIIT

An Exploratory Clinical Study of Dalpiciclib an&Amp;#39;d Letrozole Combined With Anlotinib Neoadjuvant Therapy in Stage II-III Postmenopausal HR+/HER2- Early Breast Cancer

This is a single-arm, open-label, exploratory clinical study

开始日期2024-10-31

申办/合作机构

贵州医科大学附属医院

100 项与羟乙磺酸达尔西利相关的临床结果

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100 项与羟乙磺酸达尔西利相关的转化医学

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100 项与羟乙磺酸达尔西利相关的专利（医药）

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项与羟乙磺酸达尔西利相关的文献（医药）

2024-10-01·Current gene therapy

SHR6390 Combined with Cabozantinib Inhibits Tumor Progression in the Hepatocellular Carcinoma Mouse Model

Article

作者: Wang, Yan ; Zhang, Yanqiao ; Shi, Jiaqi ; Zhou, Meng ; Nie, Jianhua ; Zheng, Tongsen ; Liu, Caiqi ; Han, Peng ; Shan, Dan ; Lin, Binlin

Background::

A novel CDK4/6 inhibitor SHR6390 has shown significant anti-tumor effects. However, its role in hepatocellular carcinoma (HCC) remains unknown.

Objective::

To explore the inhibitory effect of combination treatment with SHR6390 and cabozantinib in HCC, and its antitumor mechanism, so as to provide a more effective therapeutic strategy for HCC patients.

Methods::

We investigated SHR6390, monotherapy or combined with cabozantinib, by CCK8, wound healing, transwell, western blotting, immunohistochemistry and mouse model of a subcutaneous tumor.

Results::

Our results show that SHR6390 exhibited potent anti-proliferative activity against HCC in a dose-dependent manner. SHR6390 combined with cabozantinib exhibited more potent inhibition of cell viability, migration and invasion. In terms of potential mechanisms, we found that cabozantinib could lead to phosphorylation of Rb, which was reduced in SHR6390 and combined groups. SHR6390 monotherapy inhibited the growth of subcutaneous HCC tumors, besides, the combination treatment with SHR6390 and cabozantinib exerted synergistic anti-tumor activity in vivo.

Conclusion::

SHR6390 is effective against HCC, monotherapy or combined with cabozantinib.

2024-06-01·Heliyon

Comparative efficacy and safety of CDK4/6 inhibitors combined with endocrine therapies for HR+/HER2-breast cancer: Systematic review and network meta-analysis

Article

作者: Lu, Yi ; Ma, Hong-Fang ; Tong, Fei ; Shen, Jun

Background:

In recent years, the combination of targeted drugs, such as Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, with endocrine therapy (ET), has emerged as a new research focus in the treatment of hormone receptor-positive (HR+) human epidermal growth factor receptor 2 negative (HER2-) breast cancer. This network meta-analysis aimed to systematically evaluate the efficacy and safety of CDK4/6 inhibitors combined with ET for HR+/HER2-breast cancer.

Methods:

A systematic search was conducted across PubMed, Web of Science, Cochrane Library, and GeenMedical databases to identify randomized controlled trials investigating the use of CDK4/6 inhibitors in combination with endocrine therapy for the treatment of HR+/HER2-breast cancer. The search period spanned from the inception of each database up to February 29, 2024. Data analysis was conducted using Stata 14.0 and R 4.1.0 software.

Results:

A total of 20 randomized controlled trials (RCTs) were included in this study, investigating the effectiveness of four CDK4/6 inhibitors-Abemaciclib, Dalpiciclib, Ribociclib, and Palbociclib-when combined with ET for the treatment of HR+/HER2-breast cancer. The results indicated that Abemaciclib + ET, Dalpiciclib + ET, Palbociclib + ET, and Ribociclib + ET exhibited similar therapeutic effects in terms of improving objective response rate (ORR), disease control rate (DCR) and reducing the occurrence of fatigue, all of which were superior to ET alone. However, in terms of prolonging progression-free survival (PFS) and overall survival (OS), Dalpiciclib + ET significantly improved PFS compared to Ribociclib + ET, Palbociclib + ET, Abemaciclib and Palbociclib. Ribociclib + ET significantly improved OS compared to Palbociclib + ET. Regarding overall adverse reaction events (AREs), Dalpiciclib + ET had a higher incidence compared to Ribociclib + ET. The incidence of neutropenia caused by Dalpiciclib + ET was significantly higher compared to Palbociclib + ET, Ribociclib + ET, Abemaciclib, and Palbociclib. Abemaciclib + ET demonstrated the worst safety profile concerning diarrhea.

Conclusion:

Abemaciclib + ET likely represents the most effective option in terms of therapeutic effects, but it is prone to causing diarrhea and fatigue. On the other hand, Dalpiciclib + ET likely demonstrates the best efficacy in terms of PFS but exhibits the poorest safety profile, particularly in relation to neutropenia. Therefore, clinicians should exercise increased vigilance in monitoring and managing adverse effects when prescribing Abemaciclib + ET and Dalpiciclib + ET.

2024-03-01·Journal of evidence-based medicine

First‐line CDK4/6 inhibitor‐based combinations for HR+/HER2– advanced breast cancer: A Bayesian network meta‐analysis

Article

作者: Zhou, Yunxiang ; Zhang, Kun ; Lu, Wei ; Guo, Xianan ; Chen, Yiding ; Wu, Shijie ; Zhong, Xi ; Shen, Lu ; Chen, Huihui

Abstract:

Background:

International guidelines recommend cyclin‐dependent kinase 4/6 inhibitor (CDK4/6i)‐based first‐line therapy for hormone receptor‐positive, human epidermal growth factor receptor 2‐negative (HR+/HER2−) advanced breast cancer (ABC). However, direct drug comparisons are lacking. We aimed to identify the most effective and safe therapy through network meta‐analysis (NMA).

