The goal of this research study is to evaluate how well and safely the study drugs sasanlimab, palbociclib, and axitinib work for treatment of participants with advanced clear cell renal cell carcinoma (ccRCC) or translocation renal cell carcinoma (tRCC).
The name of the study drugs involved in this research study is:
* Sasanlimab (a type of monoclonal antibody)
* Palbociclib (a type of kinase inhibitor)
* Axitinib (a type of Vascular endothelial growth factor inhibitor)

开始日期2026-02-01

申办/合作机构

Dana-Farber Cancer Institute, Inc.

[+1]

NCT07191977

/ Not yet recruiting临床2期IIT

Neoadjuvant Camrelizumab With Palbociclib for the Treatment of Resectable Esophageal Squamous Cell Carcinoma: A Single-Arm Phase 2 Trial

The goal of this Phase 2 clinical trial is to learn if the combination of Camrelizumab and Palbociclib is a safe and effective treatment when given before surgery (neoadjuvant therapy) for patients with esophageal squamous cell carcinoma (ESCC) that can be surgically removed. Camrelizumab is an immunotherapy drug that helps the immune system fight cancer, and Palbociclib is a targeted therapy drug that stops cancer cells from growing.
The main questions it aims to answer are:
Is the combination of Camrelizumab and Palbociclib safe for patients to receive before their surgery? How effective is this treatment combination in shrinking tumors prior to surgery?

开始日期2026-01-01

申办/合作机构

四川大学华西医院（四川省国际医院）

NCT07174336

/ Not yet recruiting临床3期

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of LY4064809 Combined With a CDK4/6 Inhibitor and Endocrine Therapy in Adults With HR+, HER2-Advanced Breast Cancer With a PIK3CA Mutation Who Received No Prior Treatment for Advanced Breast Cancer (PIKALO-2)

The purpose of the study is to assess the efficacy and safety of the addition of LY4064809 to other anti-cancer drugs as first treatment for advanced hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer. Participants can remain in the study as long as the drug is helping the cancer without unbearable side effects.

开始日期2025-10-01

申办/合作机构

Eli Lilly & Co.

[+1]

100 项与哌柏西利相关的临床结果

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100 项与哌柏西利相关的转化医学

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100 项与哌柏西利相关的专利（医药）

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3,248

项与哌柏西利相关的文献（医药）

2026-01-01·EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Design and synthesis of novel cyclin-dependent kinase 4/6(CDK4/6) and histone deacetylase (HDAC) dual inhibitors: In vitro and in vivo anticancer activity

Article

作者: Neerasa, Jayaprakash ; Kim, Bongsu ; Chung, Hunsuk ; Kang, Wonku ; Kantha, Chandra

Resistance to CDK4/6 inhibitors in certain tumors arises from the upregulation of cyclin D1 and the downregulation of the cell cycle regulator p21. Conversely, HDAC inhibitors can counteract this resistance by upregulating acetyl-histone H3 and p21 expression levels. To address this challenge, we developed a series of novel dual-targeting inhibitors that simultaneously inhibit CDK4/6 and HDAC1. Among these, selected compounds MFDCH016, MFDCH022 and MFDCH025 potently inhibited CDK4 and HDAC1/6 at nM levels, inducing apoptosis and cell cycle arrest in G2/M and G₀/G₁ phase and promote apoptosis in MCF-7 cells. This effect was mediated through the modulation of the HDAC-p21-CDK signalling pathway, as evidenced by increased acetyl-H3 and p21 levels. Compound MFDCH016 demonstrated significant anti-tumor activity in breast cancer cell line and in MCF-7 xenograft model without apparent toxicity. More importantly MFDCH016 show highly selective against CDK4 over CDK2 compare to standard drug Palbociclib. Our data demonstrated that compound MFDCH016 as a single agent could be novel dual-targeting CDK4/6-HDAC inhibitor could be a promising drug candidate for cancer therapy.

2025-12-01·Eating Behaviors

Medications as precipitating factors for potential eating disorders: A disproportionality analysis using FDA adverse event reports

Article

作者: Zhang, Shuang ; Zheng, Liyun

OBJECTIVE:

Compared to psychosocial factors, medications remain less well recognized as precipitating factors for eating disorders. This study aims to identify medications potentially associated with eating disorders using the U.S. Food and Drug Administration's Adverse Event Reporting System (FAERS) database.

METHODS:

FAERS reports related to potential eating disorders from January 2004 to December 2024 were retrieved. Reporting odds ratios (RORs) were calculated to detect disproportionate signals, with Fisher's exact test and Bonferroni correction applied for adjustments in multiple comparisons. Drugs exhibiting significant positive signals (ROR 95 % confidence interval lower bound >1, adjusted p-value < 0.01) with over 100 reports were selected for LASSO regression analysis. Logistic regression, adjusted for age, sex, and reporter type, was employed to identify precipitating drugs.

RESULTS:

Among 20,145 reports, 62.7 % involved females, with a median age of 59 years (interquartile range: 42-71). Thirty drugs showed significant positive signals. Nine potential precipitating medications were identified through LASSO and logistic regression, including octreotide, ribociclib, sunitinib, rivastigmine, everolimus, quetiapine, palbociclib, esomeprazole, and pregabalin.

