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Poster Display session 2

2223 - Microsatellite Instability Status in Metastatic Colorectal Cancer and Effect of Immune Checkpoint Inhibitors on Survival in MSI-High Metastatic Colorectal Cancer

Date

29 Sep 2019

Session

Poster Display session 2

Topics

Tumour Site

Colon and Rectal Cancer

Presenters

Wataru Okamoto

Citation

Annals of Oncology (2019) 30 (suppl_5): v198-v252. 10.1093/annonc/mdz246

Authors

W. Okamoto1, Y. Nakamura2, M. Shiozawa3, Y. Komatsu4, T. Denda5, H. Hara6, Y. Kagawa7, Y. Narita8, H. Kawakami9, T. Esaki10, T. Nishina11, N. Izawa12, K. Ando13, T. Moriwaki14, T. Kato15, F. Nagashima16, T. Satoh17, S. Nomura18, T. Yoshino2, K. Akagi19

Author affiliations

  • 1 Cancer Treatment Center, Hiroshima University Hospital, 734-8551 - Hiroshima/JP
  • 2 Department Of Gastroenterology And Gastrointestinal Oncology, National Cancer Center Hospital East, 277-8577 - Kashiwa/JP
  • 3 Gastrointestinal Surgery, Kanagawa Cancer Center, 241-0815 - Yokohama/JP
  • 4 Department Of Cancer Chemotherapy, Hokkaido University Hospital Cancer Center, 060-8648 - Sapporo/JP
  • 5 Division Of Gastroenterology, Chiba Cancer Center Hospital, 260-8717 - Chiba/JP
  • 6 Department Of Gastroenterology, Saitama Cancer Center, 362-0068 - Saitama/JP
  • 7 Surgery, Kansai Rosai Hospital, 660-0064 - Amagasaki/JP
  • 8 Department Of Clinical Oncology, Aichi Cancer Center Hospital, 464-8681 - Nagoya/JP
  • 9 Department Of Medical Oncology, Kindai University Faculty of Medicine, 589-8511 - Osaka-sayama/JP
  • 10 Department Of Gastrointestinal And Medical Oncology, National Kyushu Cancer Center, 811-1395 - Fukuoka/JP
  • 11 Department Of Gastrointestinal Medical Oncology, Shikoku Cancer Center, 791-0280 - Matsuyama/JP
  • 12 Clinical Oncology, St. Marianna University School of Medicine, 2168511 - Kawasaki/JP
  • 13 Surgery And Science, Kyushu University, Fukuoka/JP
  • 14 Gastroenterology, Faculty of Medicine, University of Tsukuba, Tsukuba, 305-0005 - Tsukuba/JP
  • 15 Department Of Surgery, Osaka National Hospital, 540-0006 - Osaka/JP
  • 16 Medical Oncology, Kyorin university Hospital, 181-8611 - Tokyo/JP
  • 17 Department Of Frontier Science For Cancer And Chemotherapy, Graduate School of Medicine / Faculty of Medicine, Osaka University, 565-0871 - Suita/JP
  • 18 Clinical Research Support Office, National Cancer Center Hospital East, 277-8577 - Kashiwa/JP
  • 19 Molecular Diagnosis And Cancer Prevention, Saitama Cancer Center, Saitama/JP

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Abstract 2223

Background

Tumour mismatch repair (MMR) predicts benefit of immune checkpoint inhibitors (ICIs) in metastatic colorectal cancer (mCRC). We conducted a large-scale prospective observational trial on microsatellite instability (MSI) status in mCRC: SCRUM-Japan GI-SCREEN CRC-MSI.

Methods

mCRC patients (pts) appropriate for systemic chemotherapy were eligible. Paired tumor and normal DNA extracted from FFPE samples were analyzed by the MSI Analysis System, which includes 5 mononucleotide markers. Tumours exhibiting ≥2 unstable markers were defined as MSI-H, while those with ≤1 were labelled MSI-L/MSS.

Results

From 2/2016 to 3/2018, 1,711 pts were enrolled, and 1,696 samples were submitted. MSI status was determined in 1,676 pts (98.8%); 51 pts (3.0%) were MSI-H. For MSI-H vs. MSI-L/MSS pts: Median age (years) 64/64; male gender (%) 49.0 vs. 56.2, p = 0.31; right-sided primary (%) 70.6 vs. 25.0, p < 0.001; and poorly differentiated histology (%) 33.3 vs. 8.9, p < 0.001. Of the 864 pts who received parallel NGS testing, median tumor mutation burdens (TMB) in MSI-H and MSI-L/MSS were 32.8 and 12.6 mt/Mb, p < 0.001. High TMB, defined as > 20 mt/Mb, was observed in 27/29 (93.1%) MSI-H pts. The frequency of representative gene mutations (%) for MSI-H vs. MSI-L/MSS pts were: TP53 17.2 vs. 66.1, p < 0.001; PIK3CA 48.3 vs. 13.2, p < 0.001; BRAF 34.5 vs. 7.5, p < 0.001; MSH2 17.2 vs. 0, p < 0.001; CTNNB1 17.2 vs. 0.6, p < 0.001; and ERBB2 10.3 vs. 1.4, p < 0.001. ERBB2 amplification was detected only in MSI-L/MSS pts (2.3%). Two-year survival rates from first-line systemic therapy in 695 pts with MSI-L/MSS, 9 pts with MSI-H treated with ICI in any-line, and 13 pts with MSI-H not treated with ICI, were 72.3, 74.1, and 47.0%, respectively.

