Biomarker-driven EGFR therapy improves outcomes in patients with metastatic colorectal cancer

Abstract

As new data from randomized studies comparing EGFR-targeting therapies with VEGF inhibitors emerge, the treatment landscape for metastatic colorectal cancer is expected to change. Although both the VEGF inhibitor bevacizumab and the anti-EGFR antibody cetuximab are approved in the first-line setting, they have not until recently been compared directly in randomized studies. Unlike targeted therapy in the EGFR pathway, there are no biomarkers guiding VEGF treatment. Recent data, discussed in this review, demonstrate that patients with KRAS/NRAS wild-type tumors benefit from anti-EGFR therapy in the first-line setting and that anti-EGFR therapy may be superior when compared with anti-VEGF approaches. This review focuses on the clinical utility of targeting EGFR by revisiting the biologic rationale for EGFR inhibition in metastatic colorectal cancer and providing new insight on the advancements in biomarker analyses with the potential to change practice.

The importance of optimal drug sequencing in metastatic colorectal cancer: biological rationales for the observed survival benefit conferred by first-line treatment with EGFR inhibitors

“…Also potentially germane to these discussions is the observation that the addition of cetuximab to FOLFOX or FOLFIRI in the first-line setting elicits superior depth of response and early tumor shrinkage, relative to FOLFOX or FOLFIRI alone and FOLFIRI + bevacizumab [49,62,63]. Although depth of response and early tumor shrinkage are still emerging concepts, presently available evidence suggests that both are predictive of long-term outcome in patients with mCRC [62,82]. Accordingly, the improved depth of response and early tumor shrinkage observed in cetuximab-treated patients in the FIRE-3 trial may, at least in part, account for the OS advantage conferred by cetuximab in this trial [49].…”