Nationwide Genomic Screening for Ret Fusion in Advanced Egfr Mutation-Negative Non-Squamous Lung Cancer and Development of Molecular Targeted Therapy in Japan: Lc-Scrum-Japan

Abstract

ABSTRACT Aim: EGFR mutations and ALK fusions have emerged as important oncogenic drivers in non–small cell lung cancer (NSCLC). RET fusion have identified as new drivers of lung adenocarcinomas and these fusions are reported to be promising druggable targets. However, RET fusion is encountered rather rarely, that is observed in only 1-2% of all lung adenocarcinomas. Methods: This study was established in February 2013 as a new nationwide genomic screening project for developing individualized medicine of advanced NSCLC patients in Japan. Tumor samples of advanced EGFR mutation-negative non-squamous lung cancer patients were eligible for submission. The specimens were screened for RET, ROS1 and ALK fusions by RT-PCR and FISH methods. Results: As of March 28th in 2014, The LC-SCRUM-Japan is under way with the participation of 161 institutions in Japan, under aid from the public research fund of the Ministry of Health, Labour and Welfare of Japan. 667 patients were enrolled to this study and 581 tumor samples of enrolled patients (87%) were screened. RET fusion was detected in 23 (4%) of the 581 patients. Seventeen (74%) patients were women, and all patients had adenocarcinoma. Median age was 61 years (range, 41-79). The majority of the patients (78%) were never-smoker. We have synchronously initiated a phase II trial of vandetanib for advanced RET fusion-positive NSCLC patients (LURET study) (UMI10095). 12 of 23 patients with positive for RET fusion determined in the LC-SCRUM-Japan have been already enrolled and just treated with vandetanib in the LURET study. Conclusions: The prevalence of RET fusion in our enriched population was relatively higher compared with that reported in non-selected NSCLC population. This innovative screening project in Japan leads to the activation of screening for lung cancer with rare driver mutations and developing targeted therapy trials. Disclosure: K. Yoh: I have honoraria (reasonable payments for specific speeches) to disclose. Name of entity is AstraZeneca; M. Nishio: I have honoraria (reasonable payments for specific speeches) to disclose. Name of entity is AstraZeneca; H. Murakami: I have honoraria (reasonable payments for specific speeches) and research funding to disclose. Name of entity is AstraZeneca in all; M. Satouchi: I have honoraria (reasonable payments for specific speeches) to disclose. Name of entity is AstraZeneca; T. Seto: I have honoraria (reasonable payments for specific speeches) and research funding to disclose. Name of entity is AstraZeneca in all; Y. Ohe: I have honoraria (reasonable payments for specific speeches) and research funding to disclose. Name of entity is AstraZeneca in all; K. Goto: I have honoraria (reasonable payments for specific speeches) to disclose. Name of entity is AstraZeneca. All other authors have declared no conflicts of interest.