Association of Tumor HER3 Messenger RNA Expression With Panitumumab Efficacy in Advanced Colorectal Cancer

JAMA Oncology
Jenny F SeligmannMatthew T Seymour

Abstract

Epidermal growth factor receptor (EGFR) (HER1) signaling depends on ligand binding and dimerization with itself or other HER receptors. We previously showed in a randomized trial that high EGFR ligand expression is predictive of panitumumab benefit in advanced colorectal cancer. Tumor expression of HER3 may further refine the RAS wild-type (wt) population benefitting from anti-EGFR agents. To examine HER3 messenger RNA expression as a prognostic and predictive biomarker for anti-EGFR therapy in a randomized clinical trial of panitumumab. The study was a prospectively planned retrospective biomarker study of pretreatment samples from the PICCOLO trial that tested the addition of panitumumab to irinotecan therapy in patients with KRAS wt advanced colorectal cancer who experienced failure with prior fluoropyrimidine treatment. HER3 was assessed as a prognostic marker, then as a predictive biomarker in patients with RAS wt, first as a continuous variable and then as a binary (high vs low) variable. Relationship with MEK-AKT pathway mutations and EGFR ligands epiregulin and amphiregulin (EREG/AREG) were also assessed. Primary end point was progression-free survival (PFS); secondary end points were response rate and overall survival ...Continue Reading

Citations

Jul 21, 2021·Journal of Translational Medicine·Hong-Wei WangBao-Cai Xing

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