A network meta-analysis evaluating the efficacy and safety of adjuvant therapy after nephrectomy in renal cell carcinoma

Abstract

Background: In the past few years, there has been a continuous rise in the occurrence of renal cell carcinoma (RCC), with RCC recurrence becoming the primary factor behind fatalities. Despite numerous clinical trials, the impact of different medications on the long-term survival of patients with RCC after surgery remains uncertain. This network meta-analysis aimed to evaluate the impact of various medications on the survival and safety of drugs in individuals with RCC following nephrectomy.

Methods: We conducted a thorough search in various databases, including CNKI, WAN FANG DATA, VIP, Web of Science, Cochrane Library (CENTRAL), PubMed, Scopus, and Embase, for articles published prior to June 2, 2023. This meta-analysis incorporated randomized controlled trials (RCTs).

Results: The analysis included 17 studies with 14,298 participants. The findings from the disease-free survival (DFS) analysis indicated that pembrolizumab demonstrated efficacy in enhancing DFS among patients with RCC following nephrectomy when compared to the placebo group (HR = 0.83, 95%CI 0.70 to 0.99). None of the drugs included in the study significantly improved overall survival (OS) and recurrence-free survival (RFS) after nephrectomy. For adverse events (AEs), sorafenib, pazopanib, sunitinib, and nivolumab plus ipilimumab interventions showed a higher incidence of adverse events compared with placebo.

Conclusion: The network meta-analysis yielded strong evidence indicating that pembrolizumab could potentially enhance DFS in patients with RCC following nephrectomy, surpassing the effectiveness of a placebo.

Keywords: Adjuvant therapy; Efficacy; Network meta-analysis; Renal cell carcinoma.

Fig. 1

The flowchart shows the process of literature filtering

Fig. 2

Risk of bias for all randomized controlled trials included in this study. (A) Bar chart of bias; (B) Risk of bias summary. DFS, Disease-free survival; OS, Overall survival; RFS, Recurrence-free survival; AEs, adverse events; IL2 + IFN + 5FU, interleukin-2 + interferon-alpha2a + 5-fluorouracil

Fig. 3

Network diagrams of outcome indicators. (A) Disease-free survival (DFS); (B) Overall survival (OS); (C) Recurrence-free survival (RFS); (D) adverse events (AEs). Pla, placebo; Suni, sunitinib; Sora, sorafenib; Niv + Ipi, nivolumab + ipilimumab; IL2 + IFN + 5FU, interleukin-2 + interferon-alpha2a + 5-fluorouracil; Atez, atezolizumab; Pazo, pazopanib; Pemb, pembrolizumab; Gire, girentuximab; Teg + Ura, tegafur + uracil; Thal, thalidomide; Axit, axitinib

Fig. 4

Effects of different interventions on disease-free survival

Fig. 5

The impact of various interventions on overall survival

Fig. 6

Effects of different interventions on recurrence-free survival

Fig. 7

Effects of different interventions on adverse events