Effect of concomitant proton pump inhibitor (PPI) on effectiveness of tyrosine kinase inhibitor (TKI) in patients ,mRCC

[D.ap]

Effect of concomitant proton pump inhibitor (PPI) on effectiveness of tyrosine kinase inhibitor (TKI) in patients with metastatic renal cell carcinoma (mRCC).

Abstract

“Background: PPIs may reduce TKI bioavailability resulting in reduced efficacy, shortened time on TKI treatment, and disease progression. Axitinib, sorafenib, and pazopanib exhibit pH-dependent solubility. Esomeprazole reduced the AUC and Cmax of pazopanib by 40%, but there was no significant interaction for sorafenib with omeprazole or axitinib with rabeprazole. In real world practice, the effect of PPIs as a class on the efficacy of TKIs as a class in mRCC has not been reported. Methods: This observational cohort study evaluated adult patients treated with a TKI for mRCC. Time on TKI treatment was defined as TKI initiation date to date of discontinuation, change in therapy, lost to follow-up, or death. We performed a treatment line analysis. Time on TKI treatment was compared between patients with and without concurrent PPI (Kaplan-Meier, log-rank). Results: Analysis included 128 treatment lines, including 49 TKI with PPI and 79 TKI with no PPI treatment lines. TKIs included sunitinib, pazopanib, sorafenib, and axitinib. PPIs included omeprazole, lansoprazole, esomeprazole, pantoprazole, and rabeprazole. The three most common TKI/PPI combinations involved omeprazole with sunitinib (26), pazopanib (13), and axitinib (3). No difference in time on TKI treatment with PPI (median 8.7 months) and with no PPI (median 7.0 months, p = 0.41) was observed. In pazopanib treatment lines, no difference in time on treatment was observed in those treated with omeprazole or esomeprazole (n = 14, median 4.8 months) compared to those without PPI (n = 18, median 1.7 months, p = 0.22). Conclusions: Among the TKI/PPI combinations evaluated, there was no difference in time to TKI discontinuation with or without concurrent PPI. This suggests that concurrent PPI does not affect time to discontinuation of TKI. Study limitations include the small sample size, limited number of TKI/PPI combinations, and retrospective study design. A larger study is needed to validate these findings.”




http://ascopubs.org/doi/abs/10.1200/jco ... _suppl.608