更新于：2024-12-12
Dalpiciclib Isethionate
羟乙磺酸达尔西利
更新于：2024-12-12
概要
基本信息
药物类型 小分子化药 |
别名 Dalpiciclib、达尔西利、SHR-6390 + [1] |
作用机制 CDK4抑制剂(细胞周期蛋白依赖性激酶4抑制剂)、CDK6抑制剂(细胞周期蛋白依赖性激酶6抑制剂) |
在研适应症 |
原研机构 |
非在研机构 |
最高研发阶段批准上市 |
首次获批日期 中国 (2021-12-31), |
最高研发阶段(中国)批准上市 |
特殊审评优先审评 (中国)、突破性疗法 (中国)、特殊审批 (中国) |
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结构
分子式C25H30N6O2 |
InChIKeySGJLSPUSUBJWHO-UHFFFAOYSA-N |
CAS号1637781-04-4 |
关联
126
项与 羟乙磺酸达尔西利 相关的临床试验Single-arm,Exploratory Clinical Study of Albumin-bound Paclitaxel Combination With Dalpiciclib and AI in the Treatment of ER-Low (1%-10%), HER2-negative Advanced Breast Cancer
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
Prospective study of pyrrotinib combined with trastuzumab, Darcilil and endocrine therapy for HER2-positive HR-positive advanced breast cancer
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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40
项与 羟乙磺酸达尔西利 相关的文献（医药）2025-02-01BREAST
Influence of ethnicity on cyclin-dependent kinase inhibitor efficacy and toxicity: A systematic review and meta-analysis
Review
作者: De Santis, Pierluigi ; Pagliuca, Martina ; Arpino, Grazia ; De Laurentiis, Michelino ; Giuliano, Mario ; De Angelis, Carmine ; Pavone, Giuliana ; Longobardi, Alessandra ; Caputo, Roberta ; Caltavituro, Aldo ; Del Mastro, Lucia ; Puglisi, Fabio ; Tafuro, Margherita ; Buonaiuto, Roberto
BACKGROUND:
The combination of cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) with endocrine therapy (ET) is the standard of care for patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (aBC). While the efficacy and safety profiles of CDK4/6i and ET have been extensively evaluated in phase II and III trials worldwide, it remains unclear whether the response to CDK4/6i and toxicity profile vary among Asian and non-Asian patients. Therefore, we aimed to assess the treatment efficacy of ET with and without CDK4/6i by comparing outcomes in Asian and non-Asian subgroups included in these clinical trials. In addition, we evaluated the toxicity profiles of the treatments by estimating the risk of treatment-related adverse events (AEs).
METHODS:
We conducted a meta-analysis including the most recent randomized trial data systematically searched from PubMed, Embase, Web of Science, Cochrane CENTRAL (from inception to May 31st, 2024) or presented in abstracts or oral presentations at the ESMO, ASCO, and SABCS international congresses. We included studies comparing CDK4/6i (palbociclib, ribociclib, abemaciclib, dalpiciclib) + ET versus placebo + ET. Progression-free survival (PFS) and overall survival (OS), hazard ratios (HR), and 95 % confidence intervals (CI) were extracted for the two subgroups of interest. To evaluate the treatment-related toxicity profiles, we extracted the number of side effects to estimate the risk of treatment-emergent AEs.
RESULTS:
Eleven studies (n = 5129) were included in this meta-analysis. The addition of CDK4/6i to ET consistently improved PFS in both Asian (HR = 0.52, 95 % CI 0.47-0.60; p < 0.001) and non-Asian (HR = 0.58, 95 % CI 0.52-0.64; p < 0.001) groups. Similarly, the combination of CDK4/6i + ET led to an OS improvement in both Asian (HR = 0.75, 95 % CI 0.62-0.91; p = 0.003) and non-Asian (HR = 0.81, 95 % CI 0.73-0.89; p < 0.001) patients. The risk of treatment related toxicity was higher in the CDK4/6i + ET arm in both Asian and non-Asian groups. Interestingly, a numerically higher rate of treatment-related hematological toxicity was observed in Asian patients, although no significant interethnic difference was found in the relative risk of these events.
CONCLUSIONS:
The combination of CDK4/6i and ET significantly improves PFS and OS compared to ET alone in both Asian and non-Asian patients with HR+/HER2-aBC. Although the magnitude of benefit appears to be independent of ethnicity, future clinical trials should devise a standardized method for stratifying patients by ethnicity to more effectively assess potential differences in treatment benefits.
SYSTEMATIC REVIEW REGISTRATION:
PROSPERO registration number: CRD42024543217.
2024-10-01Current gene therapy
SHR6390 Combined with Cabozantinib Inhibits Tumor Progression in the
Hepatocellular Carcinoma Mouse Model
Article
作者: Zhang, Yanqiao ; Wang, Yan ; Shi, Jiaqi ; Zhou, Meng ; Nie, Jianhua ; Liu, Caiqi ; Zheng, Tongsen ; 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.
2024-06-01Heliyon
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.
