IUC24400-75 Real-world outcomes of second-line pembrolizumab in urothelial cancer: Campania network analysis

Abstract Background Platinum-based chemotherapy followed by immunotherapy is standard for locally advanced/metastatic urothelial cancer (La/mUC). Despite advances, La/mUC remains aggressive with poor prognosis. Real-world outcomes may differ from clinical trials. Oncology networks generating real-world data (RWD) are crucial to guide treatment. We retrospectively analyzed La/mUC patients treated with second-line pembrolizumab within the Campania Oncological Network (ROC). Methods This multicenter retrospective study included patients (≥18 years) with histologically/cytologically confirmed La/mUC, previously treated with chemotherapy, who received pembrolizumab (200 mg every 3 weeks) across 6 ROC centers. Primary endpoints were progression-free survival (PFS) and overall survival (OS); secondary endpoints included objective response rate (ORR), disease control rate (DCR), and safety. Results From January 2021 to November 2023, 132 patients received pembrolizumab. Median age was 67 years (range 30-88); 73.5% were male. Eastern Cooperative Oncology Group (ECOG) performance status was 0-1 in 82.6%. Most had pure urothelial carcinoma (87.1%), and 12.9% had rare variants. At diagnosis, 34.1% had metastatic disease, and 54.5% underwent cystectomy. Common metastatic sites were lymph nodes (74.2%), lung (38.6%), bone (34.1%), and liver (15.9%). After a median follow-up of 8.5 months, 81.8% experienced progression or death. Median PFS and OS were 3.75 (95% CI, 3.4- 4.7) and 7.3 (95% CI, 6.05-9.33) months, respectively. ORR was 13.5% (95% CI, 7.4%-19.7%), DCR 33.9% (95% CI, 25.6%-42.0%), and ORR in rare subtypes was 23.5% (95% CI, 3.3%-43.7%). Metastatic disease at diagnosis (HR = 2.01, P = .02) and liver metastases (HR = 2.11, P = .02) were associated with worse OS. Lymph node-only metastases predicted better PFS (HR = 0.46, P = .004) and OS (HR = 0.52, P = .02). Prior cystectomy improved PFS (HR = 0.67, P = .04) and OS (HR = 0.54, P = .003) in univariate analysis. Among 114 treatment-related adverse events (AEs), 79.8% were grade 1-2, and 20.2% grade 3-4. No treatment-related deaths occurred. Pembrolizumab was discontinued in 7.6% due to AEs; the most frequent were asthenia (20%), pruritus (10%), and myalgia (7%). Conclusions Second-line pembrolizumab showed clinical activity and acceptable safety in this real-world La/mUC cohort. Prognostic factors such as metastatic sites and prior cystectomy significantly influenced outcomes. These data support the role of oncology networks in guiding real-world treatment strategies.