CONCLUSION:

This study identifies certain medications that may act as precipitating factors for potential eating disorders, particularly in middle-aged and older populations. Clinicians should monitor these medications that affect appetite, weight, or carry abuse potential to prevent harm, especially in patients with eating disorders or at-risk populations.

2025-12-01·COMPUTATIONAL BIOLOGY AND CHEMISTRY

Identification of natural inhibitors against CDK6 target using pharmacophore-based screening, molecular docking, molecular dynamic simulations, and quantitative electrostatic potential analysis maps: A comprehensive study

Article

作者: Hosseinzadeh, Elaheh ; Amanlou, Massoud ; Firoozpour, Loghman

In this study, a mixing of pharmacophore-based screening, molecular docking virtual screening, molecular dynamic simulation, and quantitative electrostatic potential map analysis was performed at the binding cavity of the CDK6 target. The generated pharmacophore model has five features. After the validation of the model, a virtual screening process was conducted on the natural coconut database. The screened ligands were selected for molecular docking virtual screening. 800 ligands were docked, and the ligands were selected based on the docking scores and main interactions. The first four top-ranked compounds in the docking process were selected for the assessment of the stability of the interactions and binding site cavity through molecular dynamic simulation. Finally, MM-PBSA and electrostatic potential surface analyzes were performed on the compounds A-D and the standard and co-crystalized compounds. Compound A reveals superior features, including binding affinity, stability and binding-free energy compared to compound palbociclib ligand. These analyses lead to a deeper insight into the stability and charge distribution of selected hit compounds for further optimization of the natural ligands to achieve novel natural selective CDK6 inhibitors.

1,211

项与哌柏西利相关的新闻（医药）

2025-10-18

·药明康德

首个！优于标准疗法，罗氏小分子3期积极结果公布；PFS延长4倍！PI3K抑制剂组合3期亮眼结果公布，上市申请已启动……

首个！优于标准疗法，罗氏口服小分子3期积极结果公布罗氏（Roche）今日宣布，其3期evERA乳腺癌研究取得积极结果。数据显示，在既往接受过CDK4/6抑制剂及内分泌治疗的雌激素受体（ER）阳性、HER2阴性（HER2-）的局部晚期或转移性乳腺癌患者中，其在研口服新一代选择性雌激素受体降解剂（SERD）和完全拮抗剂giredestrant联合everolimus治疗显著降低了疾病进展或死亡风险：在意向治疗人群（ITT）中降低44%，在携带ESR1突变的人群中降低62%，相较于标准内分泌治疗联合everolimus组具有统计学意义上的显著改善。研究结果还显示，giredestrant与everolimus的联合治疗总体耐受性良好，未观察到新的安全性信号。虽然总生存期数据尚不成熟，但在ITT和ESR1突变人群中均呈现出明确的积极趋势。根据新闻稿，若获批，该方案有望成为首个在CDK抑制剂治疗后可口服的选择性雌激素受体降解剂联合疗法。首次！PI3K小分子抑制剂组合3期亮眼结果公布，上市申请递交已启动 Celcuity今日公布其进行中3期VIKTORIA-1临床试验的最新积极结果。该试验评估其在研广谱PI3K/mTORC1/2抑制剂gedatolisib组合在接受过CDK4/6抑制剂及芳香化酶抑制剂治疗后疾病进展的激素受体阳性（HR+）、HER2-晚期乳腺癌患者中的疗效与安全性。根据此积极结果，Celcuity已启动该疗法的新药申请（NDA）滚动递交。针对PIK3CA野生型（WT）亚群分析的结果显示，与活性对照药物相比，gedatolisib、palbociclib、fulvestrant三联方案使疾病进展或死亡风险降低76%，中位无进展生存期（PFS）达到9.3个月，而对照组仅为2.0个月，延长了7.3个月（HR=0.24，95% CI：0.17-0.35，p<0.0001）；客观缓解率为31.5%，中位缓解持续时间（DOR）为17.5个月。同时，gedatolisib联合fulvestrant的双联方案亦展现显著疗效，使疾病进展或死亡风险降低67%，中位无进展生存期为7.4个月，相较于活性对照药物的2.0个月延长5.4个月（HR=0.33，95% CI：0.24-0.48，p<0.0001）。双联组的客观缓解率为28.3%，中位DOR为12.0个月，而对照组因仅有一例客观缓解，未能确定DOR。根据新闻稿，gedatolisib为在接受过CDK4/6抑制剂治疗后出现疾病进展的HR+/HER2-/PIK3CA WT晚期乳腺癌患者中，在3期研究中取得积极结果的首个PI3K/AKT/mTOR通路抑制剂。过半患者肿瘤缩小！潜在“first-in-class”疗法临床结果公布 Marengo Therapeutics日前首次公布其主打项目invikafusp alfa进行中2期临床试验的数据。截至2025年7月29日，共有55例携带高突变负荷（TMB-H）或微卫星不稳定性高/错配修复缺陷（MSI-H/dMMR）的晚期实体瘤患者入组，涵盖21种肿瘤类型，其中44名患者可评估疗效。数据显示，52%的患者出现靶病灶缩小；在TMB-H人群中，总缓解率（ORR）为20.5%，疾病控制率（DCR）达79.5%，涉及结直肠癌、胃癌、肺癌、乳腺癌、胃食管交界癌及头颈癌等六种肿瘤类型；在MSI-H/dMMR人群中，ORR为30%，DCR为70%。值得注意的是，该药在PD-1耐药/复发肿瘤以及PD-1非标准治疗的肿瘤中均观察到临床疗效，显示出独立于PD-1通路的抗肿瘤活性。安全性方面，治疗相关不良事件总体可控，安全特征与其选择性T细胞激活机制一致。 Invikafusp alfa是一种潜在“first-in-class”、具有双重激动作用的双特异性T细胞激动剂，旨在选择性激活并扩增Vβ6/Vβ10 T细胞亚群，这类细胞约占肿瘤浸润性淋巴细胞（TILs）的10%。该药物通过重建并增强机体的抗肿瘤免疫反应，有望用于治疗既往对免疫检查点抑制剂无应答或耐药的患者。参考资料： [1] Marengo Presents Initial Phase 2 Results Demonstrating Broad Single-Agent Activity of Invikafusp Alfa Across Multiple PD-1-Refractory or -Resistant Solid Tumors as a Late-Breaking Oral Presentation at ESMO 2025. Retrieved October 18, 2025 from https://www.prnewswire.com/news-releases/marengo-presents-initial-phase-2-results-demonstrating-broad-single-agent-activity-of-invikafusp-alfa-across-multiple-pd-1-refractory-or--resistant-solid-tumors-as-a-late-breaking-oral-presentation-at-esmo-2025-302587142.html [2] Celcuity Provides Update on Status of the PIK3CA Mutated Cohort of Phase 3 VIKTORIA-1 Trial and Releases Additional Data Analysis From Phase 1b Clinical Trial. Retrieved October 18, 2025 from https://ir.celcuity.com/press-releases/ [3] Roche’s phase III evERA data showed giredestrant significantly improved progression-free survival in people with ER-positive advanced breast cancer. Retrieved October 18, 2025 from https://www.roche.com/media/releases/med-cor-2025-10-18 免责声明：本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