Methods:

We searched PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and OpenGrey up to September 30, 2023. Eligible studies included randomized controlled trials (RCTs) assessing endocrine therapy alone or in combination with CDK4/6i as first‐line endocrine treatment for HR+/HER2− ABC patients. The hazard ratios for progression‐free survival (PFS) and overall survival (OS) and relative risks for objective response rate and adverse events (AEs) were available in selected trials. We performed a Bayesian NMA following PRISMA guidelines.

Results:

Thirteen RCTs, involving 10 treatments, were included. Most studies were at low risk of bias. Regarding PFS, ribociclib+fulvestrant ranked first with a surface under the cumulative ranking curve (SUCRA) of 85.0%, followed by dalpiciclib+nonsteroidal aromatase inhibitor (NSAI) (SUCRA = 78.9%). Considering OS, the top three ranked treatments were ribociclib+fulvestrant (SUCRA = 94.1%), abemaciclib+NSAI (SUCRA = 69.9%), and ribociclib+NSAI (SUCRA = 68.5%). Out of four CDK4/6is, ribociclib minimized the grade 3/4 AEs, while dalpiciclib demonstrated the worst safety. Publication bias could not be ignored in our analyses, and the certainty of evidence was downgraded primarily due to imprecision.

Conclusions:

Ribociclib+fulvestrant probably represents the best option in a first‐line setting. When combined with NSAI, dalpiciclib likely showed the best efficacy but the worst safety. Abemaciclib+NSAI and ribociclib+NSAI could also be promising treatments, while palbociclib presented inferiority. (PROSPERO Registration No. CRD42022370271)

