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

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M. Del Re¹  C. Omarini²  L. Diodati³  M. Palleschi⁴  I. Meattini⁵  S. Crucitta¹  G. Lorenzini³  C. Isca²  A. Fontana³  L. Livi⁵  F. Piacentini²  S. Fogli¹  U. De Giorgi⁴  R. Danesi¹ 

[1] Unit of Clinical Pharmacology and Pharmacogenetics, Department of Clinical and Experimental Medicine, University Hospital of Pisa;Division of Medical Oncology, University Hospital of Modena;Unit of Medical Oncology, Department of Translational Research and New Technologies in Medicine, University of Pisa;Unit of Medical Oncology, IRCCS-Istituto Romagnolo per lo Studio dei Tumori;Department of Experimental and Clinical Biomedical Sciences ‘M. Serio’, University of Florence;Radiation Oncology Unit – Oncology Department, Azienda Ospedaliero Universitaria Careggi

关键词: breast cancer;    palbociclib;    proton pump inhibitors;    drug-drug interactions;    PFS;   

DOI  :  10.1016/j.esmoop.2021.100231

学科分类：社会科学、人文和艺术（综合）

来源: BMJ Publishing Group

【 摘 要 】

Background Proton-pump-inhibitors (PPIs) are frequently prescribed for the management of anticancer drug-related gastrointestinal symptoms. Palbociclib is a weak base with pH-dependent solubility and potential drug-drug interaction at the absorption level may affect clinical pharmacokinetics. The current study was aimed at investigating the effect of co-administration of PPIs and palbociclib on progression-free survival (PFS) in metastatic breast cancer (mBC) patients.Patients and methods Patients affected by estrogen receptor-positive, human epidermal growth factor receptor 2-negative mBC, who were candidates for first-line treatment with palbociclib, were enrolled in this retrospective observational study. Patients were defined as ‘no concomitant PPIs' if no PPIs were administered during palbociclib treatment, and as ‘concomitant PPIs' if the administration of PPIs covered the entire or not less than two-thirds of treatment with palbociclib. All clinical interventions were made according to clinical practice.Results A total of 112 patients were enrolled in the study; 56 belonged to the ‘no concomitant PPIs' group and 56 to the ‘concomitant PPIs' group. Seventy-one patients were endocrine-sensitive and received palbociclib and letrozole, and 43 were endocrine-resistant and were treated with palbociclib and fulvestrant. The most prescribed PPI was lansoprazole. Patients taking PPIs had a shorter PFS than those taking palbociclib and endocrine therapy alone (14.0 versus 37.9 months, P < 0.0001). Multivariate analysis confirmed concomitant PPIs as the only independent predictive factor for shorter PFS (P = 0.0002). PFS was significantly longer in estrogen-sensitive mBC with no concomitant PPIs compared with patients taking PPIs or estrogen-resistant patients, with and without PPIs (P 2 hematological toxicities [Common Terminology Criteria for Adverse Events (CTCAE) scale].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 PPIs with caution in these patients, strictly adhering to the indications in the summary of product characteristics (RCP).

【 授权许可】

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