Abstract CT078: A prospective biomarker study using digital PCR method in EGFR-mutated, advanced lung adenocarcinoma patients treated with afatinib (West Japan Oncology Group 8114LTR)
Authors: Akamatsu Hiroaki , Koh Yasuhiro , Morita Satoshi , Yamamoto Nobuyuki , Nakagawa Kazuhiko 
Published: July 2016

Abstract
Background: In epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC), EGFR-tyrosine kinase inhibitor (TKI) demonstrates durable response, but its efficacy duration varies among patients. Early remission of mutated cells was reported as a surrogate of longer efficacy in chronic myeloid leukemia. Similar approach can be done among advanced solid malignancies using highly sensitive method, like digital PCR. In addition, early detection of resistant mutation (EGFR exon20 T790M) is important in EGFR mutated NSCLC, because third generation EGFR-TKIs which specifically bind to EGFR with this mutation have been developed. Thus, monitoring genetic changes during treatment becomes important. Because it is difficult to obtain tumor tissue repeatedly from advanced NSCLC patients, liquid biopsy can be an alternative method to detect cancer less invasively. Although some reports have mentioned the utility of liquid biopsy in EGFR mutated NSCLC, most were single-institutional, retrospective studies.
Methods: West Japan Oncology Group (WJOG) 8114LTR is a multi-institutional, prospective study using highly-sensitive liquid biopsy in advanced NSCLC patients. Chemotherapy naïve, advanced NSCLC patients with EGFR sensitive mutation will receive afatinib monotherapy (40 mg/body) until progressive disease (PD) or unacceptable toxicity. Serum DNA will be obtained from patients at 0, 2, 4, 8, 12, 24, 48 weeks, and at PD. Three types of EGFR mutation (exon 19 deletion, exon 20 T790M and exon 21 L858R) will be analyzed using serum DNA with pico-droplet digital PCR (RainDrop® system, RainDance Technologies, Billerica, MA). Primary endpoint of this study is the concordance of EGFR mutation status between tissue and plasma before treatment. Secondary endpoints are overall response rate, progression-free survival and safety. Exploratory analyses include: 1. concordance of EGFR mutation status at PD between tissue and plasma, 2. longitudinal quantitative monitoring of EGFR mutation status in plasma, and its correlation with clinical efficacy, 3. comprehensive molecular analyses before and after afatinib treatment using next generation sequencing. Total number of patients will be fifty-five. This study is the first study to explore the utility of liquid biopsy in EGFR mutated NSCLC treated with afatinib. Using our highly sensitive method, we can explore whether early remission of EGFR mutational load in plasma is significant, or not. In addition, this study will clarify the molecular mechanism of disease progression on first-line afatinib in EGFR mutated NSCLC. This study was registered at UMIN (ID: 000015847).
Patients’ accrual: This study was started in Feb, 2015, and has already completed final patient's accrual in Nov 2015. Now, we are collecting samples from patients on treatment, and will launch measurement and analyses in early 2016.
Citation Format: Hiroaki Akamatsu, Yasuhiro Koh, Satoshi Morita, Nobuyuki Yamamoto, Kazuhiko Nakagawa. A prospective biomarker study using digital PCR method in EGFR-mutated, advanced lung adenocarcinoma patients treated with afatinib (West Japan Oncology Group 8114LTR). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT078.