Trifluridine/Tipiracil (TAS-102) in Refractory Metastatic Colorectal Cancer

A Multicenter Register in the Frame of the Italian Compassionate Use Program

Chiara Cremolini, Daniele Rossini, Erika Martinelli, Filippo Pietrantonio, Sara Lonardi, Silvia Noventa, Emiliano Tamburini, Giovanni Luca Frassineti, Stefania Mosconi, Federico Nichetti, Sabina Murgioni, Teresa Troiani, Beatrice Borelli, Gemma Zucchelli, Alessandro Dal Maso, Vincenzo Sforza, Gianluca Masi, Carlotta Antoniotti, Maria Di Bartolomeo, Rosalba Miceli & 2 others Fortunato Ciardiello, Alfredo Falcone

Research output: Contribution to journalArticle

Abstract

BACKGROUND: TAS-102 is indicated for patients with metastatic colorectal cancer (mCRC) previously treated with, or not considered candidates for, available therapies. Given the complete inefficacy in half of patients, the lack of predictive factors, the palliative setting, and the financial and clinical toxicity, optimizing the cost-benefit ratio is crucial. The "ColonLife" nomogram allows an estimate of the 12-week life expectancy of patients with refractory mCRC.

MATERIALS AND METHODS: We collected data from patients treated at eight Italian centers in the compassionate use program. Baseline characteristics of patients who were or were not progression free at 6 months were compared. The discriminative ability of the ColonLife nomogram was assessed. Among patients who received both TAS-102 and regorafenib, clinical outcomes of the two sequences were compared.

RESULTS: This study included 341 patients. Six (2%) and 93 (27%) patients achieved response and disease stabilization, respectively. The median progression-free survival (PFS) was 2.4 months with an estimated 6-month PFS rate of 19%; the median overall survival (OS) was 6.2 months. An Eastern Cooperative Oncology Group performance status (ECOG PS) of 0, normal lactate dehydrogenase (LDH), and a time from the diagnosis of metastatic disease of >18 months were independently associated with higher chances of a patient being progression free at 6 months. The discriminative ability of ColonLife was confirmed. Among 121 patients who received both regorafenib and TAS-102, no differences in first or second PFS or OS were reported between the two sequences.

CONCLUSION: One out of five patients achieves clinical benefit with TAS-102. ECOG PS, LDH, and time from diagnosis of metastatic disease may help to identify these patients. Excluding patients with very short life expectancy appears a reasonable approach.

IMPLICATIONS FOR PRACTICE: Improving the cost-efficacy ratio of TAS-102 in metastatic colorectal cancer is needed to spare useless toxicities in a definitely palliative setting. Eastern Cooperative Oncology Group performance status, lactate dehydrogenase levels, and time from the diagnosis of metastatic disease may help to identify patients more likely to achieve benefit. Properly designed prognostic tools (i.e., the "ColonLife" nomogram) may enable excluding from further treatments patients with very limited life expectancy.

Original languageEnglish
Pages (from-to)1178-1187
Number of pages10
JournalThe oncologist
Volume23
Issue number10
DOIs
Publication statusPublished - Oct 2018

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Trifluridine
Compassionate Use Trials
Colorectal Neoplasms
Nomograms
Life Expectancy
L-Lactate Dehydrogenase
Disease-Free Survival
TAS 102

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Trifluridine/Tipiracil (TAS-102) in Refractory Metastatic Colorectal Cancer : A Multicenter Register in the Frame of the Italian Compassionate Use Program. / Cremolini, Chiara; Rossini, Daniele; Martinelli, Erika; Pietrantonio, Filippo; Lonardi, Sara; Noventa, Silvia; Tamburini, Emiliano; Frassineti, Giovanni Luca; Mosconi, Stefania; Nichetti, Federico; Murgioni, Sabina; Troiani, Teresa; Borelli, Beatrice; Zucchelli, Gemma; Dal Maso, Alessandro; Sforza, Vincenzo; Masi, Gianluca; Antoniotti, Carlotta; Di Bartolomeo, Maria; Miceli, Rosalba; Ciardiello, Fortunato; Falcone, Alfredo.

In: The oncologist, Vol. 23, No. 10, 10.2018, p. 1178-1187.

