Panitumumab works only in wild-type KRAS colorectal tumors

NEW YORK (Reuters Health) - Pooled data from four clinical trials confirm that the epidermal growth factor receptor (EGFR) inhibitor panitumumab (Vectibix; Amgen) is only likely to be effective against advanced colorectal cancers containing the wild-type form of the KRAS gene.

Compared with patients with mutated KRAS, patients with wild-type KRAS had "superior outcomes for response rate, disease control rate, progression free survival, and overall survival," Dr. Daniel Freeman reported Tuesday in Hollywood, Florida, at the annual meeting on Molecular Markers in Cancer. The meeting is co-sponsored by the American Society of Clinical Oncology, the National Cancer Institute and the European Organization of Research and Treatment of Cancer.

The findings stem from 715 patients who received panitumumab monotherapy for metastatic colorectal cancer. Forty-five percent of patients had mutant KRAS tumors and 55% had wild-type KRAS gene, "consistent with mutation rates published in the literature," said principal investigator Dr. Freeman from oncology research at Amgen, Inc., the manufacturer of panitumumab.

Responses were observed only in patients with wild-type KRAS status; the objective response rate was 14% in patients with wild-type KRAS status and 0% in patients with mutant KRAS status, Dr. Freeman reported.

The disease control rate -- the combination of objective response rate and stable disease -- was 52% in patients with wild-type KRAS versus 14% in patients with mutant KRAS.

"The increase in disease control rate resulted in a survival benefit in patients with wild-type KRAS," Dr. Freeman said. Median progression-free survival was nearly twice as long (14.1 weeks vs 7.3 weeks) and median overall survival was 37% longer (8.3 months vs 5.7 months) in patients with wild-type KRAS compared to patients with mutant KRAS.

Dr. Bruce E. Johnson from Dana-Farber Cancer Institute, Boston, said "the timing of this analysis is quite pertinent," given the recent publication in The New England Journal of Medicine of a study showing that, when KRAS mutations are present in a colorectal cancer, treatment with the EGFR inhibitor cetuximab (Erbitux) is no better than supportive care alone.

In that study, "all the benefit of cetuximab was in the cohort that had wild-type KRAS tumors."

Taken together, "the data are quite consistent in showing that mutated KRAS appears to be a very important negative predictor of patients who are unlikely to get a benefit from epidermal growth factor receptor antibody," Dr. Johnson noted.

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