Comparative Efficacy, Safety, and Costs of Sorafenib vs. Sunitinib as First-Line Therapy for Metastatic Renal Cell Carcinoma: A Systematic Review and Meta-Analysis

Abstract

Purpose: Sorafenib and sunitinib are extensively used as first-line medications for metastatic renal cell carcinoma (mRCC). This meta-analysis was conducted to assess the antitumor efficacy, toxicity, and costs of the two drugs among mRCC patients. Materials and methods: PubMed, ScienceDirect, Scopus, Web of Science, Ovid MEDLINE, the Cochrane Library, Embase, and Google Scholar were searched for eligible articles. The endpoints consisted of progression-free survival (PFS), overall survival (OS), objective response rate (ORR), adverse effects (AEs), and per-patient-per-month (PPPM) costs. Results: We included 14 studies with 2,925 patients. Both drugs were valid for treating mRCC with equivalent PFS [hazard ratio (HR) = 0.98, 95% confidence interval (CI): 0.88–1.10, P = 0.74] and disease control rates [DCRs; risk ratio (RR) = 1.03, 95% CI: 0.98–1.08, P = 0.28], but sunitinib had a better OS (HR = 1.10, 95% CI: 1.01–1.20, P = 0.04) and higher ORR (HR = 0.66, 95% CI: 0.45–0.97, P = 0.03) than sorafenib. Furthermore, sunitinib induced more incidences of severe hematologic AEs (anemia, neutropenia, and thrombocytopenia) and stomatitis/mucositis than sorafenib. In the subanalysis, Asian patients treated with sorafenib reported a longer PFS than those treated with sunitinib (HR = 0.87, 95% CI: 0.83–0.90, P = 0.01), and European patients treated with sunitinib had a longer OS than those treated with sorafenib (HR = 1.17, 95% CI: 1.01–1.30, P = 0.04). Moreover, the pooled results of the high-quality studies reported a higher ORR with sunitinib than with sorafenib, and medium-quality studies showed a longer OS with sunitinib than with sorafenib. Conclusions: Sunitinib has more benefits (longer OS and better ORR) than sorafenib as a first-line therapy for mRCC. However, sunitinib has higher toxicity than sorafenib. Sorafenib might be more suitable than sunitinib among Asian patients, and sunitinib might be superior to sorafenib in European patients. Nevertheless, more large-scale, high-quality studies are required.

PGK1 contributes to tumorigenesis and sorafenib resistance of renal clear cell carcinoma via activating CXCR4/ERK signaling pathway and accelerating glycolysis

“…However, whether PGK1 is related to the resistance of tumor cells to TKI drugs has not been reported. Sorafenib, as a TKI drug, is still the first-line treatment for advanced RCC [ 37 ]. Our experiments confirmed that sorafenib inhibited Raf/MEK/ERK signaling pathway in all three KIRC cells (Fig.…”

“…At present, sorafenib is the first-line drug for RCC [ 37 ], but patients with advanced RCC resistant to sorafenib have limited clinical treatment options. So far, exploring sorafenib resistance mechanism in RCC is to find therapeutic targets for coping with this problem.…”

Artesunate Inhibits Growth of Sunitinib-Resistant Renal Cell Carcinoma Cells through Cell Cycle Arrest and Induction of Ferroptosis

“…Since RCC is an angiogenic disease, a promising avenue of treatment is to block angiogenesis, thereby suppressing the supply of oxygen and nutrients to the tumor. Initially, the anti-angiogenic activity of the tyrosine kinase inhibitor (TKI) sunitinib extends the progression-free survival of patients [3], but resistance occurs during treatment [4]. Thus, therapy resistance is one, if not the main, problem, in treating advanced RCC.…”

TKI-Resistant Renal Cancer Secretes Low-Level Exosomal miR-549a to Induce Vascular Permeability and Angiogenesis to Promote Tumor Metastasis

“…However, sunitinib is more toxic than sorafenib. In Asian patients, sorafenib may be more appropriate than sunitinib ( Deng et al, 2019 ). Therefore, we conducted a study on sorafenib-resistant clear cell renal cancer.…”