High RNA expression of EGFR ligands epiregulin (EREG) and amphiregulin (AREG) serve as a predictive marker for panitumumab benefit on progression-free survival (PFS) in patients with RAS wild-type (wt) advanced colorectal cancer.1

In this prospectively planned, retrospective biomarker study  of the PICCOLO trial, which studied panitumumab, irinotecan, and ciclosporin in colorectal cancer, investigators examined a novel ligand model to determine if high tumor expression of AREG or EREG would predict panitumumab efficacy. The study’s primary endpoint was PFS. Secondary endpoints included response rate and overall survival (OS).

A total of 323 patients from the PICCOLO trial in the irinotecan vs irinotecan with panitumumab arm had enough tumor tissue with measurable ligand expression available for the study.

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Results showed that high ligand expression did not serve as a prognostic marker for OS (HR, 0.79; 95% CI, 0.58 – 1.09; P = .15) or PFS (HR, 0.93; 95% CI, 0.68 – 1.27; P = .64). However, in patients with RAS wt tumors and high ligand expression, median interquartile range PFS was 8.3 months in the combination arm vs 4.4 in the monotherapy arm (HR, 0.38; 95% CI, 0.24 – 0.61; P < .001). Patients with RAS wt tumors and low ligand expression had a median interquartile range PFS of 3.2 months in the combination arm vs 4.0 months in the monotherapy arm (HR, 0.93; 95% CI, 0.64 – 1.37; P = .73).

“The current ‘opt in’ strategy for anti-EGFR therapy in all patients with RAS wt aCRC should be questioned,” the authors concluded.


  1. Seligmann JF, Elliott F, Richman SD, et al. Combined epiregulin and amphiregulin expression levels as a predictive biomarker for panitumumab therapy benefit in patients with RAS wild-type advanced colorectal cancer [published online ahead of print February 11, 2016]. JAMA Oncol. doi: 10.1001/jamaoncol.2015.6065.