Younger Age Predicts NSCLC Targetable Genetic Alterations, Survival

Younger patients are more likely to have targetable genetic alterations than their older counterparts

medwireNews: Non-small-cell lung cancer (NSCLC) in young patients is characterised by a high rate of potentially targetable genetic mutations and poor overall survival (OS), suggests research published in JAMA Oncology.

“These findings underscore the need for comprehensive genomic testing in young patients with NSCLC given their unique genomics and disease biology”, say Geoffrey Oxnard, from Dana-Farber Cancer Institute in Boston, Massachusetts, USA, and co-authors.

They recommend that “exhaustive genotyping” should be used where possible on younger NSCLC patients to detect both currently targetable mutations and potential rare drivers that could be targetable in the future.

The team analysed 2237 NSCLC patients genotyped at their institution between 2002 and 2014, the majority (63%) of whom had stage IIIB or IV disease. In all, 87% were diagnosed with adenocarcinoma, 12% had NSCLC not otherwise specified and 1% had squamous disease.

The median age of the group was 62 years, with 4% diagnosed before the age of 40 years, 11% aged 40–49 years and 27% aged 50–59 years. A further 31% and 27% of patients were aged 60–69 and at least 70 years at diagnosis, respectively.

Younger age was significantly associated with being female, having never smoked and presentation with stage IV tumours, the researchers observe.

Overall, 32% of patients carried one of six targetable genotypes associated with NSCLC.

Younger age was a significant predictor of the presence of an ALKrearrangement after adjusting for smoking status, gender and Asian race, while KRAS and BRAFV600E mutations were significantly more common with older age.

Indeed, further analysis showed that 78% of 160 patients aged less than 50 years carried a targetable genomic alteration compared with 49% of the 547 older patients, a 59% increased risk.

Patient survival was also significantly associated with age, with the lowest median OS found in patients aged less than 40 years and those aged over 70 years, at 18.2 and 13.6 months, respectively.

Subset analysis confirmed this age–OS relationship in the patients with targetable mutations whereas age was not predictive of OS in patients without such a genetic marker.

And the researchers confirmed that the youngest and oldest patients had the poorest survival after taking into consideration a raft of prognostic factors including age, gender, histology, targetable alterations, use of targeted therapy, and the presence of metastatic disease at diagnosis or brain metastases.

Patients with a targetable mutation had significantly better survival than those without in this analysis, but only if they were treated with a targeted therapy, the researchers add.

In an accompanying editor’s note, Howard West agrees the unfavourable survival of the youngest patients in the study suggests “that the clinical behaviors of cancers in young patients is particularly aggressive”.

He questions whether there may be referral bias to the centre of excellence, “most certainly creating a skewed study population that is not necessarily generalizable to the broader lung cancer population”.

Nevertheless, the editor concludes that the “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.”


Sacher AG, Dahlberg SE, Heng J, et al. Association between younger age and targetable genomic alterations and prognosis in non-small-cell lung cancer. JAMA Oncol 2015; Advance online publication 17 December.doi:10.1001/jamaoncol.2015.4482

West H(J). Young patients with lung cancer – an understudied population.JAMA Oncol 2015; Advance online publication 17 December.doi:10.1001/jamaoncol.2015.4479

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