{"title":"CDK4/6 抑制剂治疗晚期 HR+/HER2 - 乳腺癌:多中心真实世界数据分析》。","authors":"Carolin Müller, Verena Kiver, Erich-Franz Solomayer, Gudrun Wagenpfeil, Caroline Neeb, Jens-Uwe Blohmer, Alina Valik Abramian, Nicolai Maass, Florian Schütz, Cornelia Kolberg-Liedtke, Damian Johannes Ralser, Anna-Christina Rambow","doi":"10.1159/000527917","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>CDK4/6 inhibitors (CDK4/6i) combined with endocrine therapy are considered standard-of-care for first-line therapy of patients with hormone receptor positive, HER2 negative, advanced breast cancer (HR+/HER2- ABC). Superiority of combination therapy over endocrine monotherapy has been demonstrated in a multitude of randomized controlled trials (RCTs) in phase III and IV. However, RCTs reflect clinical reality only to a limited extent, as narrow inclusion criteria lead to a selected patient collective. Here, we present real-world data (RWD) on CDK4/6i treatment in patients with HR+/HER2- ABC at four certified German university breast cancer centers.</p><p><strong>Methods: </strong>Patients diagnosed with HR+/HER2- ABC who were treated in clinical routine with CDK4/6i between November 2016 and December 2020 at four certified German university breast cancer centers (Saarland University Medical Center, University Medical Center Charité Berlin, University Medical Center Bonn, and University Medical Center Hospital Schleswig-Holstein, Campus Kiel) were identified and enrolled in this retrospective study. Clinicopathological characteristics and clinical outcomes were recorded with particular emphasis on CDK4/6i therapy course [progression-free survival (PFS) following treatment initiation, toxicity, dose reduction, therapy discontinuation, prior and subsequent therapy line].</p><p><strong>Results: </strong>Data from <i>n</i> = 448 patients were evaluated. The mean patient age was 63 (±12) years. Of these patients, <i>n</i> = 165 (36.8%) were primarily metastasized, and <i>n</i> = 283 (63.2%) had secondary metastatic disease. <i>N</i> = 319 patients (71.3%) received palbociclib, <i>n</i> = 114 patients (25.4%) received ribociclib, and <i>n</i> = 15 patients (3.3%) received abemaciclib, respectively. Dose reduction was performed in <i>n</i> = 132 cases (29.5%). <i>N</i> = 57 patients (12.7%) discontinued the treatment with CDK4/6i due to side effects. <i>N</i> = 196 patients (43.8%) experienced disease progression under CDK4/6i treatment. The median PFS was 17 months. Presence of hepatic metastases and prior therapy lines were associated with shorter PFS, whereas estrogen positivity and dose reduction due to toxicity were positively associated with PFS. Presence of bone and lung metastases, progesterone positivity, Ki67 index, grading, <i>BRCA1/2</i> and <i>PIK3CA</i> mutation status, adjuvant endocrine resistance, and age did not significantly impact on PFS.</p><p><strong>Conclusion: </strong>Our RWD analysis on CDK4/6i treatment in Germany supports data from RCTs regarding both treatment efficacy and safety of CDK4/6i for treatment of patients with HR+/HER2- ABC. In comparison to data from the pivotal RCTs, median PFS was lower but within the expected range for RWD, which could result from inclusion of patients with more advanced diseases (i.e., higher therapy lines) to our dataset.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":null,"pages":null},"PeriodicalIF":4.6000,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9982335/pdf/","citationCount":"0","resultStr":"{\"title\":\"CDK4/6 Inhibitors in Advanced HR+/HER2 - Breast Cancer: A Multicenter Real-World Data Analysis.