更新于：2024-11-01

GRPR Positive/ER Positive/HER2 Negative Breast Cancer

GRPR阳性/ER阳性/HER2阴性乳腺癌

更新于：2024-11-01

基本信息

别名

GRPR+, ER+, HER2- Breast Cancer、Gastrin Releasing Peptide Receptor Positive, Estrogen Receptor-positive, Human Epidermal Growth Factor Receptor-2 Negative Breast Cancer

简介-

关联

项与 GRPR阳性/ER阳性/HER2阴性乳腺癌相关的药物

Ribociclib Succinate

琥珀酸瑞波西利

靶点

CDK4 x CDK6

作用机制

CDK4抑制剂 [+1]

在研机构

Novartis Pharmaceuticals Corp. [+13]

原研机构

Novartis Pharma AG

在研适应症

晚期乳腺癌 [+50]

非在研适应症

晚期肝细胞癌 [+29]

最高研发阶段批准上市

首次获批国家/地区

美国

首次获批日期2017-03-13

Fulvestrant

氟维司群

靶点

作用机制

ERs拮抗剂

在研机构

原研机构

在研适应症

非在研适应症

最高研发阶段批准上市

首次获批国家/地区

美国

首次获批日期2002-04-25

Capecitabine

卡培他滨

靶点

TYMS

作用机制

TYMS抑制剂

在研机构

Chugai Pharmaceutical Co., Ltd. [+12]

原研机构

F. Hoffmann-La Roche Ltd.

在研适应症

食管癌 [+23]

非在研适应症

腺癌 [+87]

最高研发阶段批准上市

首次获批国家/地区

美国

首次获批日期1998-04-30

项与 GRPR阳性/ER阳性/HER2阴性乳腺癌相关的临床试验

NCT06247995 / Recruiting临床1/2期

A Phase I/II, Open-label, Multi-center Trial of [177Lu]Lu-NeoB in Combination With Capecitabine in Adult Patients With Gastrin Releasing Peptide Receptor Positive, Estrogen Receptor-positive, Human Epidermal Growth Factor Receptor-2 Negative Metastatic Breast Cancer After Progression on Previous Endocrine Therapy in Combination With a CDK4/6 Inhibitor.

In the phase I part, to determine the recommended doses (RD) and dosing regimens of [177Lu]Lu-NeoB in combination with capecitabine in adult patients with gastrin releasing peptide receptor positive, estrogen receptor-positive, human epidermal growth factor receptor-2 negative metastatic breast cancer after progression on previous endocrine therapy in combination with a CDK4/6 inhibitor. In the phase II part, to evaluate the preliminary anti-tumor activity of two different doses/regimens of [177Lu]Lu-NeoB in combination with capecitabine (dose optimization).

开始日期2024-08-14

申办/合作机构

Novartis Pharmaceuticals Corp.

NCT06452706 / Not yet recruiting临床2期

The Phase II Clinical Trial to Evaluate the Efficacy and Safety of TQB2102 for Injection in Human Epidermal Growth Factor Receptor 2 (HER2) Negative Recurrent/Metastatic Breast Cancer

This study aims to evaluate the efficacy and safety of TQB2102 for injection in HER2 negative recurrent/metastatic breast cancer.

开始日期2024-07-01

申办/合作机构

正大天晴药业集团股份有限公司

NCT05870579 / Recruiting临床1期

A Phase Ib Dose Finding Study Assessing Safety and Activity of [177Lu]Lu-NeoB in Combination With Ribociclib and Fulvestrant in Participants With Estrogen Receptor Positive, Human Epidermal Growth Factor Receptor-2 Negative and Gastrin Releasing Peptide Receptor Positive Advanced Breast Cancer Experiencing Early Relapse From (Neo)Adjuvant Endocrine Therapy or Who Have Progressed on Endocrine Therapy in Combination With a CDK4/6 Inhibitor for Advanced Disease

The purpose of this trial is to estimate the recommended dose (RD) of [177Lu]Lu-NeoB in combination with ribociclib and fulvestrant in participants with estrogen receptor (ER) positive (ER+), human epidermal growth factor receptor-2 (HER2) negative (HER2-) and gastrin releasing peptide receptor (GRPR) positive (GRPR+) advanced breast cancer experiencing early relapse from (neo)adjuvant endocrine therapy or who have progressed on endocrine therapy in combination with a CDK4/6 inhibitor for advanced disease.

