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Concomitant Proton Pump Inhibitors and Outcome of Patients Treated with Nivolumab Alone or Plus Ipilimumab for Advanced Renal Cell Carcinoma

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Abstract

Background

Immune checkpoint inhibitors (ICIs) represent the standard of care as first- or second-line treatment in patients with renal cell carcinoma (RCC). Proton pump inhibitors (PPIs) are among the most prescribed drugs worldwide and are known to affect gut microbiota, which is gaining interest in its association with outcomes for patients on ICIs.

Objective

The aim of this study was to evaluate the impact of PPIs on outcomes in RCC patients receiving immunotherapy.

Patients and Methods

We retrospectively collected data from patients with metastatic RCC who received the combination of ipilimumab and nivolumab for first-line treatment (Cohort 1) or single-agent nivolumab for second-line or third-line treatment (Cohort 2) from five international centers with expertise in the treatment of RCC. Data about clinicopathological characteristics, PPI use, and outcome on ICIs were collected. Endpoints of the study were objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).

Results

Two hundred and eighteen patients (71% male, median age 61 years) were included in the analysis, 62 in Cohort 1 (including 25 patients receiving PPIs) and 156 in Cohort 2 (including 88 patients receiving PPIs), and were followed up for a median of 42 months. In Cohort 1, no difference was observed in ORR (48% vs 57%; p = 0.203), PFS (12.2 vs 8.5 months; p = 0.928), or OS (not reached [NR] vs 27.3 months; p = 0.84). In Cohort 2, no difference was observed in ORR (32% vs 28%; p = 0.538), PFS (6.7 vs 9.0 months; p = 0.799), or OS (16.0 vs 26.0 months; p = 0.324).

Conclusions

In patients with RCC, concomitant PPI use did not seem to affect survival outcomes on ICIs, either as combination therapy or monotherapy.

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Author notes

  1. Veronica Mollica and Matteo Santoni equally contributing first authors.

Authors and Affiliations

  1. Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni-15, Bologna, Italy

    Veronica Mollica, Alessandro Rizzo, Andrea Marchetti, Matteo Rosellini & Francesco Massari

  2. Oncology Unit, Macerata Hospital, via Santa Lucia 2, 62100, Macerata, Italy

    Matteo Santoni

  3. Department of Internal Medicine, Hematology/Oncology, Ochsner Medical Center, New Orleans, LA, USA

    Marc R. Matrana, Diana Maslov, Karine Tawagi & Ernest Philon

  4. Department of Medical Oncology, Istituto Oncologico Veneto (IOV) IRCCS, Padova, Italy

    Umberto Basso & Marco Maruzzo

  5. Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy

    Ugo De Giorgi & Sara Bleve

  6. Medical School, The University of Queensland-Ochsner Clinical School, New Orleans, LA, USA

    Zoe Blake

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Corresponding author

Correspondence to Francesco Massari.

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Funding

No external funding was used in the preparation of this manuscript.

Conflict of interest

Veronica Mollica, Matteo Santoni, Marc R. Matrana, Umberto Basso, Ugo De Giorgi, Alessandro Rizzo, Marco Maruzzo, Andrea Marchetti, Matteo Rosellini, Sara Bleve, Diana Maslov, Karine Tawagi, Ernest Philon, Zoe Blake, and Francesco Massari declare that they have no conflicts of interest that might be relevant to the contents of this manuscript.

Ethics approval and consent to participate

Not required. Informed consent was not required due to the retrospective nature of the study.

Availability of data and material

Data are available upon reasonable request.

Code availability

Not applicable.

Author contributions

Conception and design: VM, MS, and FM. Collection and assembly of data: VM, MS, and FM. Provision of study material or patients: all authors. Data analysis and interpretation: MS and FM performed the data analysis, all authors interpreted the data. Manuscript writing: VM, MS, and FM. Review of manuscript draft: all authors. Final approval of manuscript: all authors. Accountable for all aspects of the work: all authors.

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Mollica, V., Santoni, M., Matrana, M.R. et al. Concomitant Proton Pump Inhibitors and Outcome of Patients Treated with Nivolumab Alone or Plus Ipilimumab for Advanced Renal Cell Carcinoma. Targ Oncol 17, 61–68 (2022). https://doi.org/10.1007/s11523-021-00861-y

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