Use of concomitant proton pump inhibitors, statins or metformin in patients treated with pembrolizumab for metastatic urothelial carcinoma: data from the ARON-2 retrospective study

Fiala, Ondřej;Buti, Sebastiano;Takeshita, Hideki;Okada, Yohei;Santoni, Matteo;et.al.
(2023) Cancer Immunology, Immunotherapy — Vol. 72, n° 11, p. 3665-3682 (2023)

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Authors
  • Fiala, Ondřej
    Author
  • Buti, Sebastiano
    Author
  • Takeshita, Hideki
    Author
  • Okada, Yohei
    Author
  • Seront, EmmanuelUCLouvain
    Author
  • Santoni, Matteo
    Author
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Abstract
Background Concomitant medications may potentially affect the outcome of cancer patients. In this sub-analysis of the ARON-2 real-world study (NCT05290038), we aimed to assess the impact of concomitant use of proton pump inhibi-tors (PPI), statins, or metformin on outcome of patients with metastatic urothelial cancer (mUC) receiving second-line pembrolizumab. Methods We collected data from the hospital medical records of patients with mUC treated with pembrolizumab as second-line therapy at 87 institutions from 22 countries. Patients were assessed for overall survival (OS), progression-free survival (PFS), and overall response rate. We carried out a survival analysis by a Cox regression model. Results A total of 802 patients were eligible for this retrospective study; the median follow-up time was 15.3 months. PPI users compared to non-users showed inferior PFS (4.5 vs. 7.2 months, p = 0.002) and OS (8.7 vs. 14.1 months, p < 0.001). Concomitant PPI use remained a significant predictor of PFS and OS after multivariate Cox analysis. The use of statins or metformin was not associated with response or survival. Conclusions Our study results suggest a significant prognostic impact of concomitant PPI use in mUC patients receiving pembrolizumab in the real-world context. The mechanism of this interaction warrants further elucidation.
Affiliations
  • Charles University, Alej Svobody 80, 304 60 Pilsen, Czech RepublicDepartment of Oncology and Radiotherapeutics, Faculty of Medicine and University Hospital Pilsen
  • Charles University, Pilsen, Czech RepublicBiomedical Center, Faculty of Medicine in Pilsen
  • Centre Hospitalier de Jolimont, Haine Saint Paul, BelgiumDepartment of Medical Oncology
  • Macerata Hospital, Via Santa Lucia 2, 62100 Macerata, ItalyOncology Unit

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Fiala, O., Buti, S., Takeshita, H., Okada, Y., Massari, F., Palacios, G., Dionese, M., Scagliarini, S., Büttner, T., Fornarini, G., Myint, Z., Galli, L., Souza, V., Pichler, R., De Giorgi, U., Quiroga, M., Gilbert, D., Popovic, L., Grande, E., et al. (2023). Use of concomitant proton pump inhibitors, statins or metformin in patients treated with pembrolizumab for metastatic urothelial carcinoma: data from the ARON-2 retrospective study. Cancer Immunology, Immunotherapy, 72(11), 3665-3682. https://doi.org/10.1007/s00262-023-03518-z (Original work published 2023)