Gene test may change treatment, extend life for lung cancer patients

University  of Colorado Cancer Center study shows that patients who test positive for the EGFR gene live twice as long when taking a combination drug therapy as those who test negative

July 10, 2008 (Aurora, Colo.) —Researchers at the University of Colorado Cancer Center have shown that a readily available gene screening test can help doctors know which people with advanced non-small-cell lung cancer will benefit from adding a second cancer drug to standard chemotherapy.

Patients who test positive for the EGFR gene may live twice as long as those who are EGFR- when given the a combination of chemotherapy and cetuximab—a drug that blocks a key pathway particular gene-driven tumors use to grow and spread—as their first-line treatment, the study shows.

“The results of this study could very well change the way lung cancer patients are treated in the future, similarly to how screening for estrogen-driven breast cancer changed how patients with HER2+ breast tumors are treated,” said Fred Hirsch, MD, PhD, professor of Medicine at University of Colorado Denver and the paper’s lead author.

The paper, published in the July issue of the prestigious Journal of Clinical Oncology, is from a phase II randomized study out of the Southwest Oncology Group, a consortium of cancer researchers. It comes on the heels of the large, randomized European FLEX study, which showed that some advanced non-small-cell lung cancer patients who got the combination therapy lived longer than others who got the same therapy.

“We needed a tool to tell us which patients to put on cetuximab, because it does not make sense to give an expensive drug that has side effects for someone it will not help,” Hirsch said. “We believe that EGFR FISH is that tool.”

The EGFR FISH test, which was developed at the University of Colorado Cancer Center, is available in most laboratories, so lung cancer patients around the world could be quickly screened in the future to see if they would benefit from cetuximab plus chemotherapy. They will soon begin a 1,000-patient phase III trial to validate the findings, and they anticipate FDA approval of the tool to select patients for EGFR inhibitors in the near future.

“When we give patients the right drugs for their exact tumor type, we can help them live a longer, more comfortable life with the disease,” said Paul A. Bunn, Jr., MD, UCCC director and professor of Medicine at UC Denver, who co-authored the study. “I am already using this test to screen my patients for this gene, and if they test positive, I am giving them the combination therapy. They are doing very well on it. We are hopeful that this test will shift how we choose which therapies to give to each individual patient, which is key to getting the best results.”

In the UCCC study, EGFR+ patients lived an average of 15 months after diagnosis with the combination therapy, compared to an average of 7 months for EGFR- patients. EGFR+ patients’ tumors also shrunk twice as much on the combination therapy.

The Colorado group, which includes Hirsch, Bunn, and UC Denver professors of Medicine Wilbur Franklin, MD, and Marileila Varella-Garcia, PhD, previously found similar results using the EGFR FISH test to predict which patients would do well on Tarceva (erlotinib), another EGFR inhibitor drug. EGFR also plays a role in colorectal cancer, so the test could also be used to predict which of those patients may benefit from EGFR-blocking drugs.

Approximately 215,000 people in the United States will be diagnosed with lung cancer in 2008, according to the American Cancer Society. Only about 40 percent will be alive one year later, and only about 15 percent will be alive five years later. Because there is no effective screening test for lung cancer, most people are diagnosed when the disease has spread beyond the lung. Lung cancer kills more adults in the United States than any other cancer.

About UCCC

The University of Colorado Cancer Center is the Rocky Mountain region’s only National Cancer Institute-designated comprehensive cancer center. Headquartered on the University of Colorado Denver Anschutz Medical Campus , UCCC is a consortium of three state universities (Colorado State University , University of Colorado at Boulder , University of Colorado Denver ) and six institutions (AMC Cancer Research Center , Denver Health Medical Center , Denver Veterans Affairs Medical Center , National Jewish Medical and Research Center , The Children’s Hospital and University of Colorado Hospital). Together, our 400+ members are working to ease the cancer burden through cancer care, research, education and prevention and control.