Use of concomitant proton pump inhibitors, statins or metformin in patients treated with pembrolizumab for metastatic urothelial carcinoma: data from the ARON-2 retrospective study

接受帕博利珠单抗治疗的转移性尿路上皮癌患者同时使用质子泵抑制剂、他汀类药物或二甲双胍:来自 ARON-2 回顾性研究的数据

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作者:Ondřej Fiala #, Sebastiano Buti #, Hideki Takeshita, Yohei Okada, Francesco Massari, Georgia Anguera Palacios, Michele Dionese, Sarah Scagliarini, Thomas Büttner, Giuseppe Fornarini, Zin W Myint, Luca Galli, Vinicius Carrera Souza, Renate Pichler, Ugo De Giorgi, María Natalia Gandur Quiroga, Daniell

Background

Concomitant medications may potentially affect the outcome of cancer patients. In this sub-analysis of the ARON-2 real-world study (NCT05290038), we aimed to assess the impact of concomitant use of proton pump inhibitors (PPI), statins, or metformin on outcome of patients with metastatic urothelial cancer (mUC) receiving second-line pembrolizumab.

Conclusions

Our study results suggest a significant prognostic impact of concomitant PPI use in mUC patients receiving pembrolizumab in the real-world context. The mechanism of this interaction warrants further elucidation.

Methods

We collected data from the hospital medical records of patients with mUC treated with pembrolizumab as second-line therapy at 87 institutions from 22 countries. Patients were assessed for overall survival (OS), progression-free survival (PFS), and overall response rate. We carried out a survival analysis by a Cox regression model.

Results

A total of 802 patients were eligible for this retrospective study; the median follow-up time was 15.3 months. PPI users compared to non-users showed inferior PFS (4.5 vs. 7.2 months, p = 0.002) and OS (8.7 vs. 14.1 months, p < 0.001). Concomitant PPI use remained a significant predictor of PFS and OS after multivariate Cox analysis. The use of statins or metformin was not associated with response or survival. Conclusions: Our study results suggest a significant prognostic impact of concomitant PPI use in mUC patients receiving pembrolizumab in the real-world context. The mechanism of this interaction warrants further elucidation.

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