Impact of Proton Pump Inhibitor Use on the Efficacy of IO-IO Versus IO-TKI Thera...

연구 요약

Impact of Proton Pump Inhibitor Use on the Efficacy of IO-IO Versus IO-TKI Therapy in Metastatic Renal Cell Carcinoma.

Clinical genitourinary cancer 학술지에 발표된 이 연구는 Inoki L, Toyoda S, Fukuokaya W 외 연구팀이 수행하였습니다.

이 연구는 'Impact of Proton Pump Inhibitor Use on the Efficacy of IO-IO Versus IO-TKI Therapy in Metastatic Renal Cell Carcinoma.'에 대한 과학적 분석을 제공합니다.

핵심 내용

BASCKGROUND: Immune checkpoint inhibitor (ICI)-based combination therapies have become the standard first-line treatment for metastatic renal cell carcinoma (mRCC). Proton-pump inhibitors (PPIs), frequently used to treat gastrointestinal conditions, have been implicated in modulating ICI efficacy, potentially through gut microbiome dysbiosis. However, the impact of PPIs on ICI-based therapies for mRCC remains unclear. METHODS: This multicenter retrospective cohort study analyzed 427 patients with mRCC classified as intermediate or poor risk according to the IMDC criteria treated with first-line IO-IO (ipilimumab plus nivolumab) or IO-TKI (ICI plus tyrosine kinase inhibitor) therapies. Patients were stratified by PPI use during the 30 days before and including the day of ICI initiation. Overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) were compared between PPI users and nonusers. RESULTS: PPI use was significantly associated with shorter OS in patients receiving IO-IO therapy (median OS, 23.34 months vs. not reached; P = .002), but not in those receiving IO-TKI therapy (P = .909). Multivariate analysis confirmed PPIs as an independent prognostic factor for OS in the IO-IO group (HR, 1.647; 95% CI, 1.007-2.693; P = .046). No significant differences in PFS or ORR were observed between PPI users and nonusers in either group, although the complete response rate was notably lower in PPI users treated with IO-IO (1.6% vs. 10.3%; P = .025). CONCLUSIONS: PPI use was associated with inferior survival in mRCC patients receiving IO-IO therapy, potentially through microbiome modulation and other immunologic or clinical mechanisms; however, these findings are based on retrospective data and should be regarded as hypothesis-generating. Caution is advised when prescribing PPIs to patients undergoing ICI-based therapy, particularly IO-IO regimens, and prospective studies are needed to confirm whether avoiding unnecessary PPI use can improve clinical outcomes.

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