Expression of epidermal growth factor receptor ligands epiregulin (EREG) and amphiregulin (AREG) may help determine which patients with colorectal cancer are the most likely to benefit from panitumumab therapy.
The PICCOLO (Panitumumab, Irinotecan and Ciclosporin for Advanced Bowel Cancer) trial studied the effects of adding panitumumab to irinotecan therapy in patients with RAS wild-type colorectal cancer whose first chemotherapy treatment had stopped working and who were now starting a second line of therapy. Findings from the study revealed mixed results, with some patients seeming to benefit from the addition of panitumumab and others not.
To clarify the trial’s findings, investigators, led by Jenny F. Seligmann, PhD, University of Leeds (Leeds, UK), conducted a secondary analysis, published in JAMA Oncology, to study panitumumab’s effects in specific patient groups.
Investigators tested the tumor samples of 323 trial participants—all of whom had RAS wild-type colorectal cancer—for levels of two proteins, AREG and EREG, which are produced by some cancer cells to promote tumor growth. Penitumumab has been shown to be effective at blocking these proteins to inhibit tumor development, leading investigators to suspect that patients with higher expression of these proteins might benefit more from treatment with the drug.
In patients with tumors with high AREG and EREG expression, median progression-free survival was found to be significantly longer in patients treated with panitumumab and irinotecan than in those treated with irinotecan alone (8.3 months vs 4.4 months). Conversely, in patients with lower expression of the proteins, median progression-free survival was shorter in the group receiving both medications compared with the group receiving only irinotecan (3.2 months vs 4.0 months). No significant differences were seen in response rate or overall survival.
The investigators concluded that AREG and EREG expression serves as a predictive biomarker for the efficacy of panitumumab therapy in patients with colorectal cancer. Conventional strategies using only RAS wild-type as the biomarker for anti-EGFR therapy should therefore be reconsidered.
