The use of EGFR inhibitors in colorectal cancer: is it clinically efficacious and cost-effective?

Abstract

Cetuximab (Erbitux) and panitumumab (Vectibix) are monoclonal antibodies to the EGFR. They are used as monotherapy or in combination with cytotoxic chemotherapy and increase both progression-free survival and overall survival in patients with wild-type RAS metastatic colorectal cancer. The most common side effects of therapy are dermatological, including skin (acneiform) rash, pruritus and hair changes. Despite their clinical activity, cost–effectiveness of the two drugs should be addressed in a discussion of their usage in everyday care. This study provides an up-to-date review of the clinical efficacy and cost–effectiveness of anti-EGFR inhibitors.

Keywords:

• cancer
• cetuximab
• colorectal
• cost–effectiveness
• EGFR
• panitumumab

Financial & competing interests disclosure

Y-J Ko is on the speaker’s bureau for Roche and has received honoraria from Amgen. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Twenty percent of patients with colorectal cancer present with metastatic disease, which is treated with systemic chemotherapy and routinely supplemented with biological agents such as VEGF and EGFR inhibitors (bevacizumab and cetuximab/panitumumab, respectively).

• EGFR inhibitors have been shown to increase progression-free survival (PFS) and overall survival (OS) in the first-line and third-line setting, especially in combination with irinotecan-based chemotherapy. PFS is improved in the second-line setting.

• Dual biological therapy is not recommended based on two large Phase III trials, decreasing PFS and OS. When comparing bevacizumab and cetuximab, there is likely no difference between the two treatments in the first-line setting in combination with chemotherapy, based on FIRE-3 and CALGB 80405.

• EGFR inhibitors are the most effective in patients with wild-type Kirsten rat sarcoma-2 virus oncogene (KRAS) status and may be detrimental to those who have a mutant type. Other potential biomarkers include neuroblastoma RAS, BRAF and PIK3CA. Newer studies include full sequencing tests for these mutations to allow for increased selection potential.

• Costs associated with EGFR inhibitors include the drug themselves, adverse event costs for the skin-related issues that occur on treatment and KRAS testing.

• Cost–effectiveness analyses show that first-line usage of EGFR inhibitors is not cost-effective compared with bevacizumab, due to higher drug pricing. Generalization may decrease the gap between these drugs. Cetuximab and irinotecan are more cost-effective than EGFR monotherapy in the third-line setting at a WTP of US$50,000. KRAS testing before treatment decreases overall costs in these cost–effectiveness analyses.