Genomic Test Predicts Which Lung Cancer Patients Need Chemotherapy

Allison Gandey

August 18, 2006

August 18, 2006 –- Researchers report evidence of a promising new example of personalized medicine. Using a lung metagene model, the group analyzed the molecular characteristics of each patient's tumor and propose that this information may one day be used to tailor treatment decisions. Reporting in the August 10 issue of the New England Journal of Medicine, the researchers say they hope genomic tests like theirs will be used not only to predict patient outcomes but also to select individual drugs that will best match the tumor's molecular makeup.

"This is a huge deal," lead author Anil Potti, MD, from Duke University in Durham, North Carolina, emphasized to Medscape during an interview. "We are moving away from treating cancer patients as a population and are beginning to focus instead on single patients with individual characteristics." Dr. Potti says tests such as the lung metagene model may soon help clinicians decide which patients require chemotherapy and which may be at lower risk and can enjoy a better quality of life by avoiding that route.

His group hopes to make the current system of staging lung cancer tumors obsolete. "Instead of placing all patients with small tumors in the same early-stage category, as physicians currently would do, we can now assess their risk based on the tumor's genomic profile," Joseph Nevins, PhD, a professor of molecular genetics at Duke University and senior author of the study, says in a news release.

"If we can use the test to increase patient survival by even 5%, we would save 10,000 lives a year," David Harpole, MD, a professor of thoracic surgery at Duke and coauthor of the study, adds. "In reality, I think we can do much better than that."

Prognostic Tool Could Alter Clinical Decision-Making

In the present analysis funded by the National Institutes of Health, the researchers looked at 89 patients with early-stage non–small-cell lung cancer. They evaluated gene-expression profiles that predicted the risk of recurrence in 2 independent groups of 25 patients from the American College of Surgeons Oncology group study and 84 patients from the Cancer and Leukemia Group B study.

The investigators report that the lung metagene model predicted recurrence for individual patients significantly better than did clinical prognostic factors and was consistent across all early stages of non–small-cell lung cancer. Applied to the cohorts from the 2 trials, they report that the model had an overall predictive accuracy of 72% and 79%. The predictor also identified a subgroup of patients with stage IA disease who were at high risk for recurrence and who might be best treated by adjuvant chemotherapy.

"Using the unique genomic signatures from each tumor, our new test predicted with up to 90% accuracy which early-stage lung cancer patients would suffer a recurrence of their cancer and which patients would not," Dr. Potti said. "We now have a tool that can be used to move these high-risk patients from the 'no-chemotherapy' group into the aggressive-treatment group."

The researchers are now recruiting for a phase 3 clinical trial. The study, to begin within 6 months, will enroll more than 1000 patients from 50 or 60 centers in the United States and Canada.

N Engl J Med. 2006; 355:570-580.