The effect of concomitant use of proton pump inhibitors with CDK 4/6 inhibitors on survival in metastatic breast cancer

• Published in: European journal of clinical pharmacology 2023-02, Vol.79 (2), p.243-248
• Main Authors: Çağlayan, Dilek, Koçak, Mehmet Zahid, Geredeli, Çağlayan, Tatlı, Ali Murat, Göksu, Sema Sezgin, Eryılmaz, Melek Karakurt, Araz, Murat, Artaç, Mehmet
• Format: Article
• Language: English
• Subjects: Aminopyridines - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Bioavailability; Biomedical and Life Sciences; Biomedicine; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Cancer therapies; Cyclin-dependent kinase; Drug dosages; Endocrine therapy; ErbB-2 protein; Female; Humans; Metastases; Metastasis; Oncology; pH effects; Pharmacology; Pharmacology/Toxicology; Protein Kinase Inhibitors - therapeutic use; Proton pump inhibitors; Proton Pump Inhibitors - pharmacology; Proton Pump Inhibitors - therapeutic use; Purines - therapeutic use; Survival; Survival analysis; Targeted cancer therapy; Ulcers
• ISSN: 0031-6970; 1432-1041
• DOI: 10.1007/s00228-022-03435-7

Aim To evaluate the difference of progression free survival between the patients using concomitant proton pump inhibitors and non-users in the patients using CDK 4/6 inhibitors with HR + and HER2 negative mBC. Methods We included 86 patients with HR + and HER 2 negative mBC treated with CDK 4/6 inhibitors in this study. Patients were divided into two categories according to their status of PPI use. The primary end points was progression free survival (PFS). We compared PPI users and non-users. Results Forty-five (52.3%) patients used a PPI concomitantly with a CDK 4/6 inhibitor, and 41 (47.7%) did not. The median duration of follow-up was 10.68 (1.94–27.56) months. Of the patients, 50 (58.1%) palbociclib and 36 (41.9%) received ribociclib. The median progression free survival (mPFS) was 10.9 months (95% CI : 7.5–14.27) in the group with concomitant PPI use with a CDK 4/6 inhibitor, whereas the median progression free survival could not be reached in the group without concomitant PPI use ( p  = 0.04). In addition, concomitant PPI use with palbociclib was associated with a shorter PFS; there was no significant difference between the concomitant PPI users and non-users in terms of PFS in the patients using ribociclib. Conclusion Palbociclib and ribociclib are weak base drugs so their bioavailability is pH-dependent. PPIs can affect their solubility and their concentration in the plasma. Therefore, we must avoid concomitant use of PPIs and CDK 4/6 inhibitors. If we need to use concomitant PPI and CDK 4/6 inhibitors, we should prefer ribociclib than palbociclib.