72P - Leukocyte telomere length and recurrence risk after EGFR-TKIs therapy in patients with advanced lung adenocarcinoma

Abstract

Background: Gefitinib is currently one of the mostly used epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) recommended for treating non-small cell lung cancer. However, the factors that predict treatment prognosis and drug resistance to EGFR-TKIs remain elusive. The objective of this study is to exam the association between leukocyte relative telomere length (RTL) and prognosis or drug resistance of advanced lung adenocarcinoma to gefitinib treatment. Methods: In this study, three hundred and sixty-nine patients with stage IIIB or IV lung adenocarcinoma were recruited between January 2009 and June 2013. All patients were treated with gefitinib orally at a daily dose of 250 mg as first-line monotherapy. Leukocyte RTL of each patient was measured using quantitative polymerase chain reaction (qPCR) protocol on an ABI PRISM 7900HT Sequence Detection System (Applied Biosystems) and calculated according to Cawthon’s formula. Differences in patients’ characteristics were calculated by Pearson’s χ2 tests or Student’s t test. Cox proportional hazard regression analyses were used to calculate univariate and multivariate hazard ratios (HRs). Survival differences were examined using the log-rank test. Two-sided P < 0.05 indicated a significant difference. Results: Among 369 patients, EGFR mutations were positive in 181 patients (49.1%). Compared to long RTL, short leukocyte RTL was significantly associated with poor prognosis in all patients after gefitinib treatment (overall survival: 12.9 months vs. 17.8 months, P = 1.2 × 10-4; progression free survival: 7.8 months vs. 13.0 months, P = 0.043). Additionally, statistically significant association between short leukocyte RTL and shorten OS still existed among the EGFR mutant patients with gefitinib treatment (HR = 1.65, 95% CI = 1.28-2.12; P = 0.006). Besides EGFR mutation status, short RTL also contributed to significantly elevated risk of gefitinib primary resistance (HR = 1.50, 95% CI = 1.05-2.15, P = 0.027). Conclusions: Our results highlight the potential of leukocyte RTL as a novel biomarker in advanced lung adenocarcinoma treated with EGFR-TKIs and the possibility of patient-tailored decisions based on leukocyte RTL. Legal entity responsible for the study: Ming Yang. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.