A recently developed biomarker test for patients with advanced colorectal cancer could help determine the best treatment options for each patient, according to a recent study. In advanced colorectal cancer, the expression of the epidermal growth factor receptor (EGFR) ligands epiregulin (EREG) and amphiregulin (AREG) was found to predict the therapeutic benefit of adding panitumumab to irinotecan.1

Wild-type RAS is a gene necessary for EGFR antagonists to be effective. However, such therapies sometimes fail even in patients with wild-type RAS.

In this study, researchers examined data from the PICCOLO trial, which included more than 1200 patients with advanced colorectal cancer from across the United Kingdom. The PICCOLO trial examined the addition of panitumumab to irinotecan therapy in patients with wild-type RAS and advanced colorectal cancer who had treatment failure with prior fluoropyrimidine (anti-EGFR). The levels of expression of the EREG and AREG ligands were successfully measured in 323 patients among the 696 patients who were randomized in the irinotecan and irinotecan with panitumumab groups.

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Among the patients with wild-type RAS (220/323 patients), those with high EREG and AREG expression levels benefited from panitumumab but those with low EREG and AREG expression levels did not.

For those patients with both wild-type RAS and high ligand expression levels, adding panitumumab to treatment resulted in median progression-free survival (PFS) of 8.3 months vs 4.4 months on irinotecan alone (hazard ratio [HR], 0.38; 95% CI, 0.24-0.61; P<.001). Among wild-type RAS patients with low ligand expression, the addition of panitumumab resulted in median PFS of 3.2 months vs 4.0 months on irinotecan alone (HR, 0.93; 95% CI, 0.64-1.37; P=.73).

High ligand expression itself did not predict overall survival (HR, 0.79; 95% CI, 0.58-1.09; P=.15) or PFS (HR, 0.93; 95% CI, 0.68-1.27; P=.64).

“These results are very promising. Our task now is to develop a fast and reliable test for the 2 proteins that can be offered to patients before they start treatment, to help select the right drugs to use,” said Jenny Seligmann, MBChB, MRCP, PhD, Cancer Research UK clinical trial fellow, the University of Leeds, Leeds, England.

“Thanks to research we now have new cancer drugs that work in very specific ways, targeting individual rogue molecules in cancer cells. These drugs can be of enormous help to some patients, but not others, so as well as developing new treatments it is vital that we find the right way to select the best treatment for each individual patient. This will help patients to have more time with their loved ones, and to avoid the distress of going through ineffective treatment.”

This clinical trial was sponsored by Cancer Research UK.


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