Distinct Genomic Differences Evident in Younger Patients With Lung Cancer

Peter J. Sciavolino, PhD
Published: Friday, Feb 05, 2016
Geoffrey R.
Oxnard, MD

Geoffrey R. Oxnard, MD

A great deal of research effort has been devoted to studying how to treat and optimize outcomes in older, less fit patients with lung cancer. Now, a recent study has demonstrated that specimens from patients under the age of 50 years appear to be enriched with molecular alterations that are amenable to targeted treatment.1

These findings have implications for expanding the use of genomic testing—and thereby potentially increasing treatment options—for the younger lung cancer population.

Higher Incidence of Some Mutations

The study was a retrospective analysis of 2337 patients with non–small cell lung cancer (NSCLC) whose tumors were genotyped during routine testing at the Dana-Farber Cancer Institute between January 2002 and December 2014. Sixty-three percent of the patients had either stage IIIb or IV cancers, with most of those malignancies categorized as adenocarcinomas (87%).

Overall, the patient population included some 81 patients (4%) who were diagnosed at age 40 years or younger.

There was an increased likelihood of EGFR mutations (P = .02) and ALK rearrangements (P <.001) in patients diagnosed with NSCLC at a younger age. Nonsignificant trends for younger age at diagnosis were also found for ROS1 (P = .10) and ERBB2 (P = .15) mutations.

For those who had undergone testing for all five targetable alterations (n = 1325) the likelihood of harboring a targetable mutation was increased with younger age at diagnosis (P <.001). The significant association was retained in multivariate analysis controlling for smoking status, female sex, and Asian race (P = .006). Further analyses using age cut points showed that there was a 59% increased likelihood of detecting a targetable alteration in patients under 50 versus an older patient.

Notably, however, the prognosis was equally poor for the youngest age group (under age 40), with a median overall survival (OS) of 21.4 months, and for those over 70 years of age (median OS, 22.3 months). Thus, the findings suggest an important combination of opportunity (by way of targetable alterations) and risk (by way of equally poor outcome) in this younger lung cancer population.1

“It took 10 years of experience here to collect together a pretty small cohort, but compared with the rest of the cohort, we were able to see some trends,” said Geoffrey R. Oxnard, MD, a medical oncologist at the Dana-Farber Cancer Institute and corresponding author on the paper, in an interview with OncologyLive.

Targetable Mutations in NSCLC Analyzed by Age1

Targetable Mutations in NSCLC Analyzed by Age1 Targetable Mutations in NSCLC Analyzed by Age1


“Anecdotally, we think young people must be different, but it’s not been shown scientifically that young lung cancer is an outlier—there actually has been a lot more [focus on] how do you treat elderly patients differently; how do you be more delicate with the elderly; and what is the definition of elderly,” Oxnard said. “That’s sort of where the focus has been in lung cancer care, but we’ve not really said what counts as a young lung cancer patient, and how the young lung cancer patients are different, so I think this is new in that regard.”

Why Study Young Lung Cancer?

In other cancers, such as breast cancer, younger patients typically harbor unique genetics, and follow a more aggressive clinical course, and Oxnard notes that this was, in part, the impetus for conducting the study.

“There are other diseases where we think that young means different biology and that was the hypothesis we wanted to test here. Like with breast cancer, we asked, ‘Is there a genetic difference in these [younger] patients, and outcomes-wise, and is there a difference in how they do?’

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Community Practice Connections™: 18th Annual International Lung Cancer Congress®Oct 31, 20181.5
Clinical Interchange™: Translating Research to Inform Changing Paradigms: Assessment of Emerging Immuno-Oncology Strategies and Combinations across Lung, Head and Neck, and Bladder CancersOct 31, 20182.0
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