Panitumumab Responses in Refractory Colorectal Cancer

CRYSTAL CITY, Virginia—In clinical trials of panitumumab (Vectibix), 8% to 13% of patients with refractory colorectal cancer achieved a partial tumor response with the drug, according to data from five studies reviewed at the 2006 Gastrointestinal Oncology Conference. The meeting was sponsored by the International Society of Gastrointestinal Oncology.

Another 21% to 33% of patients achieved disease stability with panitumumab, said Edith Mitchell, MD, clinical professor of medical oncology and director of diversity programs, Thomas Jefferson University Kimmel Cancer Center, Philadelphia. Progression-free survival averaged 2 to 3 months across the five studies. "The objective responses were quite similar across all five studies," Dr. Mitchell said.

On September 27, 2006, Amgen (Thousand Oaks, California) won FDA approval to market panitumumab for treatment of metastatic colorectal cancer in patients whose tumors had progressed after traditional chemotherapy (see ONI October 2006, page 1).

Panitumumab is a fully humanized monoclonal antibody that blocks the epidermal growth factor receptor (EGFR), which plays a key role in tumor growth and formation. Dr. Mitchell said that 85% of colorectal tumors overexpress EGFR. "Overexpression of EGFR is associated with rapid tumor metastasis and poor prognosis," she said, adding that panitumumab has a "very high affinity" for EGFR.

Of the five studies, the largest was a phase III trial conducted in Europe and first reported by Marc Peeters, MD, PhD, and his colleagues from Ghent University Hospital, Belgium, at the 2006 Annual Meeting of the American Association for Cancer Research (AACR) (see ONI May 2006, page 1). That study enrolled 460 patients with EGFR-positive metastatic colorectal cancer that had progressed after at least two standard chemotherapy regimens. Half of the patients received panitumumab plus supportive care and half received supportive care only: 8% had a partial tumor response with panitumumab vs no responses in the control group. Another 28% achieved stable disease with panitumumab, for a "disease control rate" of 36% vs 10% for controls.

Skin rash was common with panitumumab: 90% of patients experienced skin rash and other topical reactions, and one-fifth of these were grade 3-4. No patients experienced infusion reactions, and none developed antibodies to panitumumab.

The second study reported was an extension of the first, in which patients who originally received supportive care only could opt to receive panitumumab. Of the 176 patients in this extended study, 11% experienced a partial tumor response and 33% achieved tumor stability, for a disease control rate of 44%. The three remaining studies were all smaller phase II trials conducted in the United States.

Dr. Mitchell said that the patient response rate to panitumumab was "significant" given that "nearly all of the patients in the studies had been through three lines of chemotherapy."

Amgen has also applied for marketing approval for panitumumab in Europe, Canada, and Australia. Ongoing trials are evaluating panitumumab as a monotherapy and in combination with other agents for the treatment of various cancers.