EGFR–TKI response worse in NSCLC patients with rare EGFR mutations

Jan 28 2015

By Shreeya Nanda, Senior medwireNews Reporter

In patients with non-small-cell lung cancer (NSCLC), rare epidermal growth factor receptor (EGFR) mutations are associated with a poorer response to EGFR–tyrosine kinase inhibitors (TKIs) compared with frequently occurring ones, according to a study published in Lung Cancer.

On the basis of their findings, Oscar Arrieta, from National Cancer Institute (INCan) in Mexico City, and colleagues suggest that EGFR–TKIs be reserved as second- or third-line therapy in patients with rare mutations.

This prospective observational study included 188 NSCLC patients from Mexico, Colombia or Costa Rica who had received EGFR–TKIs as either first-line therapy (30.8%) or subsequently (69.2%). All participants underwent EGFR mutation screening.

The most common mutations – exon 19 deletion and exon 21 L858R substitution – were found in 79.8% of patients, while the remaining 20.2% harboured rare mutations, of which 12.2% and 8.0% had single and complex mutations, respectively.

The overall response rate was significantly higher in patients with common mutations than in those with rare mutations, at 63.8% versus 32.4%.

Presence of common mutations was also associated with a significantly prolonged median progression-free survival (PFS) compared with rare mutations, at 16.5 and 3.9 months, respectively. Overall survival (OS) also significantly differed at 37.3 versus 17.4 months.

Multivariate analysis showed that female gender was associated with significant improvements in PFS, but no additional factors had an effect on OS.

As rare mutations occur at a low frequency and tend to be heterogeneous, the researchers call for a meta-analysis to evaluate the relationship between the type of mutation and the response to EGFR–TKI therapy, to help guide the treatment of this patient population.

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