Phase I Dose Escalation Study on Bicalutamide, an Androgen Receptor Antagonist, as a Radiosensitizer Combining With Brain Re-irradiation to Treat Recurrent/Progressive Glioblastoma/High Grade Glioma

The goal of this clinical trial is to learn about a type of brain cancer called high-grade glioma. This clinical trial is for people who have previously received treatment for their brain cancer, but their cancer has come back or gotten worse after treatment. The main question this trial aims to answer is:
- Is it safe for participants to take bicalutamide while receiving brain radiation treatment?
Participants will:
* Take bicalutamide every day for 6 months
* Receive radiation treatment to the brain
* Keep a diary of the when they take the bicalutamide and any side effects they may be experiencing
* Visit the clinic once every 8 weeks for checkups and tests

开始日期2025-01-01

申办/合作机构

University of Nebraska

NCT06650579 / Not yet recruiting临床3期IIT

Randomized Controlled Trial of Leuprolide Plus Abiraterone Acetate (AA) Versus Relugolix Plus AA for Advanced Prostate Cancer: the REVELUTION-2 Trial

This phase III/IV trial compares the impact of leuprolide and abiraterone acetate (AA) versus relugolix and AA on the heart in hormone-naive patients with advanced prostate cancer receiving pelvic radiation therapy. Leuprolide is in a class of medications called gonadotropin-releasing hormone agonists (GNRHa). It prevents the body from making luteinizing hormone-releasing hormone (LHRH) and luteinizing hormone (LH). This causes the testicles to stop making testosterone (a male hormone) in men and may stop the growth of prostate tumor cells that need testosterone to grow. Abiraterone acetate, an androgen biosynthesis inhibitor, works by decreasing the amount of certain hormones in the body. Relugolix, a GNRH antagonist, works by decreasing the amount of testosterone produced by the body. This may slow or stop the spread of prostate tumor cells that need testosterone to grow. The use of hormone therapy with radiation therapy has been shown to improve survival, however, studies have suggested that the addition of hormone therapy may worsen heart (cardiac) disease and high blood pressure. In fact, studies have shown that the most common cause of death in prostate cancer patients is due to heart disease or heart attacks. Computed tomography (CT) scans create a series of detailed pictures of areas inside the body; the pictures are created by a computer linked to an x-ray machine. In this study, sophisticated cardiac CT images are used to take pictures of patients' heart and coronary arteries to help assess damage to the heart. Using cardiac CT and blood tests, this trial may help doctors determine which patients are at risk of cardiac disease when treated with combination hormone therapy, as well as the differential risk of leuprolide versus relugolix in combination with abiraterone acetate.

开始日期2024-12-16

申办/合作机构

Emory University

[+4]

NCT06222593 / Not yet recruiting临床1/2期IIT

A Phase I/II Study to Evaluate the Safety and Efficacy of Bicalutamide in Combination with Sunitinib in Patients with Receptor Tyrosine Kinase Inhibitor Resistant Renal Cell Carcinoma

This is a Phase I/II open-label, efficacy and safety study of bicalutamide in combination with sunitinib in patients with advanced renal cell carcinoma (RCC) who have been treated with a receptor tyrosine kinase inhibitor (RTKI) and experienced disease progression.

开始日期2024-10-01

申办/合作机构

State University of New York at Buffalo

100 项与比卡鲁胺相关的临床结果

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100 项与比卡鲁胺相关的转化医学

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100 项与比卡鲁胺相关的专利（医药）

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项与比卡鲁胺相关的文献（医药）

2024-12-31·Journal of medical economics

Treatment patterns and healthcare resource utilization in patients with metastatic hormone-sensitive prostate cancer and nonmetastatic castration-resistant prostate cancer in China: a real-world observational study

Article

作者: Ban, Lu ; Niu, Yuanjie ; Lu, Yongji ; Liu, Chunxiao ; Liu, Chuan ; Wang, Yong

AIM:

This study assessed the treatment patterns, healthcare resource utilization (HRU), costs, and annual prevalence and incidence of metastatic hormone-sensitive prostate cancer (mHSPC) and nonmetastatic castration-resistant prostate cancer (nmCRPC) in China.

METHODS:

A retrospective study was conducted using electronic medical records (EMR) of patients with prostate cancer from three tertiary-care hospitals in China between January 2014 and March 2021. Descriptive statistics were used to analyze study outcomes.

RESULTS:

In total, 1086 patients with mHSPC and 679 patients with nmCRPC were included. From 2015 to 2020, the annual percentage of prevalent and incident cases of mHSPC decreased from 22.4% to 20.0% and 11.1% to 6.9%, respectively; for nmCRPC, these increased from 3.8% to 13.6% and 3.3% to 8.4%. Androgen-deprivation therapy and first-generation antiandrogens (bicalutamide or flutamide) were the most frequently prescribed prostate cancer-related medications at baseline and follow-up in patients with mHSPC. Bicalutamide was the most frequently prescribed prostate cancer-related medication during follow-up in patients with nmCRPC. For mHSPC, inpatient admission costs were the highest, with the median (interquartile range) costs per person-month being USD 403.00 (USD 85.50-1226.20), whereas outpatient visit costs were the highest for nmCRPC (USD 372.60 [USD 139.50-818.50]).

