Abstract
BACKGROUND: The KEYNOTE-045 trial showed that pembrolizumab therapy improved the survival of patients with advanced urothelial carcinoma (UC). However, its effectiveness in trial-ineligible patients remains unclear. MATERIALS AND METHODS: We conducted a multicenter retrospective study to evaluate the effectiveness of pembrolizumab in patients with metastatic UC who were trial-ineligible. The data of 164 consecutive patients with platinum-treated metastatic UC who received pembrolizumab as second-line therapy were analyzed. Trial eligibility was assessed using the KEYNOTE-045 criteria. Inverse probability of treatment weighting (IPTW) was used to balance patient characteristics. Overall survival (OS) and progression-free survival (PFS) were examined using the IPTW-adjusted Kaplan-Meier method. IPTW-adjusted restricted mean survival times (RMSTs) were compared between ineligible and eligible patients. RESULTS: Seventy-five patients (45.7%) were classified as ineligible based on the KEYNOTE-045 criteria. Baseline hemoglobin concentration of less than 9.0 g/dL was the most common reason for trial protocol violation (N = 23 [14.0%]). An IPTW-adjusted logistic regression model showed that the trial-eligibility was not significantly associated with objective response (OR: 0.65, 95% CI: 0.32 to 1.29, P = 0.22). Ineligible patients had similar RMST for PFS (difference: 3.8 months, 95% CI: -1.6 to 9.3, P = 0.17) and RMST for OS (difference: 1.4 months, 95% CI: -5.4 to 8.2, P = 0.93) compared with eligible patients. CONCLUSIONS: This study suggests that the effectiveness of pembrolizumab may be retained in ineligible patients with platinum-treated metastatic UC. Expanding trial eligibility criteria for these patients may be beneficial.