TY - JOUR
T1 - Trifluridine/Tipiracil in Metastatic Colorectal Cancer
T2 - A UK Multicenter Real-world Analysis on Efficacy, Safety, Predictive and Prognostic Factors
AU - Stavraka, Chara
AU - Pouptsis, Athanasios
AU - Synowiec, Alicja
AU - Angelis, Vasileios
AU - Satterthwaite, Liyana
AU - Khan, Sam
AU - Chauhan, Meera
AU - Holden, Chloe
AU - Young, Sally
AU - Karampera, Christina
AU - Martinou, Maria
AU - Mills-Baldock, Tina
AU - Baxter, Mark
AU - Barry, Ainsley
AU - Eccles, Bryony
AU - Iveson, Timothy
AU - Shiu, Kai-Keen
AU - Hill, Mark
AU - Abdel-Raouf, Sherif
AU - Graham, Janet Shirley
AU - Thomas, Anne
AU - Ross, Paul J.
N1 - Copyright:
© 2021 Elsevier Inc. All rights reserved.
PY - 2021/12/1
Y1 - 2021/12/1
N2 - Background: The orally administered combination trifluridine/tipiracil has been approved as third line treatment in mCRC, demonstrating survival benefit and acceptable toxicity profile in the phase III RECOURSE study.Patient and methods: We performed a multicenter retrospective real-world analysis of patients with mCRC receiving trifluridine/tipiracil between 2016 and 2019 in eight cancer centers across the United Kingdom.Results: A total of 236 patients were included with median age of 69 years. All patients had received at least 2 lines of fluoropyrimidine-based chemotherapy doublet with oxaliplatin or irinotecan. About 10% of patients had ECOG ≥ 2. Median duration of trifluridine/tipiracil treatment was 3 months with an ORR of 2.1% and disease control rate of 21.6%. Median OS was 7.6 and median PFS 3.3 months. A dose reduction was required in 27% of patients, while 7.6% discontinued treatment due to toxicity. The most common grade 3 toxicities were neutropenia (34%), fatigue (10%), anemia (9%) and febrile neutropenia (5%). Baseline NLR <5 and CEA <200 had favorable prognostic (HR: 0.52 and 0.39, P≤ .001) and predictive value (OR: 4.1 and 6.7, P< .05). Development of grade 3 neutropenia predicted treatment response (OR: 0.32, P< .001). Following treatment with trifluridine/tipiracil 41% were referred for phase I trial or rechallenged with chemotherapy.Conclusion: Trifluridine/tipiracil is well tolerated in refractory mCRC patients with comparable efficacy and toxicity profile to that of the phase III RECOURSE. Pretreatment NLR and CEA could serve as potential markers for patient selection, while treatment-induced grade 3 neutropenia predicted response. Prospective validation is needed.
AB - Background: The orally administered combination trifluridine/tipiracil has been approved as third line treatment in mCRC, demonstrating survival benefit and acceptable toxicity profile in the phase III RECOURSE study.Patient and methods: We performed a multicenter retrospective real-world analysis of patients with mCRC receiving trifluridine/tipiracil between 2016 and 2019 in eight cancer centers across the United Kingdom.Results: A total of 236 patients were included with median age of 69 years. All patients had received at least 2 lines of fluoropyrimidine-based chemotherapy doublet with oxaliplatin or irinotecan. About 10% of patients had ECOG ≥ 2. Median duration of trifluridine/tipiracil treatment was 3 months with an ORR of 2.1% and disease control rate of 21.6%. Median OS was 7.6 and median PFS 3.3 months. A dose reduction was required in 27% of patients, while 7.6% discontinued treatment due to toxicity. The most common grade 3 toxicities were neutropenia (34%), fatigue (10%), anemia (9%) and febrile neutropenia (5%). Baseline NLR <5 and CEA <200 had favorable prognostic (HR: 0.52 and 0.39, P≤ .001) and predictive value (OR: 4.1 and 6.7, P< .05). Development of grade 3 neutropenia predicted treatment response (OR: 0.32, P< .001). Following treatment with trifluridine/tipiracil 41% were referred for phase I trial or rechallenged with chemotherapy.Conclusion: Trifluridine/tipiracil is well tolerated in refractory mCRC patients with comparable efficacy and toxicity profile to that of the phase III RECOURSE. Pretreatment NLR and CEA could serve as potential markers for patient selection, while treatment-induced grade 3 neutropenia predicted response. Prospective validation is needed.
KW - Lonsurf
KW - Neutropenia
KW - Real-world evidence
KW - TAS-102
KW - Treatment outcomes
UR - http://www.scopus.com/inward/record.url?scp=85118639360&partnerID=8YFLogxK
U2 - 10.1016/j.clcc.2021.09.009
DO - 10.1016/j.clcc.2021.09.009
M3 - Article
C2 - 34696965
SN - 1533-0028
VL - 20
SP - 342
EP - 349
JO - Clinical Colorectal Cancer
JF - Clinical Colorectal Cancer
IS - 4
ER -