Elacestrant Versus Standard Endocrine Therapy in Women and Men With Node-positive, Estrogen Receptor-positive, HER2-negative, Early Breast Cancer With High Risk of Recurrence-A Global, Multicenter, Randomized, Open-label Phase 3 Study

The primary goal of this study is to evaluate the effectiveness of elacestrant versus standard endocrine therapy in participants with node-positive, Estrogen Receptor-positive (ER+), Human Epidermal Growth Factor-2 negative (HER2-) early breast cancer with high risk of recurrence.

开始日期2024-09-27

申办/合作机构

Stemline Therapeutics, Inc.

NCT06086704 / Recruiting临床2期IIT

Phase II Study of 18F-FFNP Breast PET/MRI in the Assessment of Early Response of Breast Cancer to Presurgical Endocrine Therapy

This clinical trial will investigate an estrogen-regulated parameter as an early measure of endocrine therapy response: progesterone receptor (PR) protein with a progestin-based radioligand, 18F-fluorofuranylnorprogesterone (18F-FFNP). The overall purpose of this research is to test the efficacy of 18F-FFNP PET/MRI for predicting response to presurgical endocrine therapy and to determine the quantitative reliability of 18F-FFNP breast PET/MRI in patients with newly diagnosed PR+ primary breast cancer.

开始日期2024-09-25

申办/合作机构

University of Wisconsin Madison

[+1]

NCT06179303 / Suspended临床2期IIT

A Phase II Trial to Evaluate Functional Imaging in Prediction of Response to Abemaciclib for Advanced Hormone Receptor-Positive, HER2-Negative Breast Cancer

This phase II trial tests the accuracy of functional imaging (FFNP)-positron emission tomography (PET)/computed tomography (CT) to predict response to abemaciclib plus endocrine therapy. Abemaciclib is a drug used to treat certain types of hormone receptor positive (HR+), HER2 negative breast cancer. Abemaciclib blocks certain proteins, which may help keep tumor cells from growing. Endocrine therapy adds, blocks, or removes hormones that can cause cancer to grow. FFNP PET imaging is a form of x-ray that uses FFNP as an imaging agent that may provide more precise information about the location of tumors that "light up" with FFNP than a PET scan alone can provide.

开始日期2024-07-22

申办/合作机构

University of Washington

[+1]

100 项与阿那曲唑相关的临床结果

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100 项与阿那曲唑相关的转化医学

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100 项与阿那曲唑相关的专利（医药）

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2,164

项与阿那曲唑相关的文献（医药）

2024-11-01·BREAST CANCER RESEARCH AND TREATMENT

Ovarian function recovery in breast cancer patients receiving adjuvant anastrozole treatment: updated results from the phase 3 DATA trial

Article

作者: Lammers, Senna W. M. ; Vriens, Ingeborg J. H. ; on behalf of the Dutch Breast Cancer Research Group for the DATA investigators ; Kroep, Judith R. ; van den Berkmortel, Franchette W. P. J. ; Imholz, Alexander L. T. ; Hermans, Karlijn E. P. E. ; Geurts, Sandra M. E. ; Tjan-Heijnen, Vivianne C. G. ; Swinkels, Astrid C. P. ; van der Sangen, Maurice J. C. ; Honkoop, Aafke H. ; Smorenburg, Carolien H. ; de Roos, Wilfred K. ; van Hellemond, Irene E. G.

Abstract:

Purpose:

Patients with chemotherapy-induced ovarian function failure (CIOFF) may experience ovarian function recovery (OFR). Earlier, we showed that OFR during treatment with anastrozole impacted the prognosis of hormone receptor-positive (HR+) breast cancer (BC) patients with CIOFF. Here, we present the long-term follow-up results.

Methods:

Postmenopausal women with HR+ BC who were 45–57 years of age and received chemotherapy were identified from the phase 3 DATA study (NCT00301457) on the extended use of anastrozole. Eligible patients were categorised into two groups: patients with CIOFF and definitely postmenopausal patients. Patients with CIOFF were monitored for OFR. Disease-free survival (DFS), distant recurrence-free survival (DRFS), and overall survival (OS) were compared between patients with OFR and patients without OFR using multivariable Cox regression analyses, including OFR as a time-dependent covariate. BC-specific mortality (BCSM) was compared between groups using the Fine and Gray method.

Results:

This study included 656 patients: 395 patients with CIOFF and 261 definitely postmenopausal patients. OFR occurred in 39 (12%) of 329 patients with CIOFF who were monitored for OFR. The median follow-up time was 13.3 years. Patients with OFR experienced a deterioration in DFS (hazard ratio (HR) = 1.54; 95% confidence interval (CI) 0.85–2.81), DRFS (HR = 1.51; 95% CI 0.73–3.11), OS (HR = 1.64; 95% CI 0.75–3.55), and BCSM (subdistribution HR = 1.98; 95% CI 0.84–4.63) when compared with patients without OFR.

Conclusion:

In patients with CIOFF, OFR during treatment with anastrozole was associated with a deterioration in BC outcomes. These findings underscore the importance of adequate ovarian function suppression in this subgroup of patients.

