{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T18:42:59Z","timestamp":1791571379038,"version":"4.3.4"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2021,2,25]],"date-time":"2021-02-25T00:00:00Z","timestamp":1614211200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>Cabozantinib is an oral tyrosine kinase inhibitor that is approved for the treatment of metastatic renal cell carcinoma (mRCC). Cabozantinib is a weak base that exhibits a pH-dependent solubility profile in vitro which raises concerns about its bioavailability in patients treated with proton pump inhibitors (PPIs). The purpose of this study was to investigate whether PPI use has an impact on the efficacy, safety, and residual concentration (Ctrough) of cabozantinib in patients with mRCC.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Materials and Methods<\/jats:title>\n                  <jats:p>This is a retrospective review of a prospectively collected electronic database of patients with mRCC who received cabozantinib at Gustave Roussy between February 2014 and December 2018. The Kaplan-Meier method was used for survival analysis and the Cox proportional-hazard model for uni- and multivariate analysis. In parallel, we conducted a pharmacokinetic study of cabozantinib in a distinct cohort of 50 mRCC patients, in which cabozantinib Ctrough was assayed using a validated tandem mass spectrometry\u2013liquid chromatography method.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We identified 99 patients treated with cabozantinib, including 43 patients being PPI users. With a median follow-up of 30.3 months, PPI users showed similar progression-free survival and overall survival outcomes compared with PPI nonusers. Similarly, the incidence of adverse events was not significantly different between the PPI users and nonusers, although PPI users required dose reductions more often. In the independent pharmacokinetic cohort, of whom 21 received PPI concomitantly, Ctrough was similar between the two groups.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>In line with the pharmacologic data, the concomitant use of PPI does not significantly impact the efficacy or safety of cabozantinib in patients with mRCC.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Implications for Practice<\/jats:title>\n                  <jats:p>Drug interactions, especially between targeted therapies and proton pump inhibitors (PPI), were shown to potentially impact the outcomes of cancer patients. Cabozantinib, a current therapeutic standard in metastatic renal cell carcinoma (mRCC), exhibits a pH-dependent solubility profile, which raises concerns about its bioavailability in patients treated with proton pump inhibitors (PPI). At the present time, there is no evidence regarding the effect of PPIs on cabozantinib's efficacy and safety in patients with mRCC. This study found that the concomitant use of PPI during cabozantinib treatment in mRCC patients does not appear to impact the residual concentration, efficacy, and safety of cabozantinib in a real-life context.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1002\/onco.13711","type":"journal-article","created":{"date-parts":[[2021,2,8]],"date-time":"2021-02-08T11:20:25Z","timestamp":1612783225000},"page":"389-396","source":"Crossref","is-referenced-by-count":17,"title":["The Effect of Concomitant Proton Pump Inhibitor and Cabozantinib on the Outcomes of Patients with Metastatic Renal Cell Carcinoma"],"prefix":"10.1093","volume":"26","author":[{"given":"Elie","family":"Rassy","sequence":"first","affiliation":[{"name":"Cancer Medicine Department, Gustave Roussy, Universit\u00e9 Paris-Saclay, Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Cerbone","sequence":"additional","affiliation":[{"name":"Cancer Medicine Department, Gustave Roussy, Universit\u00e9 Paris-Saclay, Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edouard","family":"Auclin","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, H\u00f4pital Europ\u00e9en Georges Pompidou, AP-HP, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axelle","family":"Benchimoll-Zouari","sequence":"additional","affiliation":[{"name":"Early Drug Development Department, Gustave Roussy, Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronan","family":"Flippot","sequence":"additional","affiliation":[{"name":"Cancer