First-Line Systemic Treatments for Advanced/Metastatic Renal Cell Carcinoma of Favorable-, Intermediate-, and Poor-Risk, Respectively: A Bayesian Network Analysis
36 Pages Posted: 28 Jan 2019More...
Background: Advanced/metastatic renal cell carcinoma (RCC) is a heterogeneous group of conditions with different risk stratification. The optimum systemic therapies for advanced/metastatic RCC of favorable-, intermediate-, and poor-risk have not been established. We aimed to compare and rank the effects associated with systemic therapies in the first-line setting.
Methods: We searched Pubmed, Cochrane databases, Web of Science, and ClinicalTrials.gov for randomized controlled trials (RCTs) published up to October 2018, of systemic therapies for advanced/metastatic RCC. Analysis was done on a Bayesian framework.
Findings: 13 unique RCTs including 7 248 patients were identified. For favorable-risk patients, temsirolimus plus bevacizumab, and nivolumab plus ipilimumab were associated with significantly worse progression-free survival (PFS) than sunitinib (HR 1.96, 95% CI 1.04-3.63; and HR 1.56, 95% CI 1.32-1.84, respectively). For intermediate-risk patients, nivolumab plus ipilimumab and cabozantinib were associated with significantly higher improvement in PFS than sunitinib (HR 0.66, 95% CI 0.54-0.81; HR 0.64, 95% CI 0.43-0.96, respectively). For poor-risk, nivolumab plus ipilimumab provided obvious PFS advantage over sunitinib (HR 0.57; 95% CI 0.4-0.70). For PFS, there was a 41.7% likelihood that sunitinib was the preferred treatment for favorable-risk patients. There was a 38.3% likelihood that cabozantinib was the preferred option for intermediate-risk patients. There was a 67.7% chance that nivolumab plus ipilimumab was the best therapy for poor-risk patients. There were no significant differences in the rate of drug-related adverse events.
Interpretation: Sunitinib, cabozantinib, and nivolumab plus ipilimumab might be the optimum treatments for advanced/metastatic RCC of favorable-, intermediate-, and poor-risk, respectively.
Funding Statement: The authors declare: "No Funding."
Declaration of Interests: The authors state: "None declared."
Ethics Approval Statement: All studies were selected compling with the search strategy on the basis of Preferred Reporting Items for Systematic Reviews and Meta-analyses criteria. (PRISMA)
Keywords: renal cell carcinoma; systemic therapy; risk stratification; efficacy; safety
Suggested Citation: Suggested Citation