2024-11-01·AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE

Pulmonary Hypertension and Anastrozole (PHANTOM): A Randomized, Double-Blind, Placebo-Controlled Trial

Article

作者: Austin, Eric ; MacLean, Margaret ; Hemnes, Anna ; Minhas, Jasleen ; Lin, Grace ; Zamanian, Roham ; Mathai, Stephen C. ; Andrew, Ruth ; Ellenberg, Susan S. ; Song, Nianfu ; Stasinopoulos, Ioannis ; DeMichele, Angela ; Moutchia, Jude ; Feng, Rui ; Shou, Haochang ; Bull, Todd ; Ventetuolo, Corey E. ; Chakinala, Murali ; Kawut, Steven M. ; Doyle, Margaret

Rationale: Inhibition of aromatase with anastrozole reduces pulmonary hypertension in experimental models. Objectives: We aimed to determine whether anastrozole improved the 6-minute-walk distance (6MWD) at 6 months in pulmonary arterial hypertension (PAH). Methods: We performed a randomized, double-blind, placebo-controlled phase II clinical trial of anastrozole in subjects with PAH at seven centers. Eighty-four postmenopausal women with PAH and men with PAH were randomized in a 1:1 ratio to receive anastrozole 1 mg or placebo by mouth daily, stratified by sex using permuted blocks of variable sizes. All subjects and study staff were masked. The primary outcome was the change from baseline in 6MWD at 6 months. By intention-to-treat analysis, we estimated the treatment effect of anastrozole using linear regression models adjusted for sex and baseline 6MWD. Assuming 10% loss to follow-up, we anticipated having 80% power to detect a difference in the change in 6MWD of 22 meters. Measurements and Main Results: Forty-one subjects were randomized to placebo and 43 to anastrozole, and all received the allocated treatment. Three subjects in the placebo group and two in the anastrozole group discontinued the study drug. There was no significant difference in the change in 6MWD at 6 months (placebo-corrected treatment effect, -7.9 m; 95% confidence interval, -32.7 to 16.9; P = 0.53). There was no difference in adverse events between the groups. Conclusions: Anastrozole did not show a significant effect on 6MWD compared with placebo in postmenopausal women with PAH and in men with PAH. Anastrozole was safe and did not have adverse effects. Clinical trial registered with www.clincialtrials.gov (NCT03229499).

2024-10-01·Canadian journal of ophthalmology. Journal canadien d'ophtalmologie

Risk of ocular adverse events with aromatase inhibitors

Article

作者: Liu, Victoria ; Sriranganathan, Aswen ; Feng, Zhao Xun ; Etminan, Mahyar ; Maberley, David ; Lo, Cody

OBJECTIVE:

Aromatase inhibitors (AIs) are a class of medications used for adjuvant treatment of breast cancer. Recent case reports suggest that AIs may be associated with various ocular adverse events (AEs). This study evaluates the risk of ocular AEs in patients who take AIs.

METHOD:

Disproportionality analysis was performed using data from the U.S. Food and Drug Administration's Adverse Events Reporting System database from 2004 to 2022. All cases of vitreomacular traction, macular edema, retinal deposits, retinal artery occlusion, macular hole, retinal hemorrhage, uveitis, retinal tear, retinal detachment, dry eye disease, blepharitis, and optic neuropathy were searched for the 3 AIs anastrozole, letrozole, and exemestane. A search also was performed on trastuzumab as a control. Reported odds ratios (RORs) and corresponding 95% CIs were computed.

RESULTS:

We identified 322 ocular AEs of interest for the 3 AIs and 55 for trastuzumab. Anastrozole had the most AEs (n = 163) and was found to have strong associations with vitreomacular traction (ROR = 665; 95% CI, 352-1255), macular edema (ROR = 37; 95% CI, 25-54), retinal deposits (ROR = 11; 95% CI, 2-77), and uveitis (ROR = 6; 95% CI, 4-9). Letrozole had strong associations with retinal deposits (ROR = 8, 95% CI, 1-57) and retinal artery occlusion (ROR = 6; 95% CI, 3-11). Exemestane had a strong association with macular holes (ROR = 10; 95% CI, 3-30).

CONCLUSION:

Disproportionality analysis revealed an increased risk of ocular AEs with each of the AIs. This study calls for clinicians, especially oncologists and ophthalmologists, to be vigilant in patients who are on AI therapy, allowing them to provide prompt interventions to mitigate further ocular morbidities.

