High Expression of Epiregulin or Amphiregulin Predicts Benefit of Panitumumab in RAS Wild-Type Advanced Colorectal Cancer


Key Points

  • High expression of epiregulin or amphiregulin was not associated with panitumumab benefit among all patients with RAS wild-type advanced colorectal cancer after fluoropyrimidine failure.
  • High ligand expression was associated with increased progression-free survival among patients with RAS wild-type receiving panitumumab.

In the UK phase III PICCOLO trial reported in JAMA Oncology, Seligmann et al found that high expression of either of the epidermal growth factor receptor (EGFR) ligands epiregulin or amphiregulin was associated with a progression-free survival benefit with panitumumab (Vectibix)/irinotecan vs irinotecan after fluoropyrimidine failure among patients with RAS wild-type advanced colorectal cancer.

Study Details

The study was a preplanned analysis in which high ligand expression was defined as the top tertile of messenger RNA for either epiregulin or amphiregulin, and low expression was defined as neither ligand in the top tertile. Of the 696 trial patients randomized to receive panitumumab/irinotecan vs irinotecan, 331 had sufficient tumor tissue available for ligand measurement, and measurement was successful in 323 patients.

Progression-Free Survival Benefit

Among all patients, high ligand expression was not prognostic for overall survival (hazard ratio [HR] = 0.79, P = .15) or progression-free survival (HR = 0.93, P = .64). Among 220 patients with wild-type RAS (99 with high and 121 with low ligand expression), median progression-free survival was significantly prolonged with panitumumab treatment among those with high ligand expression (8.3 vs 4.4 months, HR = 0.38, P < .001) but not among those with low ligand expression (3.2 vs 4.0 months, HR = 0.93, P = .73; P = .01 for interaction).

A nonsignificant improvement in overall survival was observed for panitumumab/irinotecan vs irinotecan among patients with high expression (HR = 0.82, P = .35). Low expression was associated with nonsignificantly poorer survival (HR = 1.29, P = .19; P = .11 for interaction).

The investigators concluded: “High ligand expression is a predictive marker for panitumumab therapy benefit on [progression-free survival] in RAS [wild-type] patients; conversely, patients with low ligand expression gained no benefit…. Expression of EREG/AREG is a useful biomarker for anti-EGFR therapy; optimization for clinical use is indicated.”

The study was supported by Cancer Research UK and the Yorkshire Cancer Research.

Matthew T. Seymour, MD, of St James’s University Hospital, University of Leeds, is the corresponding author of the JAMA Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.




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