115P - Impact of tissue factor on clinical and biological characteristics in patients with advanced pancreatic cancer

Background

In pancreatic cancer (PC), tissue factor (TF) has been reported to be associated with poor prognosis. However, its expression profiles and clinical implications in PC have remain poorly understood. Given the emergence of drugs targeting TF in clinical development, our study aims to investigate the impact of TF on clinical and biological characteristics in patients (pts) with PC.

Methods

This study used data from the SCRUM-Japan MONSTAR-SCREEN-2 study, a nationwide molecular profiling project (UMIN000043899). Pts with advanced PC who received first-line therapy and underwent whole exome / transcriptome sequencing by Caris Life Sciences (Phoenix, AZ, USA) were included. We analyzed the correlation of the expression between TF and genes targeted by antibody-drug conjugates or bispecific antibodies. TF transcript per million values were categorized into high and low groups based on the median. Clinical backgrounds and prognosis of these groups were compared. Furthermore, gene set enrichment analysis (GSEA) was conducted to explore the underlying signaling pathways of TF.

Results

A total of 104 pts were eligible for this study (high group [n=52], low group [n=52]). TF was weakly correlated with MET (r=0.5), HER2 (r=0.48), MSLN (r=0.48), Nectin-4 (r=0.47). The GSEA results showed significant enrichment in the high group for pathways (FDR q-value<0.05) related to hypoxia, glycolysis, TGF-β signalling, PI3K-AKT-MTOR signalling, and IL2-STAT5 signalling and so on. The objective response rate of first-line treatment was significantly lower in the high group compared to the low group (9.6% vs. 26.9%, p=0.04). There was no significant difference in progression-free survival between the groups. However, the high group had a significantly worse overall survival (OS) compared to the low group, with OS being 8.3 and 10.3 months, respectively (hazard ratio [HR]: 0.5, p=0.049). Multivariable analysis identified TF (HR: 2.8, p=0.007), and metastatic status (HR: 3.1, p=0.010) as independent prognostic factors for shorter OS.

Conclusions

Pts with PC and high TF levels showed enrichment in proliferation, migration, and microenvironment-related pathways, and exhibited lower response rates to first-line treatment, resulting in worse OS.

Editorial acknowledgement

Clinical trial identification

2020-496; Release date: 2021/03/19.

Legal entity responsible for the study

T. Yoshino.

Funding

Has not received any funding.

