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Review
. 2015 Dec 30:9:75-86.
doi: 10.2147/OTT.S68558. eCollection 2016.

Profile of panitumumab as first-line treatment in patients with wild-type KRAS metastatic colorectal cancer

Shiven B Patel  1 , David Gill  1 , Ignacio Garrido-Laguna  1
Affiliations
Review

Profile of panitumumab as first-line treatment in patients with wild-type KRAS metastatic colorectal cancer

Shiven B Patel et al. Onco Targets Ther. .

Abstract

Targeted therapies against EGFR, vascular endothelial growth factor, and vascular endothelial growth factor receptor have expanded treatment options for patients with metastatic colorectal cancer (mCRC). Unfortunately, biomarkers to identify patients that are most likely to derive benefit from targeted therapies in this disease are still needed. Indeed, only RAS mutations have been identified as predictive of lack of benefit from monoclonal antibodies against EGFR in patients with mCRC. Panitumumab is a fully humanized monoclonal antibody against EGFR. In this study, we review data to support the use of panitumumab in combination with a chemotherapy backbone, in the first line setting in patients with RAS wild-type mCRC. Ongoing efforts are aimed at identifying smaller subsets of patients within the RAS wild-type group that will derive the largest benefit from anti-EGFR therapy. In the meantime, treatment with anti-EGFR therapy should be reserved for patients with RAS wild-type mCRC.

Keywords: RAS; first-line; metastatic colorectal cancer; panitumumab.

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Figures

Figure 1
Figure 1
Schematic of EGFR with I, II, III, and IV representing extracellular domains. Notes: (A) Represents tethered and untethered nonligand bound monomer conformations of EGFR. While in the untethered conformation, EGFR is able to be bound by GF ligands at domains I and III and obtain a more stabilized conformation (B) that allows for dimerization via domain II and downstream TK activation represented in (C). (D) Cetuximab and panitumumab bind domain III of EGFR preventing untethering and subsequent ligand binding to domain I and III. Accordingly dimerization and TK activation is prevented. Abbreviations: GF, growth factor; TK, tyrosine kinase.
Figure 2
Figure 2
PFS and OS according to exon 2 KRAS or RAS status in the PRIME and PEAK trials. Note: Data from Douillard et al and Schwartzberg et al. Abbreviations: PFS, progression-free survival; OS, overall survival; PRIME, Panitumumab Randomized trial In Combination with Chemotherapy for Metastatic Colorectal Cancer to Determine Efficacy; PEAK, Panitumumab Efficacy in Combination with mFOLFOX6 Against Bevacizumab plus mFOLFOX6 in mCRC subjects with wild-type KRAS tumors.
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