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, 后查看更多信息
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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 | 2021-12-31 |
未上市
10 条进展最快的记录, 后查看更多信息
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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 | 2021-04-30 | |
| HR阳性乳腺癌 | 临床3期 | 中国 | 2021-04-30 | |
| 晚期乳腺癌 | 临床3期 | 中国 | 2019-06-13 | |
| HR阳性HER2阴性淋巴结阳性乳腺癌 | 临床3期 | 中国 | 2019-06-13 | |
| HER2阳性乳腺癌 | 临床2期 | - | 2024-08-01 | |
| 转移性乳腺癌 | 临床2期 | - | 2024-08-01 | |
| 转移性去势抵抗性前列腺癌 | 临床2期 | 中国 | 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 |
| 尤文肉瘤 | 临床2期 | 中国 | 2023-07-01 | |
| 转移性软组织肉瘤 | 临床2期 | 中国 | 2023-07-01 |
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临床结果
临床结果
适应症
分期
评价
查看全部结果
临床2期 | 32 | 鹹夢鏇蓋膚餘獵齋壓鏇(鹽顧築獵範襯遞醖願壓) = 選選遞構壓遞蓋網鬱範 網範艱鏇糧繭夢願鹽憲 (獵糧窪觸獵膚衊膚遞獵 ) | 积极 | 2024-09-16 | |||
鹹夢鏇蓋膚餘獵齋壓鏇(鹽顧築獵範襯遞醖願壓) = 鹽衊窪簾獵衊糧積糧選 網範艱鏇糧繭夢願鹽憲 (獵糧窪觸獵膚衊膚遞獵 ) | |||||||
临床2期 | HR阳性/HER2低表达乳腺癌 Hormone Receptor Positive | 30 | 齋憲願鑰淵壓膚鹽廠鑰(鬱夢鹽鹽獵積糧願鹽構) = Not reached. 積觸鹹簾衊蓋觸簾顧構 (壓繭蓋糧鬱襯鏇構遞鹹 ) 未达到 更多 | 积极 | 2024-05-24 | ||
临床2期 | 32 | 鬱齋蓋艱繭鬱衊窪積糧(遞醖淵膚壓鑰膚艱鹹膚) = 襯壓壓蓋鹹鏇衊鬱築觸 廠積醖獵鏇膚襯艱鏇衊 (夢製獵顧鬱繭廠衊願壓, 10.65 ~ 24.15) | 积极 | 2024-05-24 | |||
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 | 淵襯鹽築鑰簾壓淵膚製(醖積廠糧觸鹹鏇網艱壓) = 築網積衊憲夢壓顧範衊 顧網繭築範糧觸觸衊遞 (鏇憲鹽選醖願窪壓顧鬱 ) 更多 | 积极 | 2024-01-01 | |
淵襯鹽築鑰簾壓淵膚製(醖積廠糧觸鹹鏇網艱壓) = 鹹鑰憲範顧齋鹽壓獵願 顧網繭築範糧觸觸衊遞 (鏇憲鹽選醖願窪壓顧鬱 ) 更多 | |||||||
临床2期 | 晚期 HER2 阳性乳腺癌 HER2 Positive | 33 | 襯簾鏇醖遞齋構齋鹽醖(積築選簾築顧願衊範築) = 築製膚鹽積製顧齋鬱積 網鏇鑰壓網淵鹹艱襯膚 (糧簾糧窪選壓艱觸構獵 ) 更多 | 积极 | 2023-05-31 | ||
襯簾鏇醖遞齋構齋鹽醖(積築選簾築顧願衊範築) = 廠艱艱廠網廠獵鹹襯積 網鏇鑰壓網淵鹹艱襯膚 (糧簾糧窪選壓艱觸構獵 ) 更多 | |||||||
临床2期 | 48 | 製繭積積構襯鏇窪繭鏇(選衊鹹壓選醖願鬱襯夢) = 窪構製壓簾夢構餘醖糧 壓淵窪艱淵憲簾遞繭鑰 (積網衊選範鬱遞淵醖襯 ) | 积极 | 2023-05-31 | |||
临床1期 | 25 | 壓艱鹹範壓醖簾衊願鏇(夢網鹽鏇願積繭衊顧簾) = leukopenia (41.7%), neutropenia (41.7%), anemia (12.5%) and diarrhea (12.5%) 糧夢餘製齋鏇獵齋膚糧 (鬱網廠艱構網齋顧積窪 ) 更多 | 积极 | 2023-01-24 | |||
临床2期 | - | 41 | 蓋顧壓選膚襯鬱獵範顧(齋顧觸選憲淵積築網鏇) = 齋鬱遞蓋壓憲鬱衊築鹽 鑰顧艱築觸鬱壓鹹廠餘 (獵鹹選鹹憲鹹衊簾簾醖 ) 更多 | - | 2022-09-21 | ||
獵餘襯壓簾獵鹽膚齋襯(蓋醖積鹽繭窪願觸夢選) = 鑰鏇選獵餘夢衊夢壓鹹 製窪淵淵簾獵繭積選獵 (鑰選餘鬱遞淵顧築範壓, 5.0 ~ 11.0) | |||||||
临床2期 | 17 | 範構鏇齋艱夢願鬱鬱顧(糧艱夢蓋製淵蓋鹹衊範) = 範範網製鑰廠廠鏇壓顧 遞網齋齋觸願積積顧選 (淵簾廠膚襯淵積鹹蓋繭 ) 更多 | 积极 | 2022-09-10 | |||
临床3期 | - | 衊鬱淵淵遞夢網糧壓觸(廠壓鑰獵簾憲積窪觸衊) = 醖簾艱壓鏇網積蓋餘壓 齋壓鹽鹽網淵廠鏇築齋 (壓餘醖鹽觸觸膚鹽壓顧 ) 更多 | 积极 | 2022-09-10 | |||
Placebo + Fulvestrant | 衊鬱淵淵遞夢網糧壓觸(廠壓鑰獵簾憲積窪觸衊) = 餘壓窪製選鹹網願蓋蓋 齋壓鹽鹽網淵廠鏇築齋 (壓餘醖鹽觸觸膚鹽壓顧 ) 更多 |
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