253

项与羟乙磺酸达尔西利相关的新闻（医药）

2024-11-06

·ioncology

SABCS 2024盛幕将启，中国之声唱响全球！

点击蓝字，关注我们编者按：第47届圣安东尼奥乳腺癌研讨会（SABCS）将于当地时间2024年12月10日至13日在美国得克萨斯州圣安东尼奥举行。日前，官网已公布摘要题目，肿瘤瞭望特将General Session、Poster Spotlight Sessions和Year in Review等环节中国专家报告内容进行汇总，以飨读者。 General Session 1 时间：12月11日9:15 – 11:30 am 地点：Hall 1 GS1-03: Pyrotinib or placebo in combination with trastuzumab and docetaxel for untreated HER2-positive metastatic breast cancer (mBC): prespecified final analysis of progression-free survival (PFS) of the phase 3 PHILA trial. 吡咯替尼或安慰剂联合曲妥珠单抗和多西他赛用于未接受过治疗的HER2阳性转移性乳腺癌（mBC）：III期PHILA试验预设的无进展生存期（PFS）最终分析讲者：徐兵河（中国医学科学院肿瘤医院） GS1-04: HER2-Directed Antibody-Drug Conjugate SHR-A1811 in the Neoadjuvant Treatment of HER2-positive Early Breast Cancer: a Prospective, Randomized, Open-label, Phase 2 Trial. 靶向HER2的抗体-药物偶联物SHR-A1811用于HER2阳性早期乳腺癌的新辅助治疗：一项前瞻性、随机、开放标签的2期试验讲者：李俊杰（复旦大学附属肿瘤医院） General Session 3 时间：12月13日9:00 – 11:45 am 地点：Hall 1 GS3-06: Neoadjuvant camrelizumab plus chemotherapy (chemo) for early or locally advanced triple-negative breast cancer (TNBC): a randomized, double-blind, phase 3 trial. 卡瑞利珠单抗联合化疗（chemo）新辅助治疗早期或局部晚期三阴性乳腺癌（TNBC）：一项随机、双盲、3期试验讲者：邵志敏（复旦大学附属肿瘤医院） Concurrent Poster Spotlight Sessions 1, 3-5, 7 ▌Session 1: New Insights into Immune Biomarkers（免疫生物标志物的新见解）时间：12月11日7:00 – 8:30 am 地点：Room 221ABC 主持人：David Rimm, Yale University PS1-03: Prediction of Prognosis and Efficacy of Neoadjuvant Therapy in HER2-Positive Breast Cancer Patients Based on Tertiary Lymphoid Structures. 基于三级淋巴结构预测HER2阳性乳腺癌患者的预后和新辅助治疗的疗效讲者：张克兢（中南大学湘雅医院） ▌Session 3: Highlights on Novel Therapeutics（新型治疗亮点）时间：12月11日7:00 – 8:30 am 地点：Stars at Night 1-2 主持人：Sara Tolaney, Dana-Farber Cancer Institute PS3-01: Tislelizumab plus sitravatinib and nab-paclitaxel in patients with untreated locally recurrent or metastatic triple negative breast cancer (TNBC): updated efficacy and safety results. 替雷利珠单抗+sitravatinib+白蛋白结合型紫杉醇治疗未经治疗的局部复发或转移性三阴性乳腺癌（TNBC）：最新的疗效和安全性结果讲者：Xiyu Liu（复旦大学附属肿瘤医院） PS3-02: Induction of Cisplatin/abraxane/pembrolizumab followed by pembrolizumab ± Olaparib Maintenance in triple-negative Metastatic breast cancer patients (COMPLEMENT) – A Randomized, Open-label, Phase II Study. COMPLEMENT：一项随机、开放标签的II期研究，在转移性三阴性乳腺癌患者中，采用顺铂/白蛋白结核型紫杉醇/帕博利珠单抗诱导治疗，后续以帕博利珠单抗±奥拉帕利进行维持治疗讲者：胡夕春（复旦大学附属肿瘤医院） PS3-05: Evaluation of the safety and efficacy of ivonescimab in combination with chemotherapy as first-line (1L) treatment for triple-negative breast cancer (TNBC). 评估ivonescimab联合化疗作为三阴性乳腺癌（TNBC）一线（1L）治疗的安全性和有效性讲者：欧阳取长（湖南省肿瘤医院） PS3-08: Interim Overall Survival of Patients with Locally Advanced or Metastatic Triple-Negative Breast Cancer treated wtih First Line PM8002/BNT327 in Combination with Nab-Paclitaxel in Phase Ib/II Study. Ib/II期研究中，PM8002/BNT327联合白蛋白结合型紫杉醇一线治疗局部晚期或转移性三阴性乳腺癌患者的中期总生存讲者：吴炅（复旦大学附属肿瘤医院） ▌Session 4: Prediction of Chemotherapy Response（化疗疗效预测）时间：12月11日7:00 – 8:30 am 地点：Stars at Night 3-4 主持人：Sherene Loi, Peter Macallum Cancer Centre PS4-08: The tumor heterogeneous overexpressed CD155 promotes treatment resistance in HER2-positive breast cancer through immune microenvironment modulation. 肿瘤异质性CD155过表达通过调节免疫微环境促进HER2阳性乳腺癌的治疗抵抗讲者：Yi Zhang（复旦大学附属肿瘤医院） Concurrent Poster Spotlight Sessions 2, 6, 8, 9 and 15 ▌Session 2: Personalizing CDK 4/6 inhibitor therapy for patients with Metastatic Breast Cancer: Survival, QOL and biomarkers（转移性乳腺癌患者的个体化CDK 4/6抑制剂治疗：生存期、生活质量和生物标志物）时间：12月12日7:00 – 8:30 am 地点：Hemisfair Ballroom 1-2 主持人：Lisa Carey, Lineberger Comprehensive Cancer Center University of North Carolina PS2-01: Dalpiciclib versus placebo in combination with letrozole or anastrozole as first-line treatment for women with HR+/HER2- advanced breast cancer: prespecified final analysis of progression-free survival of the phase 3 DAWNA-2 trial. 3期DAWNA-2研究预设的无进展生存最终分析：达尔西利vs安慰剂联合来曲唑或阿那曲唑作为HR+/HER2-晚期乳腺癌女性患者一线治疗讲者：徐兵河（中国医学科学院肿瘤医院） PS2-02：Tibremciclib (BPI-16350) plus fulvestrant versus placebo plus fulvestrant for patients with HR+/HER2- advanced breast cancer after progressing on endocrine therapy: Updated analysis of the phase III study. 在内分泌治疗进展后的HR+/HER2-晚期乳腺癌患者，Tibremciclib（BPI-16350）联合氟维司群对比安慰剂联合氟维司群的疗效：III期研究的更新分析讲者：胡夕春（复旦大学附属肿瘤医院） PS2-06：First-line (1L) ribociclib (RIB) + endocrine therapy (ET) vs combination chemotherapy (combo CT) in clinically aggressive HR+/HER2- advanced breast cancer (ABC): a subgroup analysis of RIGHT Choice by intrinsic subtype & gene & signature expression. 一线（1L）瑞波西利（RIB）+内分泌治疗（ET）vs联合化疗（combo CT）治疗临床侵袭性HR+/HER2-晚期乳腺癌（ABC）：基于内在亚型、基因及特征表达的RIGHT Choice研究亚组分析讲者：卢彦伸（中国台湾大学医学院附属医院） PS2-10: Integrating ctDNA and Tumor Fraction Features for Deciphering Molecular Response and Resistance Mechanism to Endocrine Therapy and CDK4/6 Inhibition in Advanced HR-positive Metastatic Breast Cancer. 整合ctDNA和肿瘤组分特征以解析晚期激素受体阳性转移性乳腺癌对内分泌治疗和CDK4/6抑制剂的分子应答及耐药机制讲者：Hao Liao（北京大学肿瘤医院） ▌Session 8: Novel HER2 Therapeutics（新型HER2治疗）时间：12月12日7:00 – 8:30 am 地点：Stars at Night 1-2 主持人：Ian Krop, Yale School of Medicine PS8-01: ZN-1041, a potential best-in-class BBB Penetrable HER2 Inhibitor, has high antitumor activity in patients with Breast Cancer with CNS Metastases. ZN-1041是一种具有潜力的同类最佳血脑屏障（BBB）可穿透性HER2抑制剂，在中枢神经系统（CNS）转移乳腺癌患者中展现出高抗肿瘤活性讲者：马飞（中国医学科学院肿瘤医院） PS8-02: A Phase 1 study Evaluating the Safety, Efficacy and Pharmacokinetics of TL938 in HER2-Positive Patients with Advance Solid Tumors. 一项评价TL938治疗HER2阳性晚期实体瘤患者的安全性、疗效和药代动力学的1期研究讲者：石远凯（中国医学科学院肿瘤医院） PS8-05: ACE-Breast-08: a phase I study of ARX788, a novel anti-HER2 antibodydrug conjugate, in patients with TKI pretreated HER2 positive advanced breast cancer. ACE-Breast-08：一项I期研究，评估新型抗HER2抗体-药物偶联物ARX788在TKI预治疗的HER2阳性晚期乳腺癌患者中的疗效讲者：王晓稼（浙江省肿瘤医院） PS8-06: A randomized, open-label phase III study comparing disitamab vedotin (an anti-HER2 monoclonal antibody-MMAE conjugate) with lapatinib plus capecitabine in patients with HER2-positive, advanced breast cancer with liver metastasis. 一项随机、开放标签的III期研究，在伴肝转移的HER2阳性晚期乳腺癌患者中比较维迪西妥单抗（一种抗HER2单克隆抗体-MMAE偶联物）联合拉帕替尼联合卡培他滨的治疗疗效讲者：王佳玉（中国医学科学院肿瘤医院） PS8-07：Efficacy and Safety of GQ1005, a Promising HER2-ADC, in Patients with Metastatic HER2-Positive Breast Cancer. GQ1005（一种很有前景的HER2-ADC）治疗转移性HER2阳性乳腺癌患者的疗效和安全性讲者：王碧芸（复旦大学附属肿瘤医院） PS8-08: Efficacy and safety of SHR-A1811, an anti-HER2 antibody-drug conjugate (ADC), in 391 heavily pretreated multiple solid tumors with HER2-expression or mutations: a global, multi-center, first-in-human, phase 1 study. SHR-A1811是一种抗HER2抗体-药物偶联物（ADC），在391例既往接受过大量治疗且有HER2表达或突变的多种实体瘤中，SHR-A1811的疗效和安全性：一项全球性、多中心、首次人体1期研究讲者：姚和瑞（中山大学孙逸仙纪念医院） Concurrent Poster Spotlight Sessions 10-14 ▌Session 11: Imaging to Guide Breast Cancer Treatment – Molecular Imaging and AI（影像学指导乳腺癌治疗——分子影像学和人工智能）时间：12月13日7:00 – 8:30 am 地点：Hemisfair Ballroom 1-2 主持人：David Mankoff, Perelman School of Medicine University of Pennsylvania PS11-08: MRI improves multi-modal AI system for breast cancer diagnosis and prognosis. MRI提高了多模态AI系统对乳腺癌的诊断和预后判断讲者：Yanqi Xu（中国药科大学） ▌Session 12: Immunobiology Impact on Therapeutic Efficacy（免疫生物学对治疗效果的影响）时间：12月13日7:00 – 8:30 am 地点：Room 221ABC 主持人：Lajos Pusztai, Yale School of Medicine, New Haven, Connecticut PS12-04: HDACi combined with anthracycline elicits interactions between MHC-II+ triple-negative breast cancer and CD69+CD4+Trm orchestrating synergistic immunotherapy. HDACi联合蒽环类药物引发MHC-II+三阴性乳腺癌与CD69+CD4+Trm协同免疫治疗之间的相互作用讲者：Zehao Wang（复旦大学附属肿瘤医院） ▌Session 14: Brain Metastasis（脑转移）时间：12月13日7:00–8:30 am 地点：Stars at Night 3-4 主持人：William Gradishar, Northwestern University Feinberg School of Medicine, Chicago, Illinois PS14-02: A Prospective Phase II Trial of Hypofractionated Stereotactic Radiotherapy (FSRT) for Patients with 1-10 Brain Metastases from Breast Cancer. 一项前瞻性II期试验，1～10个乳腺癌脑转移患者采用大分割立体定向放疗（FSRT）讲者：Jin Meng（上海交通大学附属第六人民医院） PS14-03: Updated analyses from a Phase I study of the brain-penetrant oral SERD- SIM0270 in patients with ER-positive,HER2-negative advanced breast cancer. 脑渗透性口服SERD- SIM0270治疗ER阳性/HER2阴性晚期乳腺癌患者的I期研究的最新分析讲者：张清媛（哈尔滨医科大学附属肿瘤医院） PS14-04: SIM0270, a brain-penetrant oral SERD, in combination with everolimus in patients with ER+/HER2- advanced breast cancer: the phase Ib study. SIM0270，一种脑渗透性口服SERD，联合依维莫司在ER+/HER2-晚期乳腺癌患者中的Ⅰb期研究讲者：张剑（复旦大学附属肿瘤医院） Year in Review 时间：12月13日3:00 – 5:00 pm 地点：Stars at Night 1-2 主持人：Moderators: Carlos Arteaga, UT Southwestern Medical Center, Dallas, Texas; and Virginia Kaklamani, UT Health Mays Cancer Center, San Antonio, Texas Early Breast Cancer Updates 早期乳腺癌最新进展讲者：Janice Tsang（中国香港大学）（来源：《肿瘤瞭望》编辑部）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。

