SynthesisSystematic reviews2025
Pharmacokinetic interactions and clinical implications of PPIs and CDKIs in breast cancer: a systematic review and meta-analysis.
Synthesis in Systematic reviews, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundBreast cancer is the fourth leading cause of cancer mortality worldwide. New drugs, such as cyclin-dependent kinase 4/6 inhibitors (CDKIs), increase the life expectancy of receptor-positive (HR+) and human epidermal growth factor receptor 2 negative (HER2-) breast cancer patients. This class acts to limit the G1/S transition in tumor cells, inducing tumor cell death. Owing to the basic nature of CDKIs, their solubilities are pH dependent and could be influenced by the concurrent use of acid-reducing agents such as proton pump inhibitors (PPIs). This meta-analysis aims to assess the impact of co-administering PPIs on the pharmacokinetics and clinical efficacy of CDKIs in breast cancer patients.
methodsFour databases with English-language restriction were searched for concomitant CDKIs and PPIs keywords from their inception date to 2024 March 7th. Prospective, retrospective, randomized or nonrandomized clinical studies and observational longitudinal studies with at least one outcome of interest were included. The outcomes included pharmacokinetic variables, progression-free survival (PFS), and overall survival (OS).
resultsWe included three pharmacokinetic studies conducted in patients enrolled in clinical trials and seven clinical studies evaluating survival outcomes. When coadministered with palbociclib, PPIs significantly reduced the serum maximum concentration (Cmax) (MD -35.37 ng/mL; 95%CI from -67.59 to -3.16) and increased the clearance (CL/F) (MD 61.24 L/h; 95%CI from 14.66 to 107.82). Ribociclib Cmax and AUC did not significantly differ among the PPIs users. However, the overall PFS favored PPIs non-users (HR 1.74; 95%CI from 1.28 to 2.37). Consistently, coadministration of PPIs with CDKIs significantly increased the likelihood of reduced OS (HR 1.99; 95%CI from 1.18 to 3.33). The effect was confirmed only for the palbociclib subgroup (HR 2.11; 95%CI from 1.17 to 3.81). No data were available for OS evaluation with ribociclib. A single study on abemaciclib revealed nonsignificant differences (HR 1.30; 95%CI from 0.53 to 3.19), with similar results for OS.
conclusionsPPI use in HR + /HER2- breast cancer patients treated with palociclib should be avoided. When strictly necessary, ribociclib may be preferred to palbociclib, even though closer monitoring is strongly advised. SYSTEMATIC REVIEW REGISTRATION: PROSPERO identifier number CRD42024506456.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.