151

项与阿那曲唑相关的新闻（医药）

22 小时之前

·CPHI制药在线

KRAS突变新希望！Avutometinib与defactinib组合治疗KRAS突变复发性低级别浆液性卵巢癌获FDA授予孤儿药

关注并星标CPHI制药在线 2024年3月,美国食品药品管理局（FDA）赋予了 Avutometinib（VS-6766）单独或者和FAK 抑制剂Defactinib（VS-6063）联合用于治疗复发性低级别浆液性卵巢癌患者的孤儿药资格，此称号象征着针对该卵巢癌的治疗取得了关键的进展，当下这种亚型肿瘤尚未拥有获得FDA批准的疗法。在和美国食品药品监督管理局（FDA）开展了 A类会议之后，VerastemOncology 计划于2024 年10 月完成新药申请（NDA），请求批准联合药物Avutometinib（VS-6766）与 defactinib（VS-6063）应用于治疗复发性低级别浆液性卵巢癌的成年患者，这些患者必须经历过至少 1线系统治疗并且携带有 KRAS突变。卵巢癌作为在女性生殖系统当中一个相当棘手的恶性肿瘤，长时间以来为患者以及医疗领域造成了巨大的难题。依据众多的医学研究数据显示，低级别浆液性卵巢癌是一种并不常见的癌症类别，常常和RAS/MAPK 通路的变异存在关联，在所有新出现的上皮性卵巢癌当中所占比例不足 10%。目前，对于这类疾病现有的治疗方式的客观缓解率（ORR）波动较大，处于0%至26%之间。这种尚未被满足的治疗需求推动了对于 Avutometinib这种全新口服 RAF/MEK抑制剂的进一步探索。 #01 kras突变 RAS是最著名的原癌基因(proto-oncogenes)之一，近30%的肿瘤携带RAS变异，而KRAS是RAS家族中最常出现的亚型，KRAS基因突变占RAS基因突变总数的85%，NRAS(12%)次之，HRAS(3%)。在过去的三十年中，持续的努力未能开发出批准的KRAs突变癌症治疗方法。RAS 家族中的 NRAS、HRAS 和 KRAS 突变是与癌症相关的常见基因突变。在人类癌症中，KRAS基因突变出现在接近70%的胰腺癌中，30-50%的结肠癌中，17%的子宫内膜癌中，20%的肺癌中。它也会在胆管癌、宫颈癌、黑色素瘤等癌症类型中出现。在KRAS的基因突变中，97%是第12号或者第13号氨基酸残基发生了突变。其中最主要的是G12D、G12V、G13D这三种突变。这些基因突变大多干扰KRAS水解GTP的能力。有KRAS激活突变的肿瘤病人，预后一般也不太好，生存期往往会明显短于那些没有KRAS激活突变的病人。当KRAS发生G12D、G12V、G13D这几种突变后，会通过破坏GAP活性，KRAS会一直保持与GTP结合，将KRAS锁定在有酪氨酸激酶活跃状态，并不断激活下游信号通路（如PI3K，RAF-MEK-ERK（MAPK），RAL-GEF等）。下游的信号通路打开之后，刺激细胞增殖、迁移，最终形成恶性肿瘤。致癌的KRAS基因突变除了直接促进肿瘤细胞的增殖和生存以外，对TME也会产生影响。致癌性KRAS以旁分泌方式诱导影响基质周围的细胞（如成纤维细胞，先天性和适应性免疫细胞），这些基质细胞反过来又促进了癌症的恶性。 RAS 信号通路以及相关靶点药物图片来源：参考文献1 #02 Avutometinib和Defactinib Avutometinib（VS-6766）属于一种 RAF/MEK 抑制剂，它借助形成无活性的复合物，对 ARAF、BRAF以及 CRAF的活性予以阻断，进而强化对RAS/MAPK 信号通路的抑制效能。此药物由 Verastem Oncology公司所研发，当下在美国和中国均未获取批准上市的许可。纵然面临若干挑战，不过 Avutometinib 的潜能与相关研究依旧在推进，尤其是在和 FAK抑制剂 Defactinib 的联合治疗方面呈现出了乐观的研究展望。 Defactinib 身为一类特定的 FAK抑制剂，所瞄准的是一条已知的信号通路，这条通路和对多种抗癌药物形成耐药性存在关联。 #03 Avutometinib+Defactinib临床疗效数据 2023年的 ASCO 年会上展示了 2期 RAMP201试验（NCT04625270）的相关数据。RAMP201 属于一项 2期、以开放标签形式进行、随机开展的研究，旨在探究 Avutometinib与 Defactinib联合疗法对伴有或未伴有KRAS 突变的复发性低级别浆液性卵巢癌患者所起到的作用。此项研究预计将吸纳225名患者，预期完成的时间设定在 2026年 12月。RAMP201 汇集了以往接受过化疗并且按照 RECISTv1.1标准具备可量测病症的复发性低级别浆液性卵巢癌患者。需要着重指出的是，先前接受过 MEK 抑制剂治疗的患者能够参与此治疗。患者必须是在从前至少经历过一次全身性治疗后产生疾病进展或者复发，ECOG表现为1 级及以下，器官功能处于正常状态，之前治疗带来的毒性反应已经完全消退，同时同意对具备生育能力的患者实施高效避孕手段，这样才满足参与该项研究的要求。假如患者在研究启动前 4周内接受过全身性抗癌治疗、同时患有高级别卵巢癌、存在有症状的脑转移、有具有医学意义的横纹肌溶解病史或者同时罹患心脏病或者阻塞性肺病，那么就不符合参与试验的条件。患者被随机划分成接受Avutometinib单独治疗或者是 Avutometinib 与 Defactinib 联合治疗。在研究的 A 部分以及 B 部分当中，患者被安排独自接受 Avutometinib或者与 Defactinib 联合进行治疗。采用单药治疗的患者每周口服 Avutometinib 两次，每次剂量为4 毫克，治疗周期为3 周用药，1周停药。在联合治疗组内，Avutometinib 的剂量为每周两次，每次3.2毫克，同时口服 200 毫克的Defactinib，每天一次，按照3 周用药，1周停药的规划执行。港安健康国际医疗补充提到，该试验的主要终点在于盲法独立审查的 ORR。结果表明，复发性低级别浆液性卵巢癌患者中接受 Avutometinib 与Defactinib联合治疗的（n=29），其总反应率（ORR）达到45%（95%置信区间，26%-64%）。所有产生应答的患者皆获取了部分应答（PR），疾病稳定（SD）率和疾病进展（PD）率分别是45%和10%。疾病控制率（DCR）为 90%。接受 Avutometinib单一药物治疗的患者（n=30），其 ORR为 10%（95%置信区间，2%-24%）。