临床2期临床结果临床3期

2024-10-29

·米内网

【瞩目】恒瑞1类新药来袭，猛攻1400亿市场

精彩内容近日，CDE官网显示，恒瑞医药申报的1类新药HRS-6208胶囊首次获得临床试验默示许可，用于治疗实体瘤。米内网数据显示，2023年中国三大终端六大市场（统计范围详见本文末）抗肿瘤化药销售额超过1400亿元。今年以来，恒瑞医药有50余款1类新药获批临床，其中有27款为首次获批。 HRS-6208胶囊是恒瑞医药开发的一款化药1类新药，其临床申请于2024年8月17日获得CDE承办受理，并于近日获批临床，用于治疗实体瘤。米内网数据显示，近年来中国三大终端六大市场抗肿瘤化药（含生物药）销售额均达千亿规模，2023年超过1400亿元，2024上半年以约10%的增速继续增长。从细分终端销售看，院内市场（公立医院+公立基层医疗）为抗肿瘤化药销售主渠道，但零售药店（城市实体药店+网上药店）也不容小觑，销售占比由2019年的约14%提升至2024上半年的约20%。近年来中国零售药店终端抗肿瘤化药销售情况（单位：万元）来源：米内网格局数据库抗肿瘤药是恒瑞医药重点研发方向。在该治疗领域，公司已有甲磺酸阿帕替尼片、马来酸吡咯替尼片、注射用卡瑞利珠单抗、氟唑帕利胶囊、羟乙磺酸达尔西利片、阿得贝利单抗注射液、林普利塞片等多款1类新药获批上市。此外，苹果酸法米替尼胶囊、注射用瑞康曲妥珠单抗（SHR-A1811）、瑞拉芙普-α注射液（SHR-1701）等已提交NDA在审，重组人源化单抗MIL62注射液、SHR2554片、注射用SHR-A1921等处于III期临床。今年以来，恒瑞医药创新研发管线持续推进：富马酸泰吉利定注射液、夫那奇珠单抗注射液2款1类新药首次获批上市，氟唑帕利胶囊、脯氨酸恒格列净片2款1类新药获批新适应症，SHR2554片、瑞拉芙普-α注射液、注射用瑞康曲妥珠单抗3款1类新药首次提交NDA，50余款1类新药获批临床（含非首次获批）等。 50余款1类新药中，有27款为首次在国内获批临床，其中14款为抗肿瘤和免疫调节剂（11款抗肿瘤药、3款免疫抑制剂），3款为心脑血管系统药物，呼吸系统用药、神经系统药物、消化系统及代谢药各有2款。 2024年以来恒瑞医药首次获批临床的1类新药来源：米内网中国申报进度（MED）数据库注：米内网《中国三大终端六大市场药品竞争格局》，统计范围是：城市公立医院和县级公立医院、城市社区中心和乡镇卫生院、城市实体药店和网上药店，不含民营医院、私人诊所、村卫生室，不含县乡村药店；上述销售额以产品在终端的平均零售价计算。数据统计截至10月29日，如有疏漏，欢迎指正！本文为原创稿件，转载请注明来源和作者，否则将追究侵权责任。投稿及报料请发邮件到872470254@qq.com稿件要求详询米内微信首页菜单栏商务及内容合作可联系QQ：412539092 ●温馨提示● 因为微信公众号修改了推送规则，最近很多读者反映没有及时看到推文。把米内网设为“星标”，就能每天与我们不见不散啦，具体操作如下：【分享、点赞、在看】点一点不失联哦