Medicine Department, Gustave Roussy, Universit\u00e9 Paris-Saclay, Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Alves Costa Silva","sequence":"additional","affiliation":[{"name":"Cancer Medicine Department, Gustave Roussy, Universit\u00e9 Paris-Saclay, Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emeline","family":"Colomba","sequence":"additional","affiliation":[{"name":"Cancer Medicine Department, Gustave Roussy, Universit\u00e9 Paris-Saclay, Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur","family":"Geraud","sequence":"additional","affiliation":[{"name":"Cancer Medicine Department, Gustave Roussy, Universit\u00e9 Paris-Saclay, Villejuif, France"},{"name":"Early Drug Development Department, Gustave Roussy, Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Guida","sequence":"additional","affiliation":[{"name":"Cancer Medicine Department, Gustave Roussy, Universit\u00e9 Paris-Saclay, Villejuif, France"},{"name":"Department of Oncology, Azienda Ospedaliera Santa Maria, Terni, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Mir","sequence":"additional","affiliation":[{"name":"Cancer Medicine Department, Gustave Roussy, Universit\u00e9 Paris-Saclay, Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Combarel","sequence":"additional","affiliation":[{"name":"Medical biology and Pathology Department, Gustave Roussy, Universit\u00e9 Paris-Saclay, Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Paci","sequence":"additional","affiliation":[{"name":"Medical biology and Pathology Department, Gustave Roussy, Universit\u00e9 Paris-Saclay, Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Escudier","sequence":"additional","affiliation":[{"name":"Cancer Medicine Department, Gustave Roussy, Universit\u00e9 Paris-Saclay, Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Albiges","sequence":"additional","affiliation":[{"name":"Cancer Medicine Department, Gustave Roussy, Universit\u00e9 Paris-Saclay, Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,2,25]]},"reference":[{"key":"2021122511543179900_onco13711-bib-0001","doi-asserted-by":"crossref","first-page":"E359","DOI":"10.1002\/ijc.29210","article-title":"Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012","volume":"136","author":"Ferlay","year":"2015","journal-title":"Int J Cancer"},{"key":"2021122511543179900_onco13711-bib-0002","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.semcancer.2012.06.004","article-title":"Current and future systemic treatments for renal cell carcinoma","volume":"23","author":"Fisher","year":"2013","journal-title":"Semin Cancer Biol"},{"key":"2021122511543179900_onco13711-bib-0003","first-page":"12","article-title":"Tyrosine kinase inhibitors and immunotherapy combinations in renal cell carcinoma","author":"Rassy","year":"2020","journal-title":"Ther Adv Med Oncol"},{"key":"2021122511543179900_onco13711-bib-0004","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1056\/NEJMra1601333","article-title":"Systemic therapy for metastatic renal-cell carcinoma","volume":"376","author":"Choueiri","year":"2017","journal-title":"N Engl J Med."},{"key":"2021122511543179900_onco13711-bib-0005","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.euo.2019.06.022","article-title":"Sequencing and combination of systemic therapy in metastatic renal cell carcinoma","volume":"2","author":"Velasco","year":"2019","journal-title":"Eur Urol Oncol"},{"key":"2021122511543179900_onco13711-bib-0006","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1016\/S1470-2045(16)30107-3","article-title":"Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): Final results from a randomised, open-label, phase 3 trial","volume":"17","author":"Choueiri","year":"2016","journal-title":"Lancet Oncol"},{"key":"2021122511543179900_onco13711-bib-0007","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.ejca.2018.02.012","article-title":"Cabozantinib versus sunitinib as initial therapy for metastatic renal cell carcinoma of intermediate or poor risk (Alliance A031203 CABOSUN randomised trial): Progression-free survival by independent review and overall survival update","volume":"94","author":"Choueiri","year":"2018","journal-title":"Eur J Cancer"},{"key":"2021122511543179900_onco13711-bib-0008","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1177\/1078155214527145","article-title":"Does gastric