Role of cetuximab in first-line treatment of metastatic colorectal cancer

Abstract

The treatment of metastatic colorectal cancer (mCRC) has evolved considerably in the last decade, currently allowing most mCRC patients to live more than two years. Monoclonal antibodies targeting the epidermal growth factor receptor (EGFR) and vascular endothelial growth factor play an important role in the current treatment of these patients. However, only antibodies directed against EGFR have a predictive marker of response, which is the mutation status of v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS). Cetuximab has been shown to be effective in patients with KRAS wild-type mCRC. The CRYSTAL study showed that adding cetuximab to FOLFIRI (regimen of irinotecan, infusional fluorouracil and leucovorin) significantly improved results in the first-line treatment of KRAS wild-type mCRC. However, results that evaluate the efficacy of cetuximab in combination with oxaliplatin-based chemotherapy in this setting are contradictory. On the other hand, recent advances in the management of colorectal liver metastases have improved survival in these patients. Adding cetuximab to standard chemotherapy increases the response rate in patients with wild-type KRAS and can thus increase the resectability rate of liver metastases in this group of patients. In this paper we review the different studies assessing the efficacy of cetuximab in the first-line treatment of mCRC.

Analysis of KRAS/NRAS Mutations in a Phase III Study of Panitumumab with FOLFIRI Compared with FOLFIRI Alone as Second-line Treatment for Metastatic Colorectal Cancer

“…Evaluation of other measures of tumor response may inform clinical decision-making (although such measures require further prospective confirmation; ref. 40). Depth of tumor response was significantly greater and likelihood of achieving a !30% reduction in tumor dimensions within 8 weeks of treatment was significantly higher in panitumumab patients.…”

Role of HGF/c‐Met in the treatment of colorectal cancer with liver metastasis

“…Previous studies have shown that about 25% of patients with CRC are clinically diagnosed with liver metastasis at the initial diagnosis, and approximately 50% of patients with CRC develop symptoms of liver metastasis during the course of their disease. Around 30% to 50% of patients with CRC display recurrent liver metastasis after radical resection and more than 50% succumb to the disease . However, the current therapies for patients with CRC live metastasis, including surgery, radiotherapy, and chemotherapy treatment in the CRC metastasis, remain unsatisfactory due to rapid CRC metastasis deterioration and drug resistance …”

Overall survival of patients with KRAS wild-type tumor treated with FOLFOX/FORFIRI±cetuximab as the first-line treatment for metastatic colorectal cancer

“…Studies have reported that biologic agents with FOLFOX /FORFIRI can significantly improve the therapeutic effect compared with FOLFOX /FORFIRI alone. [1–4] Their role in wild-type KRAS mCRC as the first-line therapy, however, has not been systematically examined. For this review, cetuximab was defined as a drug targeting a specific receptor of cancer cell growth factors, epidermal growth factor receptor (EGFR).…”