Research output: Contribution to journalArticle

Cremolini, C, Rossini, D, Martinelli, E, Pietrantonio, F, Lonardi, S, Noventa, S, Tamburini, E, Frassineti, GL, Mosconi, S, Nichetti, F, Murgioni, S, Troiani, T, Borelli, B, Zucchelli, G, Dal Maso, A, Sforza, V, Masi, G, Antoniotti, C, Di Bartolomeo, M, Miceli, R, Ciardiello, F & Falcone, A 2018, 'Trifluridine/Tipiracil (TAS-102) in Refractory Metastatic Colorectal Cancer: A Multicenter Register in the Frame of the Italian Compassionate Use Program', The oncologist, vol. 23, no. 10, pp. 1178-1187. https://doi.org/10.1634/theoncologist.2017-0573
Cremolini, Chiara ; Rossini, Daniele ; Martinelli, Erika ; Pietrantonio, Filippo ; Lonardi, Sara ; Noventa, Silvia ; Tamburini, Emiliano ; Frassineti, Giovanni Luca ; Mosconi, Stefania ; Nichetti, Federico ; Murgioni, Sabina ; Troiani, Teresa ; Borelli, Beatrice ; Zucchelli, Gemma ; Dal Maso, Alessandro ; Sforza, Vincenzo ; Masi, Gianluca ; Antoniotti, Carlotta ; Di Bartolomeo, Maria ; Miceli, Rosalba ; Ciardiello, Fortunato ; Falcone, Alfredo. / Trifluridine/Tipiracil (TAS-102) in Refractory Metastatic Colorectal Cancer : A Multicenter Register in the Frame of the Italian Compassionate Use Program. In: The oncologist. 2018 ; Vol. 23, No. 10. pp. 1178-1187.
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abstract = "BACKGROUND: TAS-102 is indicated for patients with metastatic colorectal cancer (mCRC) previously treated with, or not considered candidates for, available therapies. Given the complete inefficacy in half of patients, the lack of predictive factors, the palliative setting, and the financial and clinical toxicity, optimizing the cost-benefit ratio is crucial. The {"}ColonLife{"} nomogram allows an estimate of the 12-week life expectancy of patients with refractory mCRC.MATERIALS AND METHODS: We collected data from patients treated at eight Italian centers in the compassionate use program. Baseline characteristics of patients who were or were not progression free at 6 months were compared. The discriminative ability of the ColonLife nomogram was assessed. Among patients who received both TAS-102 and regorafenib, clinical outcomes of the two sequences were compared.RESULTS: This study included 341 patients. Six (2{\%}) and 93 (27{\%}) patients achieved response and disease stabilization, respectively. The median progression-free survival (PFS) was 2.4 months with an estimated 6-month PFS rate of 19{\%}; the median overall survival (OS) was 6.2 months. An Eastern Cooperative Oncology Group performance status (ECOG PS) of 0, normal lactate dehydrogenase (LDH), and a time from the diagnosis of metastatic disease of >18 months were independently associated with higher chances of a patient being progression free at 6 months. The discriminative ability of ColonLife was confirmed. Among 121 patients who received both regorafenib and TAS-102, no differences in first or second PFS or OS were reported between the two sequences.CONCLUSION: One out of five patients achieves clinical benefit with TAS-102. ECOG PS, LDH, and time from diagnosis of metastatic disease may help to identify these patients. Excluding patients with very short life expectancy appears a reasonable approach.IMPLICATIONS FOR PRACTICE: Improving the cost-efficacy ratio of TAS-102 in metastatic colorectal cancer is needed to spare useless toxicities in a definitely palliative setting. Eastern Cooperative Oncology Group performance status, lactate dehydrogenase levels, and time from the diagnosis of metastatic disease may help to identify patients more likely to achieve benefit. Properly designed prognostic tools (i.e., the {"}ColonLife{"} nomogram) may enable excluding from further treatments patients with very limited life expectancy.",
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T1 - Trifluridine/Tipiracil (TAS-102) in Refractory Metastatic Colorectal Cancer

T2 - A Multicenter Register in the Frame of the Italian Compassionate Use Program

AU - Cremolini, Chiara

AU - Rossini, Daniele

AU - Martinelli, Erika

AU - Pietrantonio, Filippo

AU - Lonardi, Sara

AU - Noventa, Silvia

AU - Tamburini, Emiliano

AU - Frassineti, Giovanni Luca

AU - Mosconi, Stefania

AU - Nichetti, Federico

AU - Murgioni, Sabina

AU - Troiani, Teresa

AU - Borelli, Beatrice

AU - Zucchelli, Gemma

AU - Dal Maso, Alessandro

AU - Sforza, Vincenzo

AU - Masi, Gianluca

AU - Antoniotti, Carlotta

AU - Di Bartolomeo, Maria

AU - Miceli, Rosalba

AU - Ciardiello, Fortunato

AU - Falcone, Alfredo

N1 - © AlphaMed Press 2018.

