Proton pump inhibitors may reduce the efficacy of ribociclib and palbociclib in metastatic breast cancer patients

IntroductionApproximately 20-33% of all cancer patients are treated with acid reducing agents (ARAs), most commonly proton pump inhibitors (PPIs), to reduce gastro esophageal reflux disease symptoms. Palbociclib and ribociclib are weak base so their solubility depends on different pH. The solubility of palbociclib dramatically decreases to <0.5 mg/ml when pH is above 4,5 but ribociclibs’ solubility decreases when pH increases above 6,5. In the current study, we aimed to investigate the effects of concurrent PPIs on palbociclib and ribociclib efficacy in terms of progression free survival in metastatic breast cancer (mBC) patients.Patients and methodsWe enrolled hormone receptor-positive, HER2-negative mBC patients treated with endocrine treatment (Letrozole or fulvestrant) combined palbociclib or ribociclib alone or with PPI accompanying our observational study. During palbociclib/ribociclib therapy, patients should be treated with "concurrent PPIs" defined as all or more than half of treatment with palbociclib/ribociclib, if no PPI was applied, it was defined as 'no concurrent PPI', those who used PPI but less than half were excluded from the study. All data collected from real life retrospectively.ResultsOur study included 217 patients, 105 of whom received palbociclib and 112 received ribociclib treatment. Of 105 patients who received Palbociclib, 65 were on concomitant PPI therapy, 40 were not. Of the 112 patients who received ribociclib, 61 were on concomitant PPI therapy, 51 were not. In the palbociclib group, the PFS of the patients using PPI was shorter than the PFS of the patients not using (13.04 months vs. unreachable, p<0.0001). it was determined that taking PPI was an independent predictor of shortening PFS (p<0.001) in the multivariate analysis, In the ribociclib group, the PFS of the patients using PPI was shorter than the PFS of the patients not using (12.64 months vs. unreachable, p=0.003). It was determined that taking PPI was single statistically independent predictor of shortening PFS (p=0.003, univariate analysis).ConclusionsOur study demonstrated that concomitant usage of PPIs was associated with shorter PFS in mBC treated with both ribociclib and especially palbociclib. If it needs to be used, PPI selection should be made carefully and low-strength PPI or other ARAs (eg H2 antagonists, antacids) should be preferred.