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 language | English (US) |
|---|---|
| Pages (from-to) | 942-949 |
| Number of pages | 8 |
| Journal | European Journal of Cancer |
| Volume | 51 |
| Issue number | 8 |
| DOIs | |
| State | Published - May 1 2015 |
Funding
J.T., F.C., A.B. III, C.-H.K., J.Z., A.W., V.L.G. and J.G. designed the trial, developed the protocol, coordinated the study and were responsible for management, analysis and interpretation of the data. G.A., M.P.S., F.R., A.S., A.B. III, C.G.-P., S.C., E.V.C., I.R.M., D.S., C.-H.K. J.Z., J.T. and F.C. enrolled patients. G.A., J.T., and F.C. were responsible for drafting the manuscript, with writing support from Succinct Medical Communications, funded by Bayer. All authors were responsible for review and revision of the manuscript, and approval of the submitted version. Fernando Rivera: Research funding from Bayer, Amgen, Roche, Merck Serono, Sanofi, Celgene and AstraZeneca; Bayer consultant; Celgene consultant. Al Benson III: Research funding from Amgen, Genentech, Bayer, Novartis, Astellas and Gilead; scientific adviser to Bayer, Genentech, Genomic Health, Sanofi, Bristol-Myers Squibb and Lilly/Imclone. Stefano Cascinu: Bayer consultant; Roche consultant; Novartis consultant; research funding from Merck Serono. Eric Van Cutsem: Research funding from Bayer. John Zalcberg: Research funding and travel support from Bayer, Merck Serono and Roche; expert witness and member of speaker bureaux for Bayer. Fortunato Ciardiello: Research funding from Merck Serono, Bayer and AstraZeneca; Merck Serono consultant; Bayer consultant. The authors would like to thank the patients, their families and the study investigators. The CORDIAL trial was sponsored by Bayer HealthCare AG, Leverkusen, Germany. Writing support in the preparation of this manuscript was provided by Succinct Medical Communications . The authors retained full control over the content and the decision to publish the article.
Keywords
- Colorectal neoplasms
- Fluorouracil
- Leucovorin
- Oxaliplatin
- Regorafenib
- Safety
- Survival rate
- Treatment outcome
ASJC Scopus subject areas
- Oncology
- Cancer Research
