Regorafenib plus modified FOLFOX6 as first-line treatment of metastatic colorectal cancer: A phase II trial

Guillem Argilés, Mark P. Saunders, Fernando Rivera, Alberto Sobrero, Al B Benson III, Carmen Guillén Ponce, Stefano Cascinu, Eric Van Cutsem, Iain R. MacPherson, Dirk Strumberg, Claus Henning Köhne, John Zalcberg, Andrea Wagner, Vittorio Luigi Garosi, Julia Grunert, Josep Tabernero, Fortunato Ciardiello*

*Corresponding author for this work

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Background The oral multikinase inhibitor regorafenib improves overall survival (OS) in patients with metastatic colorectal cancer (CRC) for which all standard treatments have failed. This study investigated regorafenib plus modified FOLFOX (mFOLFOX6) as first-line treatment of metastatic CRC. Methods In this single-arm, open-label, multicentre, phase II study, patients received mFOLFOX6 on days 1 and 15, and regorafenib 160 mg orally once daily on days 4-10 and 18-24 of each 28-day cycle. The primary end-point was centrally assessed objective response rate (ORR). Secondary end-points included disease control rate (DCR), OS, progression-free survival (PFS) and safety. Results Median overall treatment duration with any study drug was 9.9 months (range 0.6-19.6); median treatment duration with regorafenib was 7.7 months (range 0.1-19.5); six patients remained on regorafenib for more than 1 year. Fifty-three patients received at least one dose of regorafenib. ORR was 43.9% (all partial responses); DCR was 85.4%; median OS was not reached; median PFS was 8.5 months. Treatment-emergent adverse events were experienced by all patients but were manageable with dose modifications. Conclusion Regorafenib + mFOLFOX6 as first-line treatment in patients with metastatic CRC did not improve ORR over historical controls. Regorafenib plus mFOLFOX6 did not appear to be associated with a markedly worse tolerability profile versus mFOLFOX6 alone. ClinicalTrials.gov identifier: NCT01289821.

Original languageEnglish (US)
Pages (from-to)942-949
Number of pages8
JournalEuropean Journal of Cancer
Volume51
Issue number8
DOIs
StatePublished - May 1 2015

Fingerprint

Colorectal Neoplasms
Therapeutics
Disease-Free Survival
Survival
regorafenib
Survival Rate
Safety
Pharmaceutical Preparations

Keywords

  • Colorectal neoplasms
  • Fluorouracil
  • Leucovorin
  • Oxaliplatin
  • Regorafenib
  • Safety
  • Survival rate
  • Treatment outcome

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Argilés, Guillem ; Saunders, Mark P. ; Rivera, Fernando ; Sobrero, Alberto ; Benson III, Al B ; Guillén Ponce, Carmen ; Cascinu, Stefano ; Van Cutsem, Eric ; MacPherson, Iain R. ; Strumberg, Dirk ; Köhne, Claus Henning ; Zalcberg, John ; Wagner, Andrea ; Luigi Garosi, Vittorio ; Grunert, Julia ; Tabernero, Josep ; Ciardiello, Fortunato. / Regorafenib plus modified FOLFOX6 as first-line treatment of metastatic colorectal cancer : A phase II trial. In: European Journal of Cancer. 2015 ; Vol. 51, No. 8. pp. 942-949.
@article{3ca206cd72734bf280f8d924269e2a3e,
title = "Regorafenib plus modified FOLFOX6 as first-line treatment of metastatic colorectal cancer: A phase II trial",
abstract = "Background The oral multikinase inhibitor regorafenib improves overall survival (OS) in patients with metastatic colorectal cancer (CRC) for which all standard treatments have failed. This study investigated regorafenib plus modified FOLFOX (mFOLFOX6) as first-line treatment of metastatic CRC. Methods In this single-arm, open-label, multicentre, phase II study, patients received mFOLFOX6 on days 1 and 15, and regorafenib 160 mg orally once daily on days 4-10 and 18-24 of each 28-day cycle. The primary end-point was centrally assessed objective response rate (ORR). Secondary end-points included disease control rate (DCR), OS, progression-free survival (PFS) and safety. Results Median overall treatment duration with any study drug was 9.9 months (range 0.6-19.6); median treatment duration with regorafenib was 7.7 months (range 0.1-19.5); six patients remained on regorafenib for more than 1 year. Fifty-three patients received at least one dose of regorafenib. ORR was 43.9{\%} (all partial responses); DCR was 85.4{\%}; median OS was not reached; median PFS was 8.5 months. Treatment-emergent adverse events were experienced by all patients but were manageable with dose modifications. Conclusion Regorafenib + mFOLFOX6 as first-line treatment in patients with metastatic CRC did not improve ORR over historical controls. Regorafenib plus mFOLFOX6 did not appear to be associated with a markedly worse tolerability profile versus mFOLFOX6 alone. ClinicalTrials.gov identifier: NCT01289821.",
keywords = "Colorectal neoplasms, Fluorouracil, Leucovorin, Oxaliplatin, Regorafenib, Safety, Survival rate, Treatment outcome",
author = "Guillem Argil{\'e}s and Saunders, {Mark P.} and Fernando Rivera and Alberto Sobrero and {Benson III}, {Al B} and {Guill{\'e}n Ponce}, Carmen and Stefano Cascinu and {Van Cutsem}, Eric and MacPherson, {Iain R.} and Dirk Strumberg and K{\"o}hne, {Claus Henning} and John Zalcberg and Andrea Wagner and {Luigi Garosi}, Vittorio and Julia Grunert and Josep Tabernero and Fortunato Ciardiello",
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Argilés, G, Saunders, MP, Rivera, F, Sobrero, A, Benson III, AB, Guillén Ponce, C, Cascinu, S, Van Cutsem, E, MacPherson, IR, Strumberg, D, Köhne, CH, Zalcberg, J, Wagner, A, Luigi Garosi, V, Grunert, J, Tabernero, J & Ciardiello, F 2015, 'Regorafenib plus modified FOLFOX6 as first-line treatment of metastatic colorectal cancer: A phase II trial', European Journal of Cancer, vol. 51, no. 8, pp. 942-949. https://doi.org/10.1016/j.ejca.2015.02.013

