There have been many clinical questions regarding whether the use of proton pump inhibitors (PPIs) could deteriorate the effects of cyclin-dependent kinase inhibitors (CDKIs) in HR+/HER2- advanced breast cancer patients. We performed a systematic review and meta-analysis of this clinical question, including studies enrolling HR+/HER2- metastatic breast cancer patients treated with CDKIs (Palbociclib or Ribociclib) and reporting at least one comparative survival outcome, either overall survival (OS) or progression-free survival (PFS), between concomitant PPI users and non-users. Eight studies met the eligibility criteria, with a total of 2584 patients included (PPI users: 830, PPI non-users: 1754), demonstrating that concomitant PPI use was associated with significantly higher risks of all-cause mortality (HR = 2.03; 95% CI, 1.49 to 2.77; I2= 0%) and disease progression (HR = 1.75; 95% CI, 1.26 to 2.43; I2= 59%) in breast cancer patients taking Palbociclib. In contrast, there were no significant survival impacts of PPIs on Ribociclib (HR = 1.46; 95% CI, 0.91 to 2.34; I2= 36%). Additionally, there was no significant difference in the risk associated with CDKI dose reduction due to drug toxicity (RR = 1.12; 95% CI, 0.97 to 1.29). Therefore, when HR+/HER2- advanced breast cancer patients require the use of PPIs, it may be reasonable to consider using Ribociclib.
关于质子泵抑制剂（PPIs）的使用是否会降低细胞周期蛋白依赖性激酶抑制剂（CDKIs）在HR+/HER2-晚期乳腺癌患者中的疗效，临床上存在诸多疑问。针对这一临床问题，我们进行了系统性回顾与荟萃分析，纳入的研究对象为接受CDKIs（帕博西尼或瑞博西尼）治疗且至少报告一项伴随使用PPI者与未使用PPI者生存结局比较（总生存期或无进展生存期）的HR+/HER2-转移性乳腺癌患者。共八项研究符合纳入标准，总计2584例患者（PPI使用者830例，非使用者1754例）。分析显示，在服用帕博西尼的乳腺癌患者中，伴随使用PPI与显著升高的全因死亡风险（HR=2.03；95%CI 1.49-2.77；I²=0%）和疾病进展风险（HR=1.75；95%CI 1.26-2.43；I²=59%）相关。相比之下，PPIs对瑞博西尼使用者的生存期未产生显著影响（HR=1.46；95%CI 0.91-2.34；I²=36%）。此外，因药物毒性导致CDKI剂量降低的风险在两组间无显著差异（RR=1.12；95%CI 0.97-1.29）。因此，当HR+/HER2-晚期乳腺癌患者需要使用PPIs时，考虑选用瑞博西尼可能是合理的。
肿瘤(癌症)患者之家