Freshwater T, Li H, Valiathan C, et al. - Researchers assessed the response of historic treatment options among cisplatin-ineligible patients in first-line settings, via this systematic literature review and meta-analysis. They evaluated objective response rate (ORR), duration of response (DOR), progression-free survival, and overall survival (OS) of these therapies by analyzing published relevant clinical trials identified from PubMed (Medline), Cochrane, and Embase databases. This analysis included 18 studies (21 arms; N = 810). The pooled ORR was estimated to be 0.36 for all therapies evaluated. For the carboplatin + gemcitabine arms (6 arms; N = 259), which represent the National Comprehensive Cancer Network’s suggested first-line therapy (prior to the approval of atezolizumab and pembrolizumab) for this population, the estimated ORR was 0.36. The median DOR (4 arms) and the median OS were estimated to be 7.00 months and 8.39 months, respectively. There is a lack of clinical investigations evaluating therapeutic intervention in truly cisplatin-ineligible advanced/metastatic urothelial carcinoma patients. The evolution of new treatments that can produce a real improvement in long-term results is emphasized. In the National Comprehensive Cancer Network guidance, the addition of recent approval of atezolizumab and pembrolizumab as recommended first-line therapy for cisplatin-ineligible patients with advanced/metastatic urothelial carcinoma has been done, which has offered alternatives for this patient population.