Regorafenib plus modified FOLFOX6 as first-line treatment of metastatic colorectal cancer : A phase II trial. / Argilés, Guillem; Saunders, Mark P.; Rivera, Fernando; Sobrero, Alberto; Benson III, Al B; Guillén Ponce, Carmen; Cascinu, Stefano; Van Cutsem, Eric; MacPherson, Iain R.; Strumberg, Dirk; Köhne, Claus Henning; Zalcberg, John; Wagner, Andrea; Luigi Garosi, Vittorio; Grunert, Julia; Tabernero, Josep; Ciardiello, Fortunato.

In: European Journal of Cancer, Vol. 51, No. 8, 01.05.2015, p. 942-949.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Regorafenib plus modified FOLFOX6 as first-line treatment of metastatic colorectal cancer

T2 - A phase II trial

AU - Argilés, Guillem

AU - Saunders, Mark P.

AU - Rivera, Fernando

AU - Sobrero, Alberto

AU - Benson III, Al B

AU - Guillén Ponce, Carmen

AU - Cascinu, Stefano

AU - Van Cutsem, Eric

AU - MacPherson, Iain R.

AU - Strumberg, Dirk

AU - Köhne, Claus Henning

AU - Zalcberg, John

AU - Wagner, Andrea

AU - Luigi Garosi, Vittorio

AU - Grunert, Julia

AU - Tabernero, Josep

AU - Ciardiello, Fortunato

PY - 2015/5/1

Y1 - 2015/5/1

N2 - Background The oral multikinase inhibitor regorafenib improves overall survival (OS) in patients with metastatic colorectal cancer (CRC) for which all standard treatments have failed. This study investigated regorafenib plus modified FOLFOX (mFOLFOX6) as first-line treatment of metastatic CRC. Methods In this single-arm, open-label, multicentre, phase II study, patients received mFOLFOX6 on days 1 and 15, and regorafenib 160 mg orally once daily on days 4-10 and 18-24 of each 28-day cycle. The primary end-point was centrally assessed objective response rate (ORR). Secondary end-points included disease control rate (DCR), OS, progression-free survival (PFS) and safety. Results Median overall treatment duration with any study drug was 9.9 months (range 0.6-19.6); median treatment duration with regorafenib was 7.7 months (range 0.1-19.5); six patients remained on regorafenib for more than 1 year. Fifty-three patients received at least one dose of regorafenib. ORR was 43.9% (all partial responses); DCR was 85.4%; median OS was not reached; median PFS was 8.5 months. Treatment-emergent adverse events were experienced by all patients but were manageable with dose modifications. Conclusion Regorafenib + mFOLFOX6 as first-line treatment in patients with metastatic CRC did not improve ORR over historical controls. Regorafenib plus mFOLFOX6 did not appear to be associated with a markedly worse tolerability profile versus mFOLFOX6 alone. ClinicalTrials.gov identifier: NCT01289821.

AB - Background The oral multikinase inhibitor regorafenib improves overall survival (OS) in patients with metastatic colorectal cancer (CRC) for which all standard treatments have failed. This study investigated regorafenib plus modified FOLFOX (mFOLFOX6) as first-line treatment of metastatic CRC. Methods In this single-arm, open-label, multicentre, phase II study, patients received mFOLFOX6 on days 1 and 15, and regorafenib 160 mg orally once daily on days 4-10 and 18-24 of each 28-day cycle. The primary end-point was centrally assessed objective response rate (ORR). Secondary end-points included disease control rate (DCR), OS, progression-free survival (PFS) and safety. Results Median overall treatment duration with any study drug was 9.9 months (range 0.6-19.6); median treatment duration with regorafenib was 7.7 months (range 0.1-19.5); six patients remained on regorafenib for more than 1 year. Fifty-three patients received at least one dose of regorafenib. ORR was 43.9% (all partial responses); DCR was 85.4%; median OS was not reached; median PFS was 8.5 months. Treatment-emergent adverse events were experienced by all patients but were manageable with dose modifications. Conclusion Regorafenib + mFOLFOX6 as first-line treatment in patients with metastatic CRC did not improve ORR over historical controls. Regorafenib plus mFOLFOX6 did not appear to be associated with a markedly worse tolerability profile versus mFOLFOX6 alone. ClinicalTrials.gov identifier: NCT01289821.

KW - Colorectal neoplasms

KW - Fluorouracil

KW - Leucovorin

KW - Oxaliplatin

KW - Regorafenib

KW - Safety

KW - Survival rate

KW - Treatment outcome

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U2 - 10.1016/j.ejca.2015.02.013

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JO - European Journal of Cancer

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