Trifluridine-Tipiracil and Bevacizumab in Refractory Metastatic Colorectal Cancer

SUNLIGHT Investigators; Richard Greil

doi:10.1056/NEJMoa2214963

Trifluridine-Tipiracil and Bevacizumab in Refractory Metastatic Colorectal Cancer

SUNLIGHT Investigators
, Richard Greil (Study group member)

Department of Internal Medicine III - Division of Hematology, Medical Oncology, Hemostaseology, Rheumatology, Infectiology and Oncologic Center

Research output: Contribution to journal › Original Article › peer-review

Abstract

BACKGROUND: In a previous phase 3 trial, treatment with trifluridine-tipiracil (FTD-TPI) prolonged overall survival among patients with metastatic colorectal cancer. Preliminary data from single-group and randomized phase 2 trials suggest that treatment with FTD-TPI in addition to bevacizumab has the potential to extend survival.

METHODS: We randomly assigned, in a 1:1 ratio, adult patients who had received no more than two previous chemotherapy regimens for the treatment of advanced colorectal cancer to receive FTD-TPI plus bevacizumab (combination group) or FTD-TPI alone (FTD-TPI group). The primary end point was overall survival. Secondary end points were progression-free survival and safety, including the time to worsening of the Eastern Cooperative Oncology Group (ECOG) performance-status score from 0 or 1 to 2 or more (on a scale from 0 to 5, with higher scores indicating greater disability).

RESULTS: A total of 246 patients were assigned to each group. The median overall survival was 10.8 months in the combination group and 7.5 months in the FTD-TPI group (hazard ratio for death, 0.61; 95% confidence interval [CI], 0.49 to 0.77; P<0.001). The median progression-free survival was 5.6 months in the combination group and 2.4 months in the FTD-TPI group (hazard ratio for disease progression or death, 0.44; 95% CI, 0.36 to 0.54; P<0.001). The most common adverse events in both groups were neutropenia, nausea, and anemia. No treatment-related deaths were reported. The median time to worsening of the ECOG performance-status score from 0 or 1 to 2 or more was 9.3 months in the combination group and 6.3 months in the FTD-TPI group (hazard ratio, 0.54; 95% CI, 0.43 to 0.67).

CONCLUSIONS: Among patients with refractory metastatic colorectal cancer, treatment with FTD-TPI plus bevacizumab resulted in longer overall survival than FTD-TPI alone. (Funded by Servier and Taiho Oncology; SUNLIGHT ClinicalTrials.gov number, NCT04737187; EudraCT number, 2020-001976-14.).

Original language	English
Pages (from-to)	1657-1667
Number of pages	11
Journal	NEW ENGLAND JOURNAL OF MEDICINE
Volume	388
Issue number	18
DOIs	https://doi.org/10.1056/NEJMoa2214963
Publication status	Published - 4 May 2023

Keywords

Adult
Humans
Antineoplastic Combined Chemotherapy Protocols/adverse effects
Bevacizumab/adverse effects
Colonic Neoplasms/drug therapy
Colorectal Neoplasms/drug therapy
Drug Combinations
Pyrrolidines/adverse effects
Rectal Neoplasms/drug therapy
Trifluridine/adverse effects
Uracil

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10.1056/NEJMoa2214963

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SUNLIGHT Investigators, & Greil, R. (2023). Trifluridine-Tipiracil and Bevacizumab in Refractory Metastatic Colorectal Cancer. NEW ENGLAND JOURNAL OF MEDICINE , 388(18), 1657-1667. https://doi.org/10.1056/NEJMoa2214963

SUNLIGHT Investigators ; Greil, Richard. / Trifluridine-Tipiracil and Bevacizumab in Refractory Metastatic Colorectal Cancer. In: NEW ENGLAND JOURNAL OF MEDICINE 2023 ; Vol. 388, No. 18. pp. 1657-1667.

@article{a904cf8c42c34aa8864ab4a7634a54b8,

title = "Trifluridine-Tipiracil and Bevacizumab in Refractory Metastatic Colorectal Cancer",

