The Effect of Proton Pump Inhibitors on Metastatic Breast Cancer in Patients Treated with CDK4/6i

Background: This study aimed to assess the effect of proton pump inhibitors (PPIs) on hormone receptor-positive (HR+) and her-2-negative (her2-) metastatic breast cancer (MBC) in patients receiving CDK4/6i.Method: In a retrospective study, patients were divided into two groups based on their use of PPIs: concomitant use for at least half the treatment period (C-PPIs) and non-concomitant use for less than half the treatment period (NC-PPIs). Statistical analyses were conducted using SPSS 22.0 and MedCalc Software bvba 13.Results: Out of 217 patients, 114 (52.5%) received palbociclib and 103 (47.5%) received ribociclib. Then, 71 palbociclib recipients were combined with aromatase inhibitors (AIs) (43 C-PPIs and 28 NC-PPIs), while 43 were combined with fulvastrant (25 C-PPIs and 18 NC-PPIs). For ribociclib, 82 patients were combined with AIs (71 C-PPIs and 11 NC-PPIs) and 21 were combined with fulvastrant (10 C-PPIs and 11 NC-PPIs). Patients with C-PPI had lower progression-free survival (PFS) than those without C-PPI, palbociclib recipients with AIs or fulvastrant (8.97 months vs. 19.02 months, P < 0.001; 13.72 months vs. 18.52 months, P = 0.04, respectively) and ribociclib recipients with AIs (10.7 months vs. 19.7 months, P = 0.05), but not in patients who received ribociclib with fulvastrant (P = 0.52).Conclusion: The simultaneous use of PPIs with palbociclib or ribociclib may be associated with a shorter PFS in HR+, HER2- MBC patients. These results have the potential to enhance clinical decision-making by identifying possible drug interactions and optimizing treatment plans.