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2024-10-25

·ioncology

甘露教授：精准医疗新突破——探索HR+/HER2-晚期乳腺癌患者的未来之路

点击上方蓝字关注我们编者按：激素受体阳性/人表皮生长因子受体2阴性（HR+/HER2-）乳腺癌是乳腺癌中最常见的亚型之一，约占总体乳腺癌的70%。这类患者晚期一线治疗通常依赖于内分泌治疗联合CDK4/6抑制剂，尽管这一方案显著延长了患者的无进展生存期（PFS），但大部分患者最终会出现耐药，导致疾病进展。因此，寻找新的有效治疗策略，以延长患者的生存期并提高生活质量，成为医学界亟待解决的问题。近年来，随着分子生物学研究的深入，PAM（PI3K/AKT/mTOR）信号通路在乳腺癌发生发展中的重要性逐渐凸显，为HR+/HER2-晚期乳腺癌的治疗提供了新的靶点。肿瘤瞭望特邀重庆医科大学附属第一医院甘露教授从HR+/HER2-晚期乳腺癌的治疗现状与挑战、PAM通路的重要性、后CDK4/6抑制剂时代患者治疗新选择等方面，深入探讨HR+/HER2-晚期乳腺癌患者的未来之路。一、HR+/HER2-晚期乳腺癌的治疗现状与挑战乳腺癌是全球女性最常见的恶性肿瘤，2020年中国乳腺癌新发病例41.6万例，死亡病例约11.7万例。在每年新发乳腺癌患者中，约3%～10%的患者在确诊时即有远处转移。早期患者中约有30%可发展为晚期乳腺癌，晚期乳腺癌患者5年生存率仅为20%，中位总生存时间为2～3年[1]。HR+/HER2-乳腺癌约占总体乳腺癌的70%，内分泌治疗是其重要治疗选择[2]。PALOMA、MONARCH、MONALIEESA、DAWAN等一系列研究显示[3-7]，CDK4/6抑制剂（哌柏西利、阿贝西利、瑞波西利和达尔西利）联合内分泌治疗，能显著提高乳腺癌患者的治疗敏感性，延长患者的生存时间。目前CDK4/6抑制剂联合内分泌治疗已成为HR+/HER2-晚期乳腺癌（不合并内脏危象）患者的一线治疗优选方案。 CDK4/6抑制剂联合芳香化酶抑制剂（aromatase inhibitor, AI）的临床研究结果显示（MONALEESA-2研究、PALOMA-2研究、MONARCH-3研究和DAWNA-2），一线使用 CDK4/6抑制剂联合AI后无进展生存期（PFS）约为2年左右（各研究结果存在差异），与AI单药相比，CDK4/6抑制剂联合AI方案均显著降低疾病进展风险近50%[2]。但CDK4/6抑制剂失败后的治疗选择是临床治疗难题，国内外指南无标准治疗方案推荐，且既往多项研究显示，与PAM通路正常的乳腺癌患者相比，存在通路基因改变者肿瘤进展风险更高，DFS及OS更差。二、PAM通路的重要性磷脂酰肌醇3-激酶（phosphoinositide 3-kinase，PI3K）/蛋白激酶B（protein kinase，AKT）/哺乳动物雷帕霉素靶蛋白（mammalian target of rapamycin，mTOR）信号转导通路（简称PAM通路）的过度活化广泛存在于各类癌种，包括乳腺癌、肺癌、头颈部肿瘤、子宫内膜癌、前列腺癌、结直肠癌等，调节肿瘤细胞存活、增殖、分化、凋亡等多种过程，从而对肿瘤的发生、发展起到关键性作用[8-9]。PAM信号通路过度激活是内分泌治疗、化疗、靶向治疗耐药的重要机制之一，不仅使乳腺癌细胞适应雌激素剥夺，通过多药耐药相关蛋白和抗凋亡作用促进化疗耐药，还通过激活PAM信号通路相关蛋白参与CDK4/6抑制剂和抗HER2治疗耐药的发生[10]。尽管HR+/HER2-乳腺癌细胞对CDK4/6抑制剂耐药的机制多种多样，但PAM信号通路表达上调是常见的，在HR+乳腺癌中，约30%～40%的患者存在PAM信号通路被激活的现象[11]，因此，PAM信号通路可能成为逆转耐药性的重要靶点[12]。一项针对中国乳腺癌患者的研究显示，PAM通路突变率高达62.6%，高于欧美人群，其中PIK3CA突变率为45%，这些突变的数量和位置对患者的预后有显著影响[13]。三、CDK4/6抑制剂后的新选择在CDK4/6抑制剂联合内分泌治疗成为HR+/HER2-晚期乳腺癌一线治疗优选方案后，对于治疗进展后出现耐药的患者，医学界一直在探索新的治疗方案。目前，化疗仍是治疗选择之一，但仅能带来中位4～5个月的PFS[14-15]，且接受化疗的患者会出现众多不良反应，严重影响患者生活质量。针对CDK4/6抑制剂跨线治疗的探索由来已久，但目前仅有有限数据支持CDK4/6抑制剂跨线治疗，且只有postMONARCH这一项III期研究显示了PFS获益（6.0个月 vs 5.3个月）[16]。 PAM通路抑制剂的出现，为CDK4/6抑制剂耐药后的患者提供了新的治疗选择。PI3K位于PAM信号通路上游，在该通路中扮演着重要角色[17]。PIK3CA突变可以异常激活PI3K通路，促进肿瘤的增殖、转移和侵袭，因此，PI3K通路为治疗靶点成为了PIK3CA突变乳腺癌患者的重要治疗手段，这为PIK3CA突变型HR+/HER2-晚期乳腺癌患者带来新的治疗希望。多项研究显示了PI3K抑制剂可为PIK3CA突变人群带来更长的PFS获益，2024版NCCN指南推荐对于PIK3CA突变的HR+/HER2-绝经后乳腺癌患者，二线治疗首选PI3K抑制剂联合内分泌治疗（Ⅰ级推荐）。 AKT位于PAM通路的核心位置，其异常激活在乳腺癌的发生与发展中起着重要作用。AKT信号通路的激活可以通过多种机制实现，包括PIK3CA的激活突变、PTEN的失活突变以及上游信号通路的异常激活等。AKT一旦被激活，可磷酸化细胞核和细胞质中的许多靶点并激活多个具有调控细胞增殖功能的下游底物，从而促进肿瘤细胞生长、增殖和血管生成。此外，AKT通过抑制促凋亡基因Bcl-2家族成员BAD和BAX、负向调节FOXO等叉头转录因子等机制促进肿瘤细胞存活并抑制其凋亡[11]。AKT抑制剂相关研究正在大量开展中。 mTOR是PAM信号通路的关键下游效应分子，通过其两个不同的复合体mTORC1和mTORC2，调控多种细胞内过程。mTOR信号通路的异常激活在约30%的癌症中被发现,对肿瘤的发生、发展和转移起着重要的促进作用。mTOR过度激活会增加促癌蛋白的翻译，直接影响细胞生长、迁移和血管新生等过程。mTOR通过影响细胞周期、生长、存活和代谢等多个方面来促进肿瘤进展，在乳腺癌中，mTOR通路的异常在约70%的病例中被发现[18]。我国一项多中心回顾性研究数据显示，在CDK4/6抑制剂哌柏西利治疗进展后的HR/HER2-晚期乳腺癌患者中，应用内分泌治疗联合mTOR抑制剂依维莫司的患者中位PFS获益达5.1个月[19]。四、未来展望随着分子生物学研究的不断深入和精准医疗理念的逐渐普及，针对PAM通路的精准治疗为HR+/HER2-晚期乳腺癌患者带来了新的希望。通过检测PAM通路的突变状态，并结合患者的临床特征，临床医生可以为患者制定更加个体化的治疗方案。这不仅有助于延长患者的生存期，还能提高患者的生活质量。同时，NCCN、CSCO等国内外权威指南也将PI3K抑制剂、AKT抑制剂和mTOR抑制剂依维莫司纳入到了HR+/HER2-晚期乳腺癌患者的治疗药物推荐之中，但基于药物可及性及或内获批相关原因，目前在CSCO指南中对HR+晚期乳腺癌TAM治疗失败、非甾体类AI治疗失败及甾体类AI治疗失败的患者均II级推荐依维莫司联合内分泌治疗，而对于CDK4/6抑制剂治疗失败的患者，目前暂无I级推荐，在III级推荐中提及AKT抑制剂+内分泌治疗。 △2024版CSCO BC指南HR+晚期乳腺癌的解救内分泌治疗相关推荐* *指南内容涉及AZ未获批产品/适应症，阿斯利康不推荐任何未获批药品/适应症的使用。未来，随着更多针对PAM信号通路抑制剂的研发和临床应用，HR+/HER2-晚期乳腺癌的治疗将更加精准和有效。同时，也期待更多的基础研究能够揭示PAM通路在乳腺癌发生与发展中的具体机制，为新药的研发提供理论依据，为HR+/HER2-晚期乳腺癌患者带来更多新的治疗希望。甘露教授重庆医科大学附属第一医院中国抗癌协会乳腺癌专业委员会常委中国抗癌协会肿瘤临床研究管理学专委会常委中国抗癌协会肿瘤科普防治专业委员会委员中国抗癌协会肿瘤临床化疗专业委员会委员重庆市抗癌协会肿瘤心理学专业委员会副主任委员重庆市医学会乳腺病分会常委重庆市肿瘤医疗质量控制中心乳腺癌诊疗专家组成员审批编号CN-145761 过期日期 2025-10-18 *本材料由阿斯利康提供，仅供医疗卫生专业人士参考参考文献上下滑动查看更多内容 [1]、国家肿瘤质控中心乳腺癌专家委员会, 中国抗癌协会乳腺癌专业委员会, 中国抗癌协会肿瘤药物临床研究专业委员会. 中国晚期乳腺癌规范诊疗指南(2022版)[J]. 中华肿瘤杂志, 2022, 44(12):1262-1287.DOI: 10.3760/cma.j.cn112152-20221007-00680. [2]、国家肿瘤质控中心乳腺癌专家委员会, 中国抗癌协会肿瘤药物临床研究专业委员会. CDK4/6抑制剂治疗激素受体阳性人表皮生长因子受体2阴性乳腺癌临床应用专家共识(2023版)[J]. 