Metastatic lung cancer outcomes independent of KRAS mutation subtypes

By Shreeya Nanda, Senior medwireNews Reporter

Overall survival in patients with metastatic lung cancer does not correlate with Kirsten rat sarcoma viral oncogene homologue (KRAS) mutation subtypes, US researchers report.

Although the team led by Gregory Riely (Memorial Sloan Kettering Cancer Center, New York, USA) identified a difference in survival between individuals with KRAS mutations in codon 13 and those with codon 12 mutant tumours, this finding was not confirmed in an independent validation cohort.

They write in the Journal of Thoracic Oncology that this lack of independent confirmation underscores the “importance of independent validation of observed prognostic differences”.

In light of previous research indicating an effect of KRAS mutation subtypes on clinical outcomes in various malignancies, Riely et al analysed data from 677 patients with metastatic or recurrent lung cancer harbouring KRAS mutations seen at the Memorial Sloan Kettering Cancer Center over a 6-year period.

Significant associations were assessed in an independent verification cohort consisting of 682 individuals with stage IV KRAS mutated lung cancer treated at the Dana Farber Cancer Institute, the Massachusetts General Hospital Cancer Center and the Vanderbilt Ingram Cancer Center.

Overall survival did not differ significantly in patients with transversion versus transition mutations nor in current or former smokers compared with individuals who had never smoked. Additionally, specific point mutations did not have an effect on overall survival.

However, participants with KRAS codon 13 mutant tumours (n=53) had a significantly shorter overall survival than those with mutations in codon 12 (n=624), at 1.1 years and 1.3 years, respectively. The association between KRAS codon 13 mutations and survival remained significant in a multivariate setting after adjusting for age, gender and smoking status.

But this association was not replicated in the validation cohort, for whom there was no significant difference in overall survival between patients with KRAS codon 13 and codon 12 mutations, at 1.0 year versus 1.1. years.

The researchers conclude: “Investigation into other areas such as variable gene expression and identifying concurrent mutations may identify potential molecular prognostic markers in patients with KRAS mutant lung cancers.”

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