开始日期2023-11-13

申办/合作机构

Novartis Pharmaceuticals Corp.

100 项与 GRPR阳性/ER阳性/HER2阴性乳腺癌相关的临床结果

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100 项与 GRPR阳性/ER阳性/HER2阴性乳腺癌相关的转化医学

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0 项与 GRPR阳性/ER阳性/HER2阴性乳腺癌相关的专利（医药）

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项与 GRPR阳性/ER阳性/HER2阴性乳腺癌相关的文献（医药）

2024-12-01·International Journal of Particle Therapy

Value of Carbon-Ion Radiation Therapy for Breast Cancer

Review

作者: Li, Kai-Wen ; Pei, Xiaohua ; Yu, Bowen ; Fan, Yingyi

To explore the challenges and future of carbon-ion radiation therapy (CIRT) in breast cancer, we summarized the progress of nonclinical and clinical studies on CIRT for breast cancer in this review. A total of 6 nonclinical studies have been reported, which demonstrated a better effect of Carbon-ion irradiation compared with X-ray in breast cancer cell lines (including triple-negative breast cancer and Human Epidermal Growth Factor Receptor 2-negative breast cancer). Combination with Hh inhibitor, dual tyrosine kinase inhibitor, and PARP inhibitor is promising as demonstrated in the in vitro studies. Approximately 34 patients with breast cancer went through CIRT treatment, as reported in 5 clinical studies. All studies demonstrated promising treatment effects with acceptable and manageable risks. In these studies, a total of 21 patients were reported with post-treatment response assessments, among whom 19 patients (90.48%) reported a response of complete response or partial response. The complete response rate was 66.67%. The time to complete the response ranged from 3 months to 24 months. No adverse events were observed in these studies except for grade 1 acute skin reaction in 14 out of the 21 patients (66.67%). Although the time to respond was longer than expected in some studies, the persistent responses and satisfactory safety profile provided the rationale for further research on this new therapy.

2024-12-01·The Lancet Regional Health - Europe

Axillary clearance and chemotherapy rates in ER+HER2− breast cancer: secondary analysis of the SENOMAC trial

Article

作者: Stefek, Andrea ; Fucito, Alfredo ; Askoxylakis, Ioannis ; Björkman, Johanna ; Strittmatter, Hans-Joachim ; Kontzoglou, Konstantinos ; Stachs, Angrit ; Brucker, Sara ; Metaxas, George ; Falck, Anna-Karin ; Sackey, Helena ; Bergkvist, Leif ; Wärnberg, Fredrik ; Bonatz, Gabriele ; Alkner, Sara ; Faliakou, Eleni ; Wadsten, Charlotta ; Åhsberg, Kristina ; Soe, Katrine Lydolph ; Schirrmeister, Susen ; Michalopoulos, Nikolaos ; Sigvardsson, Jeanette Liljestrand ; Kaklamanos, Ioannis ; Ohlinger, Ralf ; Nixdorf, Antje ; Eichler, Henning ; Filtenborg, Tove Tvedskov ; Gentilini, Oreste ; Cristofolini, Paolo ; Seldte, Jens-Paul ; Carstensen, Lena ; Renner, Stefan ; Gentilini, Oreste Davide ; Celebioglu, Fuat ; Christiansen, Peer ; Ollig, Stefan ; Norenstedt, Sophie ; Wångblad, Carin ; Sund, Malin ; Starck, Emma ; Polata, Silke ; Müller, Thomas ; Camara, Oumar ; Andersson, Yvette ; Hansen, Lone Bak ; Kühn, Cristin ; Lindwall, Karin Åhlander ; Franzen, Arno ; Gatzweiler, Axel ; Kjaer, Christina ; Erngrund, Maria ; Hahn, Antje ; Hammerle, Caroline ; Galimberti, Viviana ; Bagge, Roger Olofsson ; Fischer, Dorothea ; Szulkin, Robert ; Wedin, Maria ; Wallberg, Michael ; Ledwon, Peter ; Reimer, Toralf ; Nyman, Per ; Poulakaki, Nikiforita ; Keller, Markus ; Fogazzi, Gianluca ; Hoyer, Ute ; Lundstedt, Dan ; Frisell, Jan ; Malterling, Rebecka Ruderfors ; Perez, Sybille ; de Boniface, Jana ; Kühn, Thorsten ; Rydén, Lisa ; Venizelos, Vassilos ; Holsti, Caroline ; Myrskog, Lena ; Svensjö, Tor ; Schwickardi, Gabriele Feisel ; Kontos, Michalis ; Garcia-Etienne, Carlos ; Balling, Eva ; Melnichuk, Liudmila ; Tvedskov, Tove Filtenborg ; Offersen, Birgitte Vrou ; Lindner, Christoph ; Andersen, Inge Scheel ; Handler, Jürgen ; Hausmüller, Stephan ; Patil, Eva Vikhe

