FDA approves Vectibix for treatment of colon and rectal cancer

Click here for C3′s official statement on the approval of Vectibix

On September 27, 2006 the Food and Drug Administration (FDA) announced their approval of Vectibix™ (panitumumab) for the treatment of colon and rectal cancer that has spread to other parts of the body (metastasized). The FDA approved labeling is for cancer that has  progressed during or after chemotherapy treatment with fluoropyrimidine, irinotecan, and oxaliplatin regimens.

Vectibix is an entirely human monoclonal antibody that binds to and blocks the activity of the epidermal growth factor receptors (EGFR) on cancer cells.  Epidermal growth factor is a protein that promotes the growth of cells, including cancer cells.

Approval was based a randomized clinical trial that compared treatment with Vectibix and best supportive care to best supportive care alone. In the trial 463 patients were randomly assigned to receive either Vectibix as a single drug (monotherapy) every two weeks or supportive care alone.  Supportive care included medication for pain, surgery or radiation to treat pain, blood transfusions, or other treatments to manage symptoms but not chemotherapy.  All patients in the trial were no longer responding to standard treatments that included fluoropryrimidines, irinotecan, and oxaliplatin (refractory).

Patients on Vectibix in the trial had a 46% longer progression-free survival than those on best supportive care.  In addition, 8% of patients had metastatic tumors reduced during treatment while no patients in the best supportive care arm experienced tumor response.  Twenty-eight percent of Vectibix patients had a period of stable disease (no growth of cancer) while on the drug compared to 10% of those in the best supportive care arm.  These results translate into disease control for 36% of Vectibix patients and 10% of the best supportive care group.

A video web cast by Dr. Marc Peeters of the design and results of the clinical trial is available on the 2006 American Association for Cancer Research virtual meeting.  To see Dr. Peeters’ presentation enter the word “panitumumab” at the AACR webcast sessions site.  More details about the trial results are available on Medical News Today.

Skin rash was the most common side effect with 89% of patients experiencing rash and 12% having a severe rash.  Skin reactions to Vectibix included an acne-like rash, itching, redness and swelling, dry skin, and breaks in the skin. Some severe rash led to infection, abcesses, and sepsis.  Amgen, the manufacturers of Vectibix, warn, “Vectibix may need to be withheld or discontinued for severe dermatologic toxicities.”

Other side effects included fatigue, diarrhea, nausea and vomiting, and abdominal pain.  38% of patients had lowered magnesium levels with 3% experiencing severe drops in magnesium that required treatment.

Allergic reactions during infusion of monoclonal antibodies have been a problem with other biologic agents that block EGFR.  Since Vectibix contains no animal proteins, infusion reactions are expected to be less frequent and less severe. According to a press release from Amgen:

Severe infusion reactions occurred with Vectibix in approximately 1 percent of patients. Severe infusion reactions were identified as anaphylactic reactions, bronchospasm, fever, chills, and hypotension. Although fatal infusion reactions have not been reported with Vectibix, they have occurred with other monoclonal antibody products. Severe infusion reactions require stopping the infusion and possibly permanently discontinuing Vectibix, depending on the severity and/or persistence of the reaction.

While the FDA approval of Vectibix was based on progression-free survival in a randomized clinical trial of patients with refractory colorectal cancer, clinical trials are ongoing to study it in combination with chemotherapy and in other situations.  A large randomized Phase 3 trial  (PACCE) is underway to compare the effectiveness of adding Vectibix (panitumumab) to chemotherapy with bevacizumab (Avastin™) to improve progression-free survival as first-line treatment for metastatic colorectal cancer.

WHAT THIS MEANS FOR PATIENTS

There is currently evidence that Vectibix™ (panitumumab) increases the time until cancer begins to progress again for patients who have already been treated with standard chemotherapy.  Some patients (about 8%) will also experience a decrease in the size of their tumors. The FDA approval is based on this evidence.

At this time, Vectibix is an appropriate treatment:

• For patients whose cancer is refractory to standard chemotherapy — who have already been treated with a fluoropryrimidine such as 5FU (fluorouracil) or capecitabine (Xeloda™), irinotecan (Camptosar™), and oxaliplatin (Eloxatin™).
• As monotherapy (a single drug)
• In cases where the patient has not already received cetuximab (Erbitux)

While there is a strong theoretical rationale for trying Vectibix in patients who were forced to discontinue Erbitux because of allergic reactions to it, more data is needed to establish its safety in such settings.

Clinical trials are underway and seeking patients to explore the safety and effectiveness of Vectibix in other colorectal cancer situations.  Patients who are seeking a clinical trial for colon or rectal cancer can find more information on the National Cancer Institute web site or by calling the C3: Colorectal Cancer Clinical Trials Matching Service at 1–866–278–0392.