Effect of first-line treatment and CHFR and 14-3-3σ methylation status on survival to second-line chemotherapy or EGFR tyrosine kinase inhibitors (TKIs) in stage IV non-small-cell lung cancer (NSCLC).

8068 Background: We analyzed the outcome of second-line chemotherapy vs EGFR TKIs in 179 of 366 patients (p) who had been included in an ERCC1-based customized cisplatin trial and correlated the results with first-line treatment and with CHFR and 14-3-3σ methylation status.,CHFR and 14-3-3σ methylation in circulating DNA was examined by methylation-specific assay. A panel of seven human EGFR wild-type NSCLC cell lines was characterized for their sensitivity to sequential treatment with cisplatin and erlotinib, and the results were correlated with CHFR and 14-3-3σ.,Median survival (MS) for 105 p who received chemotherapy as second-line treatment was 10.8 months (m), while for 74 p who received EGFR TKIs, it was 19 m (P = 0.0002). MS for p with unmethylated CHFR was 21.4 m with EGFR TKIs and 11.2 m with chemotherapy (P = 0.0001). MS for p with methylated 14-3-3σ was 21.3 m with EGFR TKIs and 10.2 m with chemotherapy (P = 0.0004) ( table ). In the only lung tumor cell line not expressing CHFR, pretreatment with cisplatin was antagonistic with erlotinib, while it was synergistic in the other six lines.,Second-line EGFR TKIs improved survival in p receiving first-line cisplatin-based treatment. Methylated 14-3-3σ and unmethylated CHFR increased survival to EGFR TKIs. CHFR expression predicted synergism to sequential cisplatin/erlotinib in lung tumor cell lines. [Table: see text] No significant financial relationships to disclose.