Efficacy and safety of PD-1/PD-L1 inhibitor monotherapy or combination therapy versus platinum-based chemotherapy as a first-line treatment of advanced urothelial cancer: A systematic review and meta-analysis.

Background: Recent clinical trials have shown that inhibitors targeting programmed cell death protein 1 (PD-1) or its ligand (programmed cell death-ligand 1 [PD-L1]) provide significant efficacy and clinical benefit in the treatment of advanced or metastatic urothelial carcinoma (UC). This systematic review and meta-analysis aimed to compare the effectiveness and safety of PD-1/PD-L1 inhibitors in combination with chemotherapy or PD-1/PD-L1 inhibitor monotherapy versus platinum-based chemotherapy as a first-line treatment for advanced UC.

Materials and methods: From the beginning of the database construction to February 4, 2024, a combination of medical subject headings and free-text words was searched using the Population Intervention Comparison Outcome Study design framework. The PubMed, Cochrane Library, Embase, and Web of Science electronic databases were searched. Meta-analyses of progression-free survival, overall survival, objective response rate (ORR), complete remission rate, duration of remission, and grade ≥3 adverse events were performed.

Results: Four studies were included in the meta-analysis. The PD-1/PD-L1 inhibitors plus chemotherapy therapy is associated with significantly better ORR compared with chemotherapy. Unfortunately, there were no significant differences between PD-1/PD-L1 inhibitor monotherapy and chemotherapy in terms of ORR, duration of remission, or overall survival.

Conclusions: Our findings indicate that PD-1/PD-L1 inhibitors plus chemotherapy therapy provides more oncological advantages than standard chemotherapy and should be recommended as a first-line treatment for advanced or metastatic UC. Attention must also be paid to the adverse effects of the combination of PD-1/PD-L1 inhibitors and chemotherapy.