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Nivolumab versus Cabozantinib: Comparing Overall Survival in Metastatic Renal Cell Carcinoma

Witold Wiecek1, Helene Karcher1

  • 1LASER Analytica, Halton House, 20-23 Holborn, London, EC1N 2JD, United Kingdom.

Plos One
|June 9, 2016
PubMed

Insights

Comparing nivolumab and cabozantinib for metastatic renal-cell carcinoma (mRCC) shows survival benefits vary over time. Cabozantinib may offer initial advantages, while nivolumab shows better long-term overall survival (OS) in mRCC patients.

Area of Science:

  • Oncology
  • Medical Statistics
  • Pharmacoeconomics

Background:

  • Metastatic renal-cell carcinoma (mRCC) affects numerous patients, with a significant proportion requiring second-line therapy after initial treatment failure.
  • Nivolumab and cabozantinib are emerging treatments for advanced RCC, necessitating comparative effectiveness studies.
  • Traditional meta-analysis methods like the Bucher method assume proportional hazards, which may not accurately reflect survival data with intersecting curves.

Purpose of the Study:

  • To compare overall survival (OS) between nivolumab and cabozantinib in patients with relapsed or refractory metastatic renal-cell carcinoma (mRCC).
  • To evaluate survival outcomes using network meta-analysis models that account for time-varying hazard ratios, addressing limitations of traditional methods.
  • To analyze the temporal trends in treatment effectiveness for nivolumab versus cabozantinib.

Main Methods:

  • Bayesian parametric survival network meta-analysis of overall survival (OS) data digitized from Kaplan-Meier curves of pivotal trials.
  • Implementation of four models: one fixed hazard ratio (HR) model and three time-varying HR models (including log-logistic).
  • Comparison of model fits to assess the appropriateness of proportional hazards assumption.

Main Results:

  • The Bucher method (fixed HR) favored cabozantinib (HR=1.09), but models with time-varying HRs demonstrated superior data fit.
  • The log-logistic model indicated an initial OS advantage for cabozantinib, transitioning to favor nivolumab after approximately 5 months.
  • The probability of cabozantinib conferring superior OS decreased from 54% initially to 41.5% by 24 months; numerical differences in OS remained small.

Conclusions:

  • Hazard ratios for OS between nivolumab and cabozantinib are not constant over time, suggesting differential patient benefit based on prognosis.
  • Cabozantinib may benefit patients with poorer prognosis in the initial treatment phase, while nivolumab may benefit those with better prognosis long-term.
  • Further real-world evidence is required to definitively compare the effectiveness of nivolumab and cabozantinib in mRCC.

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