Abstract 239P
Background
Proton pump inhibitors (PPIs) are widely used in cancer patients to mitigate polypharmacy-associated adverse gastroesophageal events. However, drug-drug interactions (DDIs) at absorption level should be considered as it may affect clinical outcome. Palbociclib is a weak base with pH-dependent solubility that rapidly decreases as pH increases above 4.5 (Clin Pharmacol Drug Dev 2017;6:614-6). The current study was aimed at investigating the effect of concomitant PPIs on palbociclib progression-free survival (PFS) in metastatic breast cancer (mBC) patients.
Methods
ER+, HER-2- mBC patient candidates for palbociclib as first-line treatment were enrolled in this retrospective observational study. Patients were defined as “no concomitant PPIs” if no PPI were administered during palbociclib, and as “concomitant PPIs” if the administration of PPIs covered the entire or not less than 2/3 of treatment with palbociclib. All clinical interventions were made according to clinical practice.
Results
A total of 112 patients were enrolled; 56 belonged to “no concomitant PPIs” during palbociclib treatment and 56 to the “concomitant PPIs” group. Seventy-one patients were endocrine sensitive (ES) and were administered palbociclib + letrozole and 41 were endocrine resistant (ER) and were treated with palbociclib + fulvestrant. The most prescribed PPI was lansoprazol. Patients were stratified according to PFS, showing that patients taking PPIs had a shorter PFS compared to patients assuming palbociclib + hormone-therapy alone (14 vs 38 months, p<0.0001). Multivariate analysis confirmed 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 patients taking PPIs or ER patients with and without PPIs (p<0.0001). No correlation with adverse events was found considering G>2 hematological toxicities.
Conclusions
The present study demonstrates that concomitant use of PPIs in mBC patients treated with palbociclib has a detrimental effect on PFS. Therefore, it is recommended to prescribe PPI with caution in these patients, or administering H2-antagonists or PPI for very short periods.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Marzia Del Re.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.