Nationwide driver mutation analysis in advanced EGFR mutation-negative non-squamous lung cancer: LC-SCRUM-Japan

Abstract

Targeted therapy based on oncogenic driver mutations such as EGFR and ALK has recently become standard of care in patients with advanced non-small cell lung cancer (NSCLC). However, the incidence of each driver mutations is low except for EGFR mutation in Asian patients. The LC-SCRUM-Japan was established in Feb 2013 as a nationwide genomic screening project for developing individualized medicine of lung cancer in Japan. The LC-SCRUM-Japan performed multi-institutional oncogenic driver mutation analysis. First, in advanced EGFR mutation-negative non-squamous NSCLC, the tumor samples were screened for ALK/ROS1/RET fusions by RT-PCR and the positive results were confirmed by FISH. Second, between Nov 2013 and Mar 2014, ALK/ROS1/RET-negative tumors by RT-PCR were further examined using multiplex genomic analysis by Ion AmpliSeq Cancer Hotspot Panel v2. From Feb 2013 to Jan 2015, the LC-SCRUM-Japan had the participation of 190 institutions. 1438 patients were enrolled to this study and 1298 tumor samples were screened for ALK/ROS1/RET fusions by RT-PCR. Median reporting time on the results of RT-PCR was 14 days (7-38 days). A gene fusion by RT-PCR was detected in 111 of the 1298 patients as follows; ROS1 57 (4%), RET 32 (3%), and ALK 22 (2%). Multiplex genomic analysis was performed in 201 ALK/ROS1/RET-negative tumors. Among these 201 tumors, 42 tumors had KRAS mutations (21%); any EGFR, 16 (8%); ERBB2, 9 (4%); BRAF, 8 (4%); PIK3CA, 3 (1%); NRAS, 1 (0.5%). Double mutations were seen in 3 tumors. 51 any driver mutations-positive patients have participated clinical trials for each targeted therapy (26 ROS1, 18 RET, 3 ALK, 3 BRAF, and 1 ERBB2). This innovative nationwide genomic screening project in Japan leads to the activation of screening for lung cancer with rare driver mutations and developing targeted therapy trials.