Conclusions

MSI-H mCRC tumors were more frequent in right-sided colon primaries and with poorly differentiated histology. Median TMB was significantly greater in MSI-H pts, and a very high burden was frequently seen. Survival in MSI-H mCRC was poor before ICIs; these agents may improve outcomes for MSI-H pts.

Clinical trial identification

UMIN000020437.

Editorial acknowledgement

Legal entity responsible for the study

GI-SCREEN-Japan.

Funding

MSD.

Disclosure

W. Okamoto: Research grant / Funding (institution): MSD. Y. Nakamura: Research grant / Funding (institution): Ono Pharmaceutical; Research grant / Funding (institution): Taiho Pharmaceutical. Y. Komatsu: Speaker Bureau / Expert testimony, Research grant / Funding (self): Taiho Pharmaceutical; Speaker Bureau / Expert testimony, Research grant / Funding (self): Lilly; Speaker Bureau / Expert testimony, Research grant / Funding (self): Chugai Pharma; Speaker Bureau / Expert testimony: Merck Serono; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (self): Novartis; Honoraria (self), Speaker Bureau / Expert testimony: Pfizer; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (self): Bayer; Speaker Bureau / Expert testimony, Research grant / Funding (self): Ono Pharmaceutical; Speaker Bureau / Expert testimony: Yakult Honsha; Speaker Bureau / Expert testimony, Research grant / Funding (self): Takeda; Speaker Bureau / Expert testimony, Research grant / Funding (self): Sanofi; Speaker Bureau / Expert testimony: Bristol-Myers Squibb Japan; Speaker Bureau / Expert testimony: Daiichi Sankyo; Speaker Bureau / Expert testimony: TOWA; Speaker Bureau / Expert testimony: Nipro Corporation; Research grant / Funding (self): MSD; Research grant / Funding (self): Astellas Pharma; Research grant / Funding (self): Sumitomo Dainippon Pharma; Research grant / Funding (self): Boehringer Ingelheim; Research grant / Funding (self): Sysmex; Research grant / Funding (self): Yakult Pharmaceutical. T. Denda: Speaker Bureau / Expert testimony: Taiho Pharmaceutical; Speaker Bureau / Expert testimony: Yakult Honsha; Speaker Bureau / Expert testimony: Chugai Pharma; Research grant / Funding (institution): Sanofi; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): MSD. H. Hara: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Ono Pharmaceutical; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Chugai Pharma; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Merck Serono; Advisory / Consultancy, Research grant / Funding (institution): MSD; Honoraria (self), Research grant / Funding (institution): Taiho Pharmaceutical; Honoraria (self): Yakult Honsha; Honoraria (self), Research grant / Funding (institution): Lilly; Honoraria (self), Research grant / Funding (institution): Takeda; Honoraria (self): Bristol-Myers Squibb; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Sumitomo Dainippon Pharma; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): LSK BioPharma; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): Bristol-Myers Squibb-Ono Pharmaceutical; Research grant / Funding (institution): BeiGene. Y. Narita: Speaker Bureau / Expert testimony: Chugai Pharma; Speaker Bureau / Expert testimony, Research grant / Funding (self): Ono Pharmaceutical; Speaker Bureau / Expert testimony: Lilly; Speaker Bureau / Expert testimony: Taiho Pharmaceutical; Speaker Bureau / Expert testimony: Takeda; Speaker Bureau / Expert testimony, Research grant / Funding (self): Bristol-Myers Squibb. H. Kawakami: Honoraria (self), Advisory / Consultancy: Taiho Pharmaceutical; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb Japan; Honoraria (self), Advisory / Consultancy: Ono Pharmaceutical; Honoraria (self), Advisory / Consultancy: Lilly Japan; Honoraria (self): Chugai/Roche; Honoraria (self): Yakult Pharmaceutical; Honoraria (self): Takeda; Honoraria (self): MSD K.K; Honoraria (self): Merck Serono; Honoraria (self), Research grant / Funding (institution): Daiichi Sankyo; Honoraria (self): Bayer; Honoraria (self): AstraZeneca; Research grant / Funding (institution): Chugai Pharma; Research grant / Funding (institution): Eisai. T. Esaki: Honoraria (self), Research grant / Funding (institution): Lilly; Honoraria (self): Taiho Pharmaceutical; Honoraria (self), Research grant / Funding (institution): Bristol-Myers Squibb Japan; Honoraria (self): Eisai; Honoraria (self), Research grant / Funding (institution): Daiichi Sankyo; Honoraria (self), Research grant / Funding (institution): Merck Serono; Honoraria (self): Chugai Pharma; Honoraria (self), Research grant / Funding (institution): Ono Pharmaceutical; Honoraria (self): Takeda; Honoraria (self), Research grant / Funding (institution): Bayer; Honoraria (self): Sanofi; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Sumitomo Dainippon