acid suppression affect sunitinib efficacy in patients with advanced or metastatic renal cell cancer?","volume":"21","author":"Ha","year":"2015","journal-title":"J Oncol Pharm Pract"},{"key":"2021122511543179900_onco13711-bib-0009","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.cllc.2014.07.005","article-title":"Gastric acid suppression is associated with decreased erlotinib efficacy in non-small-cell lung cancer","volume":"16","author":"Chu","year":"2015","journal-title":"Clin Lung Cancer"},{"key":"2021122511543179900_onco13711-bib-0010","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1158\/1078-0432.CCR-18-2748","article-title":"Impact of concomitant administration of gastric acid-suppressive agents and pazopanib on outcomes in soft-tissue sarcoma patients treated within the EORTC 62043\/62072 trials","volume":"25","author":"Mir","year":"2019","journal-title":"Clin Cancer Res"},{"key":"2021122511543179900_onco13711-bib-0011","author":"U.S. Food and Drug Administration"},{"key":"2021122511543179900_onco13711-bib-0012","doi-asserted-by":"crossref","first-page":"1814","DOI":"10.1056\/NEJMoa1510016","article-title":"Cabozantinib versus everolimus in advanced renal-cell carcinoma","volume":"373","author":"Choueiri","year":"2015","journal-title":"N Engl J Med"},{"key":"2021122511543179900_onco13711-bib-0013","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.critrevonc.2017.01.014","article-title":"Proton pump inhibitors in cancer patients: How useful they are? A review of the most common indications for their use","volume":"111","author":"Numico","year":"2017","journal-title":"Crit Rev Oncol Hematol"},{"key":"2021122511543179900_onco13711-bib-0014","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1002\/jcph.526","article-title":"Evaluation of the effect of food and gastric pH on the single-dose pharmacokinetics of cabozantinib in healthy adult subjects","volume":"55","author":"Nguyen","year":"2015","journal-title":"J Clin Pharmacol"},{"key":"2021122511543179900_onco13711-bib-0015","doi-asserted-by":"crossref","first-page":"e315","DOI":"10.1016\/S1470-2045(13)70579-5","article-title":"Drug-drug interactions with tyrosine-kinase inhibitors: A clinical perspective","volume":"15","author":"Leeuwen","year":"2014","journal-title":"Lancet Oncol"},{"key":"2021122511543179900_onco13711-bib-0016","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1634\/theoncologist.2017-0578","article-title":"Effect of concomitant pH-elevating medications with pazopanib on progression-free survival and overall survival in patients with metastatic renal cell carcinoma","volume":"23","author":"McAlister","year":"2018","journal-title":"The Oncologist"},{"key":"2021122511543179900_onco13711-bib-0017","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/j.clgc.2017.05.019","article-title":"Proton pump inhibitors and survival outcomes in patients with metastatic renal cell carcinoma","volume":"15","author":"Lalani","year":"2017","journal-title":"Clin Genitourin Cancer"},{"key":"2021122511543179900_onco13711-bib-0018","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1002\/cncr.31917","article-title":"The Concomitant use of tyrosine kinase inhibitors and proton pump inhibitors: Prevalence, predictors and impact on survival and discontinuation of therapy in older adults with cancer","volume":"125","author":"Sharma","year":"2019","journal-title":"Cancer"},{"key":"2021122511543179900_onco13711-bib-0019","doi-asserted-by":"crossref","first-page":"2616","DOI":"10.1111\/j.1572-0241.2003.08783.x","article-title":"Chen Y e al. Gastric acid control with esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole: A five-way crossover study","volume":"98","author":"Miner","year":"2003","journal-title":"Am J Gastroenterol"},{"key":"2021122511543179900_onco13711-bib-0020","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/clpt.2012.73","article-title":"Drug absorption interactions between oral targeted anticancer agents and PPIs: Is pH-dependent solubility the Achilles heel of targeted therapy?","volume":"92","author":"Budha","year":"2012","journal-title":"Clin Pharmacol Ther"},{"key":"2021122511543179900_onco13711-bib-0021","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1136\/bmj.39406.449456.BE","article-title":"Overprescribing proton pump