Better genetic tests fine tune cancer therapy

CHICAGO (Reuters) - New cancer research is moving medicine closer to more reliable use of genetic tests to help decide which drugs to use -- good news for patients, but potentially less lucrative for drug companies.

Before now, only certain breast cancer patients have had the option of a drug determined by their genetic makeup. Genentech Inc's Herceptin and GlaxoSmithKline's Tykerb are approved for only the 25 percent to 30 percent of breast cancer patients whose tumors generate a protein called HER-2.

Research released at a meeting here of the American Society of Clinical Oncology on Sunday gives doctors insight into which patients will be helped by Erbitux, the targeted cancer therapy developed by ImClone Systems Inc.

"We have struggled with how to afford these targeted drugs. Part of the answer is to determine who will benefit," said Dr. Julie Gralow, a breast cancer specialist at the University of Washington.

Aside from biomarkers for targeted cancer drugs, data from the oncology meeting examined tailoring chemotherapy drugs to cancer patients and testing for a specific genetic marker that may be a way for doctors to predict which patients will have their cancer get worse after being treating with anemia drugs.

The Erbitux study, looking at a subset of subjects from a large clinical trial, found that colon cancer patients whose tumors contained the normal, or wild-type, version of a gene known as KRAS were significantly helped by Erbitux, while those with a mutated KRAS gene saw no benefit from the drug, also known as cetuximab.

Patients given Erbitux and chemotherapy had a 15 percent reduction in the risk of tumor growth, compared to those on chemotherapy alone, but the benefit climbed to 32 percent when looking only at patients with the normal KRAS gene.

"I believe it is now warranted to test all patients. KRAS mutants should not receive cetuximab," said Dr. Gail Eckhardt, a medical oncology professor at the University of Colorado.

About 65 percent of lung cancer patients are believed to carry the normal KRAS gene.

"These drugs are not cheap so if they're not going to help, we won't use them," said Dr. Eric Van Cutsem of the University Hospital Gasthuisberg in Belgium, who led the Erbitux research.

Erbitux costs about $10,000 a month in the United States. The wholesale U.S. price for Herceptin is about $3,300 a month, while the price for Tykerb is around $3,000 a month.

POOL OF NEW PATIENTS SHRINKS

Erbitux is an antibody designed to block a protein called epidermal growth factor, which is believed to play a role in cancer cell growth. Its main side effect is an acne-like rash.

Another drug in the same class is Amgen Inc's Vectibix, which in Europe is approved for treating advanced colon cancer only in patients with the normal KRAS gene. Last week, European medical experts recommended approval of Erbitux as an initial colon cancer treatment also in patients with normal KRAS.

New patients will likely come only from the pool of KRAS-normals.

"In the long run it will be a net positive for sales," said ImClone Chief Executive John Johnson. "Our share of the two-thirds of the wild-type patients will go up and the duration of therapy will be much longer."

But Wall Street analysts say sales are likely to take at least a short-term hit. "We expect some lag between the erosion of sales in KRAS mutants and the growth of sales in KRAS normals," Sanford Bernstein analyst Geoffrey Porges said in a research note.

ImClone shares were down about 6 percent on Monday, as investors were also disappointed by data presented at ASCO showing that Erbitux extended the lives of lung cancer patients by a modest five weeks.

Dr. Thomas Lynch, chief of hematology, oncology at Massachusetts General Hospital Cancer Center, said widespread use of Erbitux in lung cancer will ultimately depend on whether there is a biomarker to identify which patients benefit the most.

A study conducted at Columbia University Medical Center found that a cell-based test that examines the response of a patient's tumor to various chemotherapies correlates with significantly longer overall survival in patients with ovarian cancer.

The test, called ChemoFx, is being developed by Precision Therapeutics Inc.

Researchers at the University of Washington found that levels of a marker known as erythropoietin receptor messenger RNA may offer a way to predict which patients will have tumor growth after being treated with red blood cell-boosting anemia drugs.

(Editing by Maureen Bavdek, Leslie Gevirtz)