LIMITATIONS:

EMR-based study design did not capture treatment patterns, HRU and associated costs, and healthcare encounters that occurred outside of participating hospitals, which could have led to underestimation of the true disease burden.

CONCLUSIONS:

A contrasting trend of a decline in the prevalence and incidence of mHSPC and an increase in these for nmCRPC was observed between 2015 and 2020 in China. Androgen-deprivation therapy and first-generation antiandrogens were the most frequently prescribed prostate cancer-related medications. Healthcare resource utilization was driven by inpatient costs in mHSPC and outpatient costs in nmCRPC.

2024-12-01·TISSUE & CELL

Bicalutamide reveals immunomodulatory effects in prostate cancer by regulating immunogenic dendritic cell maturation

Article

作者: Nourbakhsh, Niloufar Sadat ; Moghanibashi, Mehdi ; Naeimi, Sirous ; Baradaran, Behzad

Prostate cancer poses a significant global health challenge, ranking as the second most prevalent and fifth most lethal malignancy among males. The intricate interplay between androgen signaling and the immune microenvironment underscores the complexity of prostate cancer progression. Notably, androgen receptor (AR) signaling has been shown to affect immune response mediated by tumor antigen-presenting dendritic cells (DCs). Therefore, this study aimed to explore the potential of Bicalutamide, a nonsteroidal anti-androgen, in modulating DCs-mediated immune responses. Peripheral blood mononuclear cells (PBMCs) were isolated, and monocytes were extracted, followed by their differentiation into immature dendritic cells (iDCs) using GM-CSF and IL-4. Harvested tumor cell lysates from human prostate cancer cells were then utilized to induce the transformation of iDCs into mature dendritic cells (mDCs). Then, mDCs were treated with non-toxic concentration of Bicalutamide determined by annexin V/PI assay. The morphological characteristics of mDCs were investigated using an inverted light microscope. Flow cytometry was used to determine the cell surface expression of molecular markers of DC maturation, and qRT-PCR was employed to evaluate expression levels of proinflammatory genes involved in DC maturation. The obtained results indicated that Bicalutamide treatment of monocyte-derived mDCs induces an immunogenic and matured phenotype, marked by increased expression of CD86 and HLA-DR. Besides, qRT-PCR results evidenced that Bicalutamide decreased the expression of anti-inflammatory genes, including Interleukin-10 (IL-10) and TGF-beta, as an indication of immunogenic DCs. These findings suggest that beyond its established anti-androgen role, Bicalutamide may exert anti-tumor effects through the modulation of DCs-mediated immune responses. This novel immunomodulatory feature holds promise for the development of novel therapies, including combination therapies, in prostate cancer treatment.

2024-12-01·JOURNAL OF HAZARDOUS MATERIALS

Towards sustainable water reuse: A critical review and meta-analysis of emerging chemical contaminants with risk-based evaluation, health hazard prediction and prioritization for assessment of effluent water quality

Review

作者: Stålsby Lundborg, Cecilia ; Khan, Uzair Akbar ; Wiberg, Karin ; Löffler, Paul ; Spilsbury, Francis ; Lai, Foon Yin

Reuse of treated wastewater is necessary to address water shortages in a changing climate. Sustainability of wastewater reuse requires reducing the environmental impacts of contaminants of emerging concern (CECs), but it is being questioned as CECs are not regulated in the assessment of effluent water quality for reuse both nationally in Sweden and at the broader European Union level. There is also a lack of details in this topic on which CECs to be addressed and methodologies to be used for assessing their environmental impacts. A better understanding of the ecological risks and health hazards of CECs associated with wastewater reuse will assist in the development of effective regulations on water reuse, (inter)nationally, as well as related treatment/monitoring guidelines. This review provides a list of specific chemical CECs that hinder sustainable wastewater reuse, and also demonstrates a holistic quantitative methodology for assessing, scoring and prioritizing their associated ecological risks and health hazards posed to the environment and humans. To achieve this, we compile information and concentrations of a wide range of CECs (∼15 000 data entries) identified in Swedish effluent wastewater from domestic (blackwater, greywater, mixture of both) and municipal settings, and further perform a meta-analysis of their potentials for 14 risk and hazard features, consisting of ecological risk, environmental hazard, and human health hazard. The features are then scored against defined criteria including guideline values, followed by score ranking for prioritization. This finally produces a unique list of chemical CECs from high to low priority based on risk- and hazard-evaluations. Out of the priority chemicals, 30, mainly pharmaceuticals, had risk quotient ≥ 1, indicating ecological risk, 16 had environmental hazard being persistent and mobile, and around 60 resulted in positive predictions for at least four human health hazards (particularly skin sensitization, developmental toxicity, hepatoxicity, and carcinogenicity). The 10 highest-priority chemicals (final score 2.3-3.0 out of 4.0) were venlafaxine, bicalutamide, desvenlafaxine, diclofenac, amoxicillin, clarithromycin, diethyltoluamide, genistein, azithromycin, and fexofenadine. Potential crop exposure to selected chemicals following one year of wastewater reuse for agricultural irrigation was also estimated, resulting in a range of 0.04 ng/kg (fluoxetine) to 1160 ng/kg (carbamazepine). Overall, our work will help focus efforts and costs on the critical chemicals in future (waste)water-related studies, such as, to evaluate removal efficiency of advanced treatment technologies and to study upstream source tracing (polluter-pays principle), and also in supporting policymakers to better regulate CECs for sustainable wastewater reuse in the future.