abstract = "BACKGROUND: In a previous phase 3 trial, treatment with trifluridine-tipiracil (FTD-TPI) prolonged overall survival among patients with metastatic colorectal cancer. Preliminary data from single-group and randomized phase 2 trials suggest that treatment with FTD-TPI in addition to bevacizumab has the potential to extend survival.METHODS: We randomly assigned, in a 1:1 ratio, adult patients who had received no more than two previous chemotherapy regimens for the treatment of advanced colorectal cancer to receive FTD-TPI plus bevacizumab (combination group) or FTD-TPI alone (FTD-TPI group). The primary end point was overall survival. Secondary end points were progression-free survival and safety, including the time to worsening of the Eastern Cooperative Oncology Group (ECOG) performance-status score from 0 or 1 to 2 or more (on a scale from 0 to 5, with higher scores indicating greater disability).RESULTS: A total of 246 patients were assigned to each group. The median overall survival was 10.8 months in the combination group and 7.5 months in the FTD-TPI group (hazard ratio for death, 0.61; 95\% confidence interval [CI], 0.49 to 0.77; P<0.001). The median progression-free survival was 5.6 months in the combination group and 2.4 months in the FTD-TPI group (hazard ratio for disease progression or death, 0.44; 95\% CI, 0.36 to 0.54; P<0.001). The most common adverse events in both groups were neutropenia, nausea, and anemia. No treatment-related deaths were reported. The median time to worsening of the ECOG performance-status score from 0 or 1 to 2 or more was 9.3 months in the combination group and 6.3 months in the FTD-TPI group (hazard ratio, 0.54; 95\% CI, 0.43 to 0.67).CONCLUSIONS: Among patients with refractory metastatic colorectal cancer, treatment with FTD-TPI plus bevacizumab resulted in longer overall survival than FTD-TPI alone. (Funded by Servier and Taiho Oncology; SUNLIGHT ClinicalTrials.gov number, NCT04737187; EudraCT number, 2020-001976-14.).",

keywords = "Adult, Humans, Antineoplastic Combined Chemotherapy Protocols/adverse effects, Bevacizumab/adverse effects, Colonic Neoplasms/drug therapy, Colorectal Neoplasms/drug therapy, Drug Combinations, Pyrrolidines/adverse effects, Rectal Neoplasms/drug therapy, Trifluridine/adverse effects, Uracil",

author = "\{SUNLIGHT Investigators\} and Prager, \{Gerald W\} and Julien Taieb and Marwan Fakih and Fortunato Ciardiello and \{Van Cutsem\}, Eric and Elena Elez and Cruz, \{Felipe M\} and Lucjan Wyrwicz and Daniil Stroyakovskiy and Zsuzsanna P{\'a}pai and Pierre-Guillaume Poureau and Gabor Liposits and Chiara Cremolini and Igor Bondarenko and Modest, \{Dominik P\} and Benhadji, \{Karim A\} and Nadia Amellal and Catherine Leger and Lo{\"i}ck Vidot and Josep Tabernero and Richard Greil",

note = "Copyright {\textcopyright} 2023 Massachusetts Medical Society.",

year = "2023",

month = may,

day = "4",

doi = "10.1056/NEJMoa2214963",

language = "English",

volume = "388",

pages = "1657--1667",

journal = "NEW ENGLAND JOURNAL OF MEDICINE ",

issn = "0028-4793",

publisher = "Massachusetts Medical Soc",

number = "18",

}

SUNLIGHT Investigators & Greil, R 2023, 'Trifluridine-Tipiracil and Bevacizumab in Refractory Metastatic Colorectal Cancer', NEW ENGLAND JOURNAL OF MEDICINE , vol. 388, no. 18, pp. 1657-1667. https://doi.org/10.1056/NEJMoa2214963

Trifluridine-Tipiracil and Bevacizumab in Refractory Metastatic Colorectal Cancer. / SUNLIGHT Investigators ; Greil, Richard (Study group member).
In: NEW ENGLAND JOURNAL OF MEDICINE , Vol. 388, No. 18, 04.05.2023, p. 1657-1667.

Research output: Contribution to journal › Original Article › peer-review

TY - JOUR

T1 - Trifluridine-Tipiracil and Bevacizumab in Refractory Metastatic Colorectal Cancer

