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Vinorelbine in BRAF V600E mutated metastatic colorectal cancer: a prospective multicentre phase II clinical study

BACKGROUND: BRAF V600E mutation defines a specific colorectal cancer (CRC) subgroup with poor prognosis. Promising preclinical data showed synthetically lethal activity of mitotic spindle poisons on BRAF-mutated and BRAF-like CRC models. We designed a phase II trial to test the activity of vinorelbi...

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Autores principales: Cremolini, Chiara, Pietrantonio, Filippo, Tomasello, Gianluca, Dadduzio, Vincenzo, Moretto, Roberto, Morano, Federica, Schirripa, Marta, Antoniotti, Carlotta, Fucà, Giovanni, Bergamo, Francesca, Rossini, Daniele, Nichetti, Federico, Ziampiri, Stamatia, Ghidini, Michele, Marmorino, Federica, Prisciandaro, Michele, Falcone, Alfredo, De Braud, Filippo, Loupakis, Fotios, Lonardi, Sara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5703381/
https://www.ncbi.nlm.nih.gov/pubmed/29209533
http://dx.doi.org/10.1136/esmoopen-2017-000241
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author Cremolini, Chiara
Pietrantonio, Filippo
Tomasello, Gianluca
Dadduzio, Vincenzo
Moretto, Roberto
Morano, Federica
Schirripa, Marta
Antoniotti, Carlotta
Fucà, Giovanni
Bergamo, Francesca
Rossini, Daniele
Nichetti, Federico
Ziampiri, Stamatia
Ghidini, Michele
Marmorino, Federica
Prisciandaro, Michele
Falcone, Alfredo
De Braud, Filippo
Loupakis, Fotios
Lonardi, Sara
author_facet Cremolini, Chiara
Pietrantonio, Filippo
Tomasello, Gianluca
Dadduzio, Vincenzo
Moretto, Roberto
Morano, Federica
Schirripa, Marta
Antoniotti, Carlotta
Fucà, Giovanni
Bergamo, Francesca
Rossini, Daniele
Nichetti, Federico
Ziampiri, Stamatia
Ghidini, Michele
Marmorino, Federica
Prisciandaro, Michele
Falcone, Alfredo
De Braud, Filippo
Loupakis, Fotios
Lonardi, Sara
author_sort Cremolini, Chiara
collection PubMed
description BACKGROUND: BRAF V600E mutation defines a specific colorectal cancer (CRC) subgroup with poor prognosis. Promising preclinical data showed synthetically lethal activity of mitotic spindle poisons on BRAF-mutated and BRAF-like CRC models. We designed a phase II trial to test the activity of vinorelbine in patients with BRAF V600E mutated metastatic CRC (mCRC). PATIENTS AND METHODS: Patients progressed to or not deemed eligible for standard treatments received oral (60 mg/sqm) or intravenous (25 mg/sqm) vinorelbine, on days 1 and 8 every 21 days. Primary endpoint was objective response rate (ORR). RESULTS: Twenty patients were enrolled; 75% of them were highly pretreated. No responses were observed (0%); only one patient had a confirmed disease stabilisation (5%). Median progression-free survival was 1 month (95% CI 0.8 to 1.8), median overall survival was 2.1 months (95% CI 1.6 to 3.7). No serious adverse events were observed. CONCLUSIONS: Despite encouraging preclinical data, our study did not show signs of clinical activity for vinorelbine in this patients’ population. Further investigations on molecular heterogeneity and dynamic evolution of BRAF V600E mutated mCRC are needed.
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spelling pubmed-57033812017-12-05 Vinorelbine in BRAF V600E mutated metastatic colorectal cancer: a prospective multicentre phase II clinical study Cremolini, Chiara Pietrantonio, Filippo Tomasello, Gianluca Dadduzio, Vincenzo Moretto, Roberto Morano, Federica Schirripa, Marta Antoniotti, Carlotta Fucà, Giovanni Bergamo, Francesca Rossini, Daniele Nichetti, Federico Ziampiri, Stamatia Ghidini, Michele Marmorino, Federica Prisciandaro, Michele Falcone, Alfredo De Braud, Filippo Loupakis, Fotios Lonardi, Sara ESMO Open Original Research BACKGROUND: BRAF V600E mutation defines a specific colorectal cancer (CRC) subgroup with poor prognosis. Promising preclinical data showed synthetically lethal activity of mitotic spindle poisons on BRAF-mutated and BRAF-like CRC models. We designed a phase II trial to test the activity of vinorelbine in patients with BRAF V600E mutated metastatic CRC (mCRC). PATIENTS AND METHODS: Patients progressed to or not deemed eligible for standard treatments received oral (60 mg/sqm) or intravenous (25 mg/sqm) vinorelbine, on days 1 and 8 every 21 days. Primary endpoint was objective response rate (ORR). RESULTS: Twenty patients were enrolled; 75% of them were highly pretreated. No responses were observed (0%); only one patient had a confirmed disease stabilisation (5%). Median progression-free survival was 1 month (95% CI 0.8 to 1.8), median overall survival was 2.1 months (95% CI 1.6 to 3.7). No serious adverse events were observed. CONCLUSIONS: Despite encouraging preclinical data, our study did not show signs of clinical activity for vinorelbine in this patients’ population. Further investigations on molecular heterogeneity and dynamic evolution of BRAF V600E mutated mCRC are needed. BMJ Publishing Group 2017-08-10 /pmc/articles/PMC5703381/ /pubmed/29209533 http://dx.doi.org/10.1136/esmoopen-2017-000241 Text en © European Society for Medical Oncology (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted. 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 and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
spellingShingle Original Research
Cremolini, Chiara
Pietrantonio, Filippo
Tomasello, Gianluca
Dadduzio, Vincenzo
Moretto, Roberto
Morano, Federica
Schirripa, Marta
Antoniotti, Carlotta
Fucà, Giovanni
Bergamo, Francesca
Rossini, Daniele
Nichetti, Federico
Ziampiri, Stamatia
Ghidini, Michele
Marmorino, Federica
Prisciandaro, Michele
Falcone, Alfredo
De Braud, Filippo
Loupakis, Fotios
Lonardi, Sara
Vinorelbine in BRAF V600E mutated metastatic colorectal cancer: a prospective multicentre phase II clinical study
title Vinorelbine in BRAF V600E mutated metastatic colorectal cancer: a prospective multicentre phase II clinical study
title_full Vinorelbine in BRAF V600E mutated metastatic colorectal cancer: a prospective multicentre phase II clinical study
title_fullStr Vinorelbine in BRAF V600E mutated metastatic colorectal cancer: a prospective multicentre phase II clinical study
title_full_unstemmed Vinorelbine in BRAF V600E mutated metastatic colorectal cancer: a prospective multicentre phase II clinical study
title_short Vinorelbine in BRAF V600E mutated metastatic colorectal cancer: a prospective multicentre phase II clinical study
title_sort vinorelbine in braf v600e mutated metastatic colorectal cancer: a prospective multicentre phase ii clinical study
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5703381/
https://www.ncbi.nlm.nih.gov/pubmed/29209533
http://dx.doi.org/10.1136/esmoopen-2017-000241
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