1307P - A nationwide genomic screening system in Japan for the development of molecular targeted therapies against non-small cell lung cancers with rare dr...

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Drug Development
Non-Small-Cell Lung Cancer, Metastatic
Pathology/Molecular Biology
Translational Research
Presenter Shingo Matsumoto
Citation Annals of Oncology (2014) 25 (suppl_4): iv426-iv470. 10.1093/annonc/mdu349
Authors S. Matsumoto1, K. Tsuchihara1, K. Yoh2, Y. Zenke2, T. Kohno3, G. Ishii4, K. Tsuta5, S. Umemura2, S. Niho2, H. Ohmatsu2, Y. Ohe2, T. Yamanaka6, K. Goto2
  • 1Division Of Translational Research, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, 277-8577 - Kashiwa/JP
  • 2Division Of Thoracic Oncology, National Cancer Center Hospital East, 277-8577 - Kashiwa/JP
  • 3Division Of Genome Biology, National Cancer Center Research Institute, Tokyo/JP
  • 4Pathology Division, Research Center For Innovative Oncology, National Cancer Center Hospital East, Kashiwa/JP
  • 5Pathology And Clinical Laboratory Division, National Cancer Center Hospital, Tokyo/JP
  • 6Clinical Research Center, National Cancer Research Center, East Hospital, Kashiwa/JP

Abstract

Aim

A variety of targetable driver mutations other than EGFR mutations and ALK fusions occur in 1%-2% of non-small cell lung cancers (NSCLCs). Efficient screening systems for these rare mutations are necessary for the successful development of molecular targeted therapies.

Methods

In February 2013, a new nationwide genomic screening system (LC-SCRUM-Japan) was established in Japan to screen advanced non-squamous NSCLCs without EGFR mutations for primarily ALK/RET/ROS1 fusions by RT-PCR and FISH. In November 2013, this system was amended to further screen for other driver mutations in fusion-negative cancers after the primary screening. Ten nanograms of genomic DNA extracted from biopsy or cytology specimens were subjected to the Ion Torrent AmpliSeq™ Cancer Hotspot Panel, version 2, and Ion Torrent next-generation sequencing, enabling the simultaneous analysis of ∼2800 hotspot mutations in 50 cancer-related genes.

Results

As of March 28, 2014, a total of 161 institutions were participating and 667 patients were enrolled in LC-SCRUM-Japan. Among available 581 samples, RET/ROS1/ALK fusions were detected in 23 (4%)/23 (4%)/14 (2%) cases, respectively. After the protocol amendment, 200 cases without the fusions were transferred to the multiplex mutation screening, and driver mutations were detected in 82 cases (41%). The detected mutations were comprised of 45 KRAS mutations (23%), 10 BRAF mutations (5%), 9 ERBB2 mutations (5%), 2 PIK3CA mutations (2%) and 1 NRAS mutation (1%). Among them, 2 cases with BRAF V600E mutations were enrolled in a global phase II study of a BRAF inhibitor, dabrafenib (NCT01336634).

Conclusions

This screening system enabled rare fusions and mutations in driver oncogenes, especially RET, ROS1, KRAS, BRAF and ERBB2, to be detected precisely and more frequently in limited amounts of samples from advanced NSCLCs, thereby contributing to the enrollment of patients in clinical trials for targeted therapies.

Disclosure

K. Goto: Koichi Goto received research fund from GlaxoSmithKline. All other authors have declared no conflicts of interest.