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Study Finds Targetable Mutations More Frequent in Young Lung Cancer Patients Than Old Ones

NEW YORK (GenomeWeb) – New data published today has added to growing evidence that young lung cancer patients and older lung cancer patients make up two molecularly distinct groups, and that those diagnosed with the disease at a younger age are more likely to have a cancer with a targetable genomic alteration.

The study, led by Geoffrey Oxnard of the Dana-Farber Cancer Institute, evaluated 2,237 non-small cell lung cancer patients treated at Dana-Farber who underwent genotyping between 2002 and 2014 that included analysis of at least one of eight genes targetable either by currently approved drugs, or by newer agents in development.

Previous research has suggested that certain genetic abnormalities are preferentially associated with NSCLC in young patients. However, according to the authors, the new data represent a much broader survey of the genetic features of younger and older patients' tumors than has been attempted previously.

Among the patients analyzed in the new retrospective study, 712 (32 percent) had some targetable genomic alteration for which specific approved therapies exist or against which an alternative targeted therapy might be effective based on compelling clinical trial data.

The researchers further found that among a subset of patient who were tested for alterations in multiple genes — EGFR, ALK, HER2, ROS1, and BRAF — mutations were almost 60 percent more likely to occur in patients younger than 50 than in patients older than 50.

According to the investigators, the results reinforce the value of testing young patients with NSCLC for a comprehensive set of genetic aberrations that can be therapeutically targeted, rather than using narrower single-gene testing methods.

Despite this molecular advantage for younger lung cancer patients, the researchers also found by analyzing outcomes that survival amongst younger lung cancer patients was worse than would be expected given the potential benefit of targeted therapy. This suggests that NSCLC in the young may be inherently more aggressive, counterbalancing in a way the boost offered by the possibility of targeted therapy.

"Because younger patients are more likely to have a targetable form of the disease, it's absolutely vital that their tumor tissue undergo comprehensive genetic testing including all targetable genomic alterations. This will ensure that they reap the full benefit of the targeted therapies that are now coming on line for NSCLC," study co-author Adrian Sacher of Dana-Farber and Brigham and Women's Hospital said in a statement.

The authors noted that the study was limited by the retrospective nature of their analysis, by potential bias in recruitment of patients to a single center known for advanced genomics capabilities, and by a lack of comprehensive data on individual patient treatment.

Apart from the newly published retrospective analysis, Oxnard is also currently co-leading a prospective effort called the Genomics of Young Lung Cancer Study, which is recruiting NSCLC patients under the age of 40 for genomic analyses using Foundation Medicine's Foundation One profiling test.

At the World Conference on Lung Cancer earlier this year, researchers from the project discussed the results for the first 68 subjects, in which they found that 44 percent had ALK rearrangements, 26 percent had EGFR mutations, and 6 percent had ROS1 rearrangements.