title: Immunogenicity of panitumumab in combination chemotherapy clinical trials.
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.
authors: Amgen Inc, One Amgen Center Drive, Thousand Oaks, CA 91320, USA.
authors: Dohan
authors: D
authors: Weeraratne
authors: Alin
authors: A
authors: Chen
authors: Jason J
authors: JJ
authors: Pennucci
authors: Chi-Yuan
authors: CY
authors: Wu
authors: Kathy
authors: K
authors: Zhang
authors: Jacqueline
authors: J
authors: Wright
authors: Juan José
authors: JJ
authors: Pérez-Ruixo
authors: Bing-Bing
authors: BB
authors: Yang
authors: Arunan
authors: A
authors: Kaliyaperumal
authors: Shalini
authors: S
authors: Gupta
authors: Steven J
authors: SJ
authors: Swanson
authors: Narendra
authors: N
authors: Chirmule
authors: Marta
authors: M
authors: Starcevic
mesh_terms: D000888:Antibodies, Anti-Idiotypic / Q000032:analysis*; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D057134:Antibodies, Neutralizing / Q000032:analysis; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002166:Camptothecin / Q000031:analogs & derivatives / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000150:complications / Q000188:drug therapy / Q000276:immunology; D004342:Drug Hypersensitivity / Q000097:blood / Q000150:complications / Q000453:epidemiology / Q000276:immunology*; D006801:Humans; D015994:Incidence; D000077146:Irinotecan; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D000077150:Oxaliplatin; D000077544:Panitumumab; D012720:Severity of Illness Index
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D057134:Antibodies, Neutralizing; D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000077544:Panitumumab; D000077146:Irinotecan; D002166:Camptothecin