Analysis Confirms That KRAS Status Predicts Response to Panitumumab in Colorectal Cancer Patients

October 29, 2008 — Pooled data from 4 large clinical trials confirm that, among patients with metastatic colorectal cancer, response to panitumumab (Vectibix, Amgen) is limited to those with wild-type KRAS tumors. For all efficacy end points, outcomes in patients with wild-type KRAS tumors were superior to those in patients with KRAS mutations.

The data were presented at the second Annual Molecular Markers in Cancer Meeting, in Hollywood, Florida, which is cosponsored by the American Society of Clinical Oncology, the National Cancer Institute, and the European Organisation for Research and Treatment of Cancer.

“Early studies from Amgen and others indicated that the mutational status of the KRAS gene in tumors of patients with metastatic colorectal cancer may affect response to anti-[epidermal growth-factor receptor] antibodies,” said lead author Daniel Freeman, PhD, principal scientist for oncology research at Amgen, Inc, in Thousand Oaks, California, during a press conference.

“Analysis of KRAS status and outcomes in a phase 3 randomized controlled trial demonstrated that response rates and improvements in progression-free survival with panitumumab appeared to be restricted to patients with wild-type KRAS tumor status,” said Dr. Freeman.

Panitumumab is a fully human antibody targeting the epidermal growth-factor receptor (EGFR), and has been approved as monotherapy for patients with metastatic colorectal cancer who have failed previous therapeutic regimens in the United States, and for patients with wild-type KRAS tumors in the European Union.

To evaluate the association between KRAS mutational status and the efficacy and safety of panitumumab, Dr. Freeman and colleagues analyzed pooled data from 4 clinical trials. A total of 715 patients with metastatic colorectal cancer participated in these trials, and all had been treated with panitumumab monotherapy.

Of these patients, 715 (90%) had tumor samples that could be analyzed for KRAS status. “As demonstrated in other studies, responses were observed only in patients with wild-type KRAS status,” said Dr. Freeman.

The overall response rate was 13.7% among patients with wild-type KRAS tumors, and there was no response among patients with KRAS-mutation tumors.

Source:

1. Analysis Confirms That KRAS Status Predicts Response to Panitumumab in Colorectal Cancer Patients