Quantitative Characterization of the Exposure-Response Relationship for Cancer Immunotherapy: A Case Study of Nivolumab in Patients With Advanced Melanoma

CPT Pharmacometrics Syst Pharmacol. 2017 Jan;6(1):40-48. doi: 10.1002/psp4.12133. Epub 2016 Dec 26.


To inform the benefit-risk assessment of nivolumab in patients with advanced melanoma, analyses of efficacy and safety exposure-response (E-R) relationships were conducted with data from patients with advanced melanoma enrolled in two clinical studies (phase I and phase III) who received nivolumab 0.1-10.0 mg/kg every 2 weeks. E-R efficacy analyses were performed by relating the nivolumab time-averaged concentration after the first dose (Cavg1 ) to two endpoints: RECIST objective response (OR) and overall survival (OS). E-R safety analyses characterized the relationship between nivolumab Cavg1 and the hazard of all-causality adverse events leading to discontinuation or death (AE-DC/D). Nivolumab exposure represented by Cavg1 was not a significant predictor of OR, OS, or the hazard of AE-DC/D. E-R efficacy and safety relationships were relatively flat over the exposure range.

MeSH terms

  • Aged
  • Antibodies, Monoclonal / administration & dosage*
  • Antineoplastic Agents / administration & dosage*
  • Clinical Trials, Phase I as Topic / statistics & numerical data
  • Clinical Trials, Phase III as Topic / statistics & numerical data
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Immunotherapy / methods*
  • Immunotherapy / trends
  • Internationality
  • Male
  • Melanoma / diagnosis
  • Melanoma / drug therapy*
  • Middle Aged
  • Nivolumab
  • Skin Neoplasms / diagnosis
  • Skin Neoplasms / drug therapy*
  • Treatment Outcome


  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Nivolumab