The impact of gastric acid suppressive agents on pazopanib exposure.

Abstract

e16076 Background: Pazopanib has been registered for advanced soft tissue sarcoma (STS) and metastatic renal cell carcinoma (mRCC). The uptake of pazopanib is 40% reduced when a proton pump inhibitor is concomitantly used. Nevertheless, still a large group of cancer patients need a form of gastric acid suppressive agents (GAS, e.g. proton pump inhibitors or H2-anagonists) due to gastrointestinal adverse events. Recently, it was demonstrated that the use of pazopanib with GAS resulted in shorter overall survival and progression free survival in patients with STS. In order to limit the effect of GAS on pazopanib absorption, the advice is to take the GAS 1 hour after pazopanib. In that way the pazopanib is dosed at the lowest gastric pH value. However, the effect of this most optimal controlled intake on pazopanib absorption is unknown. Therefore, we investigated whether this controlled intake algorithm affects pazopanib exposure. Methods: In the DIET study, pazopanib trough concentrations (Ctrough) were measured at predefined moments. In this study a total of 80 patients with mRCC and STS were included. The concomitant use of GAS was recorded and taken according the intake algorithm. Patients were subdivided into two groups (with GAS or without GAS). Results: Of the 80 patients, 22 patients were treated with pazopanib in combination with GAS. In patients treated with pazopanib without GAS the geometric mean(GM) pazopanib Ctrough level was 29.1 mg/L (95% CI 26.4 -31.8) compared to 22.4 mg/L (95% CI 18.0-27.8) (p = 0.01) in those treated with GAS. Conclusions: Patient who use pazopanib with controlled intake of GAS had a 23% lower pazopanib exposure. Therefore, we advice that in patients, who are unable to quit their GAS agent, pazopanib trough concentrations should be monitored in order to prevent shorter treatment benefit. Clinical trial information: NCT02138526.