Immunogenicity of panitumumab in combination chemotherapy clinical trials
Open Access
- 9 November 2011
- journal article
- research article
- Published by Springer Science and Business Media LLC in BMC Clinical Pharmacology
- Vol. 11 (1), 17
- https://doi.org/10.1186/1472-6904-11-17
Abstract
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. 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. 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. 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. ClinicalTrials.gov: NCT00339183 (study 20050181), NCT00411450 (study 20060277), NCT00332163 (study 20050184), and NCT00364013 (study 20050203).Keywords
This publication has 20 references indexed in Scilit:
- Randomized Phase III Study of Panitumumab With Fluorouracil, Leucovorin, and Irinotecan (FOLFIRI) Compared With FOLFIRI Alone As Second-Line Treatment in Patients With Metastatic Colorectal CancerJournal of Clinical Oncology, 2010
- Randomized, Phase III Trial of Panitumumab With Infusional Fluorouracil, Leucovorin, and Oxaliplatin (FOLFOX4) Versus FOLFOX4 Alone As First-Line Treatment in Patients With Previously Untreated Metastatic Colorectal Cancer: The PRIME StudyJournal of Clinical Oncology, 2010
- Development trends for human monoclonal antibody therapeuticsNature Reviews Drug Discovery, 2010
- Cetuximab-Induced Anaphylaxis and IgE Specific for Galactose-α-1,3-GalactoseThe New England Journal of Medicine, 2008
- High Incidence of Cetuximab-Related Infusion Reactions in Tennessee and North Carolina and the Association With Atopic HistoryJournal of Clinical Oncology, 2007
- A risk-based bioanalytical strategy for the assessment of antibody immune responses against biological drugsNature Biotechnology, 2007
- Clinical response to adalimumab: relationship to anti-adalimumab antibodies and serum adalimumab concentrations in rheumatoid arthritisAnnals Of The Rheumatic Diseases, 2007
- A Phase 1 Escalating Single-Dose and Weekly Fixed-Dose Study of Cetuximab: Pharmacokinetic and Pharmacodynamic Rationale for DosingClinical Cancer Research, 2007
- Immunogenicity, efficacy and adverse events of adalimumab in RA patientsRheumatology International, 2006
- Immunogenicity of engineered antibodiesMethods, 2005