临床结果临床3期临床成功

2025-10-18

·ioncology

Ann Oncol丨TOUCH研究：哌柏西利＋来曲唑能否取代紫杉醇

点击上方蓝字关注我们大约15～20%的乳腺癌为HER2阳性，其中雌激素受体阳性超过半数，与雌激素受体阴性相比，对术前标准化疗＋HER2双靶向治疗方案（紫杉醇＋曲妥珠单抗＋帕妥珠单抗）病理完全缓解率较低（26%比63.2%）。对于雌激素受体阳性HER2阳性乳腺癌晚期患者，CDK4/6抑制剂哌柏西利联合内分泌治疗和HER2靶向治疗已被证实可避免化疗。那么，对于早期患者，尤其难以耐受化疗的老年，CDK4/6抑制剂联合内分泌治疗和HER2靶向治疗能否避免化疗？ 2025年10月16日，欧洲肿瘤内科学会官方期刊《肿瘤学年鉴》在线发表意大利普拉托医院、博洛尼亚大学医院、米兰大学欧洲肿瘤研究院、乌迪内大学弗留利中心医院、塞特拉吉医院、圣玛丽亚德勒克罗奇医院、比萨大学医院、美国哈佛大学公共卫生学院和医学院、达纳法伯癌症研究院、比利时布鲁塞尔自由大学医院、朱尔博代研究院、那慕尔大学圣伊丽莎白医院、列日大学医院、瑞士圣加仑州立医院、格劳宾登州立医院、温特图尔州立医院、欧洲胸部肿瘤研究和国际乳腺癌研究协作组基金会、法国贝尔戈尼研究院、居里研究院、澳大利亚墨尔本大学彼得麦卡伦癌症中心的TOUCH研究报告，对激素受体阳性HER2阳性早期乳腺癌术前哌柏西利＋来曲唑或每周紫杉醇联合曲妥珠单抗＋帕妥珠单抗的有效性和安全性进行比较，并探讨疗效预测指标。 TOUCH (NCT03644186): To Reduce the Use of Chemotherapy in Postmenopausal Patients With ER-positive and HER2-positive Breast Cancer Official Title: Phase II Open-label, Multicentre, Randomized Trial of Neoadjuvant Palbociclib in Combination With Hormonal Therapy and HER2 Blockade Versus Paclitaxel in Combination With HER2 Blockade for Postmenopausal Patients With Hormone Receptor Positive/HER2 Positive Early Breast Cancer 该国际多中心非盲随机对照二期临床研究于2019年4月至2022年7月入组cT>1厘米、cN0或cN1、雌激素受体阳性（其中孕激素受体阳性77.2%）HER2阳性乳腺癌术前老年（年龄中位69岁，四分位63至73岁）绝经后患者147例，随机分为两组进行16周术前治疗，其中每周紫杉醇组74例、哌柏西利＋来曲唑组73例，两组全部给予曲妥珠单抗＋帕妥珠单抗。主要疗效指标为病理完全缓解（ypT0N0或ypTisN0）。由于CDK4/6抑制剂主要通过激活E2F和抑制RB1发挥作用，故该研究根据E2F活性和RB1失活相关87个基因评分RBsig，假设每周紫杉醇组中RBsig较高肿瘤的病理完全缓解更高，而哌柏西利＋来曲唑组RBsig较低肿瘤的病理完全缓解更高。通过对治疗前活检样本进行RNA测序评定RBsig，根据PAM50进行亚型分析。对于115例可评定患者，利用逻辑回归分析治疗与生物标志物的相互作用。结果，两组各有1例患者退出，145例患者开始治疗。哌柏西利＋来曲唑组与每周紫杉醇组相比：治疗完成率：94.4%比79.5% 病理完全缓解率：33.3%比32.9%（95%置信区间：22.7%～45.4%、22.3%～44.9%） 3～4级中性粒细胞减少率：43.1%比6.9% 3～4级腹泻率：8.3%比11% 未观察到治疗方案与RBsig之间存在显著相互作用（P=0.18）。 RBsig较高与较低相比，病理完全缓解：紫杉醇组：31.3%比42.3%（95%置信区间：16.1%～50.0%、23.4%～63.1%）哌＋来组：38.5%比25.8%（95%置信区间：20.2%～59.4%、11.9%～44.6%） PAM50非管腔亚型与管腔亚型相比，病理完全缓解较高（45.5%比18.4%）且与治疗方案无关（比值比：0.68，95%置信区间：0.11～3.90，P=0.66）。因此，该小样本二期临床研究结果表明，对于雌激素受体阳性HER2阳性乳腺癌术前老年绝经后患者，哌柏西利＋来曲唑与每周紫杉醇相比，联合HER2双靶向治疗16周病理完全缓解率相似，故有必要进一步开展大样本三期临床研究进行验证。E2F通路活性基因表达特征RBsig高低不能预测任何一种治疗方案获益。根据PAM50亚型分析，非管腔亚型病理完全缓解率较高，也不能预测任何一种治疗方案获益。 Ann Oncol. 2025 Oct 16. IF: 65.4 Palbociclib plus letrozole versus weekly paclitaxel, both in combination with trastuzumab plus pertuzumab, as neoadjuvant treatment for patients with HR+/HER2+ early breast cancer: primary results from the randomized phase II TOUCH trial (IBCSG 55-17). Malorni L, Tyekucheva S, Gombos A, Hasler-Strub U, Zamagni C, Chakiba-Brugère C, Colleoni M, Mueller A, Minisini AM, Taylor D, Salmon JP, Gallerani E, Cariello A, Fontana A, Roschitzki-Voser H, Kammler R, Ruepp B, Loi S, Viale G, Regan MM, Brain E, Biganzoli L; International Breast Cancer Study Group; TOUCH Trial (IBCSG 55-17) Investigators. Hospital of Prato, Azienda USL Toscana Centro, Prato, Italy; IRCCS Azienda ospedaliero-universitaria di Bologna, Italy; European Institute of Oncology, IRCCS, Milan, Italy; Azienda Sanitaria Universitaria Friuli Centrale, Udine, Italy; ASST Sette Laghi, Varese, Italy; AUSL Romagna, Ospedale Santa Maria delle Croci, Ravenna, Italy; Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy; Dana-Farber Cancer Institute and Harvard T.H. Chan School of Public Health, Boston, MA, USA; Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA; Institut Jules Bordet, Hopital Universitaire de Bruxelles and Université Libre de Bruxelles, Brussels, Belgium; CHU UCL Namur - Site Sainte-Elisabeth, Namur, Belgium; CHR Citadelle, Liege, Belgium; Kantonsspital St. Gallen, St. Gallen, Switzerland; Kantonsspital