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Matching Tumor Types to Drugs Boosts Lung Cancer Outcomes
Date:4/18/2010

First such trial finds better control of disease when chemo is targeted to specific 'molecular signatures'

SUNDAY, April 18 (HealthDay News) -- The number one cancer killer, lung cancer, may be more susceptible to treatment when doctors match up targeted drugs to tumors with key genetic traits, a new study finds.

The study -- the first of its kind -- found that, overall, 46 percent of patients with stage IV (advanced) non-small cell lung cancer gained control of their disease (a measure of overall survival) within two months of treatment when doctors matched chemotherapy to tumor biomarkers, compared to the 30 percent seen when patients were treated in the usual way.

The finding "is an important step toward personalized medicine and marks a paradigm shift for clinical trials by demonstrating the feasibility of a biopsy-based, hypothesis-driven biomarker trial," study co-principal investigator Dr. Roy Herbst, professor of thoracic/head and neck medical oncology at the University of Texas M.D. Anderson Cancer Center, said in a university news release.

The findings were presented Sunday at the annual meeting of the American Association for Cancer Research, in Washington, D.C.

According to the U.S. National Cancer Institute, lung cancer claimed almost 160,000 American lives in 2009 alone. The disease is notoriously tough to treat and only incremental advances have been made over the past few decades.

However, the new trial suggests that a "personalized" approach -- where doctors biopsy the patient's tumor, look for key "molecular signatures" and then pick a drug they believe can target that genetic anomaly -- could be a major advance in extending patient survival.

In the trial, doctors sampled the tumors of 255 patients. They were looking for mutations known to affect lung cancer cell growth, such as those in genes known as KRAS or EGFR (epidermal growth factor receptor), a signaling protein that pushes cancer cells to new growth.

The doctors then chose between one of four powerful chemotherapies: erlotinib (Tarceva), sorafenib (Nexavar), vandetanib (Zactima) or a combination drug, Targretin (erlotinib with bexarotene).

The researchers chose the eight-week disease control endpoint because recent research has suggested it is a good predictor of longer-term survival. Patients who got the personalized approach to their care had a median survival of nine months, and 38 percent survived to one year, the researchers said.

Certain drug-tumor match-ups seemed especially effective. One of the best -- and somewhat surprising -- results came when Nexavar was used in conjunction with a KRAS mutation. In that case, 61 percent of patients treated had disease control at two months. In contrast, the rate for patients with a KRAS mutation who got one of the other drugs was just 32 percent.

"KRAS is generally regarded as a very poor prognostic group of patients," study lead author Dr. Edward Kim, director of clinical research in the thoracic oncology department at M.D. Anderson, told Bloomberg News. "When we treated them with Nexavar, we saw they did very well."

According to Bloomberg, Nexavar is in the last stage of testing needed for U.S. approval as a third-line treatment for lung cancer and as a first-line therapy when used with other chemotherapies.

Other drug-biomarker match-ups also yielded good results. For example, patients whose tumors had EGFR mutations fared best on Tarceva, those with high expression (activity) of a gene called VEGF-2 did well on Zactima, while Targretin seemed best for those whose tumors had defects in producing a protein called cyclin D.

The trial could help pave the way for the routine sampling via biopsy of lung tumors during treatment, the researchers said.

"New drugs that target molecular pathways help a small percentage of lung cancer patients, but right now there's no way to determine who those patients are before treatment," Kim explained in an Anderson press release. He said the new study "evaluated tumor biomarkers in hopes that we can treat lung cancer, which kills more people than any other type of cancer, like we treat breast or colon cancer, using validated biomarkers to guide treatment and improve survival."

"Two lung cancer tumors might appear identical under a microscope and have the same staging, but they behave differently," added study co-author Dr. Waun Ki Hong, head of M.D. Anderson's Division of Cancer Medicine. "The name of the game now is to treat based on the molecular defects in the tumor."

The researchers said that in future trials they will test this approach for lung cancer patients in various stages of the disease, including its use as first-line therapy.

More information

Find out more about lung cancer care at the American Cancer Society.



-- E.J. Mundell



SOURCES: April 18, 2010, news release, University of Texas M.D. Anderson Cancer Center; Bloomberg News


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