The administration of proton pump inhibitors with the CDK4/6 inhibitor abemaciclib does not affect the clinical outcome of metastatic breast cancer patients

Background: CDK4/6 inhibitors abemaciclib, palbociclib, and ribociclib have rapidly become an established oral treatment for patients with ER+, HER2− locally advanced or metastatic breast cancer. The use of the oral route offers convenience and flexibility to the patient; however, the co-administration of proton pump inhibitors (PPIs) to mitigate gastrointestinal adverse events induced by anticancer treatments may decrease drug solubility, bioavailability, and potentially impact treatment efficacy. Objectives: The present study was aimed at investigating whether PPIs may affect the progression-free survival (PFS) of patients treated with abemaciclib. Design: Multicenter observational cohort study on clinical data collected retrospectively. Methods: Patients with ER-positive/HER2-negative mBC candidates for a first-line treatment with abemaciclib as per clinical practice were enrolled. Patients were classified as “no concomitant PPIs” or “concomitant PPIs” if PPI administration covered not less than 2/3 of the treatment period with abemaciclib. All clinical interventions were made according to clinical practice. Results: One hundred eight patients were enrolled in this study; 66 belonged to the “no concomitant PPIs” group and 42 to the “concomitant PPIs” group. No statistically significant difference in PFS was found between the two groups (p = 0.77). Likewise, no difference in PFS was observed in endocrine-sensitive or -resistant mBC in the presence or absence of concomitant PPI treatment. No correlation with adverse events, including hematological or gastrointestinal toxicities, was found. Conclusion: This study demonstrates that the administration of PPIs to patients treated with abemaciclib is not associated with clinically significant drug–drug interactions on PFS.