Phase II clinical trial evaluating the combination of cetuximab and erlotinib for the treatment of patients with metastatic colorectal cancer

This article presents the results of a phase II clinical trial that evaluated the efficacy and safety of the combination of two targeted therapies – cetuximab and erlotinib – for patients with metastatic colorectal cancer (mCRC).

Colorectal cancer that has spread outside the large intestine to other parts of the body (such as the liver or the lungs) is referred to as ‘stage IV’ or ‘metastatic CRC’.

Treatment options include surgery to remove the cancer from the bowel or other organs where the cancer may have spread, chemotherapy, biological (‘targeted’) therapy or radiation to relieve symptoms and prolong survival. However, prognosis for mCRC patients is poorer than for patients with cancer that is confined to the large intestine. For these patients, new medications are being researched in order to prolong survival and stop the disease from progressing. Cetuximab (Erbitux) and erlotinib (Tarceva) are two newly FDA approved drugs for the treatment of patients with advanced cancer. Laboratory research has showed that cetuximab and erlotinib have an additive effect on colon cancer cells by blocking the proteins that fuel their growth, thus stopping the cancer’s growth.

This study presents a phase II clinical trial which included 50 patients with refractory mCRC (which progress despite several lines of treatment). All patients were treated with the combination of cetuximab and erlotinib daily. Parameters evaluated were cancer response (defined as the percentage of patients whose cancer stops growing or shrinks following treatment), progression-free survival or PFS (defined as the percentage of patients who have survived for a defined period of time, without progression of their cancer) and overall survival (defined as the percentage of patients who have survived for a defined period of time), as well as treatment-related side effects (toxicity).

In this study there was a 31% overall response rate, but 11 patients with abnormal cancer mutations (KRAS mutation) had no response to treatment. After excluding these patients, response rate was 41%. Median PFS in all patients was 4.6 months (ranging at 2.8 to 5.6 months). At the time of analysis, after about 17.4 months of follow up, the overall survival rate was approximately one year (ranging at 8.7 to 15 months). The most common treatment-related side effects were skin rashes (48%), low magnesium levels (18%) and fatigue (10%). 

In summary, the combination of cetuximab and erlotinib appears to delay the growth of colon cancer and provide survival benefits in patients with refractory mCRC.

Despite these promising results, this treatment option needs further evaluation on larger populations, with longer follow up periods.