Effect of Acid‐Suppressive Strategies on Pazopanib Efficacy in Patients With Soft‐Tissue Sarcoma

摘要

Pazopanib (PAZ), a tyrosine kinase inhibitor used in the treatment of soft tissue sarcoma (STS), should not be administered with acid‐suppressive medications (ASMs) due to decreased drug solubility. Common practice for patients requiring ASM with PAZ is to separate administration by 12 hours; however, there is little real‐world evidence describing clinical outcomes using this strategy. The aim of this study was to determine whether concomitant ASM impacted efficacy and adverse event rates in patients with STS receiving PAZ. Medical records were retrospectively reviewed for patients with STS who received PAZ from June 2011 to July 2017. Patients were stratified into two groups, PAZ with or without ASM (PAZ + ASM or PAZ only). The primary objective was to determine whether progression‐free survival (PFS) differed between groups. Secondary objectives were to determine overall survival (OS) and occurrence of grade 3/4 toxicities. Ninety‐one patients were included in the study, 42 patients in the PAZ + ASM group and 49 in the style="fixed-case">PAZ only group. Median style="fixed-case">PFS was significantly shorter in the style="fixed-case">PAZ +  style="fixed-case">ASM group than the style="fixed-case">PAZ only group (5.3 vs. 6.7 months). The style="fixed-case">PAZ +  style="fixed-case">ASM group also had a 74% higher relative risk of progression or death than the style="fixed-case">PAZ only group, but there was no difference in style="fixed-case">OS. Regarding adverse events, the style="fixed-case">PAZ +  style="fixed-case">ASM group trended toward lower levels of grade 3/4 hypertension (19% vs. 37%). These results suggest that style="fixed-case">ASM should be avoided in patients with style="fixed-case">STS receiving PAZ. Larger studies are needed to further elucidate the impact of style="fixed-case">ASM use with PAZ in clinical practice.