1227PD - Nationwide genomic screening for RET fusion in advanced EGFR mutation-negative non-squamous lung cancer and development of molecular targeted thera...

Date 29 September 2014
Event ESMO 2014
Session NSCLC, metastatic
Topics Drug Development
Non-Small-Cell Lung Cancer, Metastatic
Pathology/Molecular Biology
Presenter Kiyotaka Yoh
Citation Annals of Oncology (2014) 25 (suppl_4): iv426-iv470. 10.1093/annonc/mdu349
Authors K. Yoh1, S. Matsumoto1, K. Tsuchihara2, T. Kohno3, G. Ishii4, K. Tsuta5, M. Nishio6, N. Yamamoto7, H. Murakami8, M. Satouchi9, N. Nogami10, T. Seto11, S. Umemura1, S. Niho1, H. Ohmatsu1, Y. Ohe1, T. Yamanaka12, K. Goto1
  • 1Division Of Thoracic Oncology, National Cancer Center Hospital East, 277-8577 - Chiba/JP
  • 2Division Of Translational Research, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Chiba/JP
  • 3Division Of Genome Biology, National Cancer Center Research Institute, Tokyo/JP
  • 4Pathology Division, Research Center For Innovative Oncology, National Cancer Center Hospital East, Chiba/JP
  • 5Pathology And Clinical Laboratory Division, National Cancer Center Hospital, Tokyo/JP
  • 6Thracic Oncology Center, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 135-8550 - Tokyo/JP
  • 7Division Of Thoracic Oncology, National Cancer Center Hospital, Tokyo/JP
  • 8Division Of Thoracic Oncology, Shizuoka Cancer Center, 411-8777 - Shizuoka/JP
  • 9Thoracic Oncology, Hyogo Cancer Center, 673-8558 - Hyogo/JP
  • 10Dept Of Thoracic Oncology, NHO Shikoku Cancer Center, Ehime/JP
  • 11Thoracic Oncology, National Kyushu Cancer Center, 811-1395 - Fukuoka/JP
  • 12Clinical Research Center, National Cancer Research Center, East Hospital, Chiba/JP

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) (UMIN000010095). 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.