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. Materials and 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 (ORR). 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 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. Table 1. Univariate and multivariate Cox analyses for overall survival (OS). Overall survival Univariate Cox regression Multivariate Cox regression HR (95%CI) p-value HR (95%CI) p-value Gender (females vs. males) 1.22 (0.99−1.50) 0.062 Age (⩾65y vs. <65y) 1.07 (0.86−1.33) 0.530 Smoking (smokers vs. non-smokers) 0.81 (0.66−0.98) 0.030 0.78 (0.64−0.95) 0.012 Histology (mixed vs. pure UC) 1.04 (0.81−1.32) 0.775 Upper vs. Lower urinary tract 1.10 (0.90−1.36) 0.353 Synchronous metastatic disease (yes vs. no) 1.32 (1.08−1.61) 0.007 1.33 (1.09−1.63) 0.005 Lymph node metastases (Y vs. N) 0.86 (0.70−1.06) 0.151 Bone metastases (Y vs. N) 1.53 (1.25−1.88) <0.001 1.51 (1.22−1.84) <0.001 Liver metastases (Y vs. N) 1.46 (1.16−1.84) 0.001 1.39 (1.10−1.75) 0.006 Proton Pump Inhibitors (Y vs. N) 1.41 (1.17−1.71) <0.001 1.41 (1.17−1.70) <0.001 Statins (Y vs. N) 1.00 (0.80−1.25) 0.999 Metformin (Y vs. N) 0.98 (0.73−1.31) 0.896
Use of concomitant proton pump inhibitors, statins, or metformin in patients treated with pembrolizumab for advanced urothelial carcinoma: data from the ARON-2 retrospective study / Maffezzoli, M.; Fiala, O.; Buti, S.; Massari, F.; Iacovelli, R.; Martignetti, A.; Morelli, F.; Mollica, V.; Porta, C.; Rizzo, M.; Rizzo, A.; Incorvaia, L.; Ciccarese, C.; Santoni, M.. - In: TUMORI. - ISSN 0300-8916. - 109:2_suppl(2023), pp. A40.30-A40.31. [10.1177/03008916231203496]
Use of concomitant proton pump inhibitors, statins, or metformin in patients treated with pembrolizumab for advanced urothelial carcinoma: data from the ARON-2 retrospective study.
Maffezzoli M.
;Buti S.Conceptualization
;
2023-01-01
Abstract
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. Materials and 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 (ORR). 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 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. Table 1. Univariate and multivariate Cox analyses for overall survival (OS). Overall survival Univariate Cox regression Multivariate Cox regression HR (95%CI) p-value HR (95%CI) p-value Gender (females vs. males) 1.22 (0.99−1.50) 0.062 Age (⩾65y vs. <65y) 1.07 (0.86−1.33) 0.530 Smoking (smokers vs. non-smokers) 0.81 (0.66−0.98) 0.030 0.78 (0.64−0.95) 0.012 Histology (mixed vs. pure UC) 1.04 (0.81−1.32) 0.775 Upper vs. Lower urinary tract 1.10 (0.90−1.36) 0.353 Synchronous metastatic disease (yes vs. no) 1.32 (1.08−1.61) 0.007 1.33 (1.09−1.63) 0.005 Lymph node metastases (Y vs. N) 0.86 (0.70−1.06) 0.151 Bone metastases (Y vs. N) 1.53 (1.25−1.88) <0.001 1.51 (1.22−1.84) <0.001 Liver metastases (Y vs. N) 1.46 (1.16−1.84) 0.001 1.39 (1.10−1.75) 0.006 Proton Pump Inhibitors (Y vs. N) 1.41 (1.17−1.71) <0.001 1.41 (1.17−1.70) <0.001 Statins (Y vs. N) 1.00 (0.80−1.25) 0.999 Metformin (Y vs. N) 0.98 (0.73−1.31) 0.896I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
