2031 - The Nationwide Cancer Genome Screening Project in Japan, SCRUM-Japan GI-SCREEN: Efficient Identification of Cancer Genome Alterations in Advanced Pancreatic Cancer.

Background

We initiated the Nationwide Cancer Genome Screening Project in Japan since February 2014. From October 2015, we have introduced the Next Generation Sequencing to detect cancer genome alterations in advanced pancreatic cancer (aPC), called as the SCRUM-Japan GI-SCREEN.

Methods

This study is ongoing with 20 major cancer centers. Patients with aPC 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

As of March 31st in 2017, total of 270 aPC patients were enrolled and 209 samples were analyzed. The sequence was successfully performed in 136 tumors (65.1%). The origin of samples included the primary site of 65.4%, metastatic site of 34.6%. The tissue samples were obtained by surgical resection 32.4%, needle biopsy 33.8%, EUS-FNA 27.9%, and other 5.9%. Rate for success sequence of EUS-FNA was 56.7%. The frequently detected mutations (≥ 2%) in 136 samples of which results were available were KRAS (91.9%), TP53 (62.5%), CDKN2A (14.0%), SMAD4 (10.3%), GNAS (4.4%), TET2(4.4%), PIK3CA(3.7%), ATM (2.9%), STK11 (2.9%), BRCA2 (2.2%). Most frequently detected CNVs (≥ 7copies) was MYC (2.9%), and no gene fusion was detected. We will show the clinical outcome based on certain key cancer genome alterations.

Conclusions

This nationwide screening system is efficient to detect rare gene alterations in aPC. This novel knowledge provides an intriguing background to investigate new targeted approaches in these patients and to progress precision medicine.

Clinical trial identification

UMIN000016344.

Legal entity responsible for the study

SCRUM-Japan GI-Screen.

Funding

15 SCRUM-Japan collaborating pharmaceutical companies, AMED, NCC.

Editorial Acknowledgement

Disclosure

N. Izawa: Consulting or advisory role: Taiho Pharmaceutical Co., Ltd., Merck Serono Co., Ltd. C. Morizane: Honoraria: Pfizer, Novartis, Yakult Honsha, Eli Lilly Japan K.K, Nobelpharma, Fujifilm, Teijin Pharma, Taiho Pharmaceutical Co., Ltd.; Consulting or advisory role: Yakult Honsha, Novartis, Taiho Pharmaceutical; Research funding (Recipient: my institution): Pfizer, Nobelpharma, Eisai, Yakult Honsha, Ono Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd. H. Takahashi: Honoraria: Taiho Pharmaceutical Co., Ltd.; Research funding: Bayer Pharmaceutical, Bristol-Myers Squibb. M. Ueno: Honoraria: Taiho Pharmaceutical Co., Ltd., Yakult Honsha, AstraZeneca, Novartis, Eli Lilly Japan K.K, Teijin Pharma, Shire, Ono Pharmaceutical Co., Ltd.; Research funding: Taiho Pharmaceutical, Shire, Daiichi Sankyo, Eisai, AstraZeneca, Ono Pharmaceutical Co., Ltd., MSD, Merck Serono Co., Ltd., NanoCarrier, Dainippon Sumitomo Pharma, Incyte. N. Okano: Honoraria: Taiho Pharmaceutical Co., Ltd., Merck Serono Co., Ltd. S. Shimizu: Honoraria: Novartis, Taiho Pharmaceutical Co., Ltd. S. Itoh: Speakers\' bureau: Otsuka Pharmaceutical, Asahi Kasei Phama; Consulting or Advisory Role: Asahi Kasei Phama, Takeda; Research funding (Recipient: our institution): Taiho Pharmaceutical Co., Ltd., Sumitomo Dainippon, Daiichi Sankyo, MSD, Yakult Honsha, Chugai Pharmaceutical Co., Ltd, Ono Pharmaceutical Co., Ltd., Astellas, CSL Behring, Novartis, Shionogi, Eli Lilly Japan K.K, Bayer, Merck Serono Co., Ltd., Kyowa Hakko Kirin, Sanofy, Pfizer, Boehringer Ingelheim, Asahi Kasei Phama, Taisho Toyama Pharmaceutical, Kaken Pharmaceutical, Hisamitsu Pharmaceutical, Nihon Pharmaceutical, Nihon Blood Products Organization, Kowa Company, Medtronic, Johnson and Johnson. T. Kudo: Research grants: Yakult Honsha, Chugai Pharmaceutical Co., Ltd, Ono Pharmaceutical Co., Ltd., Bayer Yakuhin, Ltd. S. Nomura: Honoraria: Taiho Pharmaceutical Co., Ltd. T. Kuwata: Honoraria: Chugai Pharmaceutical Co., Ltd, Daiichi-Sankyo Research funding (to institution): Daiichi-Sankyo. W. Okamoto: Grants: MSD. K. Shitara: Consulting or advisory role: Astellas Pharma, Eli Lilly Japan K.K, Bristol-Myers Squibb, Takeda, Pfizer, Ono Pharmaceutical Co., Ltd.; Personal fees: Novartis, AbbVie, Yakult Honsha; Research funding (to institution): Eli Lilly Japan K.K, Ono Pharmaceutical Co., Ltd., Dainippon Sumoitomo Pharma, Daiichi Sankyo, Taiho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd, MSD. A. Ohtsu: Honoraria: Chugai Pharmaceutical Co., Ltd, Ono Pharmaceutical Co., Ltd., Bristol-Myers Squibb; Research funding: Bristol-Myers Squibb. T. Yoshino: Grants: MSD K.K., Sumitomo Dainippon Pharma Co., Ltd., GlaxoSmithKline K.K., Nippon Boehringer Ingelheim Co., Ltd, Sanofi K.K., Chugai Pharmaceutical Co., Ltd; Personal fees: Eli Lilly Japan K.K, Merck Serono Co., Ltd, Sanofi K.K., Chugai Pharmaceutical Co., Ltd. All other authors have declared no conflicts of interest.