Effect of Concomitant Proton Pump Inhibitors with Pazopanib on Cancer Patients: A Retrospective Analysis

Abstract

The absorption of pazopanib depends on gastric pH. PPIs are frequently prescribed for cancer patients to modify gastric acidity, decreasing pazopanib absorption. The aim of our study was, retrospectively, to investigate the impact of PPIs on the clinical efficacy and safety of pazopanib in a cohort of patients treated in our health center. Of the 147 patients who were included retrospectively, 79 (54%) did not take PPIs concomitantly with pazopanib (cohort 1), while 68 (46%) patients did take PPIs concomitantly with pazopanib (cohort 2). The efficacy parameters were lower in patients taking pazopanib and PPIs: the i/tumor response was statistically different between the two cohorts (p = 0.008), in particular, with 19% vs. 3% of the objective response and 24% vs. 43% of progression in cohorts 1 and 2, respectively; ii/median overall survival was 17.6 (95% CI: 12.5–32.8) months in cohort 1 and 8.6 months (95% CI: 5.9–18.6) in cohort 2 (HR = 1.7 [95% CI: 1.2–2.5]; p < 0.006); on multivariable analysis, overall survival was associated with performance status, PPI intake, tumor location, hemoglobin, and PMN/lymphocyte ratio. In contrast, the dose reduction for toxicity and severe adverse events were (non-significantly) less frequent in cohort 1. To conclude, our study shows that combining PPIs with pazopanib has an adverse effect on overall survival. The clinical modifications that were observed are in line with a decrease in pazopanib absorption due to PPIs. This co-medication should be avoided.

Concomitant Use of Proton Pump Inhibitors and Palbociclib Among Patients With Breast Cancer

“…Proton pump inhibitors alter the gastrointestinal environment by decreasing gastric acid secretion, consequently influencing drug absorption. 18 Based on the research that reported that patient clinical outcomes deteriorate when oral weakly basic anticancer medications such as tyrosine kinase inhibitors are used in combination with PPIs, 19 , 20 , 21 it appears that complete absorption of palbociclib has been achieved, so it has not shown sufficient therapeutic performance. Even though the type of cancer studied was different from ours, this association was also confirmed from the previous studies.…”

Do proton pump inhibitors affect the effectiveness of cyclin-dependent kinase 4/6 inhibitors in advanced HR positive, HER2 negative breast cancer? A meta-analysis

“…Existing studies have indicated that the concurrent use of PPIs can diminish the antitumor effectiveness or certain drugs like capecitabine and pazopanib ( van Leeuwen et al, 2014 ; Raoul et al, 2023 ). On the other hand, it does not appear to exert a significant influence on the clinical outcomes of patients undergoing treatment with epidermal growth factor receptor (EGFR) inhibitors ( Hilton et al, 2013 ; Kumarakulasinghe et al, 2016 ; Chu et al, 2017 ; Moreau-Bachelard et al, 2022 ).…”