Study Finds NSCLC to Be Genetically Different in Younger and Older Patients, Requiring Different Treatment Approaches
Unlike a number of other cancers in which young age at diagnosis is understood to represent distinct disease biology, the genomics and clinical characteristics of non–small cell lung cancer (NSCLC) in young patients are poorly understood. A study by Sacher et al investigating the relationship between young age at diagnosis of NSCLC and both the presence of potentially targetable genomic alterations and poor prognosis has found that younger patients are more likely than older patients to have genetic subtypes of the disease that can be treated with available targeted therapies. The findings, which underscore the need for comprehensive genotyping in younger patients with lung cancer, were published in JAMA Oncology.
Study Methodology
The researchers analyzed data on a cohort of 2,237 patients, median age 62, with NSCLC who were genotyped at the Dana-Farber Cancer Institute between January 2002 and December 2014. Tumor genotype, patient characteristics (including age, sex, race, smoking status, date of diagnosis, histologic findings, stage, and date of death), and clinical outcomes were collected and studied.
Younger age was associated with increased likelihood of having never smoked (P < .001), being female (P = .002), and initial presentation with stage IV disease (P < .001). Overall, 81 patients (4%) were diagnosed with NSCLC at age 40 or younger.
Multivariate logistic regression was used to analyze the relationship between age and mutation status, and multivariate Cox proportional hazard models were fitted for survival analysis.
Study Findings
Of the 2,237 participants, 1,939 (87%) had histologically confirmed adenocarcinoma, 269 (12%) had NSCLC not otherwise specified, and 29 (1%) had squamous histologic findings; 1,396 (63%) had either stage IIIB or IV cancers. The researchers found that gene mutations for EGFR (P = .02) and ALK (P < .001) were associated with cancer diagnosis at a younger age, and a similar trend existed for ERBB2 (P = .15) and ROS1 (P = .10) but not BRAF V600E (P = .43).
Among patients tested for all five targetable genomic alterations (n = 1,325), younger age was associated with increased frequency of a targetable genotype (P < .001). Those diagnosed at age 50 or younger had a 59% increased likelihood of harboring a targetable genotype. Although the presence of a potentially targetable genomic alteration treated with a targeted agent was associated with improved survival, the youngest and oldest age groups had similarly poor outcomes, even when a targetable genotype was present.
Conclusion
“Younger age is associated with an increased likelihood of harboring a targetable genotype and is an underappreciated clinical biomarker in NSCLC,” wrote the study authors. “The survival of young patients with NSCLC is unexpectedly poor compared with other age groups, suggesting more aggressive disease biology. These findings underscore the importance of comprehensive genotyping, including next-generation sequencing, in younger patients with lung cancer.”
Geoffrey R. Oxnard, MD, of Dana-Farber Cancer Institute, is the corresponding author of this study in JAMA Dermatology.
This study was funded by the National Institutes of Health, the Conquer Cancer Foundation of ASCO, the Bonnie J. Addario Lung Cancer Foundation, the Canadian Institutes of Health Research, the Canadian Association of Medical Oncologists, the Gallup Research, and the Kaplan Research Fund.
For full disclosures of the study authors, visit jamaoncology.com.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