Pharma; Research grant / Funding (institution): Astellas Pharma; Research grant / Funding (institution): Nihonkayaku; Research grant / Funding (institution): Pfizer. T. Nishina: Honoraria (self), Research grant / Funding (institution): Taiho Pharmaceutical; Honoraria (self), Research grant / Funding (institution): Chugai Pharma; Honoraria (self): Lilly; Honoraria (self), Research grant / Funding (institution): Merck Serono; Honoraria (self): Takeda; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Nihonkayaku; Research grant / Funding (institution): Sumitomo Dainippon Pharma; Research grant / Funding (institution): Lilly Japan; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Ono Pharmaceutical. N. Izawa: Advisory / Consultancy: Taiho Pharmaceutical; Advisory / Consultancy: Sanofi; Advisory / Consultancy: MSD; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Bayer; Advisory / Consultancy: Lilly; Advisory / Consultancy: Merck Serono. T. Moriwaki: Speaker Bureau / Expert testimony, Research grant / Funding (institution): Taiho Pharmaceutical; Speaker Bureau / Expert testimony: Chugai Pharma; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Yakult Honsha; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Takeda; Speaker Bureau / Expert testimony: Novelpharm; Speaker Bureau / Expert testimony: Merck Serono; Speaker Bureau / Expert testimony: Sanofi; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Eisai. T. Kato: Honoraria (self), Research grant / Funding (self): Chugai Pharma; Honoraria (self): Takeda; Honoraria (self): Bayer; Honoraria (self): Lilly; Honoraria (self): Yakult Honsha; Honoraria (self): Sanofi. F. Nagashima: Speaker Bureau / Expert testimony, Research grant / Funding (institution): Taiho Pharmaceutical; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Ono Pharmaceutical; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Merck Serono; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Takeda; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Chugai Pharma; Speaker Bureau / Expert testimony: Yakult Honsha; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Sumitomo Dainippon Pharma; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Kyowa Hakko Kirin; Speaker Bureau / Expert testimony: Mitsubishi Tanabe Pharma; Speaker Bureau / Expert testimony: Nestle health science; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Janssen; Research grant / Funding (institution): OncoTherapy Science; Research grant / Funding (institution): Zeria Pharmaceutical; Research grant / Funding (institution): Lilly Japan; Research grant / Funding (institution): Yakult Pharmaceutical; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Shionogi; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): J-Pharma; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Mochida Pharmaceutical Co. Ltd.; Research grant / Funding (institution): Astellas Pharma; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): NanoCarrier; Research grant / Funding (institution): Baxalta/Shire. T. Satoh: Honoraria (self), Advisory / Consultancy: Bayer Yakuhin; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Lilly; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Ono Pharmaceutical; Advisory / Consultancy: Takara Bio; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Merck Serono; Honoraria (self), Advisory / Consultancy: Nihonkayaku; Advisory / Consultancy: Merck Serono; Honoraria (self), Research grant / Funding (institution): Chugai Pharma; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Takeda; Honoraria (self), Research grant / Funding (institution): Yakult Honsha; Honoraria (self), Research grant / Funding (institution): Merck; Honoraria (self): Astellas Pharma; Honoraria (self): Taiho Pharmaceutical; Research grant / Funding (institution): Sanofi; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Gilead Sciences; Research grant / Funding (institution): Sumitomo Dainippon Pharma. S. Nomura: Full / Part-time employment, An Immediate Family Member: Asahi Kasei; Honoraria (self): Taiho Pharmaceutical. T. Yoshino: Research grant / Funding (institution): Novartis Pharma; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Sumitomo Dainippon Pharma; Research grant / Funding (institution): Chugai Pharmaceutical; Research grant / Funding (institution): Sanofi; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Parexel International; Research grant / Funding (institution): Ono Pharmaceutical. K. Akagi: Advisory / Consultancy, Speaker Bureau / Expert testimony: Takeda; Speaker Bureau / Expert testimony: MSD K.K; Speaker Bureau / Expert testimony: Novartis; Speaker Bureau / Expert testimony: AstraZeneca Japan. All other authors have declared no conflicts of interest.

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