An evaluation of phosphorylated EGFR expression in predicting outcome of EGFR-TKI therapy for the advanced NSCLC patients with EGFR wild type.

Abstract

7532 Background: EGFR mutation is a strong predict factor of response and PFS to EGFR-TKI. However,at least 18% of patients with EGFR wild type are susceptible to TKIs, suggesting that might exist other mechanisms besides EGFR mutation. Here,we hypothesize that the activation (phosphorylation) of EGFR could be a potential predictive biomarkers to EGFR-TKI treatment among patients in absence of EGFR mutations. Methods: Total of 244 stage IIIb and IV NSCLC pts who had the tissue samples available for the molecular analysis were included in this study. 208 out of 244 patients received EGFR-TKI as first-or second-line therapy. the phosphorylated EGFR at tyrosine 1068 (pTyr1068) and 1173 (pTyr1173) were assessed by immunohistochemistry, and EGFR mutation were detected by denaturing high performance liquid chromatograph (DHPLC). Results: The median follow-up time of the patients was 9.4 months (range 0.4 to 77.2 months). Of the 242 patients assessable for mutation and phosphorylated EGFR expression detection, 102 (42%) were positive for EGFR mutation, and 80.2% and 57.1% of patients had pTyr1068 and pTyr1173 expressions, respectively. No significant relationship between expressions of pTyr1173 or pTyr1068 and EGFR mutation was observed. The patients with EGFR mutation had prolonged PFS than those without EGFR mutation (median PFS 9.1 ms vs 3.1 ms; P=0.024). Superior PFS for EGFR TKIs in patients with pTyr1068 expression positive was seen (median PFS 7.4 ms vs 1.3 ms; P<0.001 ). There appeared a negative correlation between pTyr1173 expression and clinical outcomes of EGFR-TKI (median PFS 4.7 ms vs 7.8 ms; P=0.009). Interestingly, in the subgroup patients with EGFR wild type, phosphorylated pTyr1068 expression predicted prolonged PFS (median PFS 5.2 ms vs 1.2 ms; P<0.001) and elevated DCR (71.6% vs 37.5%; P=0.001). Conclusions: This study provides strong evidences to suggest that phosphorylated Tyr1068 of EGFR may be an promising pridictive biomarker for screening superior population in EGFR TKIs treatment, especially in EGFR mutation negative NSCLC. A prospective, multicenter study should be performed to validate the findings.