Targetable Genotype in Non-small Cell Lung Cancer Is More Likely in Younger Patients

Patients younger than 50 years with non-small cell lung cancer (NSCLC) were more likely to have a targetable genomic alteration for which therapies exist, according to an article published in JAMA Oncology (doi:10.1001/jamaoncol.2015.4482).

NSCLC is rare younger patients; therefore, its clinical characteristics are poorly understood. A definitive age for this unique population has not been established.

Geoffrey R. Oxnard, MD, of the Dana-Farber Cancer Institute, in Boston, Massachusetts, and coauthors examined the relationship between young age at diagnosis and presence of a potentially targetable genomic alteration and prognosis.

The study included 2237 patients with NSCLC who underwent genotyping between 2002 and 2014. Of the patients, 1939 (87%) had histologically confirmed adenocarcinoma, 269 (12%) had NSCLC not otherwise specified, and 29 (1%) had squamous histologic findings. Approximately 63% (1396 patients) had either stage IIIB or stage IV cancers, median age was 62 years, and 27% (594 patients) had never smoked.

Across the whole group, 712 patients (32%) had a targetable genomic alteration for which approved therapies exist or where compelling clinical trial data suggest the potential for targeted therapy.

Among 1325 patients tested for the 5 targetable genomic alterations, younger age was associated with a greater likelihood of having a targetable genotype. Patients with a diagnosis at younger than 50 years had a 59% greater chance of detecting a targetable alteration compared with an older patient. Lowest overall median survival was in patients younger than 40 years (18.2 months) and patients older than 70 years (13.6 months), study results indicated.

Study limitations the authors noted included the retrospective nature of the data, as well as limited comprehensive data on individual patient treatment.

“Despite the aforementioned limitations, the findings of this study expand the current understanding of the genetics and biology of lung cancer in young patients. These patients possess a uniquely high incidence of targetable genomic alterations paired with an unexpectedly poor prognosis. This combination of opportunity and risk defines the treatment of NSCLC in young patients and requires unique therapeutic and research strategies,” the study concluded.

In an accompanying editor's note (doi:10.1001/jamaoncol.2015.4482), Howard (Jack) West, MD, web editor of JAMA Oncology wrote, “While these results and conclusions are limited by the referral bias to a center of excellence to which younger patients and those with an identified mutation likely gravitated, almost certainly creating a skewed study population that is not necessarily generalizable to the broader lung cancer population, this work provides an invaluable early step toward identifying the youngest patients with lung cancer as a subgroup that deserves more study and special consideration as a distinct clinical demographic most likely to benefit from a more extensive search for targetable driver mutations.”

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