\",\"authors\":\"Carolin Müller, Verena Kiver, Erich-Franz Solomayer, Gudrun Wagenpfeil, Caroline Neeb, Jens-Uwe Blohmer, Alina Valik Abramian, Nicolai Maass, Florian Schütz, Cornelia Kolberg-Liedtke, Damian Johannes Ralser, Anna-Christina Rambow\",\"doi\":\"10.1159/000527917\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>CDK4/6 inhibitors (CDK4/6i) combined with endocrine therapy are considered standard-of-care for first-line therapy of patients with hormone receptor positive, HER2 negative, advanced breast cancer (HR+/HER2- ABC). Superiority of combination therapy over endocrine monotherapy has been demonstrated in a multitude of randomized controlled trials (RCTs) in phase III and IV. However, RCTs reflect clinical reality only to a limited extent, as narrow inclusion criteria lead to a selected patient collective. Here, we present real-world data (RWD) on CDK4/6i treatment in patients with HR+/HER2- ABC at four certified German university breast cancer centers.</p><p><strong>Methods: </strong>Patients diagnosed with HR+/HER2- ABC who were treated in clinical routine with CDK4/6i between November 2016 and December 2020 at four certified German university breast cancer centers (Saarland University Medical Center, University Medical Center Charité Berlin, University Medical Center Bonn, and University Medical Center Hospital Schleswig-Holstein, Campus Kiel) were identified and enrolled in this retrospective study. Clinicopathological characteristics and clinical outcomes were recorded with particular emphasis on CDK4/6i therapy course [progression-free survival (PFS) following treatment initiation, toxicity, dose reduction, therapy discontinuation, prior and subsequent therapy line].</p><p><strong>Results: </strong>Data from <i>n</i> = 448 patients were evaluated. The mean patient age was 63 (±12) years. Of these patients, <i>n</i> = 165 (36.8%) were primarily metastasized, and <i>n</i> = 283 (63.2%) had secondary metastatic disease. <i>N</i> = 319 patients (71.3%) received palbociclib, <i>n</i> = 114 patients (25.4%) received ribociclib, and <i>n</i> = 15 patients (3.3%) received abemaciclib, respectively. Dose reduction was performed in <i>n</i> = 132 cases (29.5%). <i>N</i> = 57 patients (12.7%) discontinued the treatment with CDK4/6i due to side effects. <i>N</i> = 196 patients (43.8%) experienced disease progression under CDK4/6i treatment. The median PFS was 17 months. Presence of hepatic metastases and prior therapy lines were associated with shorter PFS, whereas estrogen positivity and dose reduction due to toxicity were positively associated with PFS. Presence of bone and lung metastases, progesterone positivity, Ki67 index, grading, <i>BRCA1/2</i> and <i>PIK3CA</i> mutation status, adjuvant endocrine resistance, and age did not significantly impact on PFS.</p><p><strong>Conclusion: </strong>Our RWD analysis on CDK4/6i treatment in Germany supports data from RCTs regarding both treatment efficacy and safety of CDK4/6i for treatment of patients with HR+/HER2- ABC. In comparison to data from the pivotal RCTs, median PFS was lower but within the expected range for RWD, which could result from inclusion of patients with more advanced diseases (i.e., higher therapy lines) to our dataset.</p>\",\"PeriodicalId\":2,\"journal\":{\"name\":\"ACS Applied Bio Materials\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2023-02-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9982335/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ACS Applied Bio Materials\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1159/000527917\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2022/12/6 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"MATERIALS SCIENCE, BIOMATERIALS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Applied Bio Materials","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1159/000527917","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/12/6 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"MATERIALS SCIENCE, BIOMATERIALS","Score":null,"Total":0}
引用次数: 0
摘要