中华肿瘤杂志, 2023, 45(12):1003-1017.lDOI: 10.3760/cma.j.cn112152-20230428-00188. [3]、Cristofanilli, Massimo et al. “Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial.” The Lancet. Oncology vol. 17,4 (2016): 425-439. doi:10.1016/S1470-2045(15)00613-0 [4]、Goetz, Matthew P et al. “MONARCH 3: Abemaciclib As Initial Therapy for Advanced Breast Cancer.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology vol. 35,32 (2017): 3638-3646. doi:10.1200/JCO.2017.75.6155 [5]、Slamon, Dennis J et al. “Phase III Randomized Study of Ribociclib and Fulvestrant in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: MONALEESA-3.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology vol. 36,24 (2018): 2465-2472. doi:10.1200/JCO.2018.78.9909 [6]、Tripathy, Debu et al. “Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial.” The Lancet. Oncology vol. 19,7 (2018): 904-915. doi:10.1016/S1470-2045(18)30292-4 [7]、Xu B, Zhang Q, Zhang P, et al. Dalpiciclib or placebo plus fulvestrant in hormone receptor-positive and HER2-negative advanced breast cancer: a randomized, phase 3 trial. Nat Med. 2021;27(11):1904-1909. doi:10.1038/s41591-021-01562-9 [8]、Dey, Nandini et al. “PI3K-AKT-mTOR inhibitors in breast cancers: From tumor cell signaling to clinical trials.” Pharmacology & therapeutics vol. 175 (2017): 91-106. doi:10.1016/j.pharmthera.2017.02.037 [9]、Castaneda, Carlos A et al. “The phosphatidyl inositol 3-kinase/AKT signaling pathway in breast cancer.” Cancer metastasis reviews vol. 29,4 (2010): 751-9. doi:10.1007/s10555-010-9261-0 [10]、中国抗癌协会肿瘤药物临床研究专业委员会, 国家肿瘤质控中心乳腺癌专家委员会, 中国抗癌协会肿瘤病理专业委员会, 等. PI3K/AKT/mTOR信号通路抑制剂治疗乳腺癌临床应用专家共识[J]. 中华肿瘤杂志, 2022, 44(7):673-692.DOI: 10.3760/cma.j.cn112152-20220412-00251. [11]、姚荟斌，赵伟鹏，史业辉. CDK4/6抑制剂治疗晚期乳腺癌的研究进展. [J].《天津医科大学学报》2021，27（5）：549 [12]、O'Brien, Neil A et al. “Targeting activated PI3K/mTOR signaling overcomes acquired resistance to CDK4/6-based therapies in preclinical models of hormone receptor-positive breast cancer.” Breast cancer research : BCR vol. 22,1 89. 14 Aug. 2020, doi:10.1186/s13058-020-01320-8 [13]、Xiao, Weikai et al. “Mutational Landscape of PI3K-AKT-mTOR Pathway in Breast Cancer: Implications for Targeted Therapeutics.” Journal of Cancer vol. 12,14 4408-4417. 27 May. 2021, doi:10.7150/jca.52993 [14]、Kaufman, Peter A et al. “Phase III open-label randomized study of eribulin mesylate versus capecitabine in patients with locally advanced or metastatic breast cancer previously treated with an anthracycline and a taxane.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology vol. 33,6 (2015): 594-601. doi:10.1200/JCO.2013.52.4892 [15]、Li, Yi et al. “A multicenter analysis of treatment patterns and clinical outcomes of subsequent therapies after progression on palbociclib in HR+/HER2- metastatic breast cancer.” Therapeutic advances in medical oncology vol. 13 17588359211022890. 11 Jun. 2021, doi:10.1177/17588359211022890 [16]、Kevin Kalinsky, et al. Abemaciclib plus fulvestrant vs fulvestrant alone for HR+, HER2- advanced breast cancer following progression on a prior CDK4/6 inhibitor plus endocrine therapy: Primary outcome of the phase 3 postMONARCH trial. 2024 ASCO abstract LBA1001. [17]、Vanhaesebroeck, Bart et al. “PI3K signalling: the path to discovery and understanding.” Nature reviews. Molecular cell biology vol. 13,3 195-203. 23 Feb. 2012, doi:10.1038/nrm3290 [18]、Marafie, Sulaiman K et al. “mTOR: Its Critical Role in Metabolic Diseases, Cancer, and the Aging Process.” International journal of molecular sciences vol. 25,11 6141. 2 Jun. 2024, doi:10.3390/ijms25116141 [19]、Mo H, et al. Real-World Outcomes of Everolimus and Exemestane for the Treatment of Metastatic Hormone Receptor-Positive Breast Cancer in Patients Previously Treated With CDK4/6 Inhibitors. Clin Breast Cancer. 2022 Feb;22(2):143-148. （来源：《肿瘤瞭望》编辑部）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。

