bims-cyhorp 2022-12-18 papers

Issue of 2022–12–18
two papers selected by
Piotr Okupski,

Eur J Clin Pharmacol. 2022 Dec 15.

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

Dilek Çağlayan, Mehmet Zahid Koçak, Çağlayan Geredeli, Ali Murat Tatlı, Sema Sezgin Göksu, Melek Karakurt Eryılmaz, Murat Araz, Mehmet Artaç.

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.

Keywords: CDK 4/6 inhibitors; Palbociclib; Progression free survival; Proton pump inhibitors; Ribociclib

DOI: https://doi.org/10.1007/s00228-022-03435-7

Int J Mol Sci. 2022 Nov 22. pii: 14534. [Epub ahead of print]23(23):

Biomarkers of Response and Resistance to CDK4/6 Inhibitors in Breast Cancer: Hints from Liquid Biopsy and microRNA Exploration.

Eriseld Krasniqi, Frauke Goeman, Claudio Pulito, Alina Catalina Palcau, Ludovica Ciuffreda, Francesca Sofia Di Lisa, Lorena Filomeno, Maddalena Barba, Laura Pizzuti, Federico Cappuzzo, Giuseppe Sanguineti, Marcello Maugeri-Saccà, Gennaro Ciliberto, Maurizio Fanciulli, Giovanni Blandino, Patrizia Vici.

New evidence on the impact of dysregulation of the CDK4/6 pathway on breast cancer (BC) cell proliferation has led to the development of selective CDK4/6 inhibitors, which have radically changed the management of advanced BC. Despite the improved outcomes obtained by CDK4/6 inhibitors, approximately 10% of tumors show primary resistance, whereas acquired resistance appears to be an almost ubiquitous occurrence, leading to treatment failure. The identification of differentially expressed genes or genomic mutational signatures able to predict sensitivity or resistance to CDK4/6 inhibitors is critical for medical decision making and for avoiding or counteracting primary or acquired resistance against CDK4/6 inhibitors. In this review, we summarize the main mechanisms of resistance to CDK4/6 inhibitors, focusing on those associated with potentially relevant biomarkers that could predict patients' response/resistance to treatment. Recent advances in biomarker identification are discussed, including the potential use of liquid biopsy for BC management and the role of multiple microRNAs as molecular predictors of cancer cell sensitivity and resistance to CDK4/6 inhibitors.

Keywords: CDK4/6 inhibitors; abemaciclib; breast cancer; liquid biopsy; microRNA; palbociclib; ribociclib

DOI: https://doi.org/10.3390/ijms232314534