在单药治疗组中，有1 名患者（3%）获得完全应答，2 名患者（7%）获得 PR。SD率、PD率和 DCR 分别是83%、10%和 93%。其他相关数据表明，接受联合疗法治疗的 KRAS基因突变患者（n=15），其 ORR为 60%，DCR 为100%。KRAS野生型疾病患者（n=14）的 ORR 和 DCR分别是29%和79%。在单药治疗组中，携带 KRAS突变的患者（n=15），已确诊的 ORR为 13%，DCR为 93%。KRAS 野生型患者的 ORR和 DCR分别是 6%和 88%。在安全性这一方面，接受 Avutometinib 单药治疗的患者中，有29%（n=70），接受联合治疗的患者中有17%（n=81）需要降低用药剂量。此外，12.3%的联合治疗组患者因为治疗中出现的不良反应（AEs）而中断Avutometinib或 Defactinib 的治疗，当中 4.9%的患者是由于血肌酸磷酸激酶（CPK）升高而中断治疗。在单药治疗组中，超过 20%的患者报告的最为常见的治疗相关不良反应（TRAEs）包含恶心（任何程度，55.7%；≥3 级，4.3%）、腹泻（71.4%；4.3%）、CPK 升高（50.0%；22.9%）、外周水肿（48.6%；0%）、呕吐（40.0%；5.7%）、视力模糊（41.4%；1.4%）、痤疮样皮炎（38.6%；8.6%）、疲劳（38.6%；2.9%）、皮疹（37.1%；1.4%）、皮肤干燥（32.9%；0%）以及贫血（27.1%；11.4%）。对于 Avutometinib 与Defactinib 的联合使用，20%以上患者最为常见的 TRAEs 涵盖恶心（任何等级，61.7%；等级≥3，0%）、腹泻（49.4%；3.7%）、CPK 升高（48.1%；18.5%）、外周水肿（42.0%；1.2%）、呕吐（37.0%；0%）、视力模糊（35.8%；0%）、痤疮样皮炎（34.6%；2.5%）、疲劳（33.3%；3.7%）、皮疹（30.9%；2.5%）、皮肤干燥（22.2%；0%）以及贫血（17.3%；3.7%）。 #04 Avutometinib+Defactinib研究展望此外，Avutometinib 与Defactinib联合疗法在 RAMP301试验（NCT06072781）的3 期确认性试验中正接受评估，且要与标准化疗或者激素疗法做对比。3 期的 RAMP201 试验（NCT04625270）也在针对复发性低级别浆液性卵巢癌患者的联合用药状况展开研究，当下已经完成了剂量优化、剂量扩大以及低剂量评估队列的入组相关工作。RAMP301 属于3 期、开放标签以及随机化的研究，其研究的对象为复发性低级别浆液性卵巢癌患者，研究的内容是 Avutometinib+Defactinib联合治疗和研究者所选择的治疗方式。港安健康国际医疗补充，次要终点涵盖了总生存期（OS）、研究者评估的无进展生存期（PFS）、客观反应率（ORR）、反应持续时间（DOR）、疾病控制率（DCR）、不良事件（AEs）发生的频次和严重程度、药代动力学以及健康相关的生活质量。实验组的患者接受 Avutometinib 3.2 毫克，每周两次，同时外加 Defactinib 200 毫克，每日两次，持续21天，休息7 天，以 28天作为一个周期。在活性对比组之中，患者接受聚乙二醇脂质体多柔比星、紫杉醇、托泊替康、阿那曲唑或者来曲唑进行治疗，周期也是28 天。患者必须在先前至少经历过一次全身治疗后出现疾病进展或者复发、ECOG 表现为 1级及更低、器官功能正常、既往治疗相关的毒性反应已经完全恢复，并且同意对具备生育能力的患者采取高效的避孕措施，才有参与试验的资格。要是患者在研究开始前4 周内接受过全身性的抗癌治疗、并存高级别卵巢癌、存在有症状的脑转移或者脊髓压迫、有医学层面上具有意义的横纹肌溶解病史或者需要全身性治疗的活动性感染，那么就不符合参与试验的条件。此项研究预计招募270名患者，预计完成的时间为2031 年2 月。总之，Avutometinib（VS-6766）与 defactinib 组合治疗 KRAS突变复发性低级别浆液性卵巢癌为这一难治疾病的治疗带来了新的曙光。尽管目前仍存在一些问题和挑战，但通过不断的研究和探索，有望为患者提供更有效的治疗方案，改善他们的生活质量和预后。相信在不久的将来，这一领域将会取得更多的突破和进展，为攻克妇科恶性肿瘤带来更大的希望。参考文献： 1.Punekar Salman R,Velcheti Vamsidhar,?Neel Benjamin G,et al. The current state of the art and future trends in RAS-targeted cancer therapies.Nat Rev Clin Oncol, 2022, 19: 637-655 2.Verastem Oncology receives orphan drug designation from FDA for avutometinib alone or in combination with defactinib in recurrent low-grade serous ovarian cancer. News release. Verastem Oncology. March 5, 2024. Accessed March 6, 2024. 3.Banerjee SN, Ring KL, Van Nieuwenhuysen E, et al. Initial efficacy and safety results from ENGOT-ov60/GOG-3052/RAMP 201: A phase 2 study of avutometinib (VS-6766) ± defactinib in recurrent low-grade serous ovarian cancer (LGSOC). J Clin Oncol. 2023;41(suppl 16):5515. doi:10.1200/JCO.2023.41.16_suppl.5515 END 【智药研习社线上研习会报名】来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com ▼更多制药资讯，请关注CPHI制药在线▼ 点击阅读原文，进入智药研习社~

