Drug-drug interactions between palbociclib and proton pump inhibitors may significantly affectclinical outcome of metastatic breast cancer patients

Background: Proton pump inhibitors (PPIs) are widely used in cancer patients to mitigate adversegastroesophageal events polypharmacy-associated. However, drugdrug interactions (DDIs) atabsorption level should be considered as it may affect clinical outcome. Palbociclib is a weak basewith pH-dependent solubility that rapidly decreases as pH increases above 4.5 (Clin Pharmacol DrugDev 2017;6:614-6). The current study was aimed at investigating the effect of concomitant PPIs on palbociclibprogression free survival (PFS) in metastatic breast cancer (mBC) patients. Materials and methods: ER+, HER-2- mBC patients candidate to palbociclib as first line treatment were enrolled in thisretrospective observational study. Patients were defined as “no concomitant PPIs” if no PPI wereadministered during palbociclib, and as “concomitant PPIs” if the administration of PPIs covered theentire or not less than 2/3 of treatment with palbociclib. All clinical interventions were madeaccording to clinical practice. Results: A total of 112 patients were enrolled; 56 belonged to “no concomitant PPIs” during palbociclibtreatment and 55 to the "concomitant PPIs” group. Seventy-one patients were endocrine sensitive(ES) and were administered palbociclib + letrozole and 43 were endocrine resistant (ER) and weretreated with palbociclib + fulvestrant. The most prescribed PPI was lansoprazol. Patients werestratified according to PFS, showing that patients taking PPIs had a shorter PFS compared to patientsassuming palbociclib + hormone-therapy alone (14 vs 38 months, p<0.0001). Multivariate analysisconfirmed the use of concomitant PPIs as the only independent predictive factor for shorter PFS(p=0.0002). PFS was significantly longer in ES mBC with no concomitant PPIs compared to patientstaking PPIs or ER patients with and without PPIs (p<0.0001). No correlation with adverse events wasfound considering G>2 hematological toxicities. Conclusions: The present study demonstrates that concomitant use of PPIs in mBC patients treated withpalbociclib A – Breast Cancer 13 has a detrimental effect on PFS. Therefore, it is recommended to prescribe PPI withcaution in these patients, or administering H2-antagonists or PPI for very short periods.