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Non-small cell lung cancer harboring wild-type EGFR: conventional chemotherapy, compared with first-generation EGFR TKI, is associated with improvement in progression-free survival

Current guidelines recommend both epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitors ( TKIs ) and cytotoxic chemotherapy drugs as standard treatment options for patients with wild-type ( WT ) EGFR who were previously treated for non–small cell lung cancer ( NSCLC ). However, it is not clear that EGFR TKIs are as efficacious as chemotherapy in patients with WT EGFR.

A meta-analysis has assessed the association between first-generation EGFR TKI versus chemotherapy and survival in advanced NSCLC patients with WT EGFR.

The primary outcome was progression-free survival ( PFS ), measured as hazard ratios ( HRs ). The secondary outcomes were objective response rate and overall survival, expressed as relative risks and HRs, respectively.

Among patients with WT EGFR tumors, chemotherapy was associated with improvement of progression-free survival, compared with TKI ( HR for TKI, 1.41 ).

No statistically significant subgroup difference was identified in terms of line of treatment ( first-line vs second- or later-line ), experimental drug, dominant ethnicity, or EGFR mutation analysis method.

Trials using more sensitive platforms than direct sequencing were associated with a significant progression-free survival benefit with chemotherapy ( HR for TKI, 1.84 ).

The association of chemotherapy with improvement in progression-free survival was also significant in second- or later-line trials ( HR, 1.34 ).

The objective response rate was higher with chemotherapy ( 16.8%, vs 7.2%, for TKI; relative risk for TKI, 1.11 ); however, no statistically significant difference was observed with respect to overall survival ( HR for TKI, 1.08 ).

In conclusion, among patients with advanced NSCLC harboring WT EGFR, conventional chemotherapy, compared with first-generation EGFR TKI, was associated with improvement in progression-free survival but not overall survival. ( Xagena )

Lee JK et al, JAMA 2014;311:1430-1437