临床结果

100 项与羟乙磺酸达尔西利相关的药物交易

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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
HR阳性/HER2阴性乳腺癌	中国	江苏恒瑞医药股份有限公司	2021-12-31

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适应症	最高研发状态	国家/地区	公司	日期
HER2 阴性乳腺癌	临床3期	中国	江苏恒瑞医药股份有限公司	2021-04-30
HR阳性乳腺癌	临床3期	中国	江苏恒瑞医药股份有限公司	2021-04-30
晚期乳腺癌	临床3期	中国	江苏恒瑞医药股份有限公司	2019-06-13
HR阳性HER2阴性淋巴结阳性乳腺癌	临床3期	中国	江苏恒瑞医药股份有限公司	2019-06-13
乳腺癌	临床2期	-	天津市肿瘤研究所	2024-08-01
转移性去势抵抗性前列腺癌	临床2期	中国	江苏恒瑞医药股份有限公司	2024-07-31
ER阳性/HER2阴性乳腺癌	临床2期	中国	山东盛迪医药有限公司初创企业	2023-12-20
肉瘤	临床2期	中国	江苏恒瑞医药股份有限公司	2023-07-01
HER2低表达乳腺癌	临床2期	-	江苏恒瑞医药股份有限公司	2023-04-01
内脏痉挛	临床2期	中国	江苏恒瑞医药股份有限公司	2022-06-01

