Clinical and Patient-Reported Outcomes of Advanced Urothelial Carcinoma Following Discontinuation of PD-1/L1 Inhibitor Therapy

Real-world patterns of care and attrition of la/mUC patients eligible for systemic therapy following PD-1/L1 inhibitors are not well understood. In an ambispective chart review of patients with la/mUC after PD-1/L1 discontinuation, only one third received subsequent treatment. Prior to the introduction of novel therapies, real-world outcomes following treatment with PD-1/L1 inhibitor therapy were poor. Introduction: The patterns of care and attrition of locally advanced or metastatic urothelial carcinoma (la/mUC) patients eligible for systemic therapy following PD-1/L1 inhibitors are unclear. The objective of this study was to evaluate the clinical characteristics and treatment patterns among patients with la/mUC following discontinuation of first-line (1L) or second-line (2L) PD-1/L1 inhibitor therapy. Methods: An ambispective, multisite, chart review study was conducted in the United States, including patients with la/mUC. Eligible patients had initiated and subsequently discontinued PD-1/L1 therapy in the 1L or 2L setting for la/mUC between May 2016 and July 2018; with follow-up through October 2019. Patient characteristics, treatments, and overall survival (OS) were described. Patients had the option to complete a 1-time patient reported outcomes (PRO) survey. Results: Among 300 patients included in the chart review, 198 (66%) received 1L PD-1/L1 inhibitor and 102 (34%) received 2L PD-1/L1 inhibitor. Following discontinuation of PD-1/L1 inhibitor therapy, 34% (n = 68) received subsequent therapy in 2L and 29% (n = 30) in third-line (3L). The median OS post-1L PD-1/L1 inhibitor was 9.4 (95% CI 8.6-NA) and 2.5 months (95% CI 2.24-3.50) for those who received and did not receive subsequent therapy, respectively. Following 2L PD-1/L1 inhibitor discontinuation, the median OS was 5.7 (95% CI 5.1-7.8) and 3.98 (95% CI 3.29-4.87) months for those who received and did not receive subsequent therapy, respectively. Among those with PRO data, 64% reported experiencing cancer-related pain and 29.6% received an opioid. Only 12.7% reported having a caregiver, requiring approximately 13 h/d of service. Conclusion: The symptom and caregiver burden are high among real-world patients with la/mUC who discontinued 1L or 2L PD-1/L1 inhibitors and outcomes are dismal, with a minority receiving subsequent therapy. Patterns of care in the setting of 1L maintenance avelumab and novel agents require further investigation.