Abstract
Approximately half of new diagnoses of mRCC occur in elderly patients (≥65 years old). The comparative efficacy of emerging and existing first-line therapies of mRCC, including combinations of immune checkpoint inhibitors, in elderly patients is not well described. The KEYNOTE-426 is an ongoing study investigating the efficacy and safety of P+A vs. sunitinib. P+A has demonstrated superiority over sunitinib in terms of overall survival (OS), progression-free survival (PFS) and overall response rate (ORR). This study was conducted to determine the relative efficacy of first-line treatments for mRCC in elderly patients. A systematic literature review identified RCTs that reported efficacy of approved systemic therapies versus investigational agents for mRCC. A subset of these trials reporting efficacy outcomes in elderly patients was selected from the larger evidence base. Hazard ratios (HRs) were synthesized with a Bayesian network meta-analysis under the proportional hazards assumption. Fixed-effect Bayesian NMA was conducted to determine the relative efficacy of treatments; PFS [hazard ratios (HRs)] was expressed with 95% credible intervals (CrIs). A network of interlinked RCTs for OS evidence to conduct NMA was not achieved. Six unique RCTs were eligible for the NMA of PFS. P+A was superior to 4 out of 5 comparators in the RCTs. P+A showed statistically significant benefit over interferon-alpha (HR=0.27, 95% CrI: 0.15-0.48), bevacizumab in combination with interferon-alpha (HR=0.35, 95% CrI:0.18-0.67), pazopanib (HR=0.43, 95% CrI: 0.29-0.64) and sunitinib (HR=0.63, 95% CrI: 0.45-0.88). PFS benefit favored P+A over avelumab in combination with axitinib (HR=0.90, 95% CrI: 0.55-1.45) but was not statistically significant. The result of this analysis suggests that, in elderly patients with mRCC, P+A seemed to extend PFS longer than other first-line systemic therapies when indirectly compared.
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