The Concomitant Use Of Proton Pump Inhibitors And Pazopanib In Patients With Soft-Tissue Sarcoma: Is It Really To Be Avoided?

Abstract

Objectives: Pazopanib is an orally administered drug and has approval for the treatment of advanced Soft Tissue Sarcomas (aSTS). The absorption of pazopanib is pH-dependent. Acid-Reducing drugs such as proton pump inhibitors (PPI) may reduce the bioavailability of pazopanib. The primary purpose of this study was to assess whether the use of concomitant PPI and pazopanib had negative effects on survival outcomes. Methods: In this retrospective cross-sectional study, age ≥18 years, having histologically proven STS, receiving pazopanib at least one day, and availability of information about the use of PPI during pazopanib treatment were the inclusion criteria. Patients with adipocytic sarcoma were excluded. Results: A total of 46 eligible patients were assessed in this study. Thirty-one patients used concomitant PPI and pazopanib, 17 of them frequently used PPI, and the others occasionally. Fifteen patients never used concomitant PPI and pazopanib. The median progression-free survival (PFS) was 2.76 months, and the median overall survival (OS) was 7.39 months for patients who never used concomitant PPI and pazopanib. Also, the median PFS was 5.22 months, and the median OS was 14.52 months for patients who used concomitant PPI and pazopanib. In univariate analysis; using concomitant PPI (p=0.049) and primarily uterine located tumors (p=0.038) were significant parameters for PFS. In multivariate logistic regression analysis; both of using concomitant PPI (Wald=6.02; p=0.014) and primarily uterine located tumors (Wald=5.69; p=0.017) retained their association with longer PFS. No parameter was significant for OS. Conclusions: We showed that the use of concomitant PPI and pazopanib was associated with improved PFS. These results may help guide clinicians and researchers for allowing patients co-administrating PPI and pazopanib, especially when treating or investigating patients with dyspeptic symptoms.