panitumumab
Overview
Panitumumab is a fully human IgG2 monoclonal antibody that binds the extracellular domain of EGFR, blocking ligand binding and downstream RAS-MAPK and PI3K signaling. FDA-approved for RAS wild-type metastatic colorectal cancer.
Evidence in the corpus
- Used in combination with sotorasib (KRASG12C inhibitor) for KRASG12C-mutant colorectal cancer (n=4 patients); response rate approximately 27% for the sotorasib + panitumumab combination. Acquired resistance developed through heterogeneous, subclonal mechanisms primarily reactivating ERK signaling PMID:36355783
- KRAS, NRAS, and BRAF driver mutations were 100% concordant between primary and metastatic tumor sites in 69 MSS CRC trios, supporting use of either tissue source for panitumumab eligibility determination; metastasis-private EGFR amplification and MAP2K1 mutations in RAS/RAF-WT tumors represent exceptions warranting metastasis sequencing PMID:25164765
- OncoKB Level 1 resistance biomarkers for panitumumab in COADREAD include hotspot KRAS (44%) and NRAS mutations identified by MSK-IMPACT in this 1,134-CRC cohort; 37% of left-sided MSS mCRC had no mitogenic-pathway mutation and may benefit from EGFR/HER2-directed antibody therapy PMID:29316426
Resistance mechanisms
- Combined KRASG12C + EGFR inhibition resistance is heterogeneous: RAS mutations (58.3% of patients), MAPK pathway alterations (58.3%), RTK activation (75%), PI3K-mTOR alterations (25%), nuclear function alterations (41.7%). All resistance alterations appeared at low VAF without clonal sweep PMID:36355783
Cancer types (linked)
- COADREAD — KRASG12C-mutant colorectal cancer treated with sotorasib + panitumumab combination
Sources
This page was processed by crosslinker on 2026-05-06. - PMID:25164765
This page was processed by wiki-cli on 2026-05-11. - PMID:29316426
This page was processed by entity-page-writer on 2026-05-15.