Graubünden, Chur, Switzerland; KSW Cantonal Hospital Winterthur, Winterthur, Switzerland; ETOP IBCSG Partners Foundation, Coordinating Center, Bern, Switzerland; Institut Bergonié, Bordeaux, France; Institut Curie, Saint Cloud, France; Peter MacCallum Cancer Center, Melbourne, Australia; The University of Melbourne, Parkville, Australia. HIGHLIGHTS Neoadjuvant palbociclib+letrozole+HP for 16 weeks yielded a pCR of 33.3% in patients with ER+/HER2+ early breast cancer Outcomes were similar with a de-escalated chemotherapy of paclitaxel+HP of the same duration A gene-expression signature of E2F-pathway-activity (RBsig) was not predictive of benefit from either treatment PAM50 subtyping was also not predictive and pCR was more frequent for cancers of non-luminal subtype A chemo-free approach with ET, CDK4/6 inhibitors and anti-HER2 blockade warrants further investigation in larger trials BACKGROUND: HR+/HER2+ breast cancer (BC) is a heterogeneous disease with low pathological complete response (pCR) to standard neoadjuvant treatment. CDK4/6 inhibitors with endocrine and anti-HER2 therapy have shown a potential for chemotherapy omission in this context. PATIENTS AND METHODS: TOUCH is an international, open-label, phase II trial for postmenopausal patients with cT>1 cm, cN0 or cN1, HR+/HER2+ BC, randomized to 16 weeks of neoadjuvant weekly paclitaxel or palbociclib and letrozole, both with trastuzumab+pertuzumab (HP). The primary objective investigated the interaction between a gene-signature of E2F-pathway-activity (RBsig) and pCR (ypT0N0 or ypTisN0), hypothesizing higher pCR for RBsig high tumors in the paclitaxel+HP group, and for RBsig low tumors in the palbociclib+letrozole+HP group. RBsig was assessed by RNA-sequencing from pre-treatment biopsies; intrinsic subtypes were estimated by AIMS. Treatment-by-biomarker interaction was estimated using logistic regression in 115 assessable patients. RESULTS: 147 patients were randomized (74 paclitaxel+HP, 73 palbociclib+letrozole+HP) and 145 constituted the treated population, with a median age of 69 years (IQR 63,73). More patients completed palbociclib vs paclitaxel (94.4% vs 79.5%). The most frequent grade 3-4 adverse events were neutropenia and diarrhea (6.9% vs 43.1% and 11% vs 8.3% in the paclitaxel+HP vs the palbociclib+letrozole+HP groups, respectively). pCR rate was: 32.9% (95% CI: 22.3%-44.9%) in the paclitaxel+HP group and 33.3% (95% CI: 22.7%-45.4%) in the palbociclib+letrozole+HP group. No significant treatment-by-RBsig interaction was observed (p=0.18): pCR in RBsig high vs low was 31.3% (95% CI: 16.1%-50.0%) vs 42.3% (95% CI: 23.4%-63.1%) in the paclitaxel+HP group, and 38.5% (95% CI: 20.2%-59.4%) vs 25.8% (95% CI: 11.9%-44.6%) in the palbociclib group. pCR was higher in non-luminal vs luminal subtypes (45.5% vs 18.4%), with no interaction with treatment. CONCLUSIONS: Although the primary hypothesis was not supported, TOUCH shows that dual anti-HER2 blockade with a chemotherapy-free backbone of palbociclib+letrozole yields pCR rates similar to paclitaxel, representing an attractive alternative treatment strategy. KEYWORDS: Early breast cancer, Hormone receptor positive, HER2 positive, post-menopausal, neoadjuvant therapy, chemotherapy de-escalation, CDK4/6 inhibitor, RBsig, gene expression signatures REGISTRATION: ClinicalTrials.gov (NCT03644186) and EudraCT (2017-005067-40). DOI: 10.1016/j.annonc.2025.10.016 （来源：SIBCS）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。

