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Real-World Activity and Safety of Trifluridine-Tipiracil Plus Bevacizumab Therapy in Patients with Refractory Metastatic Colorectal Cancer

BACKGROUND: The combination of trifluridine-tipiracil and bevacizumab was compared with trifluridine-tipiracil monotherapy in a randomized, open-label, phase II trial, resulting in a statistically significant and clinically relevant improvement in progression-free survival (PFS), with tolerable toxi...

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Autores principales: Arrichiello, Gianluca, Perrone, Alessandra, Napolitano, Stefania, Martini, Giulia, De Falco, Vincenzo, Incoronato, Pasquale, Laterza, Maria Maddalena, Facchini, Gaetano, Famiglietti, Vincenzo, Nacca, Valeria, Paragliola, Fernando, Napolitano, Rossella, Suarato, Gabriella, Nicastro, Antonella, Martinelli, Erika, Ciardiello, Davide, Ciardiello, Fortunato, Troiani, Teresa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9684226/
https://www.ncbi.nlm.nih.gov/pubmed/36239883
http://dx.doi.org/10.1007/s11523-022-00916-8
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author Arrichiello, Gianluca
Perrone, Alessandra
Napolitano, Stefania
Martini, Giulia
De Falco, Vincenzo
Incoronato, Pasquale
Laterza, Maria Maddalena
Facchini, Gaetano
Famiglietti, Vincenzo
Nacca, Valeria
Paragliola, Fernando
Napolitano, Rossella
Suarato, Gabriella
Nicastro, Antonella
Martinelli, Erika
Ciardiello, Davide
Ciardiello, Fortunato
Troiani, Teresa
author_facet Arrichiello, Gianluca
Perrone, Alessandra
Napolitano, Stefania
Martini, Giulia
De Falco, Vincenzo
Incoronato, Pasquale
Laterza, Maria Maddalena
Facchini, Gaetano
Famiglietti, Vincenzo
Nacca, Valeria
Paragliola, Fernando
Napolitano, Rossella
Suarato, Gabriella
Nicastro, Antonella
Martinelli, Erika
Ciardiello, Davide
Ciardiello, Fortunato
Troiani, Teresa
author_sort Arrichiello, Gianluca
collection PubMed
description BACKGROUND: The combination of trifluridine-tipiracil and bevacizumab was compared with trifluridine-tipiracil monotherapy in a randomized, open-label, phase II trial, resulting in a statistically significant and clinically relevant improvement in progression-free survival (PFS), with tolerable toxicity in patients with refractory metastatic colorectal cancer (mCRC); however, evidence supporting the role of this combination in a real-world setting is limited. OBJECTIVE: The aim of our work was to provide further evidence on the activity and safety of this combination in a real-world series of Western mCRC patients refractory or intolerant to previous therapies. PATIENT AND METHODS: We conducted a retrospective, observational study of patients with mCRC refractory or intolerant to standard therapies. Patients were treated with trifluridine-tipiracil and bevacizumab. Previous therapy with fluoropyrimidines, irinotecan, oxaliplatin, bevacizumab, aflibercept, regorafenib, and cetuximab or panitumumab (only RAS wild-type) was allowed, as was previous participation in clinical trials. Clinicopathological characteristics, overall response rate (ORR), disease control rate (DCR), overall survival (OS), PFS, and safety data were retrospectively collected and analyzed. RESULTS: We recorded 31 patients treated between 1 December 2017 and 30 June 2022. Median age was 69 years (range 38–82 years), 39% were male, 100% had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0–1, tumor location was left-sided in 77% of cases, 54% had synchronous presentation, 35% were RAS mutant, 3% were BRAF mutant, and 71% underwent primary tumor resection; 64% of patients had liver metastases, 55% had lung metastases, and 23% had peritoneal carcinomatosis. The median number of previous treatment lines was 2 (range 0–5), and 84% of patients received at least one previous anti-angiogenic agent. The ORR and DCR were 3% and 71%, respectively. With a median follow-up of 8 months (range 2–39), median PFS was 6 months (95% confidence interval [CI] 3.1–8.9 months) and median OS was 14 months (95% CI 10.1–17.8 months). Adverse events of any grade were reported in 58% of patients. The most common grade 3–4 toxicities were neutropenia (19%) and anemia (6%); 35% of patients required either dose delays or dose reductions due to toxicity. Granulocyte colony-stimulating factor (G-CSF) prophylaxis was administered either on first or subsequent cycles of treatment in 35% of patients. No treatment-related deaths occurred. Sixty percent of the patients who discontinued treatment eventually received one or more lines of subsequent therapy. CONCLUSIONS: Our series provides further evidence on the activity and safety of the combination of trifluridine-tipiracil and bevacizumab in a real-world series of Western refractory mCRC patients.
