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FOLFOXIRI plus bevacizumab versus FOLFOX plus bevacizumab for patients with metastatic colorectal cancer and ≥3 circulating tumour cells: the randomised phase III VISNÚ-1 trial

PURPOSE: 5-Fluorouracil/leucovorin, oxaliplatin, irinotecan (FOLFOXIRI) plus bevacizumab is more effective than doublets plus bevacizumab as first-line therapy for metastatic colorectal cancer, but is not widely used because of concerns about toxicity and lack of predictive biomarkers. This study wa...

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Autores principales: Aranda, Enrique, Viéitez, Jose Maria, Gómez-España, Auxiliadora, Gil Calle, Silvia, Salud-Salvia, Antonieta, Graña, Begoña, Garcia-Alfonso, Pilar, Rivera, Fernando, Quintero-Aldana, Guillermo Alfonso, Reina-Zoilo, Juan José, González-Flores, Encarnación, Salgado Fernández, Mercedes, Guillén‑Ponce, Carmen, Garcia-Carbonero, Rocio, Safont, María José, La Casta Munoa, Adelaida, García-Paredes, Beatriz, López López, Rafael, Sastre, Javier, Díaz-Rubio, Eduardo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7640586/
https://www.ncbi.nlm.nih.gov/pubmed/33148620
http://dx.doi.org/10.1136/esmoopen-2020-000944
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author Aranda, Enrique
Viéitez, Jose Maria
Gómez-España, Auxiliadora
Gil Calle, Silvia
Salud-Salvia, Antonieta
Graña, Begoña
Garcia-Alfonso, Pilar
Rivera, Fernando
Quintero-Aldana, Guillermo Alfonso
Reina-Zoilo, Juan José
González-Flores, Encarnación
Salgado Fernández, Mercedes
Guillén‑Ponce, Carmen
Garcia-Carbonero, Rocio
Safont, María José
La Casta Munoa, Adelaida
García-Paredes, Beatriz
López López, Rafael
Sastre, Javier
Díaz-Rubio, Eduardo
author_facet Aranda, Enrique
Viéitez, Jose Maria
Gómez-España, Auxiliadora
Gil Calle, Silvia
Salud-Salvia, Antonieta
Graña, Begoña
Garcia-Alfonso, Pilar
Rivera, Fernando
Quintero-Aldana, Guillermo Alfonso
Reina-Zoilo, Juan José
González-Flores, Encarnación
Salgado Fernández, Mercedes
Guillén‑Ponce, Carmen
Garcia-Carbonero, Rocio
Safont, María José
La Casta Munoa, Adelaida
García-Paredes, Beatriz
López López, Rafael
Sastre, Javier
Díaz-Rubio, Eduardo
author_sort Aranda, Enrique
collection PubMed
description PURPOSE: 5-Fluorouracil/leucovorin, oxaliplatin, irinotecan (FOLFOXIRI) plus bevacizumab is more effective than doublets plus bevacizumab as first-line therapy for metastatic colorectal cancer, but is not widely used because of concerns about toxicity and lack of predictive biomarkers. This study was designed to explore the role of circulating tumour cell (CTC) count as a biomarker to select patients for therapy with FOLFOXIRI-bevacizumab. PATIENTS AND METHODS: VISNÚ-1 was a multicentre, open-label, randomised, phase III study in patients with previously untreated, unresectable, metastatic colorectal carcinoma and ≥3 CTC/7.5 mL blood. Patients received bevacizumab 5 mg/kg plus FOLFOXIRI (irinotecan 165 mg/m(2), oxaliplatin 85 mg/m(2), leucovorin 400 mg/m(2) and 5-fluorouracil 3200 mg/m(2)) or FOLFOX (oxaliplatin 85 mg/m(2), leucovorin 400 mg/m(2), 5-fluorouracil 400 mg/m(2) then 2400 mg/m(2)) by intravenous administration every 2 weeks. The primary outcome was progression-free survival (PFS). RESULTS: The intention-to-treat population comprised 349 patients (FOLFOXIRI-bevacizumab, n=172; FOLFOX-bevacizumab, n=177). Median PFS was 12.4 months (95% CI 11.2 to 14.0) with FOLFOXIRI bevacizumab and 9.3 months (95% CI 8.5 to 10.7) with FOLFOX-bevacizumab (stratified HR, 0.64; 95% CI 0.49 to 0.82; p=0.0006). Grade≥3 adverse events were more common with FOLFOXIRI-bevacizumab 85.3% vs 75.1% with FOLFOX-bevacizumab (p=0.0178). Treatment-related deaths occurred in 8 (4.7%) and 6 (3.4%) patients, respectively. CONCLUSIONS: First-line FOLFOXIRI-bevacizumab significantly improved PFS compared with FOLFOX-bevacizumab in patients with metastatic colorectal cancer and ≥3 CTCs at baseline, which indicate a poor prognosis. CTC count may be a useful non-invasive biomarker to assist with the selection of patients for intensive first-line therapy.
