Abstract 1817
Background
We have conducted the Nationwide Cancer Genome Screening Project in Japan since April 2015 using Next Generation Sequencing in advanced non-colorectal gastrointestinal (GI) cancer (aNon-CRC), 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 for corresponding targeting agents.
Methods
This study is ongoing with the participation of 23 major cancer centers. Patients with aNon-CRC, including advanced esophageal cancer (aEC), 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.
Results
By the end of March 2017, a total of 220 aEC samples were analyzed. The sequence with the OCP was successfully performed in 144 (65.5%). Out of 144 patients, the proportion of sample and histology type is followed; surgical specimen 52.1%, squamous cell carcinoma 92.4%. The frequently detected mutations were TP53(76.4%), NFE2L2 (38.2%), CDKN2A (9.7%), PIK3CA (6.3%), RB1 (5.6%), and CNVs were CCND1 (38.2%), EGFR (7.6%), ATP11B (6.9%), SOX2 (6.9%). ERBB2 amplification was identified in 3 cases (2.1%) and FGFR3-TACC3 fusion was identified in one case (0.7%). Five patients with druggable genomic alterations (PIK3CA(n = 2), EGFR(n = 2), FGFR3-TACC fusion(n = 1)) were enrolled for clinical trials of targeting therapies.
Conclusions
This nationwide screening system is efficient to detect rare gene alterations in aEC. This novel knowledge provides an intriguing background to investigate new target approaches in these patients and to progress precision medicine. Clinical trial information: UMIN000016344 (Non-CRC).
Clinical trial identification
UMIN000016344.
Legal entity responsible for the study
SCRUM JAPAN.
Funding
15 SCRUM-Japan collaborating pharmaceutical companies, AMED, NCC.
Editorial Acknowledgement
Disclosure
K. Kato: Other: 15 SCRUM-Japan collaborating pharmaceutical companies; Grants: AMED; Other: NCC, during the conduct of the study; Grants: Shionogi, Ono Pharmaceuticals, Merck & Co., Merck Serono. T. Kojima: Grants: Shionogi, Ono Pharmaceutical, MSD, Oncolys BioPharma, Astellas, Amgen, BioPharama, outside the submitted work. H. Saeki, H. Hara, S. Kadowaki, Y. Kagawa, S. Hironaka, N. Izawa, S. Fujii, K. Shitara, A. Ohtsu: Other: 15 SCRUM-Japan collaborating pharmaceutical companies; Grants: AMED; Other: NCC, during the conduct of the study. T. Kajiwara: Other: 15 SCRUM-Japan collaborating pharmaceutical companies; Grants: AMED, other: NCC, during the conduct of the study; Grants and personal fees: Taiho Pharmaceutical Co., Ltd.; Grants and personal fees: Chugai Pharmaceutical Co., Ltd., Bayer Yakuhin, Ltd., Merck Serono Co., Ltd., Kyowa Hakko Kirin Co., Ltd., Yakult Honsha Co.,Ltd., Medical & Biological Laboratories Co., Ltd., outside the submitted work. H. Nakatsumi: Other: 15 SCRUM-Japan collaborating pharmaceutical companies; Grants: AMED; Other: NCC, during the conduct of the study; Personal fees: Ono Pharmaceutical, Bayer Yakuhin, Lilly Japan, outside the submitted work. T. Esaki: Other: 15 SCRUM-Japan collaborating pharmaceutical companies; Grants: AMED; Other: NCC, during the conduct of the study; Grants and personal fees: Taiho; Eli Lilly, Eisai, Daiichi-Sankyo, Merck Serono, Nihon Kayaku, Ono; Personal fees: Chugai, Bristol-Myers Squibb, Takeda, Kyowa-Kirin; Grants: DS Pharma, Novartis, AstraZeneca, Boehringer Ingelheim, MSD, Astellas, Bayer, Pfizer, Yakult, outside the submitted work. T. Moriwaki: Grants: 15 SCRUM-Japan collaborating pharmaceutical companies; Grants: AMED, during the conduct of the study; Grants and personal fees: Takeda, Chugai, Yakult; Personal fees: Taiho, Sanofi; Grants: MSD Oncology, outside the submitted work. T. Kobayashi: Grants: 15 SCRUM-Japan collaborating pharmaceutical companies; Grants: J-Pharma, Taiho, Sumitomo Dainippon, Janssen, Daiichi Sankyo, MSD, Yakult, Takeda, Chugai, Ono, Astellas, Zeria, Novartis, Nanocarrier, Shionogi, Onco Therapy Science, Eli Lilly Japan, Bayer, Bristol-Myers Squibb, Merck Serono, Kyowa Hakko Kirin, Eisai, Mochida, Baxalta, Sanofi, during the conduct of the study. S. Nomura: Other: 15 SCRUM-Japan collaborating pharmaceutical companies; Grants: AMED; Other: NCC, during the conduct of the study; Personal fees: Taiho, outside the submitted work. T. Kuwata: Other: 15 SCRUM-Japan collaborating pharmaceutical companies; Grants: AMED; Other: NCC, during the conduct of the study; Personal fees: Chugai Pharm; Grants and personal fees: Daiichi-Sankyo, outside the submitted work. W. Okamoto: Grants: MSD, outside the submitted work. T. Yoshino: Grants: MSD K.K., Sumitomo Dainippon Pharma Co., Ltd., GlaxoSmithKline K.K., Nippon Boehringer Ingelheim Co., Ltd; Grants and personal fees: Sanofi K.K., Chugai Pharmaceutical Co., Ltd; Personal fees: Eli Lilly Japan K.K, Merck Serono Co., Ltd., outside the submitted work.