EGFR and K-Ras mutations in women with lung adenocarcinoma: Implications for treatment strategy definition

Background: we aimed at investigating the outcomes of female patients with stage iiib-iv adenocarcinoma of the lung according to egfr and k-ras mutational status. methods: one hundred and three consecutive female patients genotyped at a single italian institution were analyzed. patients were planned to receive first-line platinum-based chemotherapy (ct) and a salvage treatment with anti-egfr tyrosine-kinase inhibitors (tkis) was proposed irrespective of tumor mutational status. egfr (exons 18-21) and k-ras (exon 2,codons 12-13) mutations were evaluated by real-time pcr and pyrosequencing. the association of mutational status with clinical variables and treatment benefit was investigated by chi-square test and log-rank test. results: egfr and k-ras mutations were found in 31 (30%) and 13 (15%) cases,respectively. sixty-six patients received platinum ct: no correlation was observed between egfr or k-ras mutational status and response rate (rr) (p > 0.05). however,patients treated with first-line ct harboring egfr activating mutations experienced a significantly reduced progression-free survival (pfs) in comparison with wild-type ones (4.4 vs. 6.4 months,respectively; hr 0.597,95% ci 0.287-0.975; p = 0.048). thirty-nine patients received salvage treatment with erlotinib: egfr activating mutations were significantly correlated with rr (60% vs. 12.5%; p = 0.004) and pfs (11.4 vs. 4.5 months; hr 0.491,95% ci 0.216-0.936; p = 0.044). responses to erlotinib were not reported among women with k-ras mutant tumors,while 50% of those with wild-type k-ras achieved an objective remission (p = 0.296). median pfs (3.5 vs. 8.8 months; hr 0.284,95% ci 0.015-0.510; p = 0.010) and os (3.9 vs. 19.8 months; hr 0.158,95% ci 0.001-0.075; p < 0.001) were significantly shorter among k-ras mutant patients treated with tki. conclusions: in our population of caucasian women with advanced lung adenocarcinoma we observed that the presence of egfr activating mutations correlates with a significant reduction in the benefit from first-line platinum-based ct,emphasizing the importance of an upfront use of anti-egfr tkis in this patient subset. k-ras mutations seem to correlate with a detrimental effect from anti-egfr tki,but this finding deserves further investigation. © 2014 rotella et al.; licensee biomed central ltd.