Tumor Mutation Predicts Patient Response to Colorectal Cancer Drug

Patients with advanced colorectal cancer benefit from the drug panitumumab (Vectibix) only if their tumors have a normal form, and not a mutated (changed) form, of the KRAS gene, a new study shows. About 30% to 50% of colorectal cancers have mutations in the KRAS gene.

In this study, the researchers analyzed tumor samples from 427 patients for a mutated KRAS gene and found that 43% of samples had a KRAS mutation. The patients had advanced metastatic colorectal cancer and had received all available treatments for colorectal cancer. The patients received either best supportive care (treatment of symptoms of cancer, but not treatment of the cancer itself), or best supportive care and panitumumab, which was given every two weeks.

The cancer did not worsen in patients who received panitumumab and whose tumors had a normal KRAS gene for 12 weeks, compared with seven weeks for patients with tumors with the mutated gene. In the patients receiving best supportive care and no panitumumab, the cancer did not worsen for seven weeks, regardless of the KRAS status. In addition, the tumors shrank in 17% of patients and did not grow bigger in 34% of patients who received panitumumab and had tumors with a normal KRAS gene. In the patients with a mutated KRASgene who received panitumumab, the tumors did not shrink in any of the patients and did not grow bigger in 12% of the patients.

Panitumumab is a monoclonal antibody (a substance made in the laboratory that recognizes and then attaches to specific proteins on the outside of cancer cells) approved by the U.S. Food and Drug Administration to treat metastatic colorectal cancer when other treatments have stopped working. The most common side effect of panitumumab was a rash, which went away once treatment was stopped.

The study was conducted by researchers from the academic medical centers of Ghent University Hospital and University Hospital Gasthuisberg in Belgium and Ospedale Niguarda Ca' Granda in Italy and Amgen scientists.

What This Means for Patients

"By testing for KRAS mutations, doctors may now be able to identify which patients will most likely benefit from panitumumab treatment," said the lead author, Rafael Amado, MD, Executive Director, Oncology Therapeutics at Amgen, which manufactures and markets the drug.