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spelling pubmed-96842262022-11-25 Real-World Activity and Safety of Trifluridine-Tipiracil Plus Bevacizumab Therapy in Patients with Refractory Metastatic Colorectal Cancer Arrichiello, Gianluca Perrone, Alessandra Napolitano, Stefania Martini, Giulia De Falco, Vincenzo Incoronato, Pasquale Laterza, Maria Maddalena Facchini, Gaetano Famiglietti, Vincenzo Nacca, Valeria Paragliola, Fernando Napolitano, Rossella Suarato, Gabriella Nicastro, Antonella Martinelli, Erika Ciardiello, Davide Ciardiello, Fortunato Troiani, Teresa Target Oncol Original Research Article BACKGROUND: The combination of trifluridine-tipiracil and bevacizumab was compared with trifluridine-tipiracil monotherapy in a randomized, open-label, phase II trial, resulting in a statistically significant and clinically relevant improvement in progression-free survival (PFS), with tolerable toxicity in patients with refractory metastatic colorectal cancer (mCRC); however, evidence supporting the role of this combination in a real-world setting is limited. OBJECTIVE: The aim of our work was to provide further evidence on the activity and safety of this combination in a real-world series of Western mCRC patients refractory or intolerant to previous therapies. PATIENT AND METHODS: We conducted a retrospective, observational study of patients with mCRC refractory or intolerant to standard therapies. Patients were treated with trifluridine-tipiracil and bevacizumab. Previous therapy with fluoropyrimidines, irinotecan, oxaliplatin, bevacizumab, aflibercept, regorafenib, and cetuximab or panitumumab (only RAS wild-type) was allowed, as was previous participation in clinical trials. Clinicopathological characteristics, overall response rate (ORR), disease control rate (DCR), overall survival (OS), PFS, and safety data were retrospectively collected and analyzed. RESULTS: We recorded 31 patients treated between 1 December 2017 and 30 June 2022. Median age was 69 years (range 38–82 years), 39% were male, 100% had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0–1, tumor location was left-sided in 77% of cases, 54% had synchronous presentation, 35% were RAS mutant, 3% were BRAF mutant, and 71% underwent primary tumor resection; 64% of patients had liver metastases, 55% had lung metastases, and 23% had peritoneal carcinomatosis. The median number of previous treatment lines was 2 (range 0–5), and 84% of patients received at least one previous anti-angiogenic agent. The ORR and DCR were 3% and 71%, respectively. With a median follow-up of 8 months (range 2–39), median PFS was 6 months (95% confidence interval [CI] 3.1–8.9 months) and median OS was 14 months (95% CI 10.1–17.8 months). Adverse events of any grade were reported in 58% of patients. The most common grade 3–4 toxicities were neutropenia (19%) and anemia (6%); 35% of patients required either dose delays or dose reductions due to toxicity. Granulocyte colony-stimulating factor (G-CSF) prophylaxis was administered either on first or subsequent cycles of treatment in 35% of patients. No treatment-related deaths occurred. Sixty percent of the patients who discontinued treatment eventually received one or more lines of subsequent therapy. CONCLUSIONS: Our series provides further evidence on the activity and safety of the combination of trifluridine-tipiracil and bevacizumab in a real-world series of Western refractory mCRC patients. Springer International Publishing 2022-10-14 2022 /pmc/articles/PMC9684226/ /pubmed/36239883 http://dx.doi.org/10.1007/s11523-022-00916-8 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by-nc/4.0/Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Original Research Article
Arrichiello, Gianluca
Perrone, Alessandra
Napolitano, Stefania
Martini, Giulia
De Falco, Vincenzo
Incoronato, Pasquale
Laterza, Maria Maddalena
Facchini, Gaetano
Famiglietti, Vincenzo
Nacca, Valeria
Paragliola, Fernando
Napolitano, Rossella
Suarato, Gabriella
Nicastro, Antonella
Martinelli, Erika
Ciardiello, Davide
Ciardiello, Fortunato
Troiani, Teresa
Real-World Activity and Safety of Trifluridine-Tipiracil Plus Bevacizumab Therapy in Patients with Refractory Metastatic Colorectal Cancer
title Real-World Activity and Safety of Trifluridine-Tipiracil Plus Bevacizumab Therapy in Patients with Refractory Metastatic Colorectal Cancer
title_full Real-World Activity and Safety of Trifluridine-Tipiracil Plus Bevacizumab Therapy in Patients with Refractory Metastatic Colorectal Cancer
title_fullStr Real-World Activity and Safety of Trifluridine-Tipiracil Plus Bevacizumab Therapy in Patients with Refractory Metastatic Colorectal Cancer
title_full_unstemmed Real-World Activity and Safety of Trifluridine-Tipiracil Plus Bevacizumab Therapy in Patients with Refractory Metastatic Colorectal Cancer
title_short Real-World Activity and Safety of Trifluridine-Tipiracil Plus Bevacizumab Therapy in Patients with Refractory Metastatic Colorectal Cancer
title_sort real-world activity and safety of trifluridine-tipiracil plus bevacizumab therapy in patients with refractory metastatic colorectal cancer
topic Original Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9684226/
https://www.ncbi.nlm.nih.gov/pubmed/36239883
http://dx.doi.org/10.1007/s11523-022-00916-8
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