项与比卡鲁胺相关的新闻（医药）

2024-12-12

·ioncology

恩扎卢胺mHSPC适应症成功准入医保，惠及晚期前列腺癌患者全人群

点击蓝字，关注我们 2024年6月25日，中国国家药品监督管理局批准恩扎卢胺软胶囊（安可坦®）治疗转移性激素敏感性前列腺癌（mHSPC），这是恩扎卢胺在中国获批的第三项适应症[1]。至此，恩扎卢胺成为唯一一款适用于mHSPC和CRPC阶段全人群的雄激素受体通路抑制剂（ARPI）[2]。同年11月28日，国家医保局正式公布的《2024版国家医保目录》中，恩扎卢胺的mHSPC新适应症也实现医保准入，将会造福更多前列腺癌患者[3]。 01 荆棘载途转移性前列腺癌患者占比高、预后差，亟需新型治疗方案前列腺癌是中国男性第七大癌症死亡原因，国家癌症中心公布的最新数据显示中国估计有134,200例新发和47,500例死亡病例。同时，其发病率和死亡率均呈持续上升趋势，患者基数大、增长快[4]。目前，mHSPC的治疗方案以雄激素剥夺疗法（ADT）联合ARPI为主，但部分ARPI存在获益人群有限等问题[5, 6]。同时，mHSPC主要为老年患者，存在基础状况差和合并症等情况，疾病管理更加复杂[7, 8]。现有ARPI或存在药物相关不良事件和他汀类药物相互作用，可能会进一步影响患者疗效、安全性和生活质量[9-11]。 02 披荆斩棘恩扎卢胺强效缩瘤，延缓疾病进展，延长总生存期，成为mHSPC全人群的最优选择恩扎卢胺作为全新ARPI，通过“三重阻断”机制（抑制雄激素与雄激素受体（AR）结合，抑制AR核移位以及AR与DNA的相互作用）有效控制肿瘤生长和疾病进展[12]。 2019年ASCO GU大会中首次公布的全球ARCHES研究显示，恩扎卢胺+ADT治疗mHSPC达到主要终点——影像学无进展生存期（rPFS）[13]。与安慰剂+ADT相比，恩扎卢胺+ADT显著降低mHSPC患者61%的影像学进展或死亡风险（HR 0.39，P＜0.001）；同时，恩扎卢胺+ADT可显著缩小瘤体，客观缓解率达到83.1%，36.9%的患者病灶完全消失（83.1% vs 63.7%，P＜0.001）；此外，恩扎卢胺+ADT组患者PSA不可检出应答率（PSA＜0.2 ng/ml）达到68.1%，显著降低87%的PSA进展风险[13]。最终OS分析显示，恩扎卢胺+ADT可显著延长患者生存期，降低34%的死亡风险（HR 0.66，P＜0.0001）[13, 14]。 2023年ESMO大会上首次公布中国ARCHES研究结果，这是目前唯一一项针对中国全人群mHSPC患者展开的III期临床研究[15]。研究结果显示，与安慰剂+ADT相比，恩扎卢胺+ADT可显著降低中国mHSPC患者87%的PSA进展风险（HR 0.13，P＜0.001）[15]。次要终点结果显示，恩扎卢胺+ADT可显著延长影像学无进展生存期，延缓进展至去势抵抗的时间，PSA不可检出应答率高达76.3%，并降低78.6%开始后续新抗肿瘤治疗风险（HR 0.214；P<0.0001）[15]。同时，全球ARCHES研究和中国ARCHES的安全性结果均显示，两个治疗组的治疗期间不良事件发生率相似，无新的安全性信号[13-15]。 03 全面覆盖恩扎卢胺三大联合治疗方案均纳入医保，惠及更多晚期前列腺癌患者本次恩扎卢胺mHSPC新适应症的获批和快速纳入医保也体现了国家对前列腺癌治疗的高度重视。随着医保目录的动态调整，恩扎卢胺覆盖了mHSPC、非转移性去势抵抗性前列腺癌（nmCRPC）、未经化疗的转移性去势抵抗性前列腺癌（mCRPC）三大阶段治疗方案，全球惠及超过1000000患者。恩扎卢胺进入医保，为中国广大晚期前列腺癌患者的治疗和全病程管理提供了更多的选择方案；同时也进一步减轻患者经济负担，惠及更多晚期患者人群[3, 14, 16-18]。参考文献：（滑动查看） [1] 中国医疗保障局. 2024年国家医保药品目录调整申报材料（公示版）. 20241205版. https://www.nhsa.gov.cn/attach/Ypsn2024/YPSN202400193/YPSN202400193.pdf [Z]. [2] 安可坦转移性激素敏感性前列腺癌适应症获批.（20241202）. https://www.astellas.com.cn/zh-hans/news/14671 [Z]. [3] 国家基本医疗保险、工伤保险和生育保险药品目录（2024年） [Z]. [4] HAN B, ZHENG R, ZENG H, et al. Cancer incidence and mortality in China, 2022 [J]. Journal of the National Cancer Center, 2024, 4（1）: 47-53. [5] GU W, HAN W, LUO H, et al. Rezvilutamide versus bicalutamide in combination with androgen-deprivation therapy in patients with high-volume, metastatic, hormone-sensitive prostate cancer （CHART）: a randomised, open-label, phase 3 trial [J]. The Lancet Oncology, 2022, 23（10）: 1249-60. [6] 中国临床肿瘤学会指南工作委员会. 中国临床肿瘤学会（CSCO）前列腺癌诊疗指南 [M]. 北京: 人民卫生出版社, 2024. [7] GOEBELL P J, RAINA R, CHEN S, et al. Real-world treatment of metastatic hormone-sensitive prostate cancer in the USA, Europe and Asia [J]. Future Oncol, 2024, 20（14）: 903-18. [8] BOYLE H J, ALIBHAI S, DECOSTER L, et al. Updated recommendations of the International Society of Geriatric Oncology on prostate cancer management in older patients [J]. Eur J Cancer, 2019, 116: 116-36. [9] BRETAGNE M, LEBRUN-VIGNES B, PARIENTE A, et al. Heart failure and atrial tachyarrhythmia on abiraterone: A pharmacovigilance study [J]. Arch Cardiovasc Dis, 2020, 113（1）. [10] 阿帕他胺片（分包）说明书（202408版）. [Z]. [11] 达罗他胺片说明书（20230315版）. [Z]. [12] HE Y, XU W, XIAO Y-T, et al. Targeting signaling pathways in prostate cancer: mechanisms and clinical trials [J]. Signal Transduction and Targeted Therapy, 2022, 7（1）. [13] ARMSTRONG A J, SZMULEWITZ R Z, PETRYLAK D P, et al. ARCHES: A Randomized, Phase III Study of Androgen Deprivation Therapy With Enzalutamide or Placebo in Men With Metastatic Hormone-Sensitive Prostate Cancer [J]. Journal of Clinical Oncology, 2019, 37（32）: 2974-86. [14] ARMSTRONG A J, AZAD A A, IGUCHI T, et al. Improved Survival With Enzalutamide in Patients With Metastatic Hormone-Sensitive Prostate Cancer [J]. Journal of Clinical Oncology, 2022, 40（15）: 1616-22. [15] ZHOU F, GONGQIAN Z, GUO H, et al. 1795P China ARCHES: A multicenter phase III randomized double-blind placebo （PBO）-controlled efficacy and safety trial of enzalutamide （ENZA） + androgen deprivation therapy （ADT） vs PBO + ADT in Chinese patients （pts） with metastatic hormone-sensitive prostate cancer （mHSPC） [J]. Annals of Oncology, 2023, 34: S971. [16] Internal data from Astella Pharma Inc. [Z]. [17] ARMSTRONG A J, LIN P, TOMBAL B, et al. Five-year Survival Prediction and Safety Outcomes with Enzalutamide in Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer from the PREVAIL Trial [J]. European Urology, 2020, 78（3）: 347-57. [18] STERNBERG C N, FIZAZI K, SAAD F, et al. Enzalutamide and Survival in Nonmetastatic, Castration-Resistant Prostate Cancer [J]. New England Journal of Medicine, 2020, 382（23）: 2197-206. （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。

