PhD Scientific Days 2023

Clinical Medicine V.

The Impact of Concomitant Medication on the Efficacy of Immune Checkpoint Inhibitor Therapy in Patients with Urothelial Carcinoma

Text of the abstract

Background: Immune checkpoint inhibitors (ICI) became standard of care for patients with advanced urothelial cancers (UC), however only 20-25% of patients respond to them in the second-line setting. Therefore, predictive biomarkers are needed to optimize treatment-decisions. Preclinical and clinical studies indicate that dysbiosis of the gut microbiome by antibiotics (ATB) or proton-pump inhibitors (PPI) can reduce the effectiveness of ICIs in UC. Moreover, there is emerging data showing that the concurrent use of the renin-angiotensin-aldosterone system inhibitors (RAASI) may improve outcomes in oncologic patients. Currently, there are limited data on the association between the use of ATB, PPIs and RAAS inhibitors and outcomes of ICI treatment in UC.
Aims: The aim of this study was to assess the impact of different drugs (ATBs, PPIs, RAASIs) used before and during ICI therapies on the effectiveness of ICIs.
Methods: We performed a retrospective study of UC patients treated with ICI between 2017 and 2022 in five high-volume urooncological centers in Hungary and Germany. We collected data on medication using the cloud service of the National Health Insurance Fund of Hungary. Those receiving ATBs, PPIs and RAASIs were compared with those who did not. The primary outcome was progression-free survival (PFS) for the entire cohort and in sub-groups defined by different ICI drugs. Our secondary outcome was overall survival (OS).
Results: We assessed 113 patients treated with ICIs. In the Cox proportional hazard model, the concurrent use of RAASIs was associated with better PFS and OS. Patients who received ATB or PPI before administration of ICIs had significantly worse OS than those who did not.
Conclusions: In this large multicenter retrospective UC cohort, patients who were concomitantly use of RAASI during ICI therapy had better PFS and OS. Moreover, we detected worse outcomes of patients who were treated with ATBs and PPI before ICIs indicating that alteration in gut microbiome may have a significant influence on the response to ICI treatment. Prospective randomized trials are needed to study the benefit of RAASI in patients with UC who receive ICI therapy.
Funding: Tibor Szarvas was supported by a János Bolyai Research Scholarship of the Hungarian Academy of Sciences (BO/00451/20/5). This work was supported by the ÚNKP-21-5-SE-3, ÚNKP-21-3-II-SE-13, ÚNKP-22-3-1-SE-19 New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund