Gene Mutation Improves Response to Lung Cancer Drug

WEDNESDAY, Aug. 19 (HealthDay News) -- People with lung cancer who are screened for a genetic mutation and then given a drug called Tarceva, which is believed to work well with that mutation, live longer than those without the mutation who take the drug, new research has found.

According to the Spanish authors of a study in the Aug. 20 issue of the New England Journal of Medicine, this type of widespread screening is actually doable and could lead to better decisions about treatment.

"They proved that it is worthy to test patients for the [epidermal growth factor receptor gene] mutations, and that if you have the mutations you are going to do well," said Dr. Edgardo Santos, an assistant professor of medicine in the hematology and oncology section at the University of Miami's Sylvester Comprehensive Cancer Center. "If we are moving toward personalized medicine in the future, I think this is the way to go -- that patients be tested and use the drug if indicated."

People who have advanced non-small-cell lung cancer who also have certain mutations in the epidermal growth factor receptor gene (EGFR) tend to respond better to Tarceva and Iressa. Both of these drugs are tyrosine kinase inhibitors, which interfere with cancer cells' ability to multiply. Non-small-cell lung cancer is the most common form of lung cancer.

The researchers screened lung cancer samples from 2,105 people at 129 institutions in Spain for two different EGFR mutations.

Those with mutations (16.6 percent of the sample, considered a sizable proportion) were put on Tarceva. They survived a median of 14 months without progression of their disease and 27 months overall, more than twice as long as the rates seen in other treatment groups, Santos said. This was true regardless of whether Tarceva was given as first-line, second-line or third-line therapy.

"Basically, this highlights the fact that patients with EGFR mutations should, sometime during the course of their illness, get erlotinib [Tarceva]," said Dr. George Simon, director of thoracic oncology at Fox Chase Cancer Center in Philadelphia. "However, I think for reasons of quality of life and ease of administration and differences in toxicity profiles, it may still be preferable to give gefitinib [Iressa] first-line."

But a big question still to be worked out is why people still succumbed to the disease.

"They all had progressive disease, which basically means they had developed mechanisms of resistance," Simon said. "We need to study what were these mechanisms of resistance and how can we counteract them, developing methods of either prevention of the emergence of resistance or treatment once resistance has emerged."

A second study in the same issue of the journal, conducted in East Asia, found that Iressa worked better than a chemotherapy regimen of carboplatin-paclitaxel as a first-line treatment for nonsmokers and former light smokers who also had non-small-cell lung cancer.

Here again, people with the EGFR mutation responded better to Iressa.

At one year, almost 25 percent of those on Iressa had continued without a recurrence, compared with nearly 7 percent in the other group.

"Overall, patients who got gefitinib [Iressa] had a longer time from the start of treatment to the worsening of disease," Simon said. "And it appeared that the drug's benefit was primarily seen in patients with EGFR mutations."

Overall survival, however, did not differ between the two groups, probably because many people started the other type of treatment after they had relapsed on the first treatment, Simon said.

The study was funded by AstraZeneca, which makes Iressa.

"This basically confirmed what we have thought, that in selected populations [light smokers or those who never smoked], those testing positive for EGFR mutations will do much better in progression-free survival than if you put the patient on chemo," Santos said.

"For the first time in a selected population, you have a drug which can compete with systemic chemotherapy," he said. "There is a pill that matches systemic chemotherapy."

SOURCES: George Simon, M.D., director, thoracic oncology, Fox Chase Cancer Center, Philadelphia; Edgardo Santos, M.D., assistant professor, medicine, section of hematology and oncology, Sylvester Comprehensive Cancer Center, University of Miami; Aug. 20, 2009, New England Journal of Medicine

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