We initiated the Nationwide Cancer Genome Screening Project in Japan since February 2014. From February 2015, we have introduced the Next Generation Sequencing to detect cancer genome alterations in advanced colorectal cancer (aCRC), called as the SCRUM-Japan GI-SCREEN. The objective is to evaluate the frequency of cancer genome alterations and to identify patients who are candidate for clinical trial with corresponding targeting agents.
This study is ongoing with 20 major cancer centers. Patients with aCRC who plan to or receive chemotherapy were eligible. DNA and RNA were extracted from formalin-fixed paraffin embedded (FFPE) tumor samples and were analyzed by the Oncomine Cancer Research Panel (OCP) which allows to detect mutations, copy number variant (CNV) and fusion genes in a CLIA certified CAP accredited lab. The detected genomic variant data were classified according to genetic drivers of cancer, including gain- and loss-of-function or single nucleotide variant based on the Oncomine Knowledgebase.
As of October 31st in 2016, total of 1011 aCRC patients were enrolled and 981 samples were analyzed. The sequence was successfully performed in 751 tumors (76.6%). Out of 751 patients, the origin of samples included the primary site of 83.1% (Right-side 24.6%, Left-side 58.5%), metastatic site of 15.3%, and unknown of 1.6%. The frequently detected mutations in 751 samples of which results were available were TP53 (69.0%), APC (62.8%), and KRAS (43.8%), and CNVs (≥ 7copies) were FLT3 (3.6%), ERBB2 (2.8%), and MYC (2.7%). BRAF V600E was identified in 48 cases (6.4%) and CCDC6-RET fusion was identified in one case (0.1%). We will show the clinical outcome based on certain key cancer genome alterations.
This nationwide screening system is efficient to detect rare gene alterations in aCRC. This novel knowledge provides an intriguing background to investigate new targeted approaches in these patients and represents the progress toward precision medicine.
Clinical trial identification
Legal entity responsible for the study
15 SCRUM-Japan collaborating pharmaceutical companies, AMED, NCC
S. Yuki: Honoraria: Taiho Pharmaceutical, Takeda Pharmaceutical, Merck Serono, Eli Lilly Japan, Chugai Pharmaceutical, Bayer Yakuhin, Bristol-Myers Squibb. T. Kato: Speakers’ Bureau: Takeda Pharmaceutical, Eli Lilly Japan, Chugai Pharmaceutical, Yakult Honsha. H. Taniguchi: Honoraria: Taiho Pharmaceutical, Takeda Pharmaceutical, Merck Serono, Eli Lilly Japan, Chugai Pharmaceutical, Bayer Yakuhin, Yakult Honsha. Research funding: Takeda Pharmaceutical, Otsuka Pharmaceutical, Boehringer Ingelheim Japan, MSD. T. Hamaguchi: Honoraria: Chugai, Merck Serono, Takeda, Yakult Honsha, Taiho. Advisory Role: NanoCarrier. Research funds: Dainippon Sumitomo, Sanofi, NanoCarrier, MSD, Taiho, Ono, Daiichi Sankyo, Teijin. E. Oki: Speakers’ Bureau: Taiho Pharmaceutical, Yakult Honsha, Chugai Pharmaceutical, Eli Lilly Japan, Bayer Yakuhin, Merck Serono, Takeda Pharmaceutical. T. Yamada: Speakers’ Bureau: Chugai Pharmaceutical. T. Kudo: Research funding: Yakult Honsha, Chugai Pharmaceutical, Ono Pharmaceutical. T. Esaki: Honoraria and/or research funding: Chugai Pharmaceutical, Eli Lilly Japan, Taiho Pharmaceutical, Merck Serono, Ono Pharmaceutical, Nihon Kayaku, Eisai, Novartis, Daiichi-Sankyo, DS Pharma, AstraZeneca, Boehringer-Ingelheim Japan, MSD. D. Naruge: Taiho, Ono, Onco Therapy Science, Merck Serono, Eli Lilly Japan, Takeda, Chugai, Bayer, Graxo Smith Kline, Yakult, Sumitomo Dainippom, Daiichi Sankyo, Shionogi, Novartis, Nippon Kayaku, BMS, Sanofi, Kyowa Hakko Kirin, Astellas, Hisamitsu, Pfizer. S. Nomura: Employment Asahi-Kasei Pharmaceutical. K. Shitara: Receipt of grants/research supports: Daiichi Sankyo, Chugai Pharma, Lilly, MSD, Taiho Pharmaceutical, Dainippon Sumitomo Pharma. A. Ohtsu: Employment (an immediate family member): Celgene. Research funding: BMS. T. Yoshino: Research funding: GlaxoSmithKline K. K, Boehringer-Ingelheim GmbH. All other authors have declared no conflicts of interest.