Treatment of metastatic renal cell carcinoma in older patients: A network meta-analysis

Introduction: More than half of patients diagnosed with renal cell carcinoma (RCC) are age 65 or older. However, older patients are often unable to meet eligibility criteria for clinical trial enrollment due to multiple factors, such as comorbidities and polypharmacy, which leads to under-representation of this population in clinical trials. Given this, efficacy data from the registration trials may not apply to older patients. Our objective was to evaluate the efficacy of first-line and salvage-line treatment in older patients, and compare efficacy between older and younger patients with metastatic RCC (mRCC). Methods: Pivotal phase three clinical trials for first-line and salvage-line treatments were included if they reported overall survival (OS) or progression-free survival (PFS) results stratified by age (</≥65 years). The meta-analysis of OS and PFS stratified by age </≥65 years was conducted in the context of Bayesian hierarchical log-linear models with both within and between study variance components. Results: In the first-line setting, data suggests that Nivolumab plus Ipilimumab is the most efficacious treatment for older patients (PFS hazard ratio (HR) 0.55, 95% confidence interval (CI) 0.23–1.45, probability best 39.7%). In the salvage-line setting, Cabozantinib is likely the most efficacious therapy for older patients (PFS HR 0.15, 95% CI 0.08–0.28, probability best 77.2%). Evidence suggests that the majority of first-line treatments have worse efficacy in older patients compared to younger patients. Conclusion: For older patients, first-line Nivolumab plus Ipilimumab and salvage-line Cabozantinib may offer the best survival outcomes. Most first-line drugs for mRCC have inferior performance in older patients compared to their younger counterparts.