Pooled safety analysis from phase III studies of trifluridine/tipiracil in patients with metastatic gastric or gastroesophageal junction cancer and metastatic colorectal cancer.
Adult
Humans
Trifluridine
/ adverse effects
Colorectal Neoplasms
/ drug therapy
Frontotemporal Dementia
/ chemically induced
Uracil
/ adverse effects
Thymine
/ adverse effects
Pyrrolidines
/ adverse effects
Colonic Neoplasms
/ drug therapy
Stomach Neoplasms
/ drug therapy
Esophagogastric Junction
/ pathology
Neutropenia
/ chemically induced
metastatic colorectal cancer
metastatic gastric cancer
neutropenia
renal impairment
safety
trifluridine/tipiracil
Journal
ESMO open
ISSN: 2059-7029
Titre abrégé: ESMO Open
Pays: England
ID NLM: 101690685
Informations de publication
Date de publication:
12 2022
12 2022
Historique:
received:
10
08
2022
revised:
12
10
2022
accepted:
13
10
2022
pubmed:
2
12
2022
medline:
28
12
2022
entrez:
1
12
2022
Statut:
ppublish
Résumé
Trifluridine/tipiracil (FTD/TPI) showed clinical benefit, including improved survival and manageable safety in previously treated patients with metastatic colorectal (mCRC) or gastric/gastroesophageal junction (mGC/GEJC) cancer in the phase III RECOURSE and TAGS trials, respectively. A pooled analysis was conducted to further characterize FTD/TPI safety, including management of haematologic toxicities and use in patients with renal or hepatic impairment. Adults with ≥2 prior regimens for advanced mGC/GEJC or mCRC were randomized (2 : 1) to FTD/TPI [35 mg/m TAGS and RECOURSE included 335 and 533 FTD/TPI-treated and 168 and 265 placebo-treated patients, respectively. Overall safety of FTD/TPI was similar in TAGS and RECOURSE. Haematologic (neutropenia, anaemia) and gastrointestinal (nausea, diarrhoea) AEs were most commonly observed. Laboratory-assessed grade 3-4 neutropenia occurred in 37% (TAGS)/38% (RECOURSE) of FTD/TPI-treated patients (median onset: 29 days/55 days), and 96% (TAGS)/97% (RECOURSE) of cases resolved regardless of renal/hepatic function. Supportive medications for neutropenia were received by 17% (TAGS) and 9% (RECOURSE); febrile neutropenia was reported in 2% and 4%, respectively. Overall grade ≥3 AEs were more frequent in patients with moderate renal impairment [81% (TAGS); 85% (RECOURSE)] versus normal renal function (74%; 67%); anaemia and neutropenia were more common in patients with renal impairment. FTD/TPI safety (including haematologic AEs) was consistent across patients with normal and mildly impaired hepatic function. These results support FTD/TPI as a well-tolerated treatment in patients with mGC/GEJC or mCRC, with a consistent safety profile. Safety was largely similar in patients with normal or mildly impaired renal/hepatic function; however, patients with renal impairment should be monitored for haematologic toxicities.
Sections du résumé
BACKGROUND
Trifluridine/tipiracil (FTD/TPI) showed clinical benefit, including improved survival and manageable safety in previously treated patients with metastatic colorectal (mCRC) or gastric/gastroesophageal junction (mGC/GEJC) cancer in the phase III RECOURSE and TAGS trials, respectively. A pooled analysis was conducted to further characterize FTD/TPI safety, including management of haematologic toxicities and use in patients with renal or hepatic impairment.
PATIENTS AND METHODS
Adults with ≥2 prior regimens for advanced mGC/GEJC or mCRC were randomized (2 : 1) to FTD/TPI [35 mg/m
RESULTS
TAGS and RECOURSE included 335 and 533 FTD/TPI-treated and 168 and 265 placebo-treated patients, respectively. Overall safety of FTD/TPI was similar in TAGS and RECOURSE. Haematologic (neutropenia, anaemia) and gastrointestinal (nausea, diarrhoea) AEs were most commonly observed. Laboratory-assessed grade 3-4 neutropenia occurred in 37% (TAGS)/38% (RECOURSE) of FTD/TPI-treated patients (median onset: 29 days/55 days), and 96% (TAGS)/97% (RECOURSE) of cases resolved regardless of renal/hepatic function. Supportive medications for neutropenia were received by 17% (TAGS) and 9% (RECOURSE); febrile neutropenia was reported in 2% and 4%, respectively. Overall grade ≥3 AEs were more frequent in patients with moderate renal impairment [81% (TAGS); 85% (RECOURSE)] versus normal renal function (74%; 67%); anaemia and neutropenia were more common in patients with renal impairment. FTD/TPI safety (including haematologic AEs) was consistent across patients with normal and mildly impaired hepatic function.
