Minglei Zhuo

Influence of Chemotherapy on EGFR Mutation Status Among Patients With Non–Small-Cell Lung Cancer

PURPOSEnEGFR mutation is a predictor of epidermal growth factor receptor-tyrosine kinase inhibitor treatment response in patients with non-small-cell lung cancer (NSCLC). However, it remains unclear whether chemotherapy affects EGFR mutation status in NSCLC. We investigated the influence of chemotherapy on EGFR mutations in plasma and tumor tissues from patients with NSCLC.nnnPATIENTS AND METHODSnSamples were derived from three cohorts: one, 264 patients with advanced NSCLC who received first-line chemotherapy with matched pre- and postchemotherapy blood samples; two, 63 patients with stages IIb to IIIb disease with pre- and post-neoadjuvant chemotherapy tumor tissues; and three, 79 patients with advanced NSCLC who underwent palliative surgery. EGFR mutation status was determined and analyzed to reveal potential impact of chemotherapy.nnnRESULTSnIn the first cohort, EGFR mutations were detected in 34.5% of the prechemotherapy plasma samples (91 of 264) but in only 23.1% of the postchemotherapy plasma samples (61 of 264). The decrease in EGFR mutation rate was statistically significant (P < .001). Patients whose EGFR mutations switched from positive to negative after chemotherapy had a better partial response (PR) than patients with a reverse change (P = .037). A similar decrease in EGFR mutation rate was observed in tissues after neoadjuvant chemotherapy in the second cohort (34.9% [22 of 63] v 19.0% [12 of 63]; P = .013). In the third cohort, 38.0% of the tumors (30 of 79) showed an intratumor heterogeneity of EGFR mutation, whereas 62.0% (49 of 79) were homogeneous, either with EGFR mutation or no mutation.nnnCONCLUSIONnOur results suggest that chemotherapy may reduce EGFR mutation frequency in patients with NSCLC, likely the result of a preferential response of subclones with EGFR mutations in tumors with heterogeneous tumor cell populations.

Multibiomarker analysis homing in on EGFR-TKIs therapy in non-small cell lung cancer.

e18025 Background: EGFR mutation has been identified to be a strong predictive biomarker to EGFR-TKIs in non-small cell lung cancer (NSCLC), but it isnt exclusive molecular mechanism to TKI therapy. So developing platforms of serial of biomarkers detection is important for personalized TKI therapy. This study investigated the relationships between genetic factors and clinical outcome in Chinese NSCLC patients treated by gefitinib. Methods: A total of 156 NSCLC were enrolled for genetic screening and 101 of which were treated by gefitinib. EGFR AKRAS mutation (mEGFR, mKRAS) were identified by denaturing high performance liquid chromatography (DHPLC) and EGFR copy number AEML4-ALK rearrangement were detected using fluorescent in situ hybridization (FISH). A polymorphic dinucleotide repeat (CA simple sequence repeat1 [CA-SSR1]) was determined by DNA sequencing. Results: mEGFR, mKRAS, EGFR FISH positive and EML4-ALK rearrangement were detected in 62 (39.7%),13 (8.3%), 49 (20.2%), 6 (3.8%) pts, respectively. ...