孤儿药

2024-10-24

·BioSpace

Havah Therapeutics Announces Formation of Clinical Advisory Board to Advance Its New Breast Cancer Treatment Approach

Chaired by founder Stephen Birrell, MD PhD, group includes experts in breast cancer biology, endocrine signaling and biomarker-driven risk reduction strategies BOULDER, Colo.--(BUSINESS WIRE)--Havah Therapeutics, a clinical stage biopharmaceutical company developing innovative, proprietary hormonal implant therapies for prevention and treatment of breast cancers, announced the formation of their Clinical Advisory Board Chaired by Havah Therapeutics founder Stephen Birrell, MD, PhD. “The scientific and clinical guidance of this esteemed group will be invaluable as we advance our androgen targeted therapy into late-stage clinical studies for Ductal Carcinoma In-Situ (DCIS) and investigator-sponsored combination studies in more advanced disease,” said, Matthew Brewer, CEO of Havah Therapeutics. Shelley Hwang, MD, MPH, Breast Cancer Research Foundation (BCRF) Investigator and internationally recognized expert in pre-invasive disease and DCIS, added: “I am thrilled to be involved with Havah Therapeutics at this critical stage of their development. Insights gained from their ongoing Phase 2 study ( RECAST DCIS ), coupled with my experience as the principal investigator of the COMET Study , will potentially enable the company’s androgen receptor targeting therapy to provide a much needed treatment alternative to invasive surgery and radiation treatment.” The members of Havah Therapeutics’ Clinical Advisory Board include: Stephen Birrell, MD, PhD (Chair), is founder of Havah Therapeutics and Chief Medical Officer of Wellend Health, an Australia-wide clinic that specializes in breast hormone-health, women at high-risk breast cancer and clinical trials. He is a Clinical Affiliate academic at the University of Adelaide Dame Roma Mitchell Cancer Research Laboratories. Shelley Hwang, MD, MPH is the Mary and Deryl Hart Distinguished Professor of Surgical Oncology and Radiology, Vice Chair of Research and Disease Group Leader for the Breast Cancer Program at Duke University Comprehensive Cancer Center. Her research focus includes breast cancer prevention, identifying less invasive treatments for early-stage breast cancers including DCIS and addressing and mitigating health care disparities in breast cancer. Seema A. Khan, MD is Professor of Surgery in the Feinberg School of Medicine at Northwestern University, and the Bluhm Family Professor of Cancer Research. She is the Co-Leader of the Cancer Prevention Research Program at the Robert H. Lurie Comprehensive Cancer Center. Her research focuses on applying biomarker knowledge to improve breast cancer risk stratification and develop preventive interventions for high-risk women. Her research is funded by the National Institutes of Health, The Breast Cancer Research Foundation, the Avon Foundation, and the Susan G. Komen Foundation Professor Wayne Tilley, PhD is the Inaugural Director of the Dame Roma Mitchell Cancer Research Laboratories, University of Adelaide. He completed a Fellowship at UT Southwestern in Dallas Texas in the late 1980s where he was one of the first to clone the human androgen receptor (AR) with Professor Jean Wilson, MD. A current major research focus of Professor Tilley’s lab is the development of new treatments for breast cancer that stimulate the tumor suppressive activity of the AR in the breast (Nature Medicine 2021; Lancet Oncology 2024) to counter the proliferative effects of estrogen. Additional background information on the CAB members can be found on the company’s website: About RECAST DCIS Havah Therapeutics is currently participating in the Re-Evaluating Conditions for Active Surveillance Suitability as Treatment: Ductal Carcinoma In Situ (RECAST DCIS), a Phase 2 platform study aimed at preventing the progression of DCIS to breast cancer. Havah Therapeutics’ HAVAH T+Ai™, a proprietary combination of testosterone (T) and anastrozole (Ai) that targets the androgen and estrogen receptor pathways, is being evaluated alongside two other endocrine therapy arms. About Havah Therapeutics Havah Therapeutics is developing a novel therapeutic implant for treating hormonally sensitive cancers and other breast conditions. This groundbreaking method relies on stimulating (agonizing) the androgen receptor in breast tissue, utilizing natural hormonal mechanisms to treat patients safely and with greatly reduced side effects. The product is a combination of two registered agents (testosterone and anastrozole, a low dose aromatase inhibitor) that when dosed, provides three months of continuous medication enabling a superior product pro compliance, safety and efficacy. For more information, visit . Contacts Media Contacts: Matthew Brewer mb@havahtx.com Danielle Clark-Brown dcb@havahtx.com

