Effectiveness of pembrolizumab in patients with urothelial carcinoma receiving proton pump inhibitors.

ABSTRACT

BACKGROUND: The association of concurrent proton pump inhibitor (PPI) use with treatment outcome of metastatic urothelial carcinoma (UC) remains controversial. MATERIALS AND METHODS: We retrospectively analyzed the records of 227 patients with platinum-treated metastatic UC treated with pembrolizumab. The primary outcome was overall survival (OS). Immune progression-free survival (iPFS) and objective response per immune response evaluation criteria in solid tumors were also compared. Inverse probability of treatment weighting (IPTW)-adjusted multivariable Cox regression models and an IPTW-adjusted multivariable logistic regression model were used to evaluate the oncological outcomes. Furthermore, the heterogeneity of the treatment effect on OS was examined using interaction terms within the IPTW-adjusted univariate Cox regression models. RESULTS: Overall, 86 patients (37.9%) used PPIs. After weighting, no significant differences in patient characteristics were observed between PPI users and non-users. PPI use was significantly associated with a shorter OS (hazard ratio [HR] 2.02, 95% confidence interval [CI] 1.28-3.18, P = 0.003) and iPFS (HR 1.70, 95% CI 1.23-2.35, P = 0.001). Although not statistically significant, PPI use was associated with objective response as well (OR 0.61, 95% CI 0.36-1.02, P = 0.06). The interaction analyses showed that the effect of PPI significantly decreased with age (HR 0.97, 95% CI 0.93-1.00, P[interaction] = 0.048) and was increased in males (HR 2.97, 95% CI 1.10-8.05, P[interaction] = 0.032). CONCLUSIONS: PPI use was significantly associated with worse survival of patients with metastatic UC treated with pembrolizumab. Furthermore, the results suggested that its effects decreased with age and was increased in males.