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spelling pubmed-76405862020-11-10 FOLFOXIRI plus bevacizumab versus FOLFOX plus bevacizumab for patients with metastatic colorectal cancer and ≥3 circulating tumour cells: the randomised phase III VISNÚ-1 trial Aranda, Enrique Viéitez, Jose Maria Gómez-España, Auxiliadora Gil Calle, Silvia Salud-Salvia, Antonieta Graña, Begoña Garcia-Alfonso, Pilar Rivera, Fernando Quintero-Aldana, Guillermo Alfonso Reina-Zoilo, Juan José González-Flores, Encarnación Salgado Fernández, Mercedes Guillén‑Ponce, Carmen Garcia-Carbonero, Rocio Safont, María José La Casta Munoa, Adelaida García-Paredes, Beatriz López López, Rafael Sastre, Javier Díaz-Rubio, Eduardo ESMO Open Original Research PURPOSE: 5-Fluorouracil/leucovorin, oxaliplatin, irinotecan (FOLFOXIRI) plus bevacizumab is more effective than doublets plus bevacizumab as first-line therapy for metastatic colorectal cancer, but is not widely used because of concerns about toxicity and lack of predictive biomarkers. This study was designed to explore the role of circulating tumour cell (CTC) count as a biomarker to select patients for therapy with FOLFOXIRI-bevacizumab. PATIENTS AND METHODS: VISNÚ-1 was a multicentre, open-label, randomised, phase III study in patients with previously untreated, unresectable, metastatic colorectal carcinoma and ≥3 CTC/7.5 mL blood. Patients received bevacizumab 5 mg/kg plus FOLFOXIRI (irinotecan 165 mg/m(2), oxaliplatin 85 mg/m(2), leucovorin 400 mg/m(2) and 5-fluorouracil 3200 mg/m(2)) or FOLFOX (oxaliplatin 85 mg/m(2), leucovorin 400 mg/m(2), 5-fluorouracil 400 mg/m(2) then 2400 mg/m(2)) by intravenous administration every 2 weeks. The primary outcome was progression-free survival (PFS). RESULTS: The intention-to-treat population comprised 349 patients (FOLFOXIRI-bevacizumab, n=172; FOLFOX-bevacizumab, n=177). Median PFS was 12.4 months (95% CI 11.2 to 14.0) with FOLFOXIRI bevacizumab and 9.3 months (95% CI 8.5 to 10.7) with FOLFOX-bevacizumab (stratified HR, 0.64; 95% CI 0.49 to 0.82; p=0.0006). Grade≥3 adverse events were more common with FOLFOXIRI-bevacizumab 85.3% vs 75.1% with FOLFOX-bevacizumab (p=0.0178). Treatment-related deaths occurred in 8 (4.7%) and 6 (3.4%) patients, respectively. CONCLUSIONS: First-line FOLFOXIRI-bevacizumab significantly improved PFS compared with FOLFOX-bevacizumab in patients with metastatic colorectal cancer and ≥3 CTCs at baseline, which indicate a poor prognosis. CTC count may be a useful non-invasive biomarker to assist with the selection of patients for intensive first-line therapy. BMJ Publishing Group 2020-11-03 /pmc/articles/PMC7640586/ /pubmed/33148620 http://dx.doi.org/10.1136/esmoopen-2020-000944 Text en © Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology. http://creativecommons.org/licenses/by-nc/4.0/ http://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, any changes made are indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Original Research
Aranda, Enrique
Viéitez, Jose Maria
Gómez-España, Auxiliadora
Gil Calle, Silvia
Salud-Salvia, Antonieta
Graña, Begoña
Garcia-Alfonso, Pilar
Rivera, Fernando
Quintero-Aldana, Guillermo Alfonso
Reina-Zoilo, Juan José
González-Flores, Encarnación
Salgado Fernández, Mercedes
Guillén‑Ponce, Carmen
Garcia-Carbonero, Rocio
Safont, María José
La Casta Munoa, Adelaida
García-Paredes, Beatriz
López López, Rafael
Sastre, Javier
Díaz-Rubio, Eduardo
FOLFOXIRI plus bevacizumab versus FOLFOX plus bevacizumab for patients with metastatic colorectal cancer and ≥3 circulating tumour cells: the randomised phase III VISNÚ-1 trial
title FOLFOXIRI plus bevacizumab versus FOLFOX plus bevacizumab for patients with metastatic colorectal cancer and ≥3 circulating tumour cells: the randomised phase III VISNÚ-1 trial
title_full FOLFOXIRI plus bevacizumab versus FOLFOX plus bevacizumab for patients with metastatic colorectal cancer and ≥3 circulating tumour cells: the randomised phase III VISNÚ-1 trial
title_fullStr FOLFOXIRI plus bevacizumab versus FOLFOX plus bevacizumab for patients with metastatic colorectal cancer and ≥3 circulating tumour cells: the randomised phase III VISNÚ-1 trial
title_full_unstemmed FOLFOXIRI plus bevacizumab versus FOLFOX plus bevacizumab for patients with metastatic colorectal cancer and ≥3 circulating tumour cells: the randomised phase III VISNÚ-1 trial
title_short FOLFOXIRI plus bevacizumab versus FOLFOX plus bevacizumab for patients with metastatic colorectal cancer and ≥3 circulating tumour cells: the randomised phase III VISNÚ-1 trial
title_sort folfoxiri plus bevacizumab versus folfox plus bevacizumab for patients with metastatic colorectal cancer and ≥3 circulating tumour cells: the randomised phase iii visnú-1 trial
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7640586/
https://www.ncbi.nlm.nih.gov/pubmed/33148620
http://dx.doi.org/10.1136/esmoopen-2020-000944
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