BackgroundRandomized trials have shown that axillary clearance (AC) can safely be omitted in patients with sentinel lymph node-positive breast cancer. At the same time, de-escalation of chemotherapy in postmenopausal patients with ER+HER2- breast cancer may depend on detailed axillary nodal stage. The aim of this pre-specified secondary analysis of the SENOMAC trial was to investigate whether the choice of axillary staging affected the proportion of patients receiving adjuvant chemotherapy, and recurrence-free survival (RFS).MethodsProportion receiving adjuvant chemotherapy was calculated according to AC or sentinel lymph node biopsy (SLNB) only, menopausal status, and region of inclusion, for 2168 patients with clinically node-negative ER+HER2- breast cancer and 1-2 sentinel lymph node macrometastases included in the SENOMAC trial.FindingsIn premenopausal patients, 514 out of 615 patients (83.6%) received adjuvant chemotherapy with no significant difference between randomization arms. In postmenopausal patients, the proportion receiving chemotherapy varied considerably by region and country (36.0-82.4%). In Denmark, where 194 out of 539 postmenopausal patients (36.0%) received adjuvant chemotherapy, rates differed significantly between the AC and the SLNB only arm (41.3% vs 31.4%, p = 0.019). After a median follow-up of 44.88 months for Danish postmenopausal patients, no significant difference was seen in 5-year RFS, which was 91% (85.6%-96.6%) for the SLNB only and 90.9% (86.3%-95.6%) for the AC arm (p = 0.42).InterpretationWhen omitting axillary clearance, and thus reducing the risk of long-term arm morbidity, potential under-treatment of postmenopausal patients with ER+HER2- breast cancer may require the development of new predictive and imaging tools.FundingSwedish Research Council, Swedish Cancer Society, Nordic Cancer Union, Swedish Breast Cancer Association.

2024-09-19·Journal of clinical oncology : official journal of the American Society of Clinical Oncology

PEARL: A Phase Ib/II Biomarker Study of Adding Radiation Therapy to Pembrolizumab Before Neoadjuvant Chemotherapy in Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer.

Article

作者: McAndrew, Philomena ; Karlan, Scott ; Gupta, Gaorav P ; McArthur, Heather ; Tighiouart, Mourad ; Chen, Jonathan ; Shiao, Stephen ; Kobald, Samantha A ; Duda, Dan G ; Ho, Alice Y ; Muzikansky, Alona ; Arnold, Brittany ; Bossuyt, Veerle ; Knott, Simon ; Basho, Reva ; Ly, Amy ; Cho, Hae Lin

