Panitumumab or bevacizumab for the treatment of unresectable metastatic colorectal cancer

This phase 2 trial compared the efficacy of  panitumumab and modified chemotherapy regimen (mFOLFOX6) compared to bevacizumab and mFOLFOX6 in patients with unresectable, metastatic colorectal cancer.

Unresectable metastatic colorectal cancer (mCRC) is cancer that has spread from the large intestine to other organs and tissues and cannot be removed by surgery. A chemotherapy regimen called modified FOLFOX6 (oxaliplatin plus 5–fl­uorouracil and leucovorin) is widely used as a first-line treatment in patients with metastatic colorectal cancer. Depending on the characteristics of the cancer cells, FOLFOX6 can be used as a single therapy or in combination with biological therapies (suppression of the immune response) such as panitumumab and bevacizumab.

Panitumumab (Vectibix) targets proteins (receptors) on the surface of cancer cells, called epidermal growth factor receptors (EGFRs), inhibiting them from fueling the growth and division of cancer cells. Bevacizumab (Avastin) targets a protein called vascular endothelial growth factor (VEGF), blocking its function in the formation of new blood vessel, necessary for cancer growth and spread.

This study compared their effect on disease progression and survival in patients without KRAS gene mutations (wild type KRAS exon 2). Patients with KRAS mutations typically do not benefit from anti-epidermal growth factor receptor therapy.

This trial involved 285 patients with unresectable metastatic colorectal cancer. 142 patients were randomly assigned to receive panitumumab (6 mg/kg once every 2 weeks) plus mFOLFOX6 and 143 to receive bevacizumab (5 mg/kg once every 2 weeks) plus mFOLFOX6. Of the 285 randomly assigned patients, 278 received treatment. The response rate to treatment was 57.8% in the panitumumab group and 53.5% in the bevacizumab group.

In an average follow up period of 3 years, the average progression-free survival (the time after treatment that patients survived without the cancer progressing) was similar between the two groups while in patients treated with panatimumab plus mFOLFOX6 the overall survival (life expectancy) was greater. Patients treated with panitumumab plus mFOLFOX6 had an average progression-free survival of 10.9 months. Those treated with bevacizumab plus mFOLFOX6 had a progression-free survival of 10.1 months. Patients treated with panitumumab plus mFOLFOX6 had an overall of survival of 34.2 months compared to 24.3 months in patients treated with bevacizumab plus mFOLFOX6.

However, a deeper analysis that assessed mutations beyond KRAS exon 2 (including RAS gene analysis) showed a trend towards improvement in progression-free survival in patients in the panitumumab group. Average progression-free survival in the panitumumab group was 13.0 months compared to 9.5 months in the bevacizumab group. Overall survival was 41.3 months in the the panitumumab group and 28.9 months in the bevacizumab group.

In summary, this study showed that combination therapy invoving panitumumab and mFOLFOX6 improved overall survival in patients with wild type KRAS exon 2 metastatic colorectal cancers. 

Amgen and Roche, the manufactures of panitumumab and bevacizumab respectively, jointly funded this study.