临床结果临床2期

2025-10-18

·医脉通

精准诊断为基，靶向治疗为刃：转移性乳腺癌核心生物标志物检测解析

前言近期，欧洲肿瘤内科学会（ESMO）于Annals of Oncology发布了转移性乳腺癌（MBC）生活指南系统治疗更新1，其中对诊断环节的优化尤为关键——明确强调在首次诊断MBC时需强化转移灶活检，核心目的是重新评估肿瘤生物学特征，尤其是人类表皮生长因子受体2（HER2）的表达水平。同时，指南还对生物标志物检测的推荐进行了更新：HER2阴性患者需新增PALB2突变检测，HR阳性/HER2阴性患者需加测AKT1/PTEN突变，且所有检测均结合ESMO分子靶向临床可行性量表（ESCAT）评分，依据最新证据明确临床优先级。此外，指南还特别强调芳香化酶抑制剂（AI）治疗后，通过组织或液体活检检测ESR1突变状态的重要性。这些更新为HR阳性/HER2阴性MBC的精准诊断筑牢基础，并直接关联到后续个体化治疗决策的制定。固定布局工具条上设置固定宽高背景可以设置被包含可以完美对齐背景图和文字以及制作自己的模板 ESMO转移性乳腺癌生活指南核心生物标志物检测指南围绕MBC患者的治疗需求，对生物标志物检测项目、推荐级别、证据等级及临床可行性（ESCAT评分）进行明确界定，具体推荐如下：图1. MBC患者生物标志物检测路径2 表1. MBC患者生物标志物检测更新建议1-2 注：IHC：免疫组织化学；FISH：荧光原位杂交分层解析：指导治疗决策的生物标志物 ► HER23,4 在HER2阴性晚期乳腺癌患者中，约45%-55%为HER2低表达人群（IHC 1+或IHC 2+/ISH-），而近年来的研究进一步拓宽了HER2表达的边界，HER2超低表达人群（IHC 0但≤10%浸润癌细胞呈微弱细胞膜染色）也逐渐进入临床视野。研究显示，HER2低表达在乳腺癌中并非罕见状态，原发肿瘤中HER2低表达率约为34%，转移灶中为37%，且原发肿瘤与匹配远处转移灶间HER2表达状态的不一致率可达40%-50%，这也提示了动态监测HER2表达状态的必要性。因此，精准检测HER2低表达、超低表达状态，成为筛选特定治疗方案获益人群的关键前提。 ► BRCA1/2和PALB23 抑癌基因BRCA1和BRCA2的体细胞（s）突变与种系（g）突变均与同源重组缺陷（HRD）相关，且对癌症遗传具有重要意义。PALB2与BRCA2具有协同作用，是同源重组修复的关键辅助因子。其中，gBRCA1/2基因突变与接受CDK4/6抑制剂治疗患者的不良预后独立相关。对于gBRCA1/2或gPALB2突变患者，当前指南建议可采用PARP抑制剂治疗，因此需检测HRD基因改变以指导治疗决策。 ► PD-L15 PD-1受体属于CD28超家族，当其与配体PD-L1结合时，会抑制T细胞活化及免疫应答，导致肿瘤发生免疫逃逸。目前已有大量临床试验将PD-1/PD-L1作为乳腺癌的治疗靶点展开研究，其中抗PD-1疗法（如帕博利珠单抗）与抗PD-L1疗法（如阿替利珠单抗）均得到了广泛探索，也逐渐获批应用于临床。因此，指南将PD-L1检测列为三阴性乳腺癌推荐检测标志物，为免疫治疗方案选择提供直接依据。 ► PIK3CA3 PIK3CA基因编码PI3K催化亚基，在HR阳性/HER2阴性乳腺癌患者中突变发生率达30%-40%；其突变会导致经典的PI3K/AKT/mTOR（PAM）通路异常激活，进而驱动细胞的代谢与增殖。在转移性管腔型乳腺癌中，PI3K通路的激活与内分泌治疗（ET）耐药相关，这一发现推动了针对PAM通路的抑制剂的研发。III期INAVO120试验证实，在哌柏西利与氟维司群基础上联合伊那利塞，可显著改善PIK3CA突变HR阳性/HER2阴性晚期乳腺癌患者的中位PFS，明确了该突变检测对靶向方案选择的价值。基于临床研究证据，伊那利塞（PI3Kα抑制剂）获批乳腺癌适应证；此外，针对PIK3CA/AKT1/PTEN改变的卡匹色替（AKT抑制剂）也获得批准，为该类乳腺癌患者提供更多治疗选择。 ► AKT1/PTEN3,6 AKT1/PTEN同为PAM通路中的关键分子：AKT1编码AKT激酶，激活后能够磷酸化多种下游靶点，促进细胞增殖和存活；PTEN则通过负向调控PAM通路抑制肿瘤。AKT1/PTEN发生改变时，导致PAM通路过度激活，进而促进肿瘤发生发展。 CAPItello-291研究中，对于PI3K/AKT/PTEN通路存在异常、且既往接受过一线CDK4/6抑制剂治疗的患者，卡匹色替（AKT抑制剂）联合氟维司群治疗相较于安慰剂联合氟维司群，显著延长了患者的mPFS。 ► ESR13 ESR1基因负责编码雌激素受体（ER）α。转移性HR阳性/HER2阴性乳腺癌患者使用芳香化酶抑制剂（AI）治疗后出现耐药情况时，有研究显示高达48%的患者可能检测到ESR1基因突变。此外，一线CDK4/6抑制剂联合AI治疗一年后，ESR1突变率可达50%。 ESR1突变通常导致患者对CDK4/6抑制剂联合AI治疗产生耐药性，但对CDK4/6抑制剂联合氟维司群治疗则无明显影响，提示ESR1突变可作为氟维司群（ER拮抗剂）治疗的潜在生物标志物。即使患者未见影像学进展，一旦检测到ESR1突变，及时从AI转换为氟维司群治疗，也能带来显著的临床获益。EMERALD研究进一步证实了这一点：对于ESR1突变且对CDK4/6抑制剂敏感的患者，采用新型口服选择性雌激素受体降解剂（SERD）elacestrant治疗，中位PFS得到显著改善。这一结果进一步验证了ESR1突变检测在临床实践中的重要价值。总结 2025年ESMO MBC生活指南对生物标志物检测的更新，为MBC精准诊断与治疗搭建了更清晰的“分子导航”体系。从强化转移灶活检以捕捉肿瘤动态生物学特征，到细分HER2全表达谱、完善PIK3CA/AKT1/PTEN/ESR1等核心标志物检测，每一项调整都紧扣“诊断指导治疗”的核心逻辑，尤其为HR阳性/HER2阴性这一最常见乳腺癌亚型的诊疗提供了精准依据。未来，随着液新型检测技术的普及，MBC的诊断将更趋动态化、个体化，有望实现“实时监测肿瘤分子变化、及时调整治疗策略”的精准管理目标。临床实践中，唯有严格遵循指南推荐，将生物标志物检测深度融入诊疗流程，才能真正让“精准诊断”成为提升患者生存获益、改善生活质量的坚实基石。参考资料： [1] Trapani D,et al. Ann Oncol. 2025 Aug 12. DOI:10.1016/j.annonc.2025.07.017 [2] https://www.esmo.org/guidelines/living-guidelines/esmo-living-guideline-metastatic-breast-cancer/hr-positive-her2-negative-metastatic-breast-cancer [3] Cejalvo Andújar JM, et al. Cancer Drug Resist. 2025;8:5. Published 2025 Jan 22. doi:10.20517/cdr.2024.169 [4] Shang J, Liu Y. Transl Breast Cancer Res. 2024;5:29. Published 2024 Oct 21. doi:10.21037/tbcr-24-33 [5] Jin M, et al. Mol Cancer. 2024;23(1):266. Published 2024 Nov 29. doi:10.1186/s12943-024-02176-8 [6] Miricescu D, et al. Int J Mol Sci. 2020;22(1):173. Published 2020 Dec 26. doi:10.3390/ijms22010173 本材料由阿斯利康提供，仅供医疗卫生专业人士参考审批编号：CN-168735 过期日期：2026-10-14 撰写：KIKI 审校：KIKI 排版：Mythero 执行：Atai 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。

