de Moraes Francisco Cezar Aquino, Pereira Caroline R M, Sano Vitor Kendi Tsuchiya, Laia Estella Aparecida De, Stecca Carlos, Burbano Rommel Mario Rodríguez
Department of Medicine, Federal University of Pará, Belém, Pará, Brazil.
Department of Medicine, State University of Rio de Janeiro (UERJ), Rio de Janeiro, Brazil.
Front Pharmacol. 2024 May 6;15:1352224. doi: 10.3389/fphar.2024.1352224. eCollection 2024.
The CDK 4/6 inhibitors, including palbociclib and ribociclib, are the standard first-line treatment for hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer. Proton pump inhibitors are one of the most globally prescribed types of medications as part of the treatment for gastroesophageal reflux and heartburn complaints. Medication interactions have been demonstrated, leading to a decrease in the effectiveness of chemotherapy drugs such as capecitabine and pazopanib. However, their role and interaction with targeted therapies such as CDK inhibitors are still poorly understood.
We searched PubMed, Embase and Web of Science databases for studies that investigated the use of PPI with CDK 4/6 inhibitors versus CDK4/6 alone for advanced or metastatic breast cancer. We systematically searched for the currently available CDK inhibitors: palbociclib, ribociclib and abemaciclib. We computed hazard ratios (HRs), with 95% confidence intervals (CIs). We used DerSimonian and Laird random-effect models for all endpoints. Heterogeneity was assessed using I statistics. R, version 4.2.3, was used for statistical analyses.
A total of 2,737 patients with advanced breast cancer in 9 studies were included, with six studies described the status menopausal as 217 (7.9%) pre-menopause and 1851 (67.6%) post-menopause, for endocrine sensitivity only five studies described1489 (54.4%) patients were endocrine-sensitive and 498 (182%) endocrine-resistent, 910 (33.2%) patients used PPIs. The overall Progression-Free Survival was in favor of the PPI non-users (HR 2.0901; 95% CI 1.410-2.9498; < 0.001). As well as the subgroup taking palbociclib, revealing statistical relevance for the PPI non-users (HR 2.2539; 95% CI 1.3213-3.8446; = 0.003) and ribociclib subgroup with a slight decrease in hazard ratio (HR 1.74 95% CI 1.02-2.97; = 0.04; I = 40%). In the multivariate analysis, there was no statistical signifance with ECOG (HR 0.9081; 95% CI 0.4978-16566; p 0.753) and Age (HR 1.2772; 95% CI 0.8790-1.8559; = 0.199). Either, the univariate analysis did not show statistical significance.
Women with HR+ and HER2-advanced metastatic breast undergoing treatment with targeted therapies, specifically CDK 4/6 inhibitors, should be monitored for the use of proton pump inhibitors. Therefore, the use of PPIs should be discussed, weighing the advantages and disadvantages for specific cases. It should be individualized based on the necessity in clinical practice for these cases.
identifier CRD42023484755.
包括哌柏西利和瑞博西尼在内的细胞周期蛋白依赖性激酶4/6（CDK 4/6）抑制剂是激素受体阳性（HR+）和人表皮生长因子受体2阴性（HER2-）转移性乳腺癌的标准一线治疗药物。质子泵抑制剂是全球处方量最大的药物类型之一，用于治疗胃食管反流和烧心症状。已证实药物相互作用会导致卡培他滨和帕唑帕尼等化疗药物疗效降低。然而，它们与CDK抑制剂等靶向治疗的作用及相互作用仍知之甚少。
我们在PubMed、Embase和Web of Science数据库中检索了研究PPI与CDK 4/6抑制剂联合使用与单独使用CDK4/6治疗晚期或转移性乳腺癌的研究。我们系统检索了目前可用的CDK抑制剂：哌柏西利、瑞博西尼和阿贝西利。我们计算了风险比（HRs）及95%置信区间（CIs）。我们对所有终点使用DerSimonian和Laird随机效应模型。使用I统计量评估异质性。使用R 4.2.3版本进行统计分析。
9项研究共纳入2737例晚期乳腺癌患者，6项研究描述了绝经状态，其中217例（7.9%）为绝经前，1851例（67.6%）为绝经后；仅5项研究描述了内分泌敏感性，1489例（54.4%）患者内分泌敏感，498例（18.2%）内分泌抵抗，910例（33.2%）患者使用了PPI。总体无进展生存期有利于未使用PPI的患者（HR 2.0901；95% CI 1.410 - 2.9498；P < 0.001）。在使用哌柏西利的亚组中，未使用PPI的患者也显示出统计学相关性（HR 2.2539；95% CI 1.3213 - 3.8446；P = 0.003），瑞博西尼亚组的风险比略有下降（HR 1.74，95% CI 1.02 - 2.97；P = 0.04；I = 40%）。在多变量分析中，ECOG（HR 0.9081；95% CI 0.4978 - 1.6566；P = 0.753）和年龄（HR 1.2772；95% CI 0.8790 - 1.8559；P = 0.199）无统计学意义。单变量分析也未显示统计学意义。
接受靶向治疗，特别是CDK 4/6抑制剂治疗的HR+和HER2-晚期转移性乳腺癌女性，应监测其质子泵抑制剂的使用情况。因此，应讨论PPI的使用，权衡具体病例的利弊。在临床实践中，应根据这些病例的必要性进行个体化处理。
标识符CRD42023484755 。