临床2期放射疗法

2024-10-23

·E药经理人

阿托伐他汀仿制药效果和安全性如何？真实世界研究结果揭晓

2024年9月，《中国医疗保险》杂志发表《阿托伐他汀仿制药治疗高脂血症疗效与安全性的多中心回顾性队列研究》结果，该研究由首都医科大学宣武医院牵头，并在上海交通大学医学院附属瑞金医院、吉林大学第一医院等10家国内知名三甲医院开展，收集2020年4月1日至2023年3月31日期间首次处方阿托伐他汀仿制药（美达信）或原研药（立普妥）的患者共22万余例，其中原研药组98410例，仿制药组124897例，旨在真实诊疗环境下对阿托伐他汀仿制药和原研药疗效和安全性进行综合评价，为其临床合理使用提供证据参考。研究结果表明，阿托伐他汀仿制药与原研药的临床降脂效果相当；在安全性方面，使用仿制药发生肝损伤的风险更低，相关肌肉症状与原研药无统计学差异。 01 “降脂疗效VS安全性评价” 仿制药与原研药疗效相当，肝损伤风险更低这项多中心、回顾性、队列研究结果显示，在降脂疗效评价方面，治疗后6个月内仿制药组患者血清低密度脂蛋白胆固醇（LDL-C）、总胆固醇（TC）、非高密度脂蛋白胆固醇（非HDL-C）和甘油三酯（TG）水平较基线期降低幅度分别为11.92%、8.21%、11.83%、7.35%，与原研药组的差异均无统计学意义。仿制药组患者治疗后LDL-C较基线期降低幅度≥50%的人数及比例为288例和11.1%，与原研药组的差异也无统计学意义。特别值得关注的是，肝损伤安全性评价和肌肉毒性安全评价作为安全性指标，结果显示，治疗3个月内仿制药组患者出现药物性肝损伤/肝损害诊断的人数和比例为58和0.1%，使用保肝药物的人数和比例为38和0.1%，均显著少于原研药组。仿制药组患者出现肌肉症状相关诊断的人数和比例为88和0.1%，与原研药组相比差异无统计学意义。几组统计数据意味着：在真实的诊疗环境中，阿托伐他汀仿制药与原研药的临床降脂效果相当，在治疗时以临床疗效和安全性明确的合格仿制药替代原研药，可以减少浪费性的医疗保健支出。 02 “仿制药VS原研药” 集采药品真实世界研究进展药品集中带量采购如今已经成为协同推进医药服务供给侧改革的常态化举措。那么，低价中选的集采药品疗效和质量如何？这一问题备受公众关注。为此，一些针对集采药实际疗效的真实世界研究一直在进行中。据了解，早在2019年国家医保局就设立第一批集采中选药品疗效与安全性评价的真实世界研究课题。现在已经开展了三期研究，覆盖了第一至五批国家集采部分中选仿制药，共60余个，涉及抗感染、抗肿瘤、心脑血管疾病、代谢及内分泌疾病、消化系统疾病、神经精神疾病等多个治疗领域。在调节血脂，稳定动脉粥样硬化斑块，预防心脑血管疾病等方面，他汀类药物一直占据着至关重要的基础地位，其中阿托伐他汀作为长效他汀药物的代表，是全球使用最广泛的降脂药物之一。同时，该药物也是首批国家组织药品集中带量采购的“明星”品种。 2019年12月，在“4+7”扩围国家药品集中带量采购招标中，阿托伐他汀钙的价格竞争备受市场关注。阿托伐他汀原研药“立普妥”最终未能中标，中标企业为齐鲁制药、新安药业、乐普，其中齐鲁制药的“美达信”以第一顺位中标，价格较招标前降低97%，每片价格由6元降至0.2元，打破原研的“垄断”地位。随着国采续约的不断进行，齐鲁制药的“美达信”持续发力，从2021年开始，数量市场占有率保持首位，累计销售超两百亿片，成为民族药企积极拥抱集采、实现国产替代的典型代表之一，让患者真正实现了用得上、用得起。事实上，药品集中带量采购要求中选仿制药必须通过一致性评价，尽管国内外研究显示，阿托伐他汀国产仿制药与原研药的疗效和安全性相当且仿制药的治疗成本更低，但仍有部分医师和患者在选择药品时心存疑虑，开展仿制药临床疗效与安全性等多维度的真实世界研究对于促进仿制药合理应用，以及为相关政策提供循证参考尤为重要。本次《阿托伐他汀仿制药治疗高脂血症疗效与安全性的多中心回顾性队列研究》正是探讨并回答了公众关切的仿制药疗效和安全性问题。正如研究结果展示的数据和结论，研究证实，阿托伐他汀仿制药与原研药在临床降脂效果和安全性方面基本相当，用阿托伐他汀仿制药替代原研药在真实诊疗环境中具有可行性，从而为国家组织药品集采中选仿制药的临床合理使用、集采政策的落地执行进一步提供了真实世界证据。在此前开展的一系列真实世界研究中，替吉奥、阿扎胞苷、阿比特龙、来曲唑、阿那曲唑等多款肿瘤药，以及临床常用降糖药格列美脲，研究数据结果均证实，国产仿制药与原研药的临床疗效和安全性相当。 03 “不要盲目迷信进口原研药” 国产仿制药“弯道超车” 我国药品集中带量采购改革在增进民生福祉，推动“三医联动”改革，促进医药行业健康发展等方面发挥了重要作用。基于上述真实世界研究结果，“不要盲目迷信进口原研药”显然需要更多的理性思考和科学判断。虽然进口原研药在某些方面具有领先优势，比如研发历史悠久、临床数据丰富等，但这并不意味着所有进口原研药在所有情况下都是最佳选择。行业专家表示，随着国内制药工业的快速发展，越来越多的国产仿制药通过了一致性评价，这些国产仿制药在保证质量和疗效的同时，价格更为亲民，大大降低了患者的经济负担。鼓励和支持国产仿制药发展也是促进医药产业创新升级、保障国家医药安全的重要举措，推动国内制药企业不断提升研发能力和生产工艺水平，形成与原研药竞争的市场格局，有助于打破进口药垄断，提高药品可及性。过去，部分患者往往认为“一分钱一分货”，高价购买的原研药品质更优，不过，某些药品的高价格背后其实包含了相当一部分虚高的营销费用。市场调查发现，一些进口原研药通过在境内或境外加设经销环节，部分药品一次加价80%至280%不等，价高部分用于不规范的营销行为。 “品质优异、价格合理”已经成为中国仿制药产业高质量发展的重要竞争力，这意味着只有优秀的企业和产品才能够在愈发激烈的市场赛道竞逐中脱颖而出，国家集采显然为国产仿制药提供了“弯道超车”的重要机遇。在国家集采的推动下，药物价格调整也进一步引发市场格局变化。以降脂药市场为例，米内网数据显示，国家集采执行之前，阿托伐他汀钙片在中国公立医疗机构终端为超100亿级别的头部品种，硝苯地平控释片、瑞舒伐他汀钙片为超60亿级别的重磅品种。集采执行后，存量品种销售额均大幅下滑，如阿托伐他汀钙片的销售额由2018年的超110亿元下滑至2020年的不足55亿元。虽然价格大幅下降，但是伴随慢性疾病的医疗服务刚需，自2022年开始该类药物市场已有明显复苏的趋势。2022年重点省市公立医院终端血脂调节剂品种TOP12中，他汀类前5大品种市场份额整体回升，包括阿托伐他汀、瑞舒伐他汀、普伐他汀、氨氯地平阿伐他汀及匹伐他汀。自医药集中带量采购实施五年来，已开展的9批国家组织药品集采共有1600多个产品中选，其中国产仿制药占96%，集采品种的价格大大低于进口原研药，国内用药格局逐渐回归市场价格规则和药品价值规律。一审| 黄佳二审| 李芳晨三审| 李静芝精彩推荐 CM10 | 集采 | 国谈 | 医保动态 | 药审 | 人才 | 薪资 | 榜单 | CAR-T | PD-1 | mRNA | 单抗 | 商业化 | 国际化｜猎药人系列专题 | 出海启思会 | 声音·责任 | 创百汇 | E药经理人理事会 | 微解药直播 | 大国新药 | 营销硬观点 | 投资人去哪儿 | 分析师看赛道 | 药事每周谈 | 医药界·E药经理人 | 中国医药手册创新100强榜单 | 恒瑞 | 中国生物制药 | 百济 | 石药 | 信达 | 君实 | 复宏汉霖｜翰森 | 康方生物 | 上海医药 | 和黄医药 | 东阳光药 | 荣昌 | 亚盛医药 | 齐鲁制药 | 康宁杰瑞 | 贝达药业 | 微芯生物 | 复星医药｜再鼎医药｜亚虹医药跨国药企50强榜单 | 辉瑞 | 艾伯维 | 诺华 | 强生 | 罗氏 | BMS | 默克 | 赛诺菲 | AZ | GSK | 武田 | 吉利德科学 | 礼来 | 安进 | 诺和诺德 | 拜耳 | 莫德纳 | BI | 晖致 | 再生元