ASCO会议临床3期临床结果

2024-12-09

·恒瑞医药

2024 ESMO ASIA口头报告│恒瑞创新药瑞维鲁胺治疗转移性激素敏感性前列腺癌不同年龄亚组事后分析结果公布

2024年12月6日，欧洲肿瘤内科学会亚洲年会(ESMO ASIA)在新加坡盛大召开。12月8日，由复旦大学附属肿瘤医院叶定伟教授牵头开展的国际性III期临床研究——CHART研究公布了一项年龄亚组的事后分析结果，即瑞维鲁胺联合雄激素剥夺疗法(ADT)在≤64岁、65-74岁和≥75岁高瘤负荷转移性激素敏感性前列腺癌(mHSPC)患者中的疗效和安全性。南京鼓楼医院邱雪峰教授在新加坡大会现场进行口头报告，本次分析表明，瑞维鲁胺联合ADT对所有年龄段的转移性激素敏感性前列腺癌(mHSPC)患者均有效且耐受性良好[1]。 2024 ESMO ASIA现场：邱雪峰教授进行口头报告 01 研究背景 2023年美国癌症协会公布的数据显示，前列腺癌(29%)、肺癌(12%)和结直肠癌(8%)约占男性所有新诊断癌症病例的一半，其中，前列腺癌居首位。男性患者中，前列腺癌(11%)预计死亡患者占比仅次于肺癌(21%)。2014年-2019年全球前列腺癌发病呈现每年3%的增长趋势[2]，疾病负担逐渐加重。瑞维鲁胺是恒瑞医药潜心研发的一种新型口服雄激素受体抑制剂，靶向雄激素受体轴，而雄激素受体轴是前列腺癌生长和进展的关键驱动因素[3,4]。随机III期CHART研究(NCT03520478)的中期分析表明，在mHSPC患者中，瑞维鲁胺+ADT相较对照组（比卡鲁胺+ADT）显著改善了影像学无进展生存期(rPFS)和总生存期(OS)，且具有良好的安全性[5]。基于CHART试验，瑞维鲁胺+ADT疗法于2022年在中国获批用于治疗高瘤负荷的转移性激素敏感性前列腺癌（mHSPC）患者。 02 研究方法研究纳入ECOG评分0或1，高瘤负荷，既往无ADT、化疗、手术或局部治疗的654例前列腺癌患者。按1:1随机分组，每日一次240mg口服瑞维鲁胺+ADT或比卡鲁胺+ADT。研究主要终点为rPFS(独立评审委员会[IRC)评估)和OS，次要终点为rPFS(研究者[INV)评估)、至前列腺特异抗原(PSA)进展时间、至下一次手术相关事件的时间、至开始新抗肿瘤治疗的时间、客观缓解率(ORR)和安全性。本次分析了不同年龄组中瑞维鲁胺+ADT与对照组的疗效及安全性。图1. 研究设计 03 研究结果 1．临床疗效在所有三个年龄组(≤64岁、65-74岁和≥75岁)中，瑞维鲁胺+ADT组相较于对照组均改善了患者的rPFS和总生存期(OS)，在健康状况较差的老年患者(≥75岁且ECOG评分为1)中也是如此(图2-3)。图2. 不同年龄亚组的rPFS分析图3. 不同年龄亚组的OS分析在所有3个年龄组(≤64岁、65-74岁和≥75岁)以及健康状况较差的老年患者(≥75岁且ECOG评分为1)中，在延迟PSA进展方面，瑞维鲁胺+ADT组也优于对照组(图4)。图4. 不同年龄亚组至PSA进展时间分析无论是在哪个年龄亚组，瑞维鲁胺+ADT组的PSA未检出率均高于对照组(图5)。图5. 不同年龄亚组PSA未检出率分析 2．安全性尽管瑞维鲁胺联合雄激素剥夺疗法的暴露时间更长(相较于对照组长2.0-2.3倍)，但瑞维鲁胺+ADT组和对照组在三个年龄组以及健康状况较差的老年患者中的安全性概况大致相似。 04 研究结论本次结果表明，瑞维鲁胺联合ADT对所有年龄段的mHSPC患者均有效且耐受性良好。与对照组相比，患者的rPFS和OS均获得改善，至PSA进展时间更长且PSA未检出率更高，瑞维鲁胺联合ADT为患者取得更多临床获益。在安全性方面，瑞维鲁胺联合ADT与对照组在三个年龄组中的安全性概况相似，即使在健康状况较差的老年患者中也有效且耐受性好。这项事后分析结果进一步支持瑞维鲁胺联合ADT作为高瘤负荷mHSPC的一种治疗选择。参考文献： [1]Xuefeng Qiu, Dingwei Ye, et al.Efficacy and safety of rezvilutamide (Rez) plus androgen-deprivation therapy (ADT) in patients with high-volume, metastatic, hormone-sensitive prostate cancer (mHSPC) aged ≤64, 65–74, and ≥75 years: Post-hoc analysis of randomized phase 3 CHART trial.2024 ESMO ASIA. Abstract 337MO. [2]Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023 Jan;73(1):17-48. [3]Singh K, Mandal S, Nayak P, Das M, Tripathy S. Rezvilutamide for metastatic hormone-sensitive prostate cancer. Lancet Oncol. 2022;23(11):e490. [4]Keam SJ. Rezvilutamide: First Approval. Drugs. 2023;83(2):189-193. [5]Gu W, Han W, Luo H, et al. Rezvilutamide versus bicalutamide in combination with androgen-deprivation therapy in patients with high-volume, metastatic, hormone-sensitive prostate cancer (CHART): a randomised, open-label, phase 3 trial. Lancet Oncol. 2022;23(10):1249-1260. 声明： 1.本新闻旨在分享学术前沿动态，仅供医疗卫生专业人士基于学术目的参阅，非广告用途。 2.恒瑞医药不对任何药品和/或适应症作推荐。 3.本新闻中涉及的信息仅供参考，请遵从医生或其他医疗卫生专业人士的意见或指导。医疗卫生专业人士作出的任何与治疗有关的决定应根据患者的具体情况并遵照药品说明书。撰稿：肿瘤中央医学事务部排版：程梦真责编：李玉莹往期精选 | 研发创新 | 慢病创新里程碑！恒瑞首个自免创新药夫那奇珠单抗获批上市恒瑞医药新突破！中国首个自研阿片类镇痛创新药富马酸泰吉利定获批上市 | 国际化 | 海外BD再传捷报！恒瑞医药GLP-1类创新药组合实现海外许可恒瑞医药与默克达成合作，携手推进癌症创新疗法 | 重磅奖项 | 喜报！恒瑞医药荣获2023年度国家科技进步奖恒瑞医药连续六年入选全球制药企业50强榜单！ | 社会公益 | “健康中国行·重走长征路”项目启动仪式圆满举行！恒瑞提供公益支持，助力健康中国恒瑞医药集团向中国扶贫基金会捐赠3000万设立“健康帮扶基金”