AU - SUNLIGHT Investigators

AU - Prager, Gerald W

AU - Taieb, Julien

AU - Fakih, Marwan

AU - Ciardiello, Fortunato

AU - Van Cutsem, Eric

AU - Elez, Elena

AU - Cruz, Felipe M

AU - Wyrwicz, Lucjan

AU - Stroyakovskiy, Daniil

AU - Pápai, Zsuzsanna

AU - Poureau, Pierre-Guillaume

AU - Liposits, Gabor

AU - Cremolini, Chiara

AU - Bondarenko, Igor

AU - Modest, Dominik P

AU - Benhadji, Karim A

AU - Amellal, Nadia

AU - Leger, Catherine

AU - Vidot, Loïck

AU - Tabernero, Josep

A2 - Greil, Richard

PY - 2023/5/4

Y1 - 2023/5/4

N2 - BACKGROUND: In a previous phase 3 trial, treatment with trifluridine-tipiracil (FTD-TPI) prolonged overall survival among patients with metastatic colorectal cancer. Preliminary data from single-group and randomized phase 2 trials suggest that treatment with FTD-TPI in addition to bevacizumab has the potential to extend survival.METHODS: We randomly assigned, in a 1:1 ratio, adult patients who had received no more than two previous chemotherapy regimens for the treatment of advanced colorectal cancer to receive FTD-TPI plus bevacizumab (combination group) or FTD-TPI alone (FTD-TPI group). The primary end point was overall survival. Secondary end points were progression-free survival and safety, including the time to worsening of the Eastern Cooperative Oncology Group (ECOG) performance-status score from 0 or 1 to 2 or more (on a scale from 0 to 5, with higher scores indicating greater disability).RESULTS: A total of 246 patients were assigned to each group. The median overall survival was 10.8 months in the combination group and 7.5 months in the FTD-TPI group (hazard ratio for death, 0.61; 95% confidence interval [CI], 0.49 to 0.77; P<0.001). The median progression-free survival was 5.6 months in the combination group and 2.4 months in the FTD-TPI group (hazard ratio for disease progression or death, 0.44; 95% CI, 0.36 to 0.54; P<0.001). The most common adverse events in both groups were neutropenia, nausea, and anemia. No treatment-related deaths were reported. The median time to worsening of the ECOG performance-status score from 0 or 1 to 2 or more was 9.3 months in the combination group and 6.3 months in the FTD-TPI group (hazard ratio, 0.54; 95% CI, 0.43 to 0.67).CONCLUSIONS: Among patients with refractory metastatic colorectal cancer, treatment with FTD-TPI plus bevacizumab resulted in longer overall survival than FTD-TPI alone. (Funded by Servier and Taiho Oncology; SUNLIGHT ClinicalTrials.gov number, NCT04737187; EudraCT number, 2020-001976-14.).

AB - BACKGROUND: In a previous phase 3 trial, treatment with trifluridine-tipiracil (FTD-TPI) prolonged overall survival among patients with metastatic colorectal cancer. Preliminary data from single-group and randomized phase 2 trials suggest that treatment with FTD-TPI in addition to bevacizumab has the potential to extend survival.METHODS: We randomly assigned, in a 1:1 ratio, adult patients who had received no more than two previous chemotherapy regimens for the treatment of advanced colorectal cancer to receive FTD-TPI plus bevacizumab (combination group) or FTD-TPI alone (FTD-TPI group). The primary end point was overall survival. Secondary end points were progression-free survival and safety, including the time to worsening of the Eastern Cooperative Oncology Group (ECOG) performance-status score from 0 or 1 to 2 or more (on a scale from 0 to 5, with higher scores indicating greater disability).RESULTS: A total of 246 patients were assigned to each group. The median overall survival was 10.8 months in the combination group and 7.5 months in the FTD-TPI group (hazard ratio for death, 0.61; 95% confidence interval [CI], 0.49 to 0.77; P<0.001). The median progression-free survival was 5.6 months in the combination group and 2.4 months in the FTD-TPI group (hazard ratio for disease progression or death, 0.44; 95% CI, 0.36 to 0.54; P<0.001). The most common adverse events in both groups were neutropenia, nausea, and anemia. No treatment-related deaths were reported. The median time to worsening of the ECOG performance-status score from 0 or 1 to 2 or more was 9.3 months in the combination group and 6.3 months in the FTD-TPI group (hazard ratio, 0.54; 95% CI, 0.43 to 0.67).CONCLUSIONS: Among patients with refractory metastatic colorectal cancer, treatment with FTD-TPI plus bevacizumab resulted in longer overall survival than FTD-TPI alone. (Funded by Servier and Taiho Oncology; SUNLIGHT ClinicalTrials.gov number, NCT04737187; EudraCT number, 2020-001976-14.).

KW - Adult

KW - Humans

KW - Antineoplastic Combined Chemotherapy Protocols/adverse effects

KW - Bevacizumab/adverse effects

KW - Colonic Neoplasms/drug therapy

KW - Colorectal Neoplasms/drug therapy

KW - Drug Combinations

KW - Pyrrolidines/adverse effects

KW - Rectal Neoplasms/drug therapy

KW - Trifluridine/adverse effects

KW - Uracil

U2 - 10.1056/NEJMoa2214963

DO - 10.1056/NEJMoa2214963

M3 - Original Article

C2 - 37133585

SN - 0028-4793

VL - 388

SP - 1657

EP - 1667

JO - NEW ENGLAND JOURNAL OF MEDICINE

JF - NEW ENGLAND JOURNAL OF MEDICINE

IS - 18

ER -

SUNLIGHT Investigators, Greil R. Trifluridine-Tipiracil and Bevacizumab in Refractory Metastatic Colorectal Cancer. NEW ENGLAND JOURNAL OF MEDICINE . 2023 May 4;388(18):1657-1667. doi: 10.1056/NEJMoa2214963

Trifluridine-Tipiracil and Bevacizumab in Refractory Metastatic Colorectal Cancer

Abstract

Keywords

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