The impact of proton-pump inhibitors administered with tyrosine kinase inhibitors in patients with metastatic renal cell carcinoma.

Tyrosine kinase inhibitors (TKIs) are the backbone of the systemic treatment for patients with metastatic renal cell carcinoma (mRCC). TKIs such as pazopanib and cabozantinib can interact with other drugs concomitantly administered, particularly with proton-pump inhibitors (PPIs), possibly impacting the effectiveness of the anticancer treatment and patients outcome. Few data are available about this interaction. We conducted a multicenter retrospective observational data collection of patients with mRCC treated with pazopanib or cabozantinib between January 2012 and December 2020 in nine Italian centers. Univariate and multivariate analyses were performed. The aim was to describe the impact of baseline concomitant PPIs on the outcome of patients to pazopanib and cabozantinib in terms of response, progression-free survival (PFS) and overall survival (OS), toxicity, and treatment compliance. The use of PPI in our study population (301 patients) significantly influenced the effectiveness of TKIs with worse PFS (16.3 vs. 9.9 months; P < 0.001) and OS (30.6 vs. 18.4 months; P = 0.013) in patients taking PPI at TKI initiation. This detrimental effect was maintained both in the pazopanib and cabozantinib groups. The use of PPI influenced the toxicity and TKI treatment compliance with a reduction of dose or schedule modifications, and treatment interruptions in the population taking PPIs. Our study demonstrates that the use of PPIs can significantly influence the outcome and compliance of patients with mRCC to TKI treatment, suggesting the importance of a more careful selection of patients who need a gastroprotective therapy, avoiding indiscriminate use of PPIs.

Anti-cancer drugs. 2022 Oct 22 [Epub]

Sebastiano Buti, Chiara Tommasi, Giulia Scartabellati, Ugo De Giorgi, Nicole Brighi, Sara Elena Rebuzzi, Silvia Puglisi, Orazio Caffo, Stefania Kinspergher, Alessia Mennitto, Carlo Cattrini, Matteo Santoni, Elena Verzoni, Alessandro Rametta, Marco Stellato, Andrea Malgeri, Giandomenico Roviello, Massimo de Filippo, Alessio Cortellini, Melissa Bersanelli

Medical Oncology Unit, University Hospital of Parma., Department of Medicine and Surgery, University of Parma., Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola., Medical Oncology Unit, Ospedale San Paolo, Savona., Medical Oncology Unit 1, IRCCS Ospedale Policlinico San Martino, Genova., Department of Medical Oncology, Santa Chiara Hospital, Trento., Division of Oncology, University Hospital 'Maggiore della Carità', Novara., Department of Medical Oncology, University of Marche, University Hospital Ospedali Riuniti, Ancona., Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan., Department of Medical Oncology, Università Campus Bio-Medico di Roma, Rome., Department of Health Sciences, University of Florence, Florence., Department of Surgery and Cancer, Imperial College London, London, UK.