Effect of Concomitant pH-Elevating Medications with Pazopanib on Progression-Free Survival and Overall Survival in Patients with Metastatic Renal Cell Carcinoma

Abstract

Pazopanib is a preferred category-one first-line treatment for predominant clear cell metastatic renal cell carcinoma (mRCC). However, because of an aging demographic, coupled with patients with mRCC presenting with multiple comorbidities, including symptomatic dyspepsia or gastroesophageal reflux disease, patients are commonly required to take pazopanib concomitantly with a proton pump inhibitor (PPI) or a histamine 2 receptor antagonist (H2RA). Despite earlier pharmacokinetic reports suggesting that an alkaline pH may result in poorer absorption, this institutional retrospective study found no effect on clinical outcomes. These data suggest that concurrent treatment of mRCC with pazopanib and a PPI or H2RA may be safe in everyday practice.

Imatinib, sunitinib and pazopanib: From flat‐fixed dosing towards a pharmacokinetically guided personalized dose

“…Two studies reported shorter PFS and overall survival (OS) in patients treated with pazopanib receiving concomitant pH‐elevating medication, though in one of these studies the effect on treatment outcome was not statistically significant . Unfortunately, no pazopanib plasma concentrations were measured.…”

“…Two studies reported shorter PFS and overall survival (OS) in patients treated with pazopanib receiving concomitant pH-elevating medication, though in one of these studies the effect on treatment outcome was not statistically significant. 148,149 Unfortunately, no pazopanib plasma concentrations were measured. However, considering the essential role of gastric pH in the absorption of pazopanib and the previously established decrease in pazopanib AUC when combined with a proton pump inhibitor, it is likely that the shortened survival is caused by underexposure to pazopanib.…”

Impact of Use of Gastric-Acid Suppressants and Oral Anticancer Agents on Survival Outcomes: A Systematic Review and Meta-Analysis

“…A total of 353 potentially eligible records were identified in the electronic databases. After exclusion of n=337 not pertinent papers, n=16 were selected for inclusion in quantitative analysis (n=372,418 patients included, with 12% of patients receiving concomitant GAS therapy) [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31]. The search results and characteristics of the included studies are presented in figure 1 and tables 1-2.…”

Impact of Use of Gastric-Acid Suppressants and Oral Anticancer Agents on Survival Outcomes: A Systematic Review and Meta-Analysis

“…A total of 353 potentially eligible records were identified in the electronic databases. After exclusion of n=337 not pertinent papers, n=16 were selected for inclusion in quantitative analysis (n=372,418 patients included, with 12% of patients receiving concomitant GAS therapy) [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] All studies were retrospective except for a pooled analysis of phase 2-3 studies by Lalani et al and a secondary analysis of a randomized prospective trial by Chu et al Oncologic treatment consisted in oral TKIs in n=11 studies, while in n=4 studies patients received oral chemotherapy (i.e. capecitabine); one study did not include information regarding the type of study drugs.…”