临床3期临床成功临床结果

2024-12-02

·恒瑞医药

恒瑞创新药氟唑帕利单药或氟唑帕利联合阿帕替尼乳腺癌2项新适应症获批上市

近日，恒瑞医药收到国家药品监督管理局核准签发氟唑帕利胶囊和甲磺酸阿帕替尼片的《药品注册证书》，批准增加适应症：氟唑帕利单药或联合甲磺酸阿帕替尼用于新辅助、辅助或转移阶段接受过化疗治疗的伴有胚系BRCA突变（gBRCAm）的人表皮生长因子受体（HER2）阴性转移性乳腺癌成年患者。激素受体(HR)阳性乳腺癌患者既往需接受过内分泌治疗或被认为不适合接受内分泌治疗。此前该适应症被国家药监局药品审评中心纳入优先审评。本次适应症获批上市，是基于一项氟唑帕利单药或联合阿帕替尼治疗gBRCA突变的人表皮生长因子受体2（HER2）阴性乳腺癌的Ⅲ期临床试验（FABULOUS研究），研究结果显示：与标准化疗相比，氟唑帕利联合阿帕替尼或氟唑帕利单药均显著改善BICR评估的无进展生存期（PFS），同时也显示出总生存期（OS）获益趋势[1]。这是氟唑帕利获批上市的第4及第5个适应症（单药或联合），阿帕替尼获批上市的第4个适应症，将为HER2阴性转移性乳腺癌患者提供新的治疗选择。 1 BRCA突变乳腺癌治疗需求迫切根据2020年世界卫生组织国际癌症研究机构（IARC）发布的数据，乳腺癌已成为全球第一大恶性肿瘤，是女性最常见的恶性肿瘤之一[2]。目前国内患者乳腺癌发病率增长迅速，已经位列女性肿瘤发病谱首位，并且近50%患者治疗后会出现复发和转移。人类乳腺癌易感基因（BRCA）是人体内重要的抑癌基因，包括BRCA1、BRCA2等。相较于一般人群，BRCA1和BRCA2基因突变携带者乳腺癌发病风险提高了10~20倍[3]。而在乳腺癌患者中，约5%～10%的患者携带突变的BRCA基因[4]，且BRCA突变乳腺癌患者往往分期较高，预后较差。我国BRCA基因突变的乳腺癌治疗仍以铂类化疗为主，缺乏有效的治疗手段。 2 FABULOUS研究为乳腺癌治疗带来新获益本次适应症获批上市，是基于一项氟唑帕利单药或联合阿帕替尼治疗gBRCA突变的人表皮生长因子受体2（HER2）阴性乳腺癌的Ⅲ期临床试验（FABULOUS研究）[1]，由中山大学孙逸仙纪念医院宋尔卫教授及北京大学肿瘤医院李惠平教授担任主要研究者，全国59家中心共同参与。研究主要终点为根据盲态独立中心审查(BICR)评估的无进展生存期（PFS），次要终点为根据研究者评估的无进展生存期（PFS）、至疾病再次进展/死亡时间（PFS-2）、客观缓解率（ORR）、疾病控制率（DCR）、持续缓解时间（DoR）、总生存期（OS）和安全性。主要目标为评估氟唑帕利联合阿帕替尼及氟唑帕利单药在BICR评估的PFS方面相比化疗的潜在优势，以及联合治疗相比单药的优势。研究将入组患者按1∶1∶1比例随机分配至氟唑帕利（100mg bid）联合阿帕替尼（500mg qd）、氟唑帕利（150mg bid）或标准化疗方案进行治疗。其中，在化疗组中，患者在经BICR评估为疾病进展（PD）后，允许转为接受氟唑帕利单药治疗。截至本次数据分析时，研究已达到主要终点和关键次要终点。与标准化疗相比，氟唑帕利联合阿帕替尼或氟唑帕利单药均显著改善BICR评估的无进展生存期（PFS），同时氟唑帕利联合阿帕替尼进一步优于氟唑帕利单药。氟唑帕利联合阿帕替尼组较标准化疗组经BIRC评估PFS显著延长（mPFS 11.0个月vs 2.8个月；HR：0.282；95%CI：0.179-0.445；单侧P<0.0001），疾病进展风险降低71.8%；氟唑帕利单药组较标准化疗组经BIRC评估PFS显著延长（mPFS 6.7个月vs 2.8个月；HR：0.493；95%CI：0.320–0.758；单侧P=0.0005），疾病进展风险降低50.7%；氟唑帕利联合阿帕替尼组较氟唑帕利单药组经BIRC评估PFS显著延长（HR：0.608；95% CI：0.400–0.923；单侧P=0.0092）。氟唑帕利联合阿帕替尼组、氟唑帕利单药组及化疗组的客观缓解率（ORR）分别为66.7%、43.6%及21.4%。