Abstract 695P
Background
Proton pump inhibitors (PPIs) are widely used in cancer patients to mitigate polypharmacy-associated adverse gastroesophageal events. However, pharmacokinetic data showed that concomitant administration of pazopanib and PPIs leads to decreased plasma concentrations and exposure of pazopanib by 40% (Cancer Chemother Pharmacol 2013; 71: 1635–1643). The current study aimed at investigating the effect of concomitant PPIs on pazopanib progression-free survival (PFS) in patients affected by metastatic renal cell carcinoma (mRCC).
Methods
mRCC patients candidate to pazopanib as first line treatment were enrolled in this retrospective observational study. Patients were defined as “no concomitant PPIs” if no PPIs were administered during pazopanib, and as “concomitant PPIs” if the administration of PPIs covered the entire or not less than 2/3 of treatment with pazopanib. All clinical interventions were made according to clinical practice.
Results
A total of 126 patients were enrolled; median PFS to pazopanib was 12 months. Fifty-nine patients belonged to “no concomitant PPIs” during pazopanib treatment and 67 to the “concomitant PPIs” group. Most prescribed PPIs were lansoprazole and pantoprazole. The overall population was stratified according to PFS, showing no difference in the two groups (PFS 8.9 vs 13.7 months, p=0.95). Patients were stratified based on median PFS as “short” (n=70) and “long” (n=56) responders. In the long-responders group, there was a significant difference in terms of PFS in patients assuming vs not assuming PPIs, being 24.7 vs 45.5 months, respectively (n=35 vs 21, p=0.03). Multivariate analysis included gender, age, ECOG, nephrectomy, radiotherapy, number of metastatic sites, and IMDC score and confirmed the use of concomitant PPIs as the only independent predictive factor for shorter PFS (p=0.04).
Conclusions
This study demonstrates that concomitant use of PPIs in mRCC patients treated with pazopanib for long time has a detrimental effect on PFS. Therefore, it is recommended to prescribe PPIs with strict compliance with the registered indications and for short periods (usually not more than 2 weeks) or use alternative gastroprotective procedures.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
M. Del Re.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.