A Network Meta-Analysis of the Differences in Effectiveness and Safety between Nivolumab and Targeted Drug Therapy in Metastatic Renal Cell Carcinoma

OBJECTIVE: Nivolumab plus other drugs have provided significant benefits in patients with metastatic renal cell carcinoma (mRCC), but most of the available comparisons were conducted with sunitinib, and differences in efficacy with targeted drugs were marginally reported. Thus, this study used a network meta-analysis to compare the difference in efficacy between nivolumab combination therapy and other targeted agents. METHODS: In this systematic review and network meta-analysis, we searched PubMed, Embase, and Cochrane Library databases for randomized controlled trials (RCTs) with the time set from database establishment to December 10, 2021, using programmed death factor 1 (PD-1) inhibitors, nivolumab, and sunitinib in the treatment of mRCC. Progression-free survival (PFS), overall survival (OS), response rate (RR), and adverse events (AEs) were collated and analyzed using the gemtc package in the R language. RESULTS: A total of ten studies satisfied the inclusion criteria, including 6568 RCC cases, 10 drugs, and 11 treatment protocols. The Ate_Axi protocol obtained similar PFS to the Niv_Cab protocol, which outperformed that of all other protocols. The Niv_Cab regimen showed better PFS benefits than the Niv_Ipi regimen (HR < 1, P < 0.05), and Niv_Ipi had superior PFS compared to the Ate, Eve, Paz, Sor, and Sun scheme. The regimens Cab, Niv_Cab, and Niv_Ipi were associated with the best PFS benefits, while Eve is the least favorable drug in terms of PFS. Niv_Cab showed better OS than Ate_Bev, Eve, Paz, Sor, and Sun. The patients given Ate_Bev, Eve, Paz, Sor, and Sun had inferior OS to those given Niv_Ipi. The Pem_Axi, Niv_Cab, and Niv_Ipi regimens had the best OS, and that of Eve is considered least promising. The Niv_Cab protocol showed significantly better RRs than the Eve, Paz, Sor, and Sun protocols, and the Ate_Bev, Eve, Paz, Sor, and Sun protocols presented superior RRs compared to the Niv_Ipi protocol. The Ate, Eve, and Niv_Ipi regimens had the lowest incidence of AEs, and the Sor regimen had the highest incidence of AEs. CONCLUSION: Among the targeted treatment options for mRCC, both Niv_Cab and Niv_Ipi yield better efficacy and safety in the treatment of mRCC, with Niv_Cab providing more survival benefit but with a less favorable safety profile.