一致性评价临床研究

100 项与阿那曲唑相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D00960	阿那曲唑	L02BG03	DB01217

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
多发性骨纤维性发育不良	美国	Astrazeneca Plc /Anti Infective Business/	2008-12-05
男子乳腺发育	美国	Astrazeneca Plc /Anti Infective Business/	2008-12-05
乳腺癌	日本	AstraZeneca KK	2000-12-22
转移性乳腺癌	美国	ANI Pharmaceuticals, Inc.	2000-09-01
晚期乳腺癌	澳大利亚	AstraZeneca Pty Ltd.	1996-12-17
早期乳腺癌	澳大利亚	AstraZeneca Pty Ltd.	1996-12-17
局部晚期乳腺癌	美国	ANI Pharmaceuticals, Inc.	1995-12-27

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
绝经前乳腺癌	临床3期	日本	AstraZeneca PLC	2007-10-01
复发性乳腺癌	临床3期	日本	Pfizer Inc.	2005-04-01
生长激素缺乏症	临床3期	美国	AstraZeneca PLC	2001-11-01
ER阳性乳腺癌	临床3期	美国	AstraZeneca PLC	2000-08-01
ER阳性乳腺癌	临床3期	日本	AstraZeneca PLC	2000-08-01
ER阳性乳腺癌	临床3期	比利时	AstraZeneca PLC	2000-08-01
ER阳性乳腺癌	临床3期	巴西	AstraZeneca PLC	2000-08-01
ER阳性乳腺癌	临床3期	加拿大	AstraZeneca PLC	2000-08-01
ER阳性乳腺癌	临床3期	捷克	AstraZeneca PLC	2000-08-01
ER阳性乳腺癌	临床3期	法国	AstraZeneca PLC	2000-08-01

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临床结果

适应症

分期

评价

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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


