Veronica Mollica1, Matteo Santoni2, Marc R Matrana3, Umberto Basso4, Ugo De Giorgi5, Alessandro Rizzo1, Marco Maruzzo4, Andrea Marchetti1, Matteo Rosellini1, Sara Bleve5, Diana Maslov3, Karine Tawagi3, Ernest Philon3, Zoe Blake6, Francesco Massari7. 1. Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni-15, Bologna, Italy. 2. Oncology Unit, Macerata Hospital, via Santa Lucia 2, 62100, Macerata, Italy. 3. Department of Internal Medicine, Hematology/Oncology, Ochsner Medical Center, New Orleans, LA, USA. 4. Department of Medical Oncology, Istituto Oncologico Veneto (IOV) IRCCS, Padova, Italy. 5. Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. 6. Medical School, The University of Queensland-Ochsner Clinical School, New Orleans, LA, USA. 7. Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni-15, Bologna, Italy. fmassari79@gmail.com.
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.
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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