Younger Age Linked With Targetable Genotype in NSCLC

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Younger age is associated with an increased likelihood of having a targetable genotype in patients with non-small cell lung cancer (NSCLC), a new study published online ahead of print in JAMA Oncology has shown.1

Because the genomics and clinical characteristics of NSCLC in young patients is poorly understood, researchers sought to evaluate the relationship between young age at the time of diagnosis and the presence of potentially targetable genomic alteration, disease prognosis, and natural history.

For the study, researchers analyzed data from a cohort of 2237 patients with NSCLC who were genotypes at Dana-Farber Cancer Institute between January 2002 and December 2014. Of those, 87% had histologically confirmed adenocarcinoma, 12% had NSCLC not otherwise specified, and 1% had squamous cell carcinoma.

Results showed that cancer diagnosis at a young age was associated with gene mutations for EGFR (P=.02) and ALK (P<.001). There was also a similar trend for ERBB2 (P=.15) and ROS1 (P=.10); however, there was no association between younger age and BRAF V600E (P=.43).

Researchers found that among the 1325 patients tested for all 5 targetable genomic alterations, younger age was associated with an increased likelihood of having a targetable genotype (P<.001). Specifically, patients who were 50 years or younger at diagnosis had a 59% higher chance of harboring a targetable genotype (P<.001).

The study also demonstrated that harboring a potentially targetable genomic alteration treated with a targeted agent was associated with improved survival, but the youngest patients and the oldest patients had similarly poor outcomes.

“The survival of young patients with NCSLC is unexpectedly poor compared with other age groups, suggesting more aggressive disease biology,” the investigators conclude. “These findings underscore the importance of comprehensive genotyping, including next-generation sequencing, in younger patients with lung cancer.”


1. Sacher AG, Dahlberg SE, Heng J, et al. Association between younger age and targetable genomic alterations and prognosis in non–small-cell lung cancer [published online ahead of print December 17, 2015]. JAMA Oncol. doi:10.1001/jamaoncol.2015.4482.
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