Trifluridine/tipiracil (TAS-102) is a newer generation chemotherapy that has been approved for the later-line treatment of metastatic colorectal and gastric/gastroesophageal adenocarcinomas. The oral drug provides a modest benefit of prolongation of survival over placebo in pretreated patients with these cancers with acceptable toxicity. Studies have shown rare objective responses (2-4%), and the disease control rates were 44% in both colorectal and gastric cancer randomized trials. Thus, the majority of patients progress through treatment and are burdened by toxicities. To better characterize the sub-group of patients with a higher probability of benefit from trifluridine/tipiracil, predictive biomarkers have been sought using data from randomized trials as well as from non-randomized trials and real-world series. Biomarkers examined include clinical characteristics of the patients, laboratory tests, and tumor derived biomarkers. These studies show that early neutropenia on treatment, and ratios of leukocyte subsets, are potential biomarkers able to predict trifluridine/tipiracil benefit. Combinations of laboratory values and clinical characteristics and proteins involved in trifluridine transport and activation have been examined with initial positive results.
Clin Colorectal Cancer. 2017 Mar;16(1):51-57
[PMID:
27522626]
Oncol Rep. 2014 Dec;32(6):2319-26
[PMID:
25230742]
Ann Oncol. 2020 Jan;31(1):88-95
[PMID:
31912801]
Eur J Cancer. 2016 Jul;62:46-53
[PMID:
27208903]
Anticancer Res. 2021 Jun;41(6):3131-3137
[PMID:
34083307]
Lancet Oncol. 2012 Dec;13(12):e518-9
[PMID:
23182191]
Eur J Cancer. 2017 Nov;86:197-206
[PMID:
28992563]
Ann Oncol. 2020 Sep;31(9):1160-1168
[PMID:
32497736]
N Engl J Med. 2015 May 14;372(20):1909-19
[PMID:
25970050]
Lancet Oncol. 2012 Oct;13(10):993-1001
[PMID:
22951287]
J Clin Oncol. 2018 Feb 1;36(4):350-358
[PMID:
29215955]
Gastric Cancer. 2021 Jul;24(4):970-977
[PMID:
33713215]
Br J Cancer. 2003 Mar 24;88(6):957-64
[PMID:
12644837]
Lancet Oncol. 2020 Mar;21(3):412-420
[PMID:
31999946]
Sci Rep. 2019 May 28;9(1):7964
[PMID:
31138881]
Onco Targets Ther. 2020 Jul 30;13:7459-7465
[PMID:
32801768]
Biopharm Drug Dispos. 2018 Jan;39(1):38-46
[PMID:
29055025]
J Gastrointest Cancer. 2019 Sep;50(3):493-506
[PMID:
29704170]
Lancet Oncol. 2018 Nov;19(11):1437-1448
[PMID:
30355453]
Cancer Chemother Pharmacol. 2020 Jun;85(6):1029-1038
[PMID:
32322913]
J Pharm Sci. 2015 Sep;104(9):3146-53
[PMID:
25900515]
Clin Cancer Res. 2017 Jun 15;23(12):2924-2927
[PMID:
28213365]
Cancer Manag Res. 2017 Oct 03;9:461-469
[PMID:
29056855]
Clin Colorectal Cancer. 2018 Dec;17(4):e687-e697
[PMID:
30149986]
Cancers (Basel). 2021 Sep 08;13(18):
[PMID:
34572740]
BMC Cancer. 2016 Jul 13;16:467
[PMID:
27412464]
Anticancer Res. 2019 Aug;39(8):4343-4350
[PMID:
31366528]
Int J Oncol. 2004 Sep;25(3):571-8
[PMID:
15289858]
CA Cancer J Clin. 2021 Jan;71(1):7-33
[PMID:
33433946]
Mol Cancer Ther. 2010 Apr;9(4):1047-57
[PMID:
20371715]
Drugs. 2016 Sep;76(14):1393-402
[PMID:
27568360]
Acta Oncol. 2019 Aug;58(8):1149-1157
[PMID:
31002008]
J Cell Mol Med. 2007 Mar-Apr;11(2):252-85
[PMID:
17488476]
JAMA Oncol. 2020 Jan 1;6(1):e193531
[PMID:
31600365]
Anticancer Drugs. 2005 Mar;16(3):285-92
[PMID:
15711180]
Front Oncol. 2021 Jun 15;11:688709
[PMID:
34211856]
Int J Oncol. 2015;46(6):2327-34
[PMID:
25901475]
Int J Clin Oncol. 2020 Apr;25(4):614-621
[PMID:
31838590]
Oncologist. 2018 Jan;23(1):7-15
[PMID:
28894015]
Oncol Rep. 2004 Feb;11(2):381-7
[PMID:
14719072]
Mol Cancer Res. 2018 Oct;16(10):1483-1490
[PMID:
29866926]
Oncotarget. 2017 Nov 15;9(14):11477-11488
[PMID:
29545913]
Future Oncol. 2016 Jan;12(2):153-63
[PMID:
26616466]
Ann Oncol. 2016 Aug;27(8):1386-422
[PMID:
27380959]
Clin Colorectal Cancer. 2018 Dec;17(4):e719-e732
[PMID:
30172759]
World J Gastrointest Oncol. 2011 Nov 15;3(11):153-64
[PMID:
22110842]
Med Res Rev. 2009 Nov;29(6):903-53
[PMID:
19434693]
Oncol Lett. 2021 Nov;22(5):783
[PMID:
34594424]
Cancer Chemother Pharmacol. 2016 Mar;77(3):515-26
[PMID:
26787503]
