Adjuvant Treatment Options in Renal Cell Carcinoma: A Living Systematic Review and Network 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 previously maintained the evidence by adding new data from ATLAS and SORCE trials, and updated data from S-TRAC and PROTECT. The current update includes data from KEYNOTE-564 trial which assessed pembrolizumab in patients with localized RCC and high risk of disease recurrence after nephrectomy. We are monitoring the results from on-going immune checkpoint inhibitors trials (PROSPER, IMmotion010, CheckMate 914, and RAMPART) in this space. This 'living' review will be updated as soon as new data becomes available.


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. Users can choose to view results for their outcome of interest. This analysis is limited to the trials assessing TKI as compared to placebo and does not include KEYNOTE 564 trial due to potential indirectness in intervention.


NETWORK META-ANALYSIS

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


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.


SUMMARY OF FINDINGS: NETWORK META-ANALYSIS

The Summary of Findings (SoF) table is designed to display multiple comparisons in an interactive manner. All possible combinations in network meta-analysis can be compared using this framework. Users can interactively select or deselect SoF for a given clinical outcome by clicking the outcome of interest from the left-hand panel. Users can also enter any baseline risk for an outcome, to visualize the absolute risk differences due to treatment. Clicking on any of the colored boxes displays details of that effect estimate as well as its associated certainty of evidence assessment.

Choose reference treatment, measure of effect, and denominator for absolute effect.


EVIDENCE MAP

The evidence map visually summarizes the evidence for available treatment comparisons and identifies evidence gaps that warrant future research. User can select a treatment option of interest from the dropdown to visualize whether it is comparable, beneficial or harmful (color), certainty of evidence (size of the circle) as compared to other treatment options in the network. Empty slots (no circles) denote the complete lack of evidence (either direct or indirect).


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.