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Consortium Tracking Tumor Mutations to Guide Lung Cancer Treatment, Clinical Trial Inclusion

By Andrea Anderson

CHICAGO (GenomeWeb News) – Members of the Lung Cancer Mutation Consortium are using genetic information to guide treatment and clinical trial participation for individuals with lung adenocarcinoma, Memorial Sloan-Kettering Cancer Center medical oncologist Mark Kris said at the American Society of Clinical Oncology annual meeting here yesterday.

The National Cancer Institute-sponsored effort, which received $5.2 million through the American Recovery and Reinvestment Act of 2009, is being led by University of Colorado Cancer Center Founding Director Paul Bunn and involves researchers from 14 centers across the country.

The team is prospectively enrolling more than 1,000 patients with cases of lung adenocarcinoma and working to track down driver mutations in 10 genes for the genetically heterogeneous disease, which typically shows very variable response to treatment. In the process, those involved hope to learn more about the frequency of specific mutations in lung cancer and to translate this information into more targeted treatment and clinical trial participation possibilities.

CLIA-certified labs at each site are using multiplex assays to genotype eight genes previously linked to lung cancer — KRAS, EGFR, HER2, BRAF, PIK3CA, AKT1, MEK1, and NRAS — and doing fluorescence in situ hybridization to test for rearrangements or amplifications in two others, ALK and MET.

The results of these tests are then entered into a central National Cancer Institute database and also returned to participants' physicians, Kris said. When epidermal growth factor receptor (EGFR) mutations are detected, individuals are typically treated with the EGFR-inhibiting drug erlotinib, he explained, while individuals whose tumors contain driver mutations in additional genes are directed to appropriate clinical trials.

As such, the project is intended to develop related genetic testing capability at each participating site, Kris explained, while linking lung cancer patients' genetic information to related industry-sponsored trials. Based on mutational analyses, for example, patients with ALK rearrangements might be given the opportunity to participate in crizotinib trials linked to the LCMC study and so on.

So far, the team has more than 1,200 individuals who have consented to participate in the study, and they have already tested several hundred, identifying single driver mutations in more than half of those for whom complete testing has been done. The most common alterations detected involve KRAS, EGFR, and ALK, Kris noted.

Some 97 percent of the mutations appear to be mutually exclusive, he added, though there have been several cases in which MET amplifications and PIK3CA mutations have turned up together.

At one of study site where 121 patients were enrolled, for example, preliminary data has turned up some 60 driver mutations, Kris said, with 31 individuals receiving targeted therapy so far.

Additional information about the patients, such as their age, sex, smoking status, and so on, has also been collected, Kris noted. Even so, he said, it appears likely that genetic profiles and mutation information about each tumor may eventually trump other such factors for guiding lung adenocarcinoma treatment.

The LCMC is ongoing, Kris said, noting that the team plans to continue and expand the effort after ARRA funding wraps up.

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