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A Systematic Review and Meta-analysis of Dual Therapy in Patients With Advanced Renal Cell Carcinoma of Favourable
Adi Kartolo1, Ryan G Holstead1, Ignacio Duran2
1Department of Oncology, Division of Medical Oncology, Queen's University, Kingston, Ontario, Canada.
Objective:
To define the impact of first-line dual therapy involving immune checkpoint inhibitors (ICI) on survival outcomes in patients with advanced renal cell carcinoma (aRCC) of International Metastatic RCC Database Consortium favourable-risk.
Materials And Methods:
Systematic review of Medline, EMBASE, and Cochrane Central Register of Controlled trials were conducted to select all phase II/III randomized clinical trials involving first-line, palliative-intent dual therapy in aRCC patients of favourable-risk. Inverse-variance with random-effects model was used for meta-analysis. Sensitivity analysis with exclusion of immune checkpoint inhibitors (ICI)-ICI combination was conducted. Study outcomes were overall survival (OS) and progression free survival (PFS).
Results:
Seven phase II/III randomized controlled trials (N = 1214) were included in the meta-analysis. There were no significant OS differences detected in the favourable-risk group on dual therapy in comparison to sunitinib monotherapy (HR 0.96, 95%CI 0.73-1.26, P = .79). Sensitivity analysis also did not show significant OS benefit when excluding ICI-ICI regimen (HR 0.99, 95%CI 0.69-1.43, P = .96). PFS was not shown to have significant benefit for dual therapy in the favourable-risk group (HR 0.75, 95%CI 0.50-1.13, P = .17), but it met statistical significance when ICI-ICI regimen was excluded from the analysis (HR 0.63, 95%CI 0.50-0.79, P <.001).
Conclusion:
There was no OS benefit when comparing dual therapy vs sunitinib monotherapy in aRCC favourable-risk group. Longer follow-up would be required to definitively detect potential OS benefit, if any. Careful patient-clinician discussion of alternative management options are required prior to initiating dual-therapy in all aRCC favourable-risk group.
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