NCT00072462 (IBIS-II DCIS, CTgov)	临床3期	导管癌 \| 乳腺癌 \| 非浸润性导管内癌	2,980	anastrozole (Anastrozole)	築選壓構廠廠窪構鬱餘(範鏇襯範鹽醖製範遞顧) = 淵顧鹽鹹獵觸鏇艱衊夢襯餘繭壓簾觸繭築積齋 (衊鬱範遞觸簾鑰衊獵鏇, 構範窪鑰夢繭齋願鏇淵 ~ 鬱齋憲餘壓積襯簾壓膚) 更多	-	2024-09-19
				tamoxifen citrate (Tamoxifen)	築選壓構廠廠窪構鬱餘(範鏇襯範鹽醖製範遞顧) = 簾餘襯獵願憲夢顧鑰積襯餘繭壓簾觸繭築積齋 (衊鬱範遞觸簾鑰衊獵鏇, 衊糧夢顧鹹築廠壓齋製 ~ 製鹹鏇壓糧製範積觸鹹) 更多
NCT03229499 (PHANTOM, Pubmed) 人工标引	临床2期	肺性高血压 post-menopausal	84	Anastrozole 1 mg	憲繭積鬱襯鑰廠鹹窪醖(鹹顧膚鹹廠夢遞積鹹憲) = 餘願遞膚構鏇淵齋襯齋簾襯築蓋製壓衊鹹襯鹽 (網鹽簾選構淵鏇窪蓋鏇, -32.7 ~ 16.9)	不佳	2024-05-15
NCT03229499 (PHANTOM, CTgov)	临床2期	肺动脉高压	84	anastrozole (Anastrozole)	夢觸積糧餘鹹艱夢獵築(構鏇鑰膚獵網餘選窪鹹) = 選網壓艱夢簾憲淵蓋鏇窪築繭觸壓鑰觸願網憲 (獵膚醖餘襯憲願夢願鑰, 遞衊淵願築憲鹽範鬱願 ~ 壓膚觸衊糧糧顧築網選) 更多	-	2024-05-01
				Placebo Oral Tablet (Placebo)	夢觸積糧餘鹹艱夢獵築(構鏇鑰膚獵網餘選窪鹹) = 衊壓憲鹽簾衊獵範築壓窪築繭觸壓鑰觸願網憲 (獵膚醖餘襯憲願夢願鑰, 鏇鬱網膚鏇糧鹹鑰齋鹹 ~ 壓窪選顧網觸糧窪築襯) 更多
NCT03822468 (AMALEE, CTgov)	临床2期	晚期癌症 \| HR阳性/HER2阴性乳腺癌	376	Letrozole+Ribociclib+Goserelin+anastrozole (Ribociclib 400 mg)	顧製鹽淵齋鹹顧廠構鏇(艱築觸淵齋壓衊鹹鑰鏇) = 窪構範餘艱積願網繭淵簾鹽衊糧衊醖鬱窪醖範 (觸糧觸餘膚醖蓋淵範憲, 願選製襯製構積繭範顧 ~ 壓蓋願餘製襯網遞觸夢) 更多	-	2024-04-05
				Letrozole+Ribociclib+Goserelin+anastrozole (Ribociclib 600 mg)	顧製鹽淵齋鹹顧廠構鏇(艱築觸淵齋壓衊鹹鑰鏇) = 齋廠艱糧齋積鹹積鹽蓋簾鹽衊糧衊醖鬱窪醖範 (觸糧觸餘膚醖蓋淵範憲, 衊窪壓遞憲糧製糧蓋夢 ~ 鹹蓋夢繭構願膚醖鬱簾) 更多
NCT00295646 (ABCSG-12, CTgov)	临床3期	HR阳性乳腺癌	1,803	goserelin+zoledronic acid+anastrozole (AZ (Arimidex+Zoledronate))	壓廠淵壓築繭鏇淵壓觸(鹽廠鑰繭糧淵糧顧網鹽) = 鑰範網鑰選鏇鏇鑰壓顧餘網鏇繭夢襯鏇築鬱淵 (艱艱網網繭積遞膚壓衊, 膚窪築餘繭鏇餘繭鹽鬱 ~ 鹽衊繭糧製衊鬱觸鏇壓) 更多	-	2024-03-15
				goserelin+Tamoxifen+zoledronic acid (TZ (Tamoxifen+Zoledronate))	壓廠淵壓築繭鏇淵壓觸(鹽廠鑰繭糧淵糧顧網鹽) = 鏇鬱願鹹鹹膚鏇廠壓鬱餘網鏇繭夢襯鏇築鬱淵 (艱艱網網繭積遞膚壓衊, 醖淵觸醖醖鹹窪範齋觸 ~ 繭選獵醖壓壓遞構廠製) 更多
NCT01953588 (Pubmed)	临床3期	ER阴性乳腺癌新辅助 Ki67	1,362	Anastrozole	願鏇築醖壓鑰築範襯網(顧糧製齋衊遞鬱製膚繭) = 醖襯獵獵獵築獵網衊壓築鬱獵範願窪廠窪壓糧 (夢衊獵網憲膚鹽願遞築, 15.1 ~ 22.7)	-	2024-01-18
				Fulvestrant	願鏇築醖壓鑰築範襯網(顧糧製齋衊遞鬱製膚繭) = 遞廠鹽獵繭網構齋糧簾築鬱獵範願窪廠窪壓糧 (夢衊獵網憲膚鹽願遞築, 18.9 ~ 27.1)
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	衊蓋齋築顧觸繭選繭壓(窪衊醖窪網網鹹鏇膚簾) = 鹽簾窪夢糧襯網鑰網衊簾淵鏇壓夢鏇鹽網廠顧 (糧簾醖糧糧鹽蓋簾選顧 ) 更多	积极	2024-01-01
				Dalpiciclib 150 mg	衊蓋齋築顧觸繭選繭壓(窪衊醖窪網網鹹鏇膚簾) = 窪糧衊範夢構選網窪襯簾淵鏇壓夢鏇鹽網廠顧 (糧簾醖糧糧鹽蓋簾選顧 ) 更多
NCT01674140 (S1207 \| e3, CTgov)	临床3期	HR阳性/HER2阴性乳腺癌	1,939	placebo+letrozole+tamoxifen citrate+exemestane+leuprolide acetate+goserelin acetate+anastrozole (Placebo)	願憲選製蓋築簾鬱淵積(鏇襯選鏇餘鬱遞醖網鬱) = 餘鑰鬱願鏇糧艱糧窪構憲糧醖壓繭積鑰製淵獵 (繭蓋積構壓鏇簾遞醖窪, 網觸繭齋積淵鬱構願蓋 ~ 製淵襯壓壓醖齋觸鹹淵) 更多	-	2023-12-20
				Everolimus (Everolimus)	願憲選製蓋築簾鬱淵積(鏇襯選鏇餘鬱遞醖網鬱) = 選網夢醖壓獵製鹽廠網憲糧醖壓繭積鑰製淵獵 (繭蓋積構壓鏇簾遞醖窪, 壓憲蓋憲憲構壓築餘鏇 ~ 網鏇壓繭窪蓋遞願淵窪) 更多
IBIS-II Prevention Trial (SABCS2023)	N/A	oestradiol \| testosterone \| SHBG	3,864	Anastrozole	餘鹽膚襯願獵網簾製糧(齋築淵鬱壓顧築鏇鹹製): OR = 0.49 (95% CI, 0.37 ~ 0.66), P-Value = < 0.0001	-	2023-12-05
				Placebo
ASPIRE 1.0 (SABCS2023)	临床1/2期	HER2阳性转移性乳腺癌 HR-positive \| HER2-positive	30	Anastrozole	齋鏇膚顧餘艱憲襯選餘(餘遞夢窪遞選獵憲顧鏇) = 網鑰蓋蓋願製範蓋築鑰願獵衊製顧選顧蓋蓋蓋 (構鹹蓋築願夢鹽顧窪壓, 0.83 ~ 1.0) 更多	积极	2023-12-05