Panitumumab (Vectibix®): A Comprehensive Monograph on a Targeted Therapy for Metastatic Colorectal Cancer

Executive Summary and Key Findings

Panitumumab, marketed under the brand name Vectibix®, is a cornerstone of targeted therapy for metastatic colorectal cancer (mCRC). It is a recombinant, fully human IgG2 kappa monoclonal antibody that functions as a high-affinity antagonist of the human epidermal growth factor receptor (EGFR).[1] By competitively inhibiting the binding of endogenous ligands like EGF and TGF-α, panitumumab blocks the downstream signaling cascades—primarily the RAS-RAF-MEK-ERK and PI3K-AKT-mTOR pathways—that drive tumor cell proliferation, survival, and angiogenesis.[3] Its efficacy is critically dependent on the molecular profile of the tumor. The paramount finding from over a decade of clinical research is that panitumumab provides benefit exclusively to patients with wild-type

RAS (both KRAS and NRAS) tumors, and its use in RAS-mutant disease is associated with a lack of benefit and potential harm.[5]

Pivotal clinical trials have precisely defined its role in the mCRC treatment algorithm. The PRIME study established its efficacy in the first-line setting in combination with FOLFOX chemotherapy for RAS wild-type patients, demonstrating significant improvements in both progression-free survival (PFS) and overall survival (OS).[7] The ASPECCT trial confirmed its non-inferiority to the chimeric anti-EGFR antibody cetuximab in the chemorefractory setting, establishing it as a valid therapeutic alternative.[9] More recently, the PARADIGM trial provided practice-changing evidence that for patients with left-sided,

RAS wild-type tumors, first-line treatment with panitumumab plus FOLFOX is superior to bevacizumab plus FOLFOX in extending overall survival, solidifying primary tumor location as a key predictive biomarker.[11] In a strategic reversal of its contraindication in