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临床结果

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


NCT06009627 (ESMO2024) 人工标引	临床2期	绝经前乳腺癌新辅助 HER2 Negative \| Hormone Receptor Positive	32	Dalpiciclib, Exemestane, and Goserelin	壓顧醖選選網餘廠繭鑰(夢網鹹鏇構鹹積膚範淵) = 鑰顧艱選衊選鏇夢齋顧窪糧鏇積醖積餘鹹構鏇 (積醖壓憲餘淵顧顧壓蓋 )	积极	2024-09-16
NCT06009627 (ESMO2024) 人工标引	临床2期	绝经前乳腺癌新辅助 HER2 Negative \| Hormone Receptor Positive	32	TAC (docetaxel, doxorubicin, and cyclophosphamide)	壓顧醖選選網餘廠繭鑰(夢網鹹鏇構鹹積膚範淵) = 遞膚鑰觸糧夢築衊衊鹽窪糧鏇積醖積餘鹹構鏇 (積醖壓憲餘淵顧顧壓蓋 )	积极	2024-09-16
NCT05721443 (ESMO2024)	临床2期	头颈部鳞状细胞癌 p16-negative	14	Dalpiciclib 150 mg	鬱範顧窪製鬱觸積齋鑰(憲衊膚製夢齋夢憲遞膚) = 壓獵憲願齋積衊鏇範廠糧膚鑰顧鑰衊艱糧獵醖 (夢夢窪網網鏇獵廠繭鬱, 38.6 ~ 83.8) 更多	积极	2024-09-14
NCT05640778 (DANCER, ASCO2024) 人工标引	临床2期	HER2 阴性乳腺癌新辅助 HER2 Negative \| Hormone Receptor Positive	23	Dalpiciclib + Letrozole/anastrozole	窪鬱選鏇範憲襯膚齋鬱(襯選夢餘簾糧蓋夢糧繭) = 鏇顧襯鬱襯網糧襯醖齋觸構蓋艱積廠壓鑰衊鏇 (繭構鹹衊簾衊構願製糧, 76.0% ~ 98.8) 更多	积极	2024-05-24
ChiCTR2200062868 (phase 2, ASCO2024)	临床2期	去分化脂肪肉瘤	32	Dalpiciclib 150 mg	構蓋窪鑰糧積膚廠淵鏇(簾鏇觸鹽糧鑰鑰築醖膚) = 獵艱獵窪鑰鏇遞鑰鏇夢簾製繭獵糧齋築膚範齋 (網衊膚獵鏇選顧廠獵餘, 10.65 ~ 24.15)	积极	2024-05-24
NCT05806671 (Bayesian optimal phase II trial, ASCO2024)	临床2期	晚期乳腺癌 HR+ \| HER2-low	30	Dalpiciclib 125 mg/day	鏇觸衊膚窪鹹蓋獵鹽鏇(觸製齋願餘遞壓簾鏇製) = The median PFS has not been reached 窪鑰繭壓壓夢憲夢遞獵 (窪構膚廠築製淵鹹窪積 ) 更多	积极	2024-05-24
NCT03481998 (phase Ib, Pubmed \| Ther Adv Med Oncol)	临床1期	HR阳性HER2阴性淋巴结阳性乳腺癌 HR-positive \| HER2-negative	-	Dalpiciclib 125 mg	鬱鹹選製選膚壓膚齋醖(蓋築積鹽構網鑰構築蓋) = 鑰艱壓願範糧願範淵窪範觸範艱鹽獵鏇選鬱艱 (艱願廠觸網積鑰繭遞糧 ) 更多	积极	2024-01-01
NCT03481998 (phase Ib, Pubmed \| Ther Adv Med Oncol)	临床1期	HR阳性HER2阴性淋巴结阳性乳腺癌 HR-positive \| HER2-negative	-	Dalpiciclib 150 mg	鬱鹹選製選膚壓膚齋醖(蓋築積鹽構網鑰構築蓋) = 鑰鹽齋淵製淵築觸艱糧範觸範艱鹽獵鏇選鬱艱 (艱願廠觸網積鑰繭遞糧 ) 更多	积极	2024-01-01
NCT04095390 (ASCO2023) 人工标引	临床2期	晚期 HER2 阳性乳腺癌 HER2 Positive	33	Pyrotinib+Dalpiciclib+Letrozole	積製襯艱壓鑰構簾積衊(鹽繭願積糧衊膚鑰範觸) = 製餘鹹範積窪製衊獵夢製衊衊遞鹽鬱繭製鑰鏇 (廠艱選壓鑰願顧鏇網構 ) 更多	积极	2023-05-31
NCT04095390 (ASCO2023) 人工标引	临床2期	晚期 HER2 阳性乳腺癌 HER2 Positive	33	Pyrotinib+Dalpiciclib+Capecitabine	積製襯艱壓鑰構簾積衊(鹽繭願積糧衊膚鑰範觸) = 廠鑰顧夢蓋糧膚淵製鹽製衊衊遞鹽鬱繭製鑰鏇 (廠艱選壓鑰願顧鏇網構 ) 更多	积极	2023-05-31
NCT03772353 (PLEASURABLE, ASCO2023)	临床2期	HER2阳性转移性乳腺癌二线	48	Dalpiciclib+Pyrotinib+Letrozole	積鏇壓衊繭糧夢鑰選艱(醖觸築壓製構網襯構鹽) = 願艱鏇糧觸築襯醖襯憲鏇壓壓艱糧範鑰糧壓製 (鏇繭衊鹹淵鏇壓積膚鹹 )	积极	2023-05-31
NCT05132790 (MUKDEN 03, ASCO2023) 人工标引	N/A	HR阳性/HER2阴性乳腺癌新辅助 HR Positive \| HER2 Negative	12	exemestane+SBRT+dalpiciclib	鏇膚選夢簾膚築範醖蓋(構膚顧夢襯構獵窪鹽糧) = 夢艱鑰夢襯範糧構鑰鹽憲壓淵襯積簾壓糧製膚 (顧淵選遞積鑰繭糧鏇製, 3.5 ~ 46.0) 达到更多	积极	2023-05-26
NCT04293276 (HR BLTN 014, ASCO2023) 人工标引	临床2期	晚期 HER2 阳性乳腺癌 HER2 Positive	40	pyrotinib+dalpiciclib	襯遞網膚願繭膚鏇積顧(齋餘鹹獵製觸淵艱壓遞) = 壓憲繭艱簾蓋製獵遞窪顧膚遞獵齋築網蓋觸蓋 (醖襯襯餘鹽獵蓋齋遞網, 7.3 ~ 19.3)	积极	2023-05-26
NCT04293276 (HR BLTN 014, ASCO2023) 人工标引	临床2期	晚期 HER2 阳性乳腺癌 HER2 Positive	40	pyrotinib+dalpiciclib (HR-negative patients)	襯遞網膚願繭膚鏇積顧(齋餘鹹獵製觸淵艱壓遞) = 製鏇選願積鑰觸夢廠遞顧膚遞獵齋築網蓋觸蓋 (醖襯襯餘鹽獵蓋齋遞網, 7.3 ~ NA)	积极	2023-05-26