抗体药物偶联物

100 项与哌柏西利相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10372	哌柏西利	L01XE33	DB09073

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
复发性乳腺癌	日本	Pfizer Japan, Inc.	2017-09-27
HR阳性/HER2阴性乳腺癌	美国	Pfizer Inc.	2016-02-19
ER阳性/HER2阴性乳腺癌	美国	Pfizer Inc.	2015-02-03

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
HPV相关鳞状细胞癌	临床3期	美国	Pfizer Inc.	2022-04-06
头颈部鳞状细胞癌	临床3期	美国	Pfizer Inc.	2022-04-06
转移性头颈部鳞状细胞癌	临床3期	美国	Pfizer Inc.	2022-04-06
HR阳性HER2阴性淋巴结阳性乳腺癌	临床3期	奥地利	Pfizer Inc.	2019-08-27
HR阳性HER2阴性淋巴结阳性乳腺癌	临床3期	法国	Pfizer Inc.	2019-08-27
HR阳性HER2阴性淋巴结阳性乳腺癌	临床3期	匈牙利	Pfizer Inc.	2019-08-27
HR阳性HER2阴性淋巴结阳性乳腺癌	临床3期	意大利	Pfizer Inc.	2019-08-27
HR阳性HER2阴性淋巴结阳性乳腺癌	临床3期	西班牙	Pfizer Inc.	2019-08-27
HR阳性HER2阴性淋巴结阳性乳腺癌	临床3期	瑞士	Pfizer Inc.	2019-08-27
HER2 阴性乳腺癌	临床3期	美国	Pfizer Inc.	2019-07-16

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临床结果

适应症

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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