inhibitors","volume":"336","author":"Forgacs","year":"2008","journal-title":"BMJ"},{"key":"2021122511543179900_onco13711-bib-0022","doi-asserted-by":"crossref","first-page":"e556","DOI":"10.1016\/j.clgc.2019.02.002","article-title":"Real-world experience of cabozantinib as second- or subsequent line treatment in patients with metastatic renal cell carcinoma: Data from the polish managed access program","volume":"17","author":"Bodnar","year":"2019","journal-title":"Clin Genitourin Cancer"},{"key":"2021122511543179900_onco13711-bib-0023","doi-asserted-by":"crossref","first-page":"e945","DOI":"10.1016\/j.clgc.2018.03.014","article-title":"Safety and efficacy of cabozantinib in metastatic renal-cell carcinoma: Real-world data from an Italian managed access program","volume":"16","author":"Procopio","year":"2018","journal-title":"Clin Genitourin Cancer"},{"key":"2021122511543179900_onco13711-bib-0024","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1200\/JCO.1987.5.9.1469","article-title":"Compliance with oral drug therapy in patients with hematologic malignancy","volume":"5","author":"Levine","year":"1987","journal-title":"J Clin Oncol"},{"key":"2021122511543179900_onco13711-bib-0025","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1093\/annonc\/mdz056","article-title":"Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"30","author":"Escudier","year":"2019","journal-title":"Ann Oncol"},{"key":"2021122511543179900_onco13711-bib-0026","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.eururo.2019.05.022","article-title":"Updated European Association of Urology Guidelines on Renal Cell Carcinoma: Immune checkpoint inhibition is the new backbone in first-line treatment of metastatic clear-cell renal cell carcinoma","volume":"76","author":"Albiges","year":"2019","journal-title":"Eur Urol"},{"key":"2021122511543179900_onco13711-bib-0027","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1007\/s40265-020-01327-7","article-title":"Immunomodulatory roles of VEGF pathway inhibitors in renal cell carcinoma","volume":"80","author":"Hirsch","year":"2020","journal-title":"Drugs"},{"key":"2021122511543179900_onco13711-bib-0028","doi-asserted-by":"crossref","first-page":"TPS767a","DOI":"10.1200\/JCO.2020.38.6_suppl.TPS767","article-title":"A phase III study (COSMIC-313) of cabozantinib (C) in combination with nivolumab (N) and ipilimumab (I) in patients (pts) with previously untreated advanced renal cell carcinoma (aRCC) of intermediate or poor risk","volume":"38","author":"Choueiri","year":"2020","journal-title":"J Clin Oncol"},{"key":"2021122511543179900_onco13711-bib-0029","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.critrevonc.2019.07.005","article-title":"Concomitant medications during immune checkpoint blockage in cancer patients: Novel insights in this emerging clinical scenario","volume":"142","author":"Rossi","year":"2019","journal-title":"Crit Rev Oncol Hematol"},{"key":"2021122511543179900_onco13711-bib-0030","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/j.annonc.2020.01.006","article-title":"Efficacy of chemotherapy and atezolizumab in patients with non-small-cell lung cancer receiving antibiotics and proton pump inhibitors: Pooled post hoc analyses of the OAK and POPLAR trials","volume":"31","author":"Chalabi","year":"2020","journal-title":"Ann Oncol"}],"container-title":["The Oncologist"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/onco.13711","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/onco.13711","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/oncolo\/article-pdf\/26\/5\/389\/41923817\/oncolo_26_5_389.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/oncolo\/article-pdf\/26\/5\/389\/41923817\/oncolo_26_5_389.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,25]],"date-time":"2021-12-25T11:55:42Z","timestamp":1640433342000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/oncolo\/article\/26\/5\/389\/6445647"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,25]]},"references-count":30,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,2,25]]},"published-print":{"date-parts":[[2021,5,1]]}},"URL":"https:\/\/doi.org\/10.1002\/onco.13711","relation":{},"ISSN":["1083-7159","1549-490X"],"issn-type":[{"value":"1083-7159","type":"print"},{"value":"1549-490X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,5,1]]},"published":{"date-parts":[[2021,2,25]]}}}