Immunogenicity of panitumumab in combination chemotherapy clinical trials

BMC Clin Pharmacol. 2011 Nov 9;11:17. doi: 10.1186/1472-6904-11-17.

Abstract

Background: Panitumumab is a fully human antibody against the epidermal growth factor receptor that is indicated for the treatment of metastatic colorectal cancer (mCRC) after disease progression on standard chemotherapy. The purpose of this analysis was to examine the immunogenicity of panitumumab and to evaluate the effect of anti-panitumumab antibodies on pharmacokinetic and safety profiles in patients with mCRC receiving panitumumab in combination with oxaliplatin- or irinotecan-based chemotherapies.

Methods: Three validated assays (two screening immunoassays and a neutralizing antibody bioassay) were used to detect the presence of anti-panitumumab antibodies in serum samples collected from patients enrolled in four panitumumab combination chemotherapy clinical trials. The impact of anti-panitumumab antibodies on pharmacokinetic and safety profiles was analyzed using population pharmacokinetic analysis and descriptive statistics, respectively.

Results: Of 1124 patients treated with panitumumab in combination with oxaliplatin- or irinotecan-based chemotherapy with postbaseline samples available for testing, 20 (1.8%) patients developed binding antibodies and 2 (0.2%) developed neutralizing antibodies. The incidence of anti-panitumumab antibodies was similar in patients with tumors expressing wild-type or mutant KRAS and in patients receiving oxaliplatin- or irinotecan-based chemotherapies. No evidence of an altered pharmacokinetic or safety profile was found in patients who tested positive for anti-panitumumab antibodies.

Conclusions: The immunogenicity of panitumumab in the combination chemotherapy setting was infrequent and similar to the immunogenicity observed in the monotherapy setting. Panitumumab immunogenicity did not appear to alter pharmacokinetic or safety profiles. This low rate of immunogenicity may be attributed to the fully human nature of panitumumab.

Trial registration: ClinicalTrials.gov NCT00332163 NCT00339183 NCT00364013 NCT00411450.

Publication types

  • Clinical Trial, Phase II
  • Clinical Trial, Phase III
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Anti-Idiotypic / analysis*
  • Antibodies, Monoclonal / adverse effects*
  • Antibodies, Monoclonal / blood
  • Antibodies, Monoclonal / pharmacokinetics
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized / adverse effects*
  • Antibodies, Monoclonal, Humanized / blood
  • Antibodies, Monoclonal, Humanized / pharmacokinetics
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antibodies, Neutralizing / analysis
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / blood
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Camptothecin / analogs & derivatives
  • Camptothecin / therapeutic use
  • Colorectal Neoplasms / complications
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / immunology
  • Drug Hypersensitivity / blood
  • Drug Hypersensitivity / complications
  • Drug Hypersensitivity / epidemiology
  • Drug Hypersensitivity / immunology*
  • Humans
  • Incidence
  • Irinotecan
  • Organoplatinum Compounds / therapeutic use
  • Oxaliplatin
  • Panitumumab
  • Severity of Illness Index

Substances

  • Antibodies, Anti-Idiotypic
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Neutralizing
  • Antineoplastic Agents
  • Organoplatinum Compounds
  • Oxaliplatin
  • Panitumumab
  • Irinotecan
  • Camptothecin

Associated data

  • ClinicalTrials.gov/NCT00332163
  • ClinicalTrials.gov/NCT00339183
  • ClinicalTrials.gov/NCT00364013
  • ClinicalTrials.gov/NCT00411450