The impact of hepatic and renal function on panitumumab exposures in patients with metastatic RAS wild-type colorectal cancer

Cancer Chemother Pharmacol. 2021 Oct;88(4):665-672. doi: 10.1007/s00280-021-04319-w. Epub 2021 Jul 2.


Purpose: Panitumumab is a human monoclonal antibody targeting the epidermal growth factor receptor for the treatment of wild-type RAS metastatic colorectal cancer (mCRC). Currently, no dedicated clinical studies have evaluated the effect of organ impairment on the pharmacokinetics of panitumumab. Here, we present data from late phase studies of panitumumab in patients with mCRC and analyses of the effect of hepatic or renal impairment on the exposure of panitumumab.

Methods: From three multicenter, open-label, phase 2 and phase 3 studies, 349 and 351 patients were included in hepatic and renal function subgroup analyses, respectively. Patients who received IV panitumumab and serum exposures were compared to patients with varying degrees of hepatic and renal organ dysfunction.

Results: The Cmax and Ctrough values for patients with mild (n = 119) and moderate (n = 4) hepatic impairment were within the range of serum concentrations of panitumumab for the normal hepatic function subgroup. The distributions of serum concentration of panitumumab in patients with mild (n = 85) or moderate (n = 19) renal impairment were similar to the serum concentrations of panitumumab in the normal renal function subgroup. Population pharmacokinetic modeling and covariate analysis results were also consistent with lack of any significant effect of renal or hepatic impairment on the pharmacokinetics of panitumumab. Additionally, real-world evidence from case studies of patients with mCRC and severe hepatic or renal impairment, which is a rare patient population to study, indicated lack of clinically relevant differences in exposure of panitumumab compared with patients with mCRC and normal hepatic or renal function.

Conclusions: Mild-to-moderate hepatic or renal dysfunction had no clinically meaningful impact on the pharmacokinetics of panitumumab in patients with mCRC. No dose adjustments for panitumumab are warranted in patients with mCRC with mild-to-moderate hepatic or renal dysfunction.

Trial registration:; NCT00083616, NCT00089635, NCT00113763.

Keywords: Dose adjustment; Hepatic impairment; Panitumumab; Pharmacokinetics; RAS wild-type; Renal impairment.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intravenous
  • Aged
  • Antineoplastic Agents, Immunological / administration & dosage
  • Antineoplastic Agents, Immunological / pharmacokinetics
  • Clinical Trials, Phase II as Topic
  • Clinical Trials, Phase III as Topic
  • Colorectal Neoplasms / drug therapy*
  • Female
  • Humans
  • Kidney Diseases / physiopathology*
  • Liver Diseases / physiopathology*
  • Male
  • Middle Aged
  • Panitumumab / administration & dosage*
  • Panitumumab / pharmacokinetics
  • Randomized Controlled Trials as Topic
  • Severity of Illness Index
  • ras Proteins / genetics


  • Antineoplastic Agents, Immunological
  • Panitumumab
  • ras Proteins

Associated data