在OS方面，尽管数据尚未成熟，但与标准化疗相比，氟唑帕利联合阿帕替尼（HR：0.597；95%CI：0.334-1.064）或氟唑帕利单药（HR：0.629；95%CI：0.355-1.116）显示出OS获益趋势。在安全性方面，整体来看，患者对治疗的整体耐受性良好，未发生新的安全性信号[1]。 3 恒瑞医药持续满足临床急需，惠及更多患者氟唑帕利是恒瑞医药研发的一种新型口服聚腺苷二磷酸核糖聚合酶（PARP）抑制剂，是中国首个自主原研的PARP抑制剂，于2020年12月获批上市，可特异性杀伤BRCA突变的肿瘤细胞。氟唑帕利此前已获批3个适应症，分别为：2020年12月获批用于既往经过二线及以上化疗的伴有胚系BRCA突变(gBRCAm)的铂敏感复发性卵巢癌、输卵管癌或原发性腹膜癌患者的治疗；2021年6月获批用于铂敏感的复发性上皮性卵巢癌、输卵管癌或原发性腹膜癌成人患者在含铂化疗达到完全缓解或部分缓解后的维持治疗；2024年5月获批用于晚期上皮性卵巢癌、输卵管癌或原发性腹膜癌成人患者在一线含铂化疗达到完全缓解或部分缓解后的维持治疗。阿帕替尼是恒瑞医药自主研发的一款针对血管内皮生长因子受体（VEGFR）的小分子酪氨酸激酶抑制剂，于2014年10月获批上市。甲磺酸阿帕替尼片此前已获批3个适应症，分别为：2014年10月获批单药用于既往至少接受过2种系统化疗后进展或复发的晚期胃腺癌或胃-食管结合部腺癌患者的治疗；2020年12月获批单药用于既往接受过至少一线系统性治疗后失败或不可耐受的晚期肝细胞癌患者的治疗；2023年1月获批联合注射用卡瑞利珠单抗用于不可切除或转移性肝细胞癌患者的一线治疗。多年来，恒瑞医药深刻关注中国乳腺癌领域的治疗现状，持续探索更多乳腺癌治疗方案。除氟唑帕利和阿帕替尼外，目前公司仍有多款不同作用机制的创新产品布局乳腺癌治疗领域，覆盖了乳腺癌各亚型及晚期、辅助、新辅助各疾病阶段，多个乳腺癌相关适应症已被国家药品监督管理局药品审评中心纳入突破性疗法认定。未来，恒瑞医药将始终坚持以患者为中心，聚焦乳腺癌等多个肿瘤领域，加强创新药研究与开发，力争研制出更多更好的乳腺癌防治新药，为广大患者带来新的治疗选择。参考文献： [1].氟唑帕利胶囊、甲磺酸阿帕替尼片药品说明书 202412. [2].GLOBOCAN database. Accessed August 2020. [3].Dias Nunes J, Demeestere I, Devos M. BRCA Mutations and Fertility Preservation. Int J Mol Sci. 2023 Dec 22;25(1):204. [4].Lang G T, Shi J X, Hu X, et al. The spectrum of BRCA mutations and characteristics of BRCA‐associated breast cancers in China: Screening of 2,991 patients and 1,043 controls by next‐generation sequencing[J]. International journal of cancer, 2017, 141(1): 129-142. 声明： 1.本新闻旨在分享研发注册进展，仅供医疗卫生专业人士参阅，非广告用途。 2.恒瑞医药不对任何药品和/或适应症作推荐。 3.本新闻中涉及的信息仅供参考，请遵从医生或其他医疗卫生专业人士的意见或指导。医疗卫生专业人士作出的任何与治疗有关的决定应根据患者的具体情况并遵照药品说明书。撰稿：王昱婷靳云鹏排版：程梦真责编：王玲往期精选 | 研发创新 | 慢病创新里程碑！恒瑞首个自免创新药夫那奇珠单抗获批上市恒瑞医药新突破！中国首个自研阿片类镇痛创新药富马酸泰吉利定获批上市 | 国际化 | 海外BD再传捷报！恒瑞医药GLP-1类创新药组合实现海外许可恒瑞医药与默克达成合作，携手推进癌症创新疗法 | 重磅奖项 | 喜报！恒瑞医药荣获2023年度国家科技进步奖恒瑞医药连续六年入选全球制药企业50强榜单！ | 社会公益 | “健康中国行·重走长征路”项目启动仪式圆满举行！恒瑞提供公益支持，助力健康中国恒瑞医药集团向中国扶贫基金会捐赠3000万设立“健康帮扶基金”

