Is Immunotherapy With Concomitant Proton Pump Inhibitor Use a Viable Combination?

Stefani, Alessio; Bria, Emilio

doi:10.1001/jamanetworkopen.2023.22922

Cited by 1 publication

(2 citation statements)

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“…This phenomenon could be due to the combination of pembrolizumab and conventional chemotherapy. In this sense, the present study shows a high percentage of patients benefiting from this combination regimen, and recent studies have been able to demonstrate the potential attenuating effect of chemotherapy on the effect of PPIs when associated with concomitant treatment with ICIs 27,28 …”

Section: Discussionsupporting

confidence: 69%

“…This can be explained as a consequence of the change in the composition of the gut microbiota caused by chronic or peri-ICI use of PPIs. In this sense, the bacterial microenvironment itself plays a key role in the response to treatment with PPIs, and it has been shown that the presence of certain symbiotic microorganisms can have as much or even more effect and relevance on long-term clinical outcomes than currently crucial factors such as the expression of the tumor biomarker PD-L1 28 …”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Effect of Concomitant Use of Proton Pump Inhibitors on Immunotherapy Clinical Response in Advanced Cancer Patients: Real-Life Setting

Cantarelli,

Gutiérrez Nicolás,

García Gil

et al. 2023

Journal of Immunotherapy

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The alteration of the gut microbiota mediated by proton pump inhibitor (PPI) drugs could be involved in the clinical response associated with immunotherapy [immunocheckpoint inhibitors (ICIs)] in cancer patients. Due to the current controversy in the scientific evidence, it has been proposed to evaluate the correlation between the concomitant use of PPIs and the effectiveness of immunotherapy in a real clinical practice setting. Single-center retrospective cohort study that included patients treated with anti-PD-1 or anti-CTLA4, including nivolumab, pembrolizumab, atezolizumab, or the combination ipilimumab-nivolumab in metastatic neoplastic disease. The clinical effectiveness of ICI, measured in progression-free survival (PFS) and overall survival (OS), was compared between the PPI-use versus PPI-no-use group. PPI-use group was associated with lower PFS [hazard ratio (HR):1.89 (1.38–2.59), P<0.001] and OS [HR: 2.02 (1.45–2.82), P<0.001] versus PPI-no-use group. However, this difference was not observed for pembrolizumab PFS [HR: 1.38 (0.93–2.39), P=0.160] and OS [HR: 1.41 (0.81–2.44), P=0.187]. The study showed significantly lower PFS and OS in the chronic PPI-use group (P<0.001), recent PPI-use group (P<0.001) and concomitant PPI-use group (P=0.001, 0.007) versus PPI-no-use group. However, late PPI use >30 days after the onset of ICI has no significant effect on the efficacy of treatment [HR: 0.92 (0.49–1.70), P=0.791; HR: 1.10 (0.59–2.05), P=0.756]. The concomitant use of PPIs in immunotherapy is associated with worse clinical outcomes compared with the group without PPI use. In addition, the study shows how the late use of PPIs does not have a significant effect on clinical benefit.

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Section: Discussionsupporting

confidence: 69%

Section: Discussionmentioning

confidence: 99%