Cancer Drug’s Success Explained

When the lung cancer drug Iressa won approval from the Food and Drug Administration almost a year ago, it showed great promise as a tumor suppressor with side effects far less severe than those of chemotherapy.

But the mystery of why Iressa, also called gefitinib, slowed tumor growth in only 10 percent of the patients who used it was solved only this month.

A team of researchers at the Dana-Farber Cancer Institute, which is affiliated with Harvard Medical School, found that a specific mutation in receptors in tumors cells is closely linked to the effectiveness of Iressa, according to the team’s report in yesterday’s online edition of Science magazine.

“The new piece of information is that all the patients that we studied whose tumors shrank [from Iressa] have a mutation,” said Dr. Bruce E. Johnson ’75, an associate professor of medicine at Brigham and Women’s Hospital who co-authored the study.

If a patient has a mutation in the human gene known as epidermal growth factor receptor (EGFR), Iressa has a much greater chance of slowing the growth of that patient’s tumor, the report said.

If a patient tests positive for the EGFR mutation, then there is an 80-percent chance that Iressa will be effective, according to Johnson.

The group’s research estimated that about 10 percent of patients with non-small cell lung cancer (NSCLC) carry the mutation. A written statement from the research team claimed that the discovery “stands to benefit thousands of patients with non-small cell lung cancer around the world.”

In the press release, Matthew L. Meyerson ’85, an assistant professor of pathology at the Medical School and a senior author of the report, called the study “the first indication that a therapy targeted for a specific group of patients can have an impact on this diseases.”

“It demonstrates how the growing understanding of human biology and the Human Genome Project are converging to produce an immediate effect on cancer care,” he added.

Johnson said the discovery of the linkage between the EGFR mutation and the drug effectiveness will reduce indiscriminate use of Iressa. “Before you decide to treat [a patient], you can sequence their tumor tissue for the appropriate mutation,” he said.

According to the report, there is hope that similar genetic identification techniques will allow drugs such as Iressa to be used on other types of cancer, including colorectal cancer.

The team also found that some groups of patients with lung carcinomas are significantly more likely than others to carry the EGFR mutation, which warranted further study, according to the report.

“We were struck that certain groups of NSCLC patients appear to be more likely to have EGFR mutations,” Johnson said in the press release. “Mutations were more frequent in women, in Japanese patients, and in patients with adenocarcinoma,” a condition where cancer has spread to the lining of the lungs.

The next step in the group’s research is developing a simple test that can determine whether a patient has an EGFR mutation.

The press release said the group will also conduct research to determine whether targeted treatments will benefit patients for whom Iressa alone does not help.