CONCLUSIONS
These results support FTD/TPI as a well-tolerated treatment in patients with mGC/GEJC or mCRC, with a consistent safety profile. Safety was largely similar in patients with normal or mildly impaired renal/hepatic function; however, patients with renal impairment should be monitored for haematologic toxicities.
Identifiants
pubmed: 36455504
pii: S2059-7029(22)00267-8
doi: 10.1016/j.esmoop.2022.100633
pmc: PMC9808443
pii:
doi:
Substances chimiques
tipiracil
NGO10K751P
Trifluridine
RMW9V5RW38
Uracil
56HH86ZVCT
Thymine
QR26YLT7LT
Pyrrolidines
0
Types de publication
Randomized Controlled Trial
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
100633Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Informations de copyright
Copyright © 2022. Published by Elsevier Ltd.
Références
Curr Oncol. 2019 Oct;26(5):319-329
pubmed: 31708650
Ther Adv Med Oncol. 2018 Jun 18;10:1758835918780140
pubmed: 29977352
J Clin Oncol. 2016 Jul 10;34(20):2428
pubmed: 27185847
Lancet Oncol. 2018 Nov;19(11):1437-1448
pubmed: 30355453
Eur J Cancer. 2016 Jul;62:46-53
pubmed: 27208903
Tumori. 1982 Dec 31;68(6):505-10
pubmed: 7168016
Int J Oncol. 2004 Sep;25(3):571-8
pubmed: 15289858
Am J Cancer Res. 2021 Jul 15;11(7):3461-3474
pubmed: 34354855
Biochem Pharmacol. 2000 May 15;59(10):1227-36
pubmed: 10736423
Cancer Treat Rev. 2015 Nov;41(9):777-83
pubmed: 26428513
Nat Rev Cancer. 2003 May;3(5):330-8
pubmed: 12724731
Future Oncol. 2018 Jul;14(16):1629-1645
pubmed: 29701076
Ann Oncol. 2016 Aug;27(8):1386-422
pubmed: 27380959
Cancer. 2007 Sep 15;110(6):1376-84
pubmed: 17634949
Clin Colorectal Cancer. 2016 Dec;15(4):e205-e211
pubmed: 27324983
Int J Clin Oncol. 2018 Jun;23(3):482-489
pubmed: 29204933
Ann Oncol. 2016 Sep;27(suppl 5):v38-v49
pubmed: 27664260
Lancet Oncol. 2012 Oct;13(10):993-1001
pubmed: 22951287
Ann Oncol. 2020 Jan;31(1):88-95
pubmed: 31912801
Cancer Chemother Pharmacol. 2020 Sep;86(3):427-433
pubmed: 32816155
BMC Cancer. 2016 Jul 13;16:467
pubmed: 27412464
Cochrane Database Syst Rev. 2017 Aug 29;8:CD004064
pubmed: 28850174
Cancer Treat Rev. 2013 Dec;39(8):974-84
pubmed: 23582737
Oncology (Williston Park). 2005 Jul;19(8):1057-63; discussion 1063-4, 1069
pubmed: 16131047
Curr Treat Options Oncol. 2020 Mar 19;21(4):27
pubmed: 32266582
Br J Clin Pharmacol. 2019 Jun;85(6):1239-1246
pubmed: 30628113
Cancer Chemother Pharmacol. 2021 Sep;88(3):485-497
pubmed: 34097100
Oncologist. 2001;6(2):162-76
pubmed: 11306728
N Engl J Med. 2015 May 14;372(20):1909-19
pubmed: 25970050
Int J Mol Med. 2004 Apr;13(4):545-9
pubmed: 15010854