EGFR Ligands May Predict Panitumumab Benefit In RAS Wild-Type, Advanced CRC

Epiregulin and amphiregulin expression could serve as a biomarker for panitumumab use in patients with advanced colorectal cancer

medwireNews: Researchers believe that measuring expression of two epidermal growth factor receptor (EGFR) ligands may help identify which advanced colorectal cancer patients with RASwild-type tumours will benefit from the addition of panitumumab to chemotherapy.

The retrospective analysis of tumour tissue samples from 323 patients in the PICCOLO trial of irinotecan alone or alongside the anti-EGFR agent did not find a significant correlation between patient outcome and expression of the EGFR ligands epiregulin and amphiregulin.

However, when assessing only the 220 patients whose colorectal cancer was wild-type for RAS, the researchers found that patients in the top tertile for messenger RNA expression of epiregulin or amphiregulin who received irinotecan plus panitumumab had significantly longer progression-free survival (PFS) than those given irinotecan alone, at a median of 8.3 versus 4.4 months and a hazard ratio of 0.38.

By contrast, for RASwild-type patients not in the top tertile for expression of either ligand, PFS was comparable for those who received irinotecan plus panitumumab and the patients who received irinotecan alone, at 3.2 versus 4.0 months.

And patients with tumours that were RASmutated gained no benefit from the addition of panitumumab regardless of their ligand expression status, report Matthew Seymour, from St James’s University Hospital in Leeds, UK, and co-workers.

There was increased overall survival in RASwild-type patients with high ligand expression who received panitumumab but this did not reach significance, they add in JAMA Oncology.

A similar non-significant trend was also detected for tumour response in this patient group but the authors note that the low rate of RECIST response in the PICCOLO study means that the analysis is “underpowered” for this secondary endpoint.

Describing epiregulin/amphiregulin expression as a “useful biomarker for anti-EGFR therapy”, the team recommends optimising its use, stating that the “current ‘opt-in’ strategy for anti-EGFR therapy in all patients with RAS[wild-type advanced colorectal cancer] should be questioned”.

In an accompanying editorial opinion, David Cunningham, from the Royal Marsden Hospital in London, UK, and co-authors say the study’s small size and lack of overall survival benefit for this biomarker means the results are “intriguing” but not sufficient to change clinical practice.

“However, this does not mean that it is lacking in potential clinical utility”, they write, encouraging trial investigators of metastatic colorectal cancer to collaborate and qualify the biomarkers as a potential tool to improve the value of anti-EGFR treatment.


Seligmann JF, Elliott F, Richman SD, et al. Combined epiregulin and amphiregulin expression levels as a predictive biomarker for panitumumab therapy benefit or lack of benefit in patients withRAS wild-type advanced colorectal cancer. JAMA Oncol 2016; Advance online publication 11 February.doi:10.1001/jamaoncol.2015.6065

Smyth EC, Khan K, Cunningham D. AREG and EREG as predictive biomarkers forRASwild-type colorectal cancer treated with panitumumab. A fresh approach to an old puzzle.JAMA Oncol 2016; Advance online publication 11 February.doi:10.1001/jamaoncol.2015.6274.

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