PY - 2018/10

Y1 - 2018/10

N2 - BACKGROUND: TAS-102 is indicated for patients with metastatic colorectal cancer (mCRC) previously treated with, or not considered candidates for, available therapies. Given the complete inefficacy in half of patients, the lack of predictive factors, the palliative setting, and the financial and clinical toxicity, optimizing the cost-benefit ratio is crucial. The "ColonLife" nomogram allows an estimate of the 12-week life expectancy of patients with refractory mCRC.MATERIALS AND METHODS: We collected data from patients treated at eight Italian centers in the compassionate use program. Baseline characteristics of patients who were or were not progression free at 6 months were compared. The discriminative ability of the ColonLife nomogram was assessed. Among patients who received both TAS-102 and regorafenib, clinical outcomes of the two sequences were compared.RESULTS: This study included 341 patients. Six (2%) and 93 (27%) patients achieved response and disease stabilization, respectively. The median progression-free survival (PFS) was 2.4 months with an estimated 6-month PFS rate of 19%; the median overall survival (OS) was 6.2 months. An Eastern Cooperative Oncology Group performance status (ECOG PS) of 0, normal lactate dehydrogenase (LDH), and a time from the diagnosis of metastatic disease of >18 months were independently associated with higher chances of a patient being progression free at 6 months. The discriminative ability of ColonLife was confirmed. Among 121 patients who received both regorafenib and TAS-102, no differences in first or second PFS or OS were reported between the two sequences.CONCLUSION: One out of five patients achieves clinical benefit with TAS-102. ECOG PS, LDH, and time from diagnosis of metastatic disease may help to identify these patients. Excluding patients with very short life expectancy appears a reasonable approach.IMPLICATIONS FOR PRACTICE: Improving the cost-efficacy ratio of TAS-102 in metastatic colorectal cancer is needed to spare useless toxicities in a definitely palliative setting. Eastern Cooperative Oncology Group performance status, lactate dehydrogenase levels, and time from the diagnosis of metastatic disease may help to identify patients more likely to achieve benefit. Properly designed prognostic tools (i.e., the "ColonLife" nomogram) may enable excluding from further treatments patients with very limited life expectancy.

AB - BACKGROUND: TAS-102 is indicated for patients with metastatic colorectal cancer (mCRC) previously treated with, or not considered candidates for, available therapies. Given the complete inefficacy in half of patients, the lack of predictive factors, the palliative setting, and the financial and clinical toxicity, optimizing the cost-benefit ratio is crucial. The "ColonLife" nomogram allows an estimate of the 12-week life expectancy of patients with refractory mCRC.MATERIALS AND METHODS: We collected data from patients treated at eight Italian centers in the compassionate use program. Baseline characteristics of patients who were or were not progression free at 6 months were compared. The discriminative ability of the ColonLife nomogram was assessed. Among patients who received both TAS-102 and regorafenib, clinical outcomes of the two sequences were compared.RESULTS: This study included 341 patients. Six (2%) and 93 (27%) patients achieved response and disease stabilization, respectively. The median progression-free survival (PFS) was 2.4 months with an estimated 6-month PFS rate of 19%; the median overall survival (OS) was 6.2 months. An Eastern Cooperative Oncology Group performance status (ECOG PS) of 0, normal lactate dehydrogenase (LDH), and a time from the diagnosis of metastatic disease of >18 months were independently associated with higher chances of a patient being progression free at 6 months. The discriminative ability of ColonLife was confirmed. Among 121 patients who received both regorafenib and TAS-102, no differences in first or second PFS or OS were reported between the two sequences.CONCLUSION: One out of five patients achieves clinical benefit with TAS-102. ECOG PS, LDH, and time from diagnosis of metastatic disease may help to identify these patients. Excluding patients with very short life expectancy appears a reasonable approach.IMPLICATIONS FOR PRACTICE: Improving the cost-efficacy ratio of TAS-102 in metastatic colorectal cancer is needed to spare useless toxicities in a definitely palliative setting. Eastern Cooperative Oncology Group performance status, lactate dehydrogenase levels, and time from the diagnosis of metastatic disease may help to identify patients more likely to achieve benefit. Properly designed prognostic tools (i.e., the "ColonLife" nomogram) may enable excluding from further treatments patients with very limited life expectancy.

U2 - 10.1634/theoncologist.2017-0573

DO - 10.1634/theoncologist.2017-0573

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JO - Oncologist

JF - Oncologist

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