PURPOSETo assess safety and immune biomarkers after preoperative radiation therapy (RT) and anti-PD1 therapy in breast cancer.MATERIALS AND METHODSA phase I/IIb trial of pembrolizumab with RT was conducted in patients with triple-negative breast cancer (TNBC) and hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer. All received pembrolizumab followed by a second cycle + RT (anti-PD1/RT) of 24 Gy/three daily fractions delivered to the breast tumor and then neoadjuvant chemotherapy (NAC). Blood and tumor biopsies were obtained at baseline, after anti-PD1, and after anti-PD-RT. Coprimary end points were safety and change in tumor-infiltrating lymphocytes (TILs). Secondary end points were pathologic complete response (pCR), residual cancer burden (RCB) rates, and event-free survival (EFS).RESULTSSixty-six patients with stage I-III breast cancer (54 TNBC, 12 HR+/HER2-) were enrolled. The median follow-up was 32 months. Safety end point was met. Incidence of grade ≥3 toxicities was 41%. The pCR rate was 59.2%, 33.3%, and 54.5% for the TNBC, HR+/HER2-, and entire cohort, respectively. A total of 77.8% of TNBC and 41.6% of HR+/HER2- had a near pCR (RCB 0-1). The 3-year EFS was 80%. In the entire cohort, PD-L1 expression increased after anti-PD1 (median Combined Positive Score [CPS], 7.49-23.20; 95% CI, -41.88 to -6.30; P = .044) and anti-PD1/RT (median CPS, 7.49-23.41; 95% CI, -41.88 to -6.30; P = .009), compared with baseline. In TNBC, adding RT to anti-PD1 significantly decreased TILs (28.9%-17.1%; 95% CI, 2.46 to 21.09; P = .014). Baseline TILs correlated with PD-L1 expression and TNF-a.CONCLUSIONPreoperative RT with pembrolizumab is safe and results in high pCR rates and 3-year EFS, despite the lack of pembrolizumab during NAC. PD-L1 and TILs may be predictive biomarkers for preoperative anti-PD1/RT response. Reduction in TILs after adding RT to anti-PD1 highlights the importance of treatment sequencing.

项与 GRPR阳性/ER阳性/HER2阴性乳腺癌相关的新闻（医药）

2024-07-23

·PMLiVE

MHRA approves first generic raltegravir medicines to treat HIV in adults and children

The Medicines and Healthcare products Regulatory Agency (MHRA) has approved the first generic raltegravir medicines to treat human immunodeficiency virus (HIV) in adult and paediatric patients. The marketing authorisations granted to Lupin Healthcare and Zentiva Pharma specifically apply to patients weighing at least 40kg. The number of people living with a diagnosed HIV infection and accessing care in England rose from 91,368 in 2021 to 94,397 in 2022. Merck & Co’s – known as MSD outside the US and Canada – Isentress (raltegravir) is an antiretroviral drug licensed for use in HIV patients. Its active ingredient, raltegravir, stops the HIV integrase enzyme, which enables multiplication of the virus in cells within the body, from functioning. When used with other medicines, it can decrease the amount of HIV in patients’ blood and increase their CD4-cell count, which plays a vital role in maintaining a healthy immune system. The recommended dosage for the medicine, which must be used in combination with other HIV drugs, is 1,200mg as two 600mg tablets taken orally once daily. The MHRA’s decision on the raltegravir generics was supported by evidence from studies of healthy volunteers, which demonstrated that they were bioequivalent to Isentress, meaning their benefits and possible side effects are considered to be the same. Shirley Hopper, MHRA deputy director of innovative medicines, said: “Ensuring timely access to generic medicines is a key priority for us. “Appropriate data has been provided to assure us that these medicines are the same as, and considered interchangeable with an already licensed reference medicine…” The approval comes just days after the MHRA approved AstraZeneca’s orally-administered AKT inhibitor, Truqap (capivasertib), to treat a subset of adults with advanced breast cancer. Patients eligible for the therapy will have hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer with at least one PIK3CA, AKT1 or PTEN alteration and will not have responded to other anti-hormonal-based therapies. The UK regulator also recently approved a subcutaneous formulation of Roche’s Ocrevus (ocrelizumab) to treat adults with relapsing and primary progressive multiple sclerosis.