NCT03446157 (LCCC1717, Pubmed \| Oncologist)	临床2期	RAS/BRAF基因野生型结直肠癌 KRAS/NRAS/BRAF wild-type	12	Palbociclib and cetuximab	築糧構廠願網憲餘製簾(築淵廠鬱鬱獵鹽鏇齋淵) = 夢蓋構鬱簾觸壓鏇鏇蓋構鏇觸齋願蓋襯遞築膚 (鹹範繭築艱鹹襯鹹選構, 15 ~ 72) 更多	不佳	2025-09-24
NCT03280303 (POLARIS, Pubmed \| Oncologist)	N/A	HR阳性/HER2阴性乳腺癌 HR+/HER2−	1,250	Palbociclib plus endocrine therapy	選繭衊鹹範壓製觸構壓(觸齋鑰顧艱壓築製蓋製) = 顧鑰夢範簾構積觸膚製窪鬱夢醖獵網糧蓋獵壓 (鹹簾憲膚觸範顧醖積壓 ) 更多	积极	2025-09-15
NCT04735367 (Pubmed \| Breast Cancer)	临床2期	ER阳性/HER2阴性乳腺癌一线 ER+/HER2−	42	Palbociclib plus letrozole	遞鹹餘鹽夢簾艱鹽選膚(憲窪醖構觸糧窪餘糧糧) = 襯淵獵鹹簾選鑰觸築壓餘鹽壓築衊築壓鹹夢遞 (襯衊廠鑰憲壓遞築蓋鏇, 64.3 ~ NE) 更多	积极	2025-08-21
NCT03280303 (POLARIS, Pubmed \| Target Oncol)	N/A	HR阳性乳腺癌 \| 转移性乳腺癌 \| 晚期乳腺癌一线	1,250	Endocrine Therapy Alone	願鹹鹹夢範鹽築廠繭蓋(獵鹽遞艱鏇襯膚憲淵蓋) = 鏇獵選獵範積壓構鹽獵願範繭積餘淵糧鏇淵鏇 (壓構觸製選顧餘選鬱觸 ) 更多	-	2025-07-01
				Chemotherapy Alone	願鹹鹹夢範鹽築廠繭蓋(獵鹽遞艱鏇襯膚憲淵蓋) = 夢鏇鹹構構膚鑰積齋獵願範繭積餘淵糧鏇淵鏇 (壓構觸製選顧餘選鬱觸 ) 更多
NCT05361655 (Pubmed \| Breast)	N/A	转移性乳腺癌一线	1,302	Palbociclib dose adjustments	廠鬱繭醖齋積築構顧齋(觸蓋構衊網製糧壓鏇構) = 鏇觸獵遞簾製觸遞襯衊鏇積餘範選衊觸顧憲膚 (鹽糧簾願鹽願鏇鏇鏇廠 ) 更多	积极	2025-06-01
				No palbociclib dose adjustments	廠鬱繭醖齋積築構顧齋(觸蓋構衊網製糧壓鏇構) = 繭鏇觸餘選範繭簾鹹醖鏇積餘範選衊觸顧憲膚 (鹽糧簾願鹽願鏇鏇鏇廠 ) 更多
NCT03844997 (CTgov)	临床1/2期	急性髓性白血病 \| 治疗相关性急性髓系白血病 \| 急性早幼粒细胞白血病	35	Palbociclib+cytarabine+daunorubicin+CPX-351 (Phase I)	壓選鬱醖繭襯襯範夢鏇 = 鹹襯選遞築襯夢顧製糧鹹艱遞夢繭積夢餘衊獵 (糧夢鬱範鏇遞齋壓膚網, 鹹廠選獵壓衊窪鹽襯鑰 ~ 夢餘淵鬱鑰膚願醖餘鹹) 更多	-	2025-05-31
				Palbociclib+CPX-351 (Phase II)	範範鑰繭淵廠壓蓋網憲 = 鹹憲夢簾襯獵獵夢餘鬱壓鬱獵醖襯築獵鏇選鏇 (簾衊構積積蓋糧夢衊艱, 糧糧觸膚積艱窪窪範壓 ~ 醖觸壓簾獵壓構積窪選) 更多
JPRN-UMIN000035863 (Prospective cohort study of palbociclib in HR+/HER2- metastatic breast cancer in Japan, ASCO2025)	N/A	HR阳性/HER2阴性乳腺癌一线 HR+ \| HER2-	700	Cohort A (1st line)	夢構觸窪繭襯襯蓋壓齋(網鹽簾觸壓觸鏇襯糧醖) = 鹽衊遞網願積襯壓觸艱觸繭選網襯憲鹹築鬱艱 (獵獵顧選繭積獵鹹鹹糧, 21.4) 更多	积极	2025-05-30
				Cohort B (2nd line)	夢構觸窪繭襯襯蓋壓齋(網鹽簾觸壓觸鏇襯糧醖) = 鹹衊遞構窪簾築繭簾遞觸繭選網襯憲鹹築鬱艱 (獵獵顧選繭積獵鹹鹹糧, 14.0 ~ 22.7) 更多
NCT03088059 (EORTC-HNCG-1559, ASCO2025)	临床2期	头颈部鳞状细胞癌 EGFR \| HER2 \| PTEN ... 更多	250	Afatinib in pts with EGFR amp/mut and/or HER2 amp/mut and/or PTEN high	鑰憲鑰醖糧選艱廠簾願(窪積膚顧膚鏇艱醖選醖) = 膚憲網蓋簾鏇選繭積鏇簾窪願艱餘鏇壓觸淵製 (餘顧齋壓壓衊憲蓋鬱選 )	不佳	2025-05-30
				Afatinib in cetuximab-naïve pts	鑰憲鑰醖糧選艱廠簾願(窪積膚顧膚鏇艱醖選醖) = 獵製餘鏇願鏇衊夢繭齋簾窪願艱餘鏇壓觸淵製 (餘顧齋壓壓衊憲蓋鬱選 )
NCT02693535 (TAPUR, ASCO2025)	临床2期	局部晚期恶性实体瘤 \| 晚期恶性实体瘤 \| 多发性骨髓瘤 CDKN2A	28	Palbociclib	範簾醖鑰窪衊繭糧鑰蓋(繭鏇鏇餘製憲願蓋繭醖) = 壓艱選艱鹽餘鬱淵餘餘遞膚夢艱顧壓鏇餘壓構 (窪簾夢鹽憲醖襯餘網蓋, 24 ~ 100) 更多	积极	2025-05-30
ASCO2025	N/A	转移性乳腺癌 HR+ve \| HER2-ve	200	Generic Palbociclib + Letrozole	鏇壓艱餘齋廠鑰窪遞壓(鬱壓齋顧築蓋鬱觸憲衊) = 鏇製構糧蓋醖壓蓋製鑰夢齋簾襯願觸鹽蓋膚艱 (選窪淵築襯鬱簾鹹衊窪 ) 更多	积极	2025-05-30
				Generic Palbociclib + Fulvestrant	鏇壓艱餘齋廠鑰窪遞壓(鬱壓齋顧築蓋鬱觸憲衊) = 醖膚醖襯築蓋廠製網鏇夢齋簾襯願觸鹽蓋膚艱 (選窪淵築襯鬱簾鹹衊窪 ) 更多