Researchers involved in the international randomized trial, PRIME, have reported that the addition of Vectibix® (panitumumab) to FOLFOX4 chemotherapy improves progression-free survival (PFS) compared with FOLFOX4 alone in patients with previously untreated metastatic colorectal cancer. This benefit was only observed in patients whose tumors did not contain a mutation in the KRAS gene (those with wild type). These results were presented at the Joint ECCO 15 -34^th ESMO Multidisciplinary Congress in Berlin, September 20-24, 2009.[1] 

Vectibix is a new targeted therapy that binds to specific targets on cancer cells. Vectibix targets the epidermal growth factor receptor (EGFR), a biologic pathway that is involved in the growth and spread of cancer. Vectibix is approved by the U.S. Food and Drug Administration (FDA) for the second-line treatment of patients with metastatic colorectal cancer. Vectibix appears to benefit only those patients who have cancers that express wild-type KRAS and do not have KRAS mutations, which occur in an estimated 40-50% of metastatic colorectal cancers. KRAS mutation status can be identified by testing a sample of tumor tissue.

To evaluate the effectiveness of Vectibix in first-line treatment of metastatic colorectal cancer, researchers conducted a Phase III clinical trial known as PRIME (Panitumumab Randomized trial In combination with chemotherapy for Metastatic colorectal cancer to determine Efficacy). Chemotherapy consisted of FOLFOX4, (Exoxatin® [oxaliplatin], 5-FU, and leucovorin). The study enrolled 1,183 patients. Study participants were assigned to receive treatment with FOLFOX chemotherapy alone or FOLFOX plus Vectibix. Ninety-three percent of patients had KRAS results with 60% having wild-type and 40% having KRAS mutations.

These authors reported that PFS for patients with KRAS mutations receiving Vectibix plus FOLFOX4 was inferior to that of patients receiving FOLFOX4 alone, with a median of 7.3 months versus 8.8 months, respectively. (P=0.0227).

The following summarizes the results observed in patients with wild-type KRAS:

• Patients receiving Vectibix had an overall response rate of 55% compared with 48% for patients receiving FOLFOX4 alone.
• PFS was 9.6 months for patients receiving Vectibix versus 8.0 months for patients receiving FOLFOX4 alone (P-0.0234).
• Side effects of Vectibix included skin rash, low magnesium levels, and diarrhea.

Comments: The results of this study suggest that the addition of the targeted therapy Vectibix to first-line chemotherapy improves PFS among newly diagnosed patients with metastatic colorectal cancer. The benefit only applies to patients whose tumors do not contain KRAS mutations.