临床3期上市批准优先审批临床结果

100 项与比卡鲁胺相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D00961	比卡鲁胺	L02BB03	DB01128

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
转移性前列腺癌	美国	ANI Pharmaceuticals, Inc.	1995-10-04
前列腺癌	英国	阿斯利康制药有限公司	1995-02-23

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
男子乳腺发育	临床3期	意大利	AstraZeneca PLC	2003-12-01
非转移性前列腺癌	临床3期	美国	AstraZeneca PLC	1995-08-01
非转移性前列腺癌	临床3期	加拿大	AstraZeneca PLC	1995-08-01
晚期前列腺癌	临床3期	美国	AstraZeneca PLC	1994-12-01
转移性乳腺癌	临床2期	美国	AstraZeneca PLC	2007-03-23
近端肾小管性酸中毒伴有眼部异常和智力低下	临床2期	美国	AstraZeneca PLC	2007-03-23
家族性睾丸毒症	临床2期	美国	AstraZeneca PLC	2004-11-22
家族性睾丸毒症	临床2期	加拿大	AstraZeneca PLC	2004-11-22
家族性睾丸毒症	临床2期	法国	AstraZeneca PLC	2004-11-22
家族性睾丸毒症	临床2期	印度	AstraZeneca PLC	2004-11-22

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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


