, Volume 70, Issue 8, pp 1059-1078
Date: 19 Sep 2012

Panitumumab

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Abstract

Panitumumab (Vectibix®) is a recombinant, fully human, IgG2 anti-epidermal growth factor receptor (EGFR) monoclonal antibody. This article reviews the clinical efficacy of intravenous panitumumab in combination with chemotherapy in the first- and second-line treatment of metastatic colorectal cancer and as monotherapy in chemotherapy-refractory metastatic colorectal cancer, as well as summarizing its pharmacological properties and tolerability. Panitumumab is indicated for use in patients with wild-type rather than mutant KRAS tumours.

The efficacy of intravenous panitumumab 6 mg/kg administered every 2 weeks was examined in randomized, open-label, multicentre, phase III trials in patients with metastatic colorectal cancer. When administered as first- or second-line treatment in combination with chemotherapy, panitumumab plus chemotherapy prolonged progression-free survival to a significantly greater extent than chemotherapy alone in patients with wild-type KRAS tumours; no significant between-group difference in overall survival was seen in the second-line treatment trial. In patients with mutant KRAS tumours, progression-free survival was significantly shorter with panitumumab plus oxaliplatin-based chemotherapy than with oxaliplatin-based chemotherapy alone in the first-line treatment trial, with no significant difference between patients receiving panitumumab plus irinotecan-based chemotherapy (FOLFIRI) and those receiving FOLFIRI alone in the second-line treatment trial. In chemotherapy-refractory patients with metastatic colorectal cancer, panitumumab monotherapy plus best supportive care prolonged progression-free survival to a significantly greater extent than best supportive care alone in both the overall population and in patients with wild-type KRAS tumours, but not in those with mutant KRAS tumours; there was no significant between-group difference in overall survival.

Panitumumab has an acceptable tolerability profile when administered as monotherapy or in combination with chemotherapy. It is associated with the skin-related toxicities characteristic of EGFR inhibitors and appears to have a low risk of immunogenicity.

In conclusion, in patients with wild-type KRAS tumours, panitumumab is a useful option in combination with chemotherapy for the first- and second-line treatment of metastatic colorectal cancer or as monotherapy for the treatment of chemotherapy-refractory metastatic colorectal cancer.

Various sections of the manuscript reviewed by: A.B. Benson III, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois, USA; J.-L. Canon, Medical Oncology, Grand Hopital de Charleroi, Charleroi, Belgium; J. Cassidy, Cancer Research UK, Glasgow, Scotland; A. Hendlisz, Medical Oncology Clinic, Institut Jules Bordet, Brussels, Belgium; T.J. Price, Department of Oncology, The Queen Elizabeth Hospital and University of Adelaide, Adelaide, South Australia, Australia; W. Scheithauer, Division of Clinical Oncology, Department of Internal Medicine I and Cancer Center, Medical University Vienna, Vienna, Austria; J.-L. Van Laethem, Department of Gastroenterology–GI Cancer Unit, Erasme University Hospital, Brussels, Belgium.

Data Selection

Sources: Medical literature published in any language since 1980 on ‘panitumumab’, identified using MEDLINE and EMBASE, supplemented by AdisBase (a proprietary database). Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from the company developing the drug.
Search strategy: MEDLINE, EMBASE and AdisBase search terms were ‘panitumumab’ and ‘colorectal cancer’. Searches were last updated 27 April 2010.
Selection: Studies in patients with metastatic colorectal cancer who received panitumumab. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data are also included.
Index terms: Panitumumab, metastatic colorectal cancer, pharmacodynamics, pharmacokinetics, therapeutic use, tolerability.