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ePoster Display

695P - Drug-drug interactions between pazopanib and proton pump inhibitors may significantly affect clinical outcome of patients affected by metastatic renal cell carcinoma

Date

16 Sep 2021

Session

ePoster Display

Presenters

Marzia Del Re

Citation

Annals of Oncology (2021) 32 (suppl_5): S678-S724. 10.1016/annonc/annonc675

Authors

M. Del Re1, N. Brighi2, M. Rizzo3, F. Paolieri4, S.E. Rebuzzi5, T. Beninato6, S. Crucitta1, C. Mercinelli4, N. Gri3, S. Puglisi5, E. Verzoni6, S. Bleve2, F. Cucchiara1, G. Procopio6, G. Fornarini5, L. Galli4, C.G. Porta7, U. De Giorgi2, R. Danesi1

Author affiliations

  • 1 Clinical And Experimental Medicine - Unit Of Clinical Pharmacology And Pharmacogenetics, University Hospital of Pisa, 56100 - Pisa/IT
  • 2 Oncology Department, IRCCS Istituto Scientifico Romagnolo Per Lo Studio Dei Tumori (IRST) “Dino Amadori”, 47014 - Meldola/IT
  • 3 Division Of Translational Oncology, I, IRCCS Istituti Clinici Scientifici Maugeri, NA - Pavia/IT
  • 4 Medical Oncology, Azienda Ospedaliero Universitaria Pisana, Santa Chiara Hospital, 56100 - Pisa/IT
  • 5 Department Of Internal Medicine And Medical Specialties (di.m.i.), University Of Genova, IRCCS Ospedale San Martino of Genova, Medical Oncology Unit 1, 16132 - Genova/IT
  • 6 Oncology Department, Istituto Nazionale dei Tumori di Milano - Fondazione IRCCS, 20133 - Milan/IT
  • 7 Biomedical Sciences And Human Oncology, Division Of Medical Oncology, Università degli Studi di Bari Aldo Moro, 70121 - Bari/IT
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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.

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