A Phase 2 study demonstrated that Panitumumab, a fully human monoclonal antibody directed against the epidermal growth factor receptor ( EGFR ), has antitumor activity when administered as a single-agent treatment to patients with metastatic colorectal cancer who have failed standard chemotherapy.

An independent central radiology review determined that treatment with panitumumab resulted in a nine percent overall response rate and median time to progression of 11.4 weeks.

Investigators reported that patients with metastatic colorectal cancer expressing the EGFR protein who received Panitumumab monotherapy demonstrated a median survival time of 37.6 weeks and a median duration of tumor response of 18.1 weeks.
Stabilization of disease was observed in 29 percent of patients ( n=43 ). Median progression-free survival time was 13.6 weeks.

Patients in the study ( n=148 ) were previously treated with 5-FU ( with or without Leucovorin ) and either Irinotecan or Oxaliplatin, or both.
Patients received 2.5 mg/kg of Panitumumab by weekly one-hour intravenous infusion without premedication. Tumor responses were confirmed no less than four weeks after the initial response was observed.

In this Phase 2 study, the most common side effect was skin toxicity ( 95 percent, 7 percent grade 3 ).
Other side effects experienced by some patients were fatigue, nausea and mild diarrhea. One infusion reaction ( grade 3 ) was reported per investigator assessment and the patient continued on full-dose Panitumumab with pre-medication.
There were no instances of anaphylaxis observed.
In those patients tested who had a baseline and a post-baseline assessment ( n=107 ), no human antihuman antibodies ( HAHAs ) formation was observed.

Colorectal cancer is the third most common cancer diagnosed in men and in women in the United States.
The American Cancer Society estimates that about 104,950 new cases of colon cancer ( 48,290 men and 56,660 women ) and 40,340 new cases of rectal cancer ( 25,530 men and 16,810 women ) will be diagnosed in 2005.

Panitumumab ( formerly ABX-EGF ) is the first fully human monoclonal antibody directed against EGFR.
Although EGFR normally helps regulate the growth of many different cells in the body, EGFR can also stimulate cancer cells to grow.
In fact, many cancer cells actually require signals mediated by EGFR for their survival. Residing on the surface of these tumor cells, EGFR is activated when naturally occurring proteins in the body, epidermal growth factor ( EGF ) or transforming growth factor alpha ( TGFa ), bind to it.
This binding changes the shape of EGFR, which, in turn, triggers internal cellular signals that stimulate tumor cell growth.

Panitumumab binds to EGFR, preventing EGF and TGFa from binding to the receptor and interfering with the signals that would otherwise stimulate growth of the cancer cell and allow it to survive.

Source: 41st Annual Meeting of the American Society of Clinical Oncology ( ASCO ), 2005


XagenaMedicine2005