Disclosure

C. Morizane: Financial Interests, Personal, Advisory Board: Yakult, MSD, Servier, Boehringer Ingelheim, AstraZeneca, Taiho Pharmaceutical, Merck biopharma; Financial Interests, Personal, Invited Speaker: Novartis, Myriad Genetics, Guardant, Toray, Boehringer Ingelheim; Financial Interests, Institutional, Invited Speaker: Yakult Honsha, Ono Pharmaceutical, Taiho Pharmaceutical, Eisai, MSD K.K., J-Pharma, AstraZeneca, Merck Biopharma, Boehringer Ingelheim; Financial Interests, Institutional, Funding: Daiichi Sankyo RD Novare, Hitachi; Financial Interests, Institutional, Research Grant: Labcorp. M. Ueno: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai Pharmaceutical, Incyte, MSD, Nihon Servier, Ono Pharmaceutical, Taiho Pharmaceutical, Daiichi Sankyo, Takeda Pharmaceutical, J-Pharma, Eisai, Yakult Honsha; Financial Interests, Personal, Advisory Board: Nippon Boehringer Ingelheim, Novartis; Financial Interests, Institutional, Invited Speaker: Astellas Pharma, AstraZeneca, Chugai Pharmaceutical, DFP, Daiichi Sankyo, Eisai, Incyte, MSD, Merck Biopharma, Ono Pharmaceutical, Taiho Pharmaceutical, Novartis, J-Pharma, Novocure, Chiome Bioscience. S. Boku: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Bristol Myers Squibb, MSD Japan, Eisai Co., Ltd., Nippon Kayaku Co., Ltd., Asahi Kasei Pharma Co.; Financial Interests, Institutional, Funding: Kyo Diagnostics Co., Ltd. M. Furukawa: Financial Interests, Institutional, Principal Investigator: Nobelpharma, Incyte Corporation, Astellas, Merck, MSD, Eisai, Ono, J-Pharma, Yakult, Servier, Taiho, Chugai, Daiichi Sankyo, Otsuka; Financial Interests, Personal, Speaker’s Bureau: Yakult, Ono, Servier, Daiichi Sankyo, Taiho, Chugai, AstraZeneca. N. Matsuhashi: Financial Interests, Personal, Invited Speaker: Abbott, AMCO Inc., Asahi Kasei Pharma, AstraZeneca, Bayer Yakuhin, Bristol Myers Squibb, Chugai Pharm, Covidien Japan, Daiichi Sankyo, EA Pharma, Eisai, Eli Lilly Japan, Gunze Medical Limited, Johnson & Johnson, Kaken Pharm, Kyowa Kirin, MC Medical, Merck Biopharma Japan, Miyarisan Pharm, MSD, Miyarisan Pharm, Ono Pharm, Stryker, Taiho Pharm, Takeda Pharma, Terumo, Tsumura, Viatris and Yakult Honsha; Financial Interests, Institutional, Principal Investigator: Asahi Kasei Pharma, Chugai Pharm, Covidien Japan, Daiichi Sankyo, Eisai, Johnson & Johnson, Kaken Pharm, Kyowa Kirin, Nippon Kayaku, Taiho Pharm, Toray Medical, EPS Corporation, EP-CRSU, MSD, Ono Pharma, Shift Zero K.K. S. Itoh: Financial Interests, Personal, Invited Speaker: Chugai Pharma, AstraZeneca, Eisai, Takeda, Incyte Japan, Ono Pharmaceutical. N. Okano: Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical, Eli Lilly Japan, Eisai, Bayer Yakuhin, Chugai Pharma, Ono Pharmaceutical, Daiichi Sankyo, AstraZeneca, MSD, Incyte, Nihon Servier; Financial Interests, Personal, Funding: J-Pharma. T. Ohta: Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb Japan, Chugai Pharma, Daiichi Sankyo Company, Limited, Eisai Co., Ltd., Eli Lilly Japan K.K., Merck & Co, MSD K.K., Ono Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited., Teijin Pharma, Yakult Honsha; Financial Interests, Personal and Institutional, Principal Investigator: Takeda Pharmaceutical Company Limited. T. Hashimoto: Financial Interests, Personal, Invited Speaker: Cytogen, Takata Pharma. T. Fujisawa: Financial Interests, Personal, Invited Speaker: Amelieff Co. Ltd. M. Imai-Sumida: Financial Interests, Personal, Invited Speaker: Caris Life Sciences, Sumitomo Corp., Guardant. Y. Nakamura: Financial Interests, Personal, Invited Speaker: Chugai, Merck Biopharma, Guardant Health Pte Ltd., MSD K.K, Eisai, Zeria Pharmaceutical, Miyarisan Pharmaceutical, CareNet, Inc., Hisamitsu Pharmaceutical, Taiho Pharmaceutical, Daiichi Sankyo Co., Ltd., Becton Dickinson, Guardant Health Japan Corp.; Financial Interests, Personal, Advisory Board: Natera, Inc., Roche Ltd., Seagen, Inc., Premo Partners, Inc., Daiichi Sankyo Co., Ltd., Takeda, Exact Sciences, Gilead Sciences, Guardant Health Pte Ltd.; Financial Interests, Institutional, Funding: Taiho, Chugai, Guardant Health, Genomedia, Daiichi Sankyo, Roche Diagnostics, Guardant Health Amea, Inc., Tempus; Financial Interests, Institutional, Invited Speaker: Seagen. H. Bando: Financial Interests, Institutional, Research Grant: Ono Pharmaceutical; Other, Personal, Other, Lecture fee: Ono Pharmaceutical, Taiho Pharmaceutical, Eli Lilly Japan. T. Yoshino: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co., Ltd., Merck Biopharma Co., Ltd., Bayer Yakuhin, Ltd., Ono Pharmaceutical Co., Ltd., MSD K.K., Takeda Pharmaceutical Co., Ltd.; Financial Interests, Personal, Other, Consultancy: Sumitomo Corp.; Financial Interests, Institutional, Research Grant: Ono Pharmaceutical Co., Ltd., Sanofi K.K., MSD K.K., Taiho Pharmaceutical Co., Ltd., Molecular Health GmbH, Amgen K.K., Pfizer Japan Inc., Genomedia Inc., Sysmex Corp., Daiichi Sankyo Co., Ltd., Chugai Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Eisai Co., Ltd., Roche Diagnostics K.K., Falco Biosystems Ltd., Merus N.V., Bristol Myers Squibb K.K., Medical & Biological Laboratories Co., Ltd., Takeda Pharmaceutical Co., Ltd. M. Ikeda: Financial Interests, Personal, Advisory Board: AstraZeneca, Chugai, Eisai, Nihon Servier, Novartis, Bristol Myers Squibb, MSD, Boehringer Ingelheim, Astellas Pharma, GSK; Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai, Eli Lilly Japan, Eisai, Nihon Servier, Novartis, Taiho, Yakult, Teijin Pharma, AbbVie, Fujifilm Toyama Chemical, Incyte Biosciences Japan, Takeda, Ono, MSD, Taisho Pharmaceutical, Nippon Kayaku, Guardant Health Japan, Nobelpharma, EA Pharma, Chugai, Nihon Servier, Takeda, Novartis, Eisai, Rakuten Medical; Financial Interests, Institutional, Invited Speaker: Bayer, Bristol Myers Squibb, Eisai, AstraZeneca, Eli Lilly Japan, Chugai Pharmaceutical, MSD, Ono, Novartis, J-Pharma, Chiome Bioscience, Nihon Servier, Delta-Fly Pharma, Syneos Health, Merus.N.V., Merck Biopharma, Boehringer Ingelheim, Invitae, Nobelpharma. All other authors have declared no conflicts of interest.