Adjuvant Tyrosine Kinase Inhibitors in Renal Cell Carcinoma: A Living Systematic Review and Meta-Analysis

The treatment landscape of adjuvant renal cell carcinoma (aRCC) is evolving which prompted us to create a living review to assess tyrosine kinase inhibitors (TKIs) in aRCC in 2018. The initial report included data from three trials (ASSURE, S-TRAC, and PROTECT). We have maintained the evidence current by adding new data from ATLAS and SORCE trials, and updated data from S-TRAC and PROTECT. The final update of this living review shows consistently high-certainty lack of benefit with TKIs in aRCC. Therefore, the living review has now been closed and the process is terminated with this final update owing to conclusive results which are unlikely to be changed significantly in the future.


INTERACTIVE, MODIFIED PRISMA

The search strategy has been developed in consultation with an information specialist. The strategy is used to generate “auto” searches every month (from Medline, Embase and Cochrane Central Register of Controlled Trials [CENTRAL]). The numbers in the flowsheet are dynamically updated as new studies are considered for inclusion. The red limb on the right-hand side of the flowsheet represents real-time living updates. Users can click the colored boxes for additional details.

How to use this flowsheet? Video demonstration


INTERACTIVE TABLE

The interactive table summarizes study characteristics, population characteristics and results from the clinical trials included in this systematic review and meta-analysis. This table is dynamically updated as new studies are included in the living review. Users can select filter options to view only studies with certain characteristics or interactively construct the results table from the available menu.

How to use this table? Video demonstration


PAIRWISE META-ANALYSIS

Results are summarized as forest plots for primary analysis, sensitivity analysis and subgroup pairwise meta-analysis. Users can choose to view results for their outcome of interest using the dropdown menu (“Select outcome”).


Primary Analysis

Disease free survival Overall survival All cause AE grade ≥3 All cause AE all grades TrAE grade ≥ 3 TrAE all grades Disease free survival (Cumulative) Overall survival (Cumulative) All cause AE grade ≥3 (Cumulative) All cause AE all grades (Cumulative) TrAE grade ≥ 3 (Cumulative) TrAE all grades (Cumulative)

Sensitivity Analysis

Disease free survival (ATLAS excluded) Overall survival (ATLAS excluded) All cause AE grade ≥3 (ATLAS excluded) All cause AE all grades (ATLAS excluded) Disease free survival (PROTECT 800 mg excluded) All cause AE grade ≥3 (PROTECT 800 mg excluded) All cause AE all grades (PROTECT 800 mg excluded)

Subgroup Analysis

Disease free survival by risk category

SUMMARY OF FINDINGS: PAIRWISE META-ANALYSIS

The Summary of Findings (SoF) table is designed to summarize the key results of pairwise meta-analysis and to evaluate confidence in the estimates of effect. This table summarizes results for patient-important outcomes for all treatment options investigated in included trials as compared to control, in adjuvant RCC. Users can select their outcome of interest from the left-hand panel by clicking on it and enter any baseline risk for that outcome, to visualize the absolute risk differences due to treatment.

Choose measure of effect and denominator for absolute effect.


PUBLICATIONS

Riaz IB, Malik S, Husnain M, Sipra QUAR, Faridi W, Gondal FR, et al. A meta-analysis of randomized controlled trials for efficacy and safety of vascular endothelial growth factor tyrosine kinase inhibitors (VEGF-TKIs) adjuvant therapy in high-risk renal cell cancer (RCC). Journal of Clinical Oncology. 2018;36(15_suppl):4567-. doi: 10.1200/JCO.2018.36.15_suppl.4567

Riaz IB, Faridi W, Husnain M, Malik SU, Sipra Q, Gondal FR, et al. Adjuvant Therapy in High-Risk Renal Cell Cancer: A Systematic Review and Meta-analysis. Mayo Clin Proc. 2019;94(8):1524-34. Epub 2019/07/16. doi: 10.1016/j.mayocp.2019.01.045. PubMed PMID: 31303430.

Siddiqi R, Riaz IB, Islam M, Sipra QUAR, Ryu AJ, Raina A, et al. Adjuvant therapy in high-risk renal cell cancer: A systematic review and cumulative meta-analysis. Journal of Clinical Oncology. 2020;38(6_suppl):708-. doi: 10.1200/JCO.2020.38.6_suppl.708

Riaz IB, Siddiqi R, Islam M, He H, Riaz A, Asghar N, Naqvi SAA, Warner JL, Murad MH, Kohli M. Adjuvant Tyrosine Kinase Inhibitors in Renal Cell Carcinoma: A Concluded Living Systematic Review and Meta-Analysis. JCO Clin Cancer Inform. 2021 May;5:588-599. doi: 10.1200/CCI.21.00035. PMID: 34043431.