目的:CDK4/6抑制剂(CDK4/6i)联合内分泌治疗被认为是激素受体阳性、HER2阴性晚期乳腺癌(HR+/HER2- ABC)患者一线治疗的标准疗法。大量 III 期和 IV 期随机对照试验(RCT)已证明,联合疗法优于内分泌单药疗法。然而,随机对照试验只能在一定程度上反映临床实际情况,因为狭窄的纳入标准导致了患者群体的选择性。在此,我们介绍了德国四所经认证的大学乳腺癌中心对HR+/HER2- ABC患者进行CDK4/6i治疗的真实世界数据(RWD):方法:在2016年11月至2020年12月期间,在四家经认证的德国大学乳腺癌中心(萨尔州大学医学中心、柏林夏里特大学医学中心、波恩大学医学中心和石勒苏益格-荷尔斯泰因大学医学中心基尔校区医院)接受CDK4/6i临床常规治疗的确诊为HR+/HER2- ABC的患者被确定并纳入这项回顾性研究。研究记录了临床病理特征和临床结果,特别强调了 CDK4/6i 治疗过程[治疗开始后的无进展生存期(PFS)、毒性、剂量减少、治疗中止、之前和之后的治疗方案]:评估了 n = 448 名患者的数据。患者平均年龄为 63 (±12) 岁。在这些患者中,n = 165(36.8%)主要为转移性疾病,n = 283(63.2%)为继发性转移性疾病。n=319例患者(71.3%)分别接受了palbociclib治疗,n=114例患者(25.4%)接受了ribociclib治疗,n=15例患者(3.3%)接受了abemaciclib治疗。132例患者(29.5%)接受了减量治疗。有57例患者(12.7%)因副作用停止了CDK4/6i的治疗。196例患者(43.8%)在接受CDK4/6i治疗后出现疾病进展。中位 PFS 为 17 个月。肝转移和既往治疗与较短的PFS相关,而雌激素阳性和因毒性导致的剂量减少与PFS呈正相关。骨转移和肺转移、孕激素阳性、Ki67指数、分级、BRCA1/2和PIK3CA突变状态、辅助内分泌耐药和年龄对PFS没有显著影响:我们在德国对CDK4/6i治疗进行的RWD分析支持有关CDK4/6i治疗HR+/HER2- ABC患者的疗效和安全性的RCT数据。与关键RCT的数据相比,中位PFS较低,但在RWD的预期范围内,这可能是由于我们的数据集中纳入了更晚期的患者(即更高的治疗线)。
CDK4/6 Inhibitors in Advanced HR+/HER2 - Breast Cancer: A Multicenter Real-World Data Analysis.
Purpose: CDK4/6 inhibitors (CDK4/6i) combined with endocrine therapy are considered standard-of-care for first-line therapy of patients with hormone receptor positive, HER2 negative, advanced breast cancer (HR+/HER2- ABC). Superiority of combination therapy over endocrine monotherapy has been demonstrated in a multitude of randomized controlled trials (RCTs) in phase III and IV. However, RCTs reflect clinical reality only to a limited extent, as narrow inclusion criteria lead to a selected patient collective. Here, we present real-world data (RWD) on CDK4/6i treatment in patients with HR+/HER2- ABC at four certified German university breast cancer centers.
Methods: Patients diagnosed with HR+/HER2- ABC who were treated in clinical routine with CDK4/6i between November 2016 and December 2020 at four certified German university breast cancer centers (Saarland University Medical Center, University Medical Center Charité Berlin, University Medical Center Bonn, and University Medical Center Hospital Schleswig-Holstein, Campus Kiel) were identified and enrolled in this retrospective study. Clinicopathological characteristics and clinical outcomes were recorded with particular emphasis on CDK4/6i therapy course [progression-free survival (PFS) following treatment initiation, toxicity, dose reduction, therapy discontinuation, prior and subsequent therapy line].
Results: Data from n = 448 patients were evaluated. The mean patient age was 63 (±12) years. Of these patients, n = 165 (36.8%) were primarily metastasized, and n = 283 (63.2%) had secondary metastatic disease. N = 319 patients (71.3%) received palbociclib, n = 114 patients (25.4%) received ribociclib, and n = 15 patients (3.3%) received abemaciclib, respectively. Dose reduction was performed in n = 132 cases (29.5%). N = 57 patients (12.7%) discontinued the treatment with CDK4/6i due to side effects. N = 196 patients (43.8%) experienced disease progression under CDK4/6i treatment. The median PFS was 17 months. Presence of hepatic metastases and prior therapy lines were associated with shorter PFS, whereas estrogen positivity and dose reduction due to toxicity were positively associated with PFS. Presence of bone and lung metastases, progesterone positivity, Ki67 index, grading, BRCA1/2 and PIK3CA mutation status, adjuvant endocrine resistance, and age did not significantly impact on PFS.
Conclusion: Our RWD analysis on CDK4/6i treatment in Germany supports data from RCTs regarding both treatment efficacy and safety of CDK4/6i for treatment of patients with HR+/HER2- ABC. In comparison to data from the pivotal RCTs, median PFS was lower but within the expected range for RWD, which could result from inclusion of patients with more advanced diseases (i.e., higher therapy lines) to our dataset.