The Association between Proton Pump Inhibitors and the Effectiveness of CDK Inhibitors in HR+/HER- Advanced Breast Cancer Patients: A Systematic Review and Meta-Analysis

SIMPLE SUMMARY: Proton pump inhibitors (PPIs) are frequently used in many patients with advanced breast cancer who are being treated with cyclin-dependent kinase inhibitors. In this study, our aim was to determine if there is an association between the use of PPIs and the effectiveness of cyclin-dependent kinase inhibitors, specifically Palbociclib and Ribociclib. We conducted a systematic review and meta-analysis through which to address this clinical question and found that the use of Palbociclib resulted in a lower survival rate for both overall and progression-free survival. However, the concurrent use of PPIs and Ribociclib did not lead to a decrease in the survival rates. Therefore, for cases in which advanced breast cancer patients require the use of PPIs, it may be reasonable to consider using Ribociclib. ABSTRACT: 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; I(2) = 0%) and disease progression (HR = 1.75; 95% CI, 1.26 to 2.43; I(2) = 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; I(2) = 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.