Test predicts who shouldn’t take colon cancer drug

Researchers at Amgen found more mutations that show who will not be helped by its colon cancer drug Vectibix and said on Sunday the study shows companies can find efficient ways to find the right drugs for the right patients.

The company did a unique analysis of nine different genes that are mutated in colon cancers, all at once, to see if they could parse out any mutations that would lead to patients more likely to benefit from the drug, a so-called targeted therapy.

They did not find anything that pointed to patients who should take the drug, but found more mutations that show who should not, said Amgen’s Dr. David Reese.

“We have to identify the patient population that will benefit from the drug,” Reese told a news conference at a meeting of the American Association for Cancer Research.

Companies making targeted therapies for cancer have realized that they will also need to identify just who will be helped by these drugs. Standard cancer chemotherapy and radiation both target any growing cell - tumor or healthy cells.

That makes cancer treatments highly toxic. Targeted therapies can be gentler and more effective but only work against certain tumors.

Vectibix, known generically as panitumumab, is an engineered immune system molecule called a monoclonal antibody. It goes after a gene called EGFR, mutated in several types of cancer.

But cancer involves mutations of many genes and for some reason, patients who have a mutation in another gene called KRAS are not helped by Vectibix and some other drugs that target EGFR. About 40 to 50 percent of colon cancer patients have KRAS mutations.

MUTANT COUSIN

The Amgen team tested some other genes and found when a cousin of KRAS called NRAS was mutated, those patients also got no benefit from Vectibix. A second gene, BRAF, may also have interfered with the drug’s success but Reese said the results were unclear.

Mutations on the six other genes - AKT1, CTNNB1, EGFR, PIK3CA, PTEN and TP53 - did not predict how well a patient would do on the drug, Reese said.

But he said the study was proof of principle that next-generation sequencing, looking at many mutations in many genes all at once, would be useful for cancer biomarker testing.

“For each patient specimen all genes could be analyzed in the same sequence run,” Reese said.

The researchers also noticed that 50 of the patients had more than one of the mutations.

Erbitux, discovered by ImClone which is now part of Eli Lilly and Co. and sold by Merck KGaA and Bristol-Myers Squibb, dominates the so-called anti-EGFR market with 2008 sales of $1.6 billion - 10 times more than Vectibix.

Erbitux also only works in patients whose tumors contain the normal, or wild-type, version of KRAS.

Colon cancer is the second-biggest cancer killer in the United States, after lung cancer. More than 106,000 cases are diagnosed in the United States alone in a year and nearly 50,000 people will die of it.

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By Maggie Fox

WASHINGTON (Reuters)