Relationship Between Thymidine Kinase 1 Expression and Trifluridine/Tipiracil Therapy in Refractory Metastatic Colorectal Cancer: A Pooled Analysis of 2 Randomized Clinical Trials

被引：10

作者：

Yoshino, Takayuki ^{[1
]}

Yamazaki, Kentaro ^{[2
]}

Shinozaki, Eiji ^{[3
]}

Komatsu, Yoshito ^{[4
]}

Nishina, Tomohiro ^{[5
]}

Baba, Hideo ^{[6
]}

Tsuji, Akihito ^{[7
,8
]}

Tsuji, Yasushi ^{[9
]}

Yamaguchi, Kensei ^{[10
]}

Sugimoto, Naotoshi ^{[11
]}

Denda, Tadamichi ^{[12
]}

Muro, Kei ^{[13
]}

Takayama, Tetsuji ^{[14
]}

Esaki, Taito ^{[15
]}

Hamamoto, Yasuo ^{[16
,17
]}

Moriwaki, Toshikazu ^{[18
]}

Shimada, Yasuhiro ^{[19
]}

Goto, Masahiro ^{[20
]}

Nakayama, Norisuke ^{[21
]}

Fujii, Hirofumi ^{[22
]}

Tanase, Takanori ^{[23
]}

Ohtsu, Atsushi ^{[1
]}

机构：

[1] Natl Canc Ctr Hosp East, Dept Gastroenterol & Gastrointestinal Oncol, 6-5-1 Kashiwanoha, Kashiwa, Chiba 2778577, Japan

[2] Shizuoka Canc Ctr, Div Gastrointestinal Oncol, Shizuoka, Japan

[3] Japanese Fdn Canc Res, Dept Gastroenterol Canc, Inst Hosp, Tokyo, Japan

[4] Hokkaido Univ Hosp, Dept Canc Chemotherapy, Sapporo, Hokkaido, Japan

[5] Natl Hosp Org, Dept Gastrointestinal Med Oncol, Shikoku Canc Ctr, Matsuyama, Ehime, Japan

[6] Kumamoto Univ, Grad Sch Med Sci, Dept Gastroenterol Surg, Kumamoto, Japan

[7] Kochi Hlth Sci Ctr, Dept Clin Oncol, Kochi, Japan

[8] Kobe City Med Ctr Gen Hosp, Dept Clin Oncol, Kobe, Hyogo, Japan

[9] Tonan Hosp, Dept Med Oncol, Sapporo, Hokkaido, Japan

[10] Saitama Canc Ctr, Dept Gastroenterol, Ina, Saitama, Japan

[11] Osaka Int Canc Inst, Dept Med Oncol, Osaka, Japan

[12] Chiba Canc Ctr, Div Gastroenterol, Chiba, Japan

[13] Aichi Canc Ctr Hosp, Dept Clin Oncol, Nagoya, Aichi, Japan

[14] Univ Tokushima, Dept Gastroenterol & Oncol, Tokushima, Japan

[15] Natl Hosp Org, Dept Gastrointestinal & Med Oncol, Kyushu Canc Ctr, Fukuoka, Japan

[16] Tochigi Canc Ctr, Dept Chemotherapy, Utsunomiya, Tochigi, Japan

[17] Keio Univ, Dept Internal Med, Sch Med, Tokyo, Japan

[18] Univ Tsukuba, Div Gastroenterol, Tsukuba, Ibaraki, Japan

[19] Natl Canc Ctr, Gastrointestinal Oncol Div, Tokyo, Japan

[20] Osaka Med Coll Hosp, Canc Chemotherapy Ctr, Osaka, Japan

[21] Kanagawa Canc Ctr, Dept Gastroenterol, Yokohama, Kanagawa, Japan

[22] Jichi Med Univ Hosp, Dept Clin Oncol, Shimotsuke, Tochigi, Japan

[23] Taiho Pharmaceut Co Ltd, Tokyo, Japan

来源：

CLINICAL COLORECTAL CANCER | 2018年 / 17卷 / 04期

关键词：

Biomarker; Disease control rate; Next-generation sequencing; Overall survival; Progression-free survival; PHASE-III TRIAL; ANTITUMOR-ACTIVITY; DOUBLE-BLIND; COMBINATION ANTIMETABOLITE; THYMIDYLATE SYNTHASE; TAS-102; MONOTHERAPY; 1ST-LINE THERAPY; OXALIPLATIN; PLACEBO; CHEMOTHERAPY;

