The Efficacy of Adjuvant Targeted Therapy in Patients with Advanced Renal Cell Carcinoma: A Systematic Review and Meta-Analysis

Abstract

Background. The aim of this systematic evaluation and meta-analysis was to analyze the efficacy and adverse effects of adjuvant targeted therapy regimens in advanced or metastatic renal cell carcinoma (RCC). Methods. Studies eligible for the efficacy of adjuvant targeted therapy regimens in advanced or metastatic RCC published before December 2021 in PubMed, Embase, Cochrane Clinical Trials Database (CENTRAL), and Web of Science were searched for (1) patients with locally advanced renal cell carcinoma (RCC) who received adjuvant postoperative targeted therapy versus those not receiving active treatment; (2) primary endpoint outcomes of disease-free survival (DFS), overall survival (OS), and adverse events (AEs); and (3) design: randomized controlled trial (RCT) as inclusion criteria. Data on DFS and OS were extracted or recalculated by meta-analysis as hazard ratios (HRs), and AEs were compared using a dominance ratio (OR). Result. This systematic evaluation will provide evidence on the effectiveness and adverse effects of adjuvant targeted therapy in patients with advanced RCC. The results of meta-analysis showed that all of the three adjuvant targeted therapeutic drugs (sorafenib, sunitinib, and pazopanib) did not benefit from the adjuvant targeted therapy for DFS and OS and even increase the incidence of AEs compared to the placebo. Conclusions. The aim of this study was to summarize data on DFS, OS, and AEs in patients with advanced RCC treated with targeted therapies. The evidence provided by this systematic evaluation and meta-analysis will help guide clinical decision-making and provide insight into the future management of patients with advanced RCC.

Cabozantinib-Loaded PLGA Nanoparticles: A Potential Adjuvant Strategy for Surgically Resected High-Risk Non-Metastatic Renal Cell Carcinoma

“…Despite the extensive efforts to identify effective adjuvant therapies, no drugs are recommended for routine clinical use in high-risk RCC due to their poor benefit-to-harm ratios [ 5 , 8 , 9 , 12 , 13 , 14 , 15 , 16 , 18 , 19 , 22 , 23 , 24 , 25 ]. Further research on the nano-delivery of antimetastatic TKIs for toxicity reduction and efficacy enhancement may be increasingly important.…”

“…Surgical tumor resection is the standard treatment for high-risk localized and locally advanced renal cell carcinoma (RCC) [ 1 , 2 , 3 , 4 ]. However, patients with this condition are at significant risk of metastatic relapse following nephrectomy (40–60%), which is also reflected by the low five-year metastasis-free and overall survival rates of 31.2% and 44.0%, respectively [ 4 , 5 , 6 , 7 , 8 , 9 , 10 ]. Therefore, effective adjuvant therapies that can ultimately improve survival outcomes are warranted, particularly for RCC patients who are at high risk of distant metastasis.…”

“…Molecular targeted therapies for metastatic RCC, such as vascular endothelial growth factor (VEGF)–targeting tyrosine kinase inhibitors (TKIs)—and inhibitors of the mechanistic target of rapamycin have been extensively tested as adjuvant therapies aiming to eliminate micro-metastasis that may be present at the time of the nephrectomy [ 6 , 7 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ]. Unfortunately, in the adjuvant setting, multiple meta-analyses failed to identify such TKIs that can demonstrate an overall survival benefit in surgically resected RCC with a high risk of metastatic relapse [ 5 , 6 , 7 , 8 , 9 , 10 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ]. Given the high risk of high-grade adverse events and the higher frequency of treatment withdrawal leading to suboptimal dose-intensity of adjuvant TKIs [ 7 , 17 , 19 , 20 , 24 ], there is currently no globally accepted standard adjuvant TKIs for non-metastatic high-risk RCC patients following nephrectomy [ 5 , 6 , 7 , 8 , 9 , 10 , 12 , 13 , 14 , 15 , 16 , 18 , 19 , 20 , 21 , 22 , 23 , ...…”

“…Unfortunately, in the adjuvant setting, multiple meta-analyses failed to identify such TKIs that can demonstrate an overall survival benefit in surgically resected RCC with a high risk of metastatic relapse [ 5 , 6 , 7 , 8 , 9 , 10 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ]. Given the high risk of high-grade adverse events and the higher frequency of treatment withdrawal leading to suboptimal dose-intensity of adjuvant TKIs [ 7 , 17 , 19 , 20 , 24 ], there is currently no globally accepted standard adjuvant TKIs for non-metastatic high-risk RCC patients following nephrectomy [ 5 , 6 , 7 , 8 , 9 , 10 , 12 , 13 , 14 , 15 , 16 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ]. Furthermore, long-term exposure to oral TKIs is associated with decreased drug concentration in the plasma and tumor tissues over time, thereby causing a reduction in the efficacy and therapeutic failures of TKIs [ 26 ].…”

Construction and Validation of a Novel Cuproptosis-Related Seven-lncRNA Signature to Predict the Outcomes, Immunotherapeutic Responses, and Targeted Therapy in Patients with Clear Cell Renal Cell Carcinoma

“…With few effective treatments for RCC other than surgical resection, many novel therapies, such as targeted therapies and ICI agents, have been emerging or available and show significant efficacy. Recently, ICI-based combinations (ICI-targeted agents or ICI-ICI) have gained widespread acceptance as an effective therapy and have been authorized as a first-line treatment for advanced RCC [45][46][47]. Therefore, identifying patients who are candidates for ICI in clinical practice is critical.…”