Effect Of Abundance Of Egfr Activating Mutations And Presence Of T790m Imitation In Tkis-Naive Tumor Specimen On Gefitinib Response Duration In Patients With Non-Small Cell Lung Cancer.

e19077 Background: T790M mutation has been suggested to be present in pre-TKIs treatment samples in some patients and associated with EGFR-TKIs response duration, but the results were conflicted. Abundance of EGFR activating mutations might be an influence factor. So we used highly sensitive methods to detect T790M mutation and quantify EGFR activating mutations in TKIs naïve specimens and investigated the clinical significance of them. Methods: A highly sensitive ACB-PCR was used to detect T790M mutation in NSCLC patients with EGFR activating mutations. The abundance of EGFR activating mutations was relatively quantified by MALDI-TOF MS. The association between T790M mutation, abundance of EGFR activating mutations and clinical benefit from TKIs treatment was analyzed. Results: In the pre-TKIs treatment samples from 27 patients, ACB-PCR identified 6 patients with T790M mutation. 18 patients had high abundance of EGFR activating mutations quatified by MALDI-TOF MS. Smoking was significantly associated with low abundance of EGFR activating mutations (P<0.05). Although not reaching significant difference, median PFS in patients with T790M in pre-TKIs samples was shorter than that without T790M mutation (3.2 v 15.9 months). Patients with high abundance of EGFR activating mutations had longer median PFS than those with low abundance (20 v 4 months, respectively; P<0.05). When the patients were subdivided into three groups (Group A, both T790M and low abundance of EGFR activating mutations; Group B, either T790M or low abundance; Group C, high abundance without T790M), the median PFS for three groups was 2, 4.2, and 20 months, respectively and had significant difference (P<0.05). In multivariate Cox regression model, abundance of EGFR activating mutations was associated with PFS (HR 14.698; 95% CI, 3.609 to 59.868; P<0.05). Conclusions: T790M mutation and abundance of EGFR activating mutations were associated with TKIs response duration. Using highly sensitive methods, the detection of de novo T790M and quantification of abundance of EGFR activating mutations should be recommended before EGFR-TKIs individualized therapy.