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Outcomes Improved by Targeting Lung Cancer Genes

by Kathy Jones on  June 2, 2013 at 3:43 PM Genetics & Stem Cells News   - G J E 4
A new study has suggested that lung cancer patients who received a drug designed to target a genetic dysfunction lived longer with fewer side effects than those who received traditional chemotherapy.
 Outcomes Improved by Targeting Lung Cancer Genes
Outcomes Improved by Targeting Lung Cancer Genes
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Researchers found that patients with an abnormal ALK gene who received Pfizer's targeted drug crizotinib remained cancer-free for nearly five months longer.

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"This study demonstrates the value of testing lung cancer tissue for an ALK rearrangement, and it underscores the potential of cancer genomics to target cancer treatments to each patient," said senior author Pasi Janne of Harvard's Dana-Farber Cancer Institute in Massachusetts.

"ALK now becomes the second abnormal gene that we are able to successfully target in lung cancer with drugs other than chemotherapy."

Just five percent of the patients with the most common form of lung cancer have an abnormal ALK gene, but crizotinib could nonetheless help 5,000 patients a year in the United States.

The phase III trial of 347 patients with advanced non-small cell lung cancer found that those who received the drug went a median time of 7.7 months before their disease began to worsen, compared with three months for those who received traditional chemotherapy.

The response rate of 65 percent was also more than triple that of chemotherapy. Survival rates were similar because chemotherapy patients whose tumors progressed were switched over to crizotinib.

The side effects -- visual disorders, gastrointestinal problems, elevated liver enzymes, and leg swelling -- were generally mild and not as severe as the fatigue and hair loss associated with chemotherapy.

While this study examined the impact of crizotinib on patients who had already received one round of chemotherapy, another phase III study is currently underway to see how it performs as the first treatment for newly diagnosed patients.

A second study reported the first case of resistance to crizotinib among patients with a different and recently-identified genetic mutation, ROS1.

The patient initially responded to the drug, with her symptoms improving in less than a week. But the symptoms returned three months later and her tumor resumed growing, leading to her death.

The researchers were able to identify a secondary mutation in the ROS1 and determine that it interferes with binding and prevents the drug from inhibiting the tumor growth.

"A similar and highly resistant mutation also occurs in ALK-positive tumors treated with crizotinib, so finding therapies that can overcome this particular type of mutation will be very important," said study author Jeffrey Engelman of the Massachusetts General Hospital.

The studies were published in the New England Journal of Medicine Saturday to coincide with its presentation at the American Society of Clinical Oncology's annual meeting.

Source: AFP
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