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Trifluridine/Tipiracil in metastatic colorectal cancer: A UK multicenter real-world analysis on efficacy, safety, predictive and prognostic factors

Trifluridine/Tipiracil in metastatic colorectal cancer: A UK multicenter real-world analysis on efficacy, safety, predictive and prognostic factors
Trifluridine/Tipiracil in metastatic colorectal cancer: A UK multicenter real-world analysis on efficacy, safety, predictive and prognostic factors

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.

Lonsurf, Neutropenia, Real-world evidence, TAS-102, Treatment outcomes
1533-0028
342-349
Stavraka, Chara
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Pouptsis, Athanasios
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Synowiec, Alicja
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Angelis, Vasileios
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Satterthwaite, Liyana
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Khan, Sam
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Chauhan, Meera
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Holden, Chloe
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Young, Sally
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Karampera, Christina
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Martinou, Maria
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Mills-Baldock, Tina
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Baxter, Mark
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Barry, Ainsley
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Eccles, Bryony
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Iveson, Timothy
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Shiu, Kai-Keen
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Hill, Mark
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Abdel-Raouf, Sherif
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Graham, Janet Shirley
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Thomas, Anne
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Ross, Paul J
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Stavraka, Chara
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Pouptsis, Athanasios
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Synowiec, Alicja
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Angelis, Vasileios
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Satterthwaite, Liyana
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Khan, Sam
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Chauhan, Meera
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Holden, Chloe
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Young, Sally
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Karampera, Christina
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Martinou, Maria
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Mills-Baldock, Tina
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Baxter, Mark
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Barry, Ainsley
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Eccles, Bryony
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Iveson, Timothy
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Shiu, Kai-Keen
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Hill, Mark
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Abdel-Raouf, Sherif
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Graham, Janet Shirley
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Thomas, Anne
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Ross, Paul J
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Stavraka, Chara, Pouptsis, Athanasios, Synowiec, Alicja, Angelis, Vasileios, Satterthwaite, Liyana, Khan, Sam, Chauhan, Meera, Holden, Chloe, Young, Sally, Karampera, Christina, Martinou, Maria, Mills-Baldock, Tina, Baxter, Mark, Barry, Ainsley, Eccles, Bryony, Iveson, Timothy, Shiu, Kai-Keen, Hill, Mark, Abdel-Raouf, Sherif, Graham, Janet Shirley, Thomas, Anne and Ross, Paul J (2021) Trifluridine/Tipiracil in metastatic colorectal cancer: A UK multicenter real-world analysis on efficacy, safety, predictive and prognostic factors. Clinical Colorectal Cancer, 20 (4), 342-349. (doi:10.1016/j.clcc.2021.09.009).

Record type: Article

Abstract

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.

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More information

e-pub ahead of print date: 26 September 2021
Published date: December 2021
Keywords: Lonsurf, Neutropenia, Real-world evidence, TAS-102, Treatment outcomes

Identifiers

Local EPrints ID: 453021
URI: http://eprints.soton.ac.uk/id/eprint/453021
ISSN: 1533-0028
PURE UUID: ac982445-2bdc-4b05-b2c9-4922a70508a5
ORCID for Timothy Iveson: ORCID iD orcid.org/0000-0002-4681-2712

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Date deposited: 07 Jan 2022 17:05
Last modified: 17 Mar 2024 02:45

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Contributors

Author: Chara Stavraka
Author: Athanasios Pouptsis
Author: Alicja Synowiec
Author: Vasileios Angelis
Author: Liyana Satterthwaite
Author: Sam Khan
Author: Meera Chauhan
Author: Chloe Holden
Author: Sally Young
Author: Christina Karampera
Author: Maria Martinou
Author: Tina Mills-Baldock
Author: Mark Baxter
Author: Ainsley Barry
Author: Bryony Eccles
Author: Timothy Iveson ORCID iD
Author: Kai-Keen Shiu
Author: Mark Hill
Author: Sherif Abdel-Raouf
Author: Janet Shirley Graham
Author: Anne Thomas
Author: Paul J Ross

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