ATS2024	N/A	肺损伤	-	Casodex	膚範築製遞簾網鑰範繭(憲選衊壓遞窪淵鑰餘淵) = pH 7.42, PCO2 32, and PO2 66 遞鏇鹽蓋繭廠築選糧餘 (鏇壓窪鬱壓憲廠鑰餘廠 ) 更多	-	2024-05-19
AUA2024 人工标引	临床2期	去势抵抗性前列腺癌 ERBB3 Expression	28	Bicalutamide+RAD001	齋築衊餘鏇觸艱襯鏇膚(網構夢膚築夢鬱膚築簾) = Patients with higher serum levels of ErbB3 exhibited a better response to the bicalutamide+RAD001 treatment 壓顧製顧觸醖製鹽鏇齋 (觸衊鏇積餘遞衊廠衊衊 ) 更多	积极	2024-05-01
				Bicalutamide+RAD001(low serum ErbB3)
NCT03141671 (FORMULA-509, ASCO_GU2024) 人工标引	临床2期	前列腺癌	345	GnRH + Bicalutamide	顧築齋壓願憲廠襯膚網(範繭簾鏇壓膚築鏇艱鏇) = 構鬱鹹繭夢衊齋夢膚廠淵積餘積壓選齋鑰醖遞 (餘廠積積衊築遞鑰鬱夢 ) 更多	积极	2024-01-25
				GnRH+Abiraterone+Apalutamide+Prednisone	顧築齋壓願憲廠襯膚網(範繭簾鏇壓膚築鏇艱鏇) = 蓋製積窪醖餘鹹淵鹽夢淵積餘積壓選齋鑰醖遞 (餘廠積積衊築遞鑰鬱夢 ) 更多
NCT00002874 (ASCO_GU2024) 人工标引	临床3期	前列腺癌	760	RT + bicalutamide	窪襯鏇鏇範衊淵選鏇鹽(構網簾壓衊廠蓋淵選築) = 衊醖鹽餘簾積選願壓壓築築網鹹網糧築鑰壓範 (廠齋鬱遞選鹹製衊襯鏇, 47 ~ 58) 更多	积极	2024-01-25
				RT + placebo	窪襯鏇鏇範衊淵選鏇鹽(構網簾壓衊廠蓋淵選築) = 願構獵顧襯襯顧選網構築築網鹹網糧築鑰壓範 (廠齋鬱遞選鹹製衊襯鏇, 38 ~ 48) 更多
ASCO_GU2024	N/A	去势抵抗性前列腺癌	-	Bicalutamide and dutasteride	醖膚鏇鹽餘艱憲積繭鹽(餘築醖醖齋鏇繭顧顧淵) = 壓觸鏇鹹齋獵顧夢醖窪壓鹹構範製廠繭憲構範 (壓選鏇範築願繭獵醖獵 ) 更多	-	2024-01-25
NCT03141671 (FORMULA-509, Pubmed \| Int J Radiat Oncol Biol Phys)	临床2期	视网膜色素变性 Gleason 8-10 \| pT3/T4 \| pN1 ... 更多	-	Bicalutamide	觸範鹽積鹹艱繭鹹蓋鏇(範糧願鏇鑰壓積積淵觸): HR = 0.71 (90% CI, 0.49 ~ 1.03), P-Value = 0.06 更多	积极	2023-10-01
				Abiraterone Acetate/Prednisone (AAP) and Apalutamide (Apa)
NCT03043807 (CTgov)	临床2期	寡转移性前列腺癌	26	Radiation+Abiraterone Acetate+Docetaxel+Bicalutamide+Leuprolide Acetate	齋觸糧鹽構觸範糧鏇艱(壓鏇觸齋壓鏇餘選蓋鹹) = 夢選繭鏇鏇範繭襯遞繭廠鬱鏇艱蓋鏇製衊夢襯 (鑰遞餘窪獵網遞衊膚鬱, 鏇鹽簾遞齋壓積觸顧觸 ~ 構顧範醖遞遞觸觸選鬱) 更多	-	2023-02-16
PROSPERO (ASTRO2022)	N/A	前列腺癌	5,336	Bicalutamide (Standard of care (SOC) + ADT)	壓襯顧製廠齋製蓋遞觸(獵壓襯壓餘壓窪觸醖觸): HR = 0.83 (95% CI, 0.72 ~ 0.96) 更多	不佳	2022-11-01
				Standard of care (SOC) + Bicalutamide monotherapy (BICmono)
NCT02716974 (oligo-mets, CTgov)	临床2期	寡转移性前列腺癌	26	Prostatectomy+Docetaxel+Bicalutamide+Leuprolide Acetate	蓋鹹壓範醖範鬱艱餘鏇(窪壓願製網積壓獵廠鬱) = 積廠簾衊鹽廠積構淵糧壓願鏇淵膚遞憲獵窪築 (蓋憲齋遞衊鹹顧選餘廠, 醖餘衊鏇鑰襯廠簾餘襯 ~ 廠艱簾簾夢淵憲壓齋衊) 更多	-	2022-08-04
NCT00468715 (CTgov)	临床2期	转移性乳腺癌 \| 近端肾小管性酸中毒伴有眼部异常和智力低下	28	immunohistochemistry staining method+bicalutamide	鏇觸遞糧鹽遞鹽夢鏇簾(鏇廠餘襯襯顧鹹醖窪範) = 遞餘壓鹹襯選選襯簾窪襯膚糧淵構壓壓壓積憲 (繭膚鬱築廠鏇糧簾衊鹽, 鹽廠鹹齋選襯襯願網網 ~ 淵窪網鬱蓋鹹齋遞夢糧) 更多	-	2022-08-03