D O I：

10.1016/j.clcc.2018.07.009

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

No predictive biomarker to indicate the clinical benefit of trifluridine/tipiracil (FTD/TPI) has been identified. Individual patient data from 329 patients from 2 randomized placebo-controlled trials were analyzed to determine the relationship between thymidine kinase 1 (TK1) expression and FTD/TPI efficacy in refractory metastatic colorectal cancer. Patients with high TK1 expression showed an improvement in overall survival when treated with FTD/TPI. Background: High thymidine kinase 1 (TK1) activity increases the incorporation of trifluridine (FTD) into DNA; thus, D antitumor activity is likely to increase in patients with high tumoral TM activity. To date, no established predictive biomarker to indicate the clinical benefit of FTD/tipiracil (TPI) has been identified. We aimed to determine the relaionship between TK1 expression and FTD/TPI efficacy in refractory metastatic colorectal cancer. Patients and Methods: Individual patient data from 2 randomized placebo-controlled trials were analyzed. We measured TK1 protein expression in tumor tissue samples and its relationship with FTD/TPI clinical efficacy using overall survival (OS), progression-free survival, and disease control rate. Results: This study comprised 329 patients (FTD/TPI, 224; placebo, 105). FTD/TPI significantly improved OS versus placebo in the high-expression (cutoff > 15%) TK1 group (median OS, 7.8 vs. 6.8 months; hazard ratio - 0.65; 95% confidence interval, 0.46-0.93; P = .018). The low-expression (cutoff < 15%) TK1 group experienced a smaller OS benefit (9.3 vs. 7.4 months; hazard ratio - 0.88; 95% confidence interval, 0.63-1.23; P = .45). For patients who received placebo, the high-expression TK1 group had a slightly worse prognosis than the low-expression TK1 group. The tendency of FTD/TPI efficacy concerning progression-free survival and disease control rate was not similar to that concerning OS between groups. Conclusion: Patients with high TK1 expression showed an improvement in OS when treated with FTD/TPI. Further investigations are warranted to confirm this relationship. (C) 2018 The Authors. Published by Elsevier Inc.

引用

页码：E719 / E732

页数：14

共 50 条

[31] Safety of Bevacizumab in Treating Metastatic Colorectal Cancer: A Systematic Review and Meta-analysis of All Randomized Clinical Trials [J].

Dai, Fei ;

Shu, Lixing ;

Bian, Yangfang ;

Wang, Zhuo ;

Yang, Zhangwei ;

Chu, Wengong ;

Gao, Shen .

CLINICAL DRUG INVESTIGATION, 2013, 33 (11) :779-788

[32] Plasma thymidine kinase 1 activity and outcome of ER+HER2-metastatic breast cancer patients treated with palbociclib and endocrine therapy [J].

Cabel, Luc ;

Rosenblum, Dan ;

Lerebours, Florence ;

Brain, Etienne ;

Loirat, Delphine ;

Bergqvist, Mattias ;

Cottu, Paul ;

Donnadieu, Anne ;

Bethune, Anne ;

Kiavue, Nicolas ;

Rodrigues, Manuel ;

Pierga, Jean-Yves ;

Tanguy, Marie-Laure ;

Bidard, Francois-Clement .

BREAST CANCER RESEARCH, 2020, 22 (01)

[33] Safety and efficacy of panitumumab in combination with trifluridine/tipiracil for pre-treated patients with unresectable, metastatic colorectal cancer with wild-type RAS: The phase 1/2 APOLLON study [J].

Kato, Takeshi ;

Kagawa, Yoshinori ;

Kuboki, Yasutoshi ;

Gamoh, Makio ;

Komatsu, Yoshito ;

Yasui, Hirofumi ;

Satake, Hironaga ;

Oki, Eiji ;

Tanioka, Hiroaki ;

Kotaka, Masahito ;

Makiyama, Akitaka ;

Denda, Tadamichi ;

Goto, Masahiro ;

Yoshino, Takayuki ;

Yamazaki, Kentaro ;

Soeda, Junpei ;

Shibuya, Kazunori ;

Iwata, Masaru ;

Oba, Koji ;

Yamaguchi, Kensei .

INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY, 2021, 26 (07) :1238-1247

[34] Clinical outcome of panitumumab for metastatic colorectal cancer with wild-type KRAS status: a meta-analysis of randomized clinical trials [J].

Ibrahim, Ezzeldin M. ;

Abouelkhair, Khaled M. .

MEDICAL ONCOLOGY, 2011, 28 :S310-S317

[35] Correlation Between Imaging-Based Intermediate Endpoints and Overall Survival in Men With Metastatic Castration-Resistant Prostate Cancer: Analysis of 28 Randomized Trials Using the Prostate Cancer Clinical Trials Working Group (PCWG2) Criteria in 16,511 Patients [J].

Woo, Sungmin ;

Suh, Chong Hyun ;

Wibmer, Andreas G. ;

Becker, Anton S. ;

Teo, Min Yuen ;

Gonen, Mithat ;

Hricak, Hedvig ;

Scher, Howard, I ;

Morris, Michael J. ;

Vargas, Hebert Alberto .

CLINICAL GENITOURINARY CANCER, 2022, 20 (01) :69-79

[36] Efficacy of trifluridine and tipiracil (TAS-102) versus placebo, with supportive care, in a randomized, controlled trial of patients with metastatic colorectal cancer from Spain: results of a subgroup analysis of the phase 3 RECOURSE trial [J].

F. Longo-Muñoz ;

G. Argiles ;

J. Tabernero ;

A. Cervantes ;

C. Gravalos ;

C. Pericay ;

S. Gil-Calle ;

H. Mizuguchi ;

A. Carrato-Mena ;

M. L. Limón ;

R. Garcia-Carbonero .

Clinical and Translational Oncology, 2017, 19 :227-235

[37] Cetuximab-based therapy vs noncetuximab therapy in advanced or metastatic colorectal cancer: a meta-analysis of seven randomized controlled trials [J].

Liu, L. ;

Cao, Y. ;

Tan, A. ;

Liao, C. ;

Mo, Z. ;

Gao, F. .

COLORECTAL DISEASE, 2010, 12 (05) :399-406

[38] Role of Anti-Epidermal Growth Factor Receptor Therapy Compared with Anti-Vascular Endothelial Growth Factor Therapy for Metastatic Colorectal Cancer: an Update Meta-Analysis of Randomized Clinical Trials [J].

Wang, Jian-Xiang ;

Wu, Hai-Long ;

Zhu, Meng ;

Zhou, Rui .

PATHOLOGY & ONCOLOGY RESEARCH, 2020, 26 (01) :159-166

[39] Association of Circulating Tumor Cells and Tumor Molecular Profile With Clinical Outcomes in Patients With Previously Untreated Metastatic Colorectal Cancer: A Pooled Analysis of the Phase III VISNu-1 and Phase II VISNu-2 Randomized Trials [J].

Jimenez-Fonseca, P. ;

Sastre, J. ;

Garcia-Alfonso, P. ;

Gomez-Espana, M. A. ;

Salud, A. ;

Gil, S. ;

Rivera, F. ;

Reina, J. J. ;

Quintero, G. ;

Valladares-Ayerbes, M. ;

Safont, M. J. ;

La Casta, A. ;

Robles-Diaz, L. ;

Garcia-Paredes, B. ;

Lopez, R. Lopez ;

Guillot, M. ;

Gallego, J. ;

Alonso-Orduna, V. ;

Diaz-Rubio, E. ;

Aranda, E. .

CLINICAL COLORECTAL CANCER, 2023, 22 (02) :222-230

[40] TK-1, TP, Ang-2, and Tie-2 mRNA expression in plasma-derived microvesicles of chemo-refractory metastatic colorectal cancer patients [J].

Borelli, Beatrice ;

Crucitta, Stefania ;

Boccaccino, Alessandra ;

Antista, Maria ;

Antoniotti, Carlotta ;

Marmorino, Federica ;

Rossini, Daniele ;

Conca, Veronica ;

Germani, Marco Maria ;

Provenzano, Leonardo ;

Spagnoletti, Andrea ;

Leone, Alberto Giovanni ;

Cucchiara, Federico ;

Pietrantonio, Filippo ;

Del Re, Marzia ;

Danesi, Romano ;

Masi, Gianluca ;

Cremolini, Chiara ;

Moretto, Roberto .

TUMORI JOURNAL, 2023, 109 (05) :481-489

← 1 2 3 4 5 →