Colon Cancer Gene Test Can Predict Disease Return

A gene test for colon cancer, developed by Genomic Health Inc., can help alert patients their cancer may recur after surgery, giving them a chance to protect themselves with chemotherapy, researchers said.

The test, called Oncotype DX for colon cancer, sifts through patients’ tumor cells for a telltale pattern of genes that indicate a two-fold increased risk of relapse, according to a study previewed yesterday by the American Society of Clinical Oncology. The test failed to predict whether chemotherapy drugs would actually work for high-risk patients.

Doctors can’t absolutely predict when colon cancer, diagnosed in 146,970 Americans yearly, might return in early- stage patients. While the new test may be useful “as a tie- breaker” in patients whose need for chemotherapy is unclear, it isn’t the final answer, said Alan Venook, professor of medicine at the University of California San Francisco.

“You got half a loaf, instead of a whole loaf,” said Venook, who has consulted for Genomic Health, in a telephone interview yesterday.

The study, led by David Kerr at the University of Oxford in England, is one of about 4,000 presentations planned for the American Society of Clinical Oncology’s annual meeting May 29 to June 2 in Orlando, Florida.

Genomic Health of Redwood City, California, plans to launch Oncotype DX for colon cancer in early 2010, said Emily Faucette, a company spokeswoman. The company already markets a similar gene test for breast cancer, at a cost of $3,820, to gauge risk of relapse as well as predicting if they will benefit from chemotherapy.

The research summary noted lead author Kerr is a consultant and has received research funding from Genomic Health.

Shares Rise

Genomic Health rose as high as 11 percent to $21.00 in extended trading, after closing up 1 cent at $18.91 in Nasdaq Stock Market composite trading prior to release of the report.

The research confirmed that in colon cancer patients taking a new version of the Oncotype DX test, those with a particular 18-gene signature had a 25 percent risk of relapse. People who did not show the same gene pattern had a 10 percent risk that the malignancy would return, the study found.

That information is valuable to doctors who otherwise can’t predict which colon cancer patients will relapse, said Richard Schilsky, president of the cancer organization, in a briefing.

“Twenty percent of cancers recur and we can’t tell who the 20 percent are,” Schilsky said. “It’s a big black box.” The test is “not as powerful as we would like,” he said.

Other Predictive Factors

Schilsky said doctors may want to use this method along with other predictive factors, including a patient’s age, general health, tumor stage, and willingness to get chemotherapy.

The colon cancer gene study, called Quasar, was “a landmark” because it selected patients who should consider chemotherapy after surgery, even though the study failed to meet its second goal of predicting clear benefit from such treatment, said Steven Shak, Genomic Health’s chief medical officer, in a telephone interview.

Shak said the company worked almost four years to identify an 18-gene signature from a bank of tumor samples collected from more than 1,851 patients. Quasar confirmed that the 18-gene test identified recurrence risk in 1,436 patients with stage 2 colon cancer.

Failure to Predict

Use of the gene test failed to predict whether patients would get better using the standard chemotherapy drugs 5-FU and leucovorin, the study abstract concluded.

A separate study previewed yesterday by the oncology society found another genetic test can tell lung cancer patients whether to get chemotherapy or a new drug, according to Schilsky. The research by Masahiro Fukuoka in Japan found that certain gene mutations can inform patients whether their lung cancer will respond best to AstraZeneca Plc’s Iressa or standard chemotherapy drugs carboplatin and paclitaxel.

“Patients showed some striking differences,” said Fukuoka, a professor of medicine at Kinki University School of Medicine in Osaka, Japan, in the telephone briefing yesterday.

In patients who had the gene glitches, Iressa stopped tumor growth for an average 9.5 months, while chemotherapy stopped tumor growth for 6.3 months. In patients with the normal genes, chemotherapy stopped tumor growth for 5.5 months compared with just 1.5 months for Iressa, the study found.

Drug Response Predicted

The study evaluated genes of 437 patients with non-small- cell lung cancer that had spread to their lymph nodes and other body organs. Gene mutations correctly predicted whether they would respond to the drugs, according to the study summary.

Fukuoka has received honoraria from AstraZeneca and other drugmakers, the study said.

Lung cancer is the most lethal malignancy, with an estimated 219,440 new cases and 159,390 deaths in the U.S. in 2009, according to the National Cancer Institute.

While cigarette smoking is the largest risk factor for lung cancer, according to the American Cancer Society, the malignancy can occur in nonsmokers. The Fukuoka study focused on non small- cell lung cancer patients in Asia who had never smoked or were classified as by researchers as “light ex-smokers,” the study abstract said.

Gene Mutations

The gene in question is called EGFr -- for epidermal growth factor receptor. Patients with mutated forms of the gene responded better to Iressa than to chemotherapy, the study said. Chemotherapy worked better in people without the mutations, Schilsky noted.

Drugs like AstraZeneca Plc’s Iressa and Tarceva, by Roche Holding AG’s Genentech unit and OSI Pharmaceuticals, are directed against EGFr, Schilsky said, adding early studies showed only “modest results.” Now that cancer patients can be grouped according to the gene test, candidates for such treatment can be selected according to who will benefit.

“Everybody with non small-cell lung cancer needs to get mutation analysis,” said Schilsky in a May 11 telephone briefing.“If you have lung cancer and your tumor has EGFr mutations, you do far better if you get Iressa,” said Schilsky in the telephone briefing. Patients lacking that glitch, he added, “need to get chemotherapy, which works better in the non-mutated tumors.”

Source : www.bloomberg.com