The administration of proton pump inhibitors (PPIs) is a common practice to reduce gastro-esophageal adverse events associated with drug treatments but may impair absorption and exposure to oncology drugs. This study investigated the effect of concomitant administration of PPIs and pazopanib, sunitinib and cabozantinib on survival of patients with metastatic clear cell renal carcinoma (mRCC).
Total 451 patients receiving pazopanib, sunitinib and cabozantinib as first line treatment were enrolled in this retrospective study. Patients were defined as "no concomitant PPIs (PPI-)" if no PPIs were administered during TKIs, and as "concomitant PPIs (PPI+)" if the administration of PPIs was at least 75% of the time during which TKIs were given.
Eighty patients administered pazopanib were PPI- and 86 PPI+; no difference in PFS was observed (10.7 vs. 11.9 months, P = .79). If patients were stratified as short (n = 89) and long (n = 77) responders, there was a significant difference in terms of PFS in PPI+ (n = 47) versus PPI- (n = 30) in long responders, being 24.7 versus 38 months (P = .04), respectively. In the sunitinib cohort, no significant difference of PFS in PPI+ (n = 102) versus PPI- (n = 131) was found, being 11.3 versus 18.1 months, respectively (P=0.15). In the cabozantinib cohort, there was a statistically significant difference in PFS of PPI+ versus PPI- (6 months vs. not reached, P = .04). No correlation with adverse events was found.
This study demonstrates an association between PPIs and impaired PFS in mRCC patients given pazopanib and cabozantinib and recommends caution on their concomitant use.
Clinical genitourinary cancer. 2024 Jun 27 [Epub ahead of print]
Marzia Del Re, Stefania Crucitta, Nicole Brighi, Stefania Kinspergher, Chiara Mercinelli, Mimma Rizzo, Vincenza Conteduca, Sara Elena Rebuzzi, Teresa Beninato, Giulia Venturi, Laura Doni, Elena Verzoni, Silvia Puglisi, Matteo Landriscina, Camillo Porta, Fiorella Manfredi, Orazio Caffo, Ugo De Giorgi, Stefano Fogli, Romano Danesi
Department of Clinical and Experimental Medicine, Unit of Clinical Pharmacology and Pharmacogenetics, University of Pisa, Pisa, Italy., Oncology Department, IRCCS Istituto Scientifico Romagnolo per lo Studio dei Tumori "Dino Amadori", Meldola, Italy., Department of Medical Oncology, Santa Chiara Hospital, Trento, Italy., Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy., Division of Medical Oncology, Azienda Ospedaliero-Universitaria Policlinico di Bari, Bari, Italy., Unit of Medical Oncology and Biomolecular Therapy, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy., Unit of Medical Oncology 1, Department of Internal Medicine and Medical Specialties, University of Genova, IRCCS Ospedale San Martino, Genova, Italy., Department of Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy., Department of Oncology, Azienda Ospedaliero-Universitaria Careggi, Firenze, Italy., Division of Medical Oncology, Azienda Ospedaliero-Universitaria Policlinico di Bari, Bari, Italy; Interdisciplinary Department of Medicine, University of Bari "A. Moro", Bari, Italy., Department of Oncology and Hemato-Oncology, University of Milano, Milano, Italy. Electronic address: .