Chemotherapy, immunotherapy, or combination first-line treatment for metastatic urothelial carcinoma of the bladder: A large real-world experience.

Abstract

477 Background: First-line therapy for metastatic urothelial carcinoma of the bladder (mUC) consists of platinum-based chemotherapy in most patients and PD1/L1 inhibitors in selected patients. Multiple combination chemo-immunotherapy trials failed to show a clear benefit over chemotherapy alone. We sought to use real-world data to evaluate clinical and sociodemographic factors associated with receipt of first-line chemotherapy, immunotherapy or combination chemo-immunotherapy treatment for metastatic bladder cancer and examined differences in overall survival (OS). Methods: We used the National Cancer Database to identify patients with stage IV UCB diagnosed between 2014 and 2018, who were treated with first-line immunotherapy, chemotherapy, or combination treatment. We performed multivariable logistic regression modeling to determine factors associated with treatment receipt. An extension of inverse probability treatment weighting (IPTW) obtained from multinomial logistic regression was used to balance clinical and sociodemographic differences between treatment groups. Adjusted Kaplan-Meier survival analysis and multivariable Cox proportional hazards regression were used to evaluate the association between treatment and OS. Results: A total of 4,169 patients were identified in the cohort; 3,255 (78.1%) were treated with chemotherapy, 601 (14.4%) with immunotherapy, and 313 (7.5%) with combination treatment. Multivariable analysis identified increasing age (RRR: 1.07, 95% CI, 1.06-1.08), comorbidity burden (Charlson-Deyo 2, RRR: 1.65, 95% CI, 1.21-2.24 and Charlson-Deyo 3, RRR: 2.11; 95% CI, 1.51-2.93), and treatment at an academic facility (RRR: 1.26; 95% CI, 1.03-1.53) as independent predictors of receiving immunotherapy. Treatment at an academic facility (RRR: 1.29, 95% CI, 1.01-1.65) was associated with receipt of combination treatment. After IPTW, we found that combination therapy (hazard ratio [HR]: 0.72; 95% CI, 0.62-0.83), but not immunotherapy alone, was associated with improved survival compared to chemotherapy. These data are limited by inability to determine platinum eligibility, and residual confounding. Conclusions: Patients with older age and more comorbidities were more likely to receive immunotherapy than chemotherapy for first-line treatment of metastatic urothelial carcinoma of the bladder. Modest real-world utilization of chemo-immunotherapy was observed to be higher in academic centers and was associated with improved survival compared to chemotherapy. The study is limited by retrospective design; prospective data are necessary to identify patients who may benefit from combination chemo-immunotherapy.