Test Helps Select Best Treatment for Bowel Cancer Patients

In a recent clinical trial each patient had their cancer tested for a gene called rat sarcoma (RAS). If there were no faults in the gene, they went on to receive irinotecan either alone or together with a new targeted cancer drug called panitumumab. The study showed that some patients benefitted from adding the new drug but others did not and further studies were carried out to find out the reason.

Scientists at the St James’s University Hospital (Leeds, UK) and their colleagues studied tumor samples from 323 patients who were tested for levels of two proteins, called Amphiregulin (AREG) and Epiregulin (EREG), which are produced by some cancer cells to help them grow. Panitumumab blocks these proteins, stopping tumors developing. The analysis was conducted between 2012 and 2014. A predefined dichotomous model classified tumors as “high expressor” (either EREG or AREG in top tertile for messenger ribonucleic acid (mRNA) level) or “low expressor” (neither EREG nor AREG in top tertile). Ligand expression was assessed as a prognostic and predictive biomarker. Expression of AREG/EREG and RAS and BRAF mutations were assessed in archival tumor tissue.

The team showed that for patients with high levels of the proteins, the drug combination stopped cancer growth for nearly twice as long as irinotecan alone with a mean of eight months compared with four and a half months, but the drug did not work for patients with low levels of the proteins. High ligand expression is a predictive marker for panitumumab therapy benefit on progression-free survival (PFS) in RAS wild type (wt) patients; conversely, patients with low ligand expression gained no benefit. The current “opt-in” strategy for anti-EGFR therapy in all patients with RAS wt advanced colorectal cancer should be questioned. Expression of EREG/AREG is a useful biomarker for anti-EGFR therapy; optimization for clinical use is indicated.

Jenny F. Seligmann, PhD, the lead author, said, “These results are very promising. Our task now is to develop a fast and reliable test for the two proteins that can be offered to patients before they start treatment, to help select the right drugs to use. 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.” The study was published on February 11, 2016, in JAMA Oncology.

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