Dutton, P

Findlay, M

Gebski, V

Gibbs, P

Gray, A

Heinemann, V

Love, SB

Moschandreas, Joanna

Peeters, M

Ricke, J

Sharma, N

Sharma, R

Taieb, J

van Hazel, G

Virdee, Pradeep

Wasan, HS

Annals of Oncology

English

Virdee, PS

Moschandreas, J

Oxford University Research Archive (ORA)

Overall survival in the FOXFIRE-SIRFLOX-FOXFIRE Global prospective randomized studies of first-line SIRT in patients with mCRC

H. Wasan

G. van Hazel

V. Heinemann

N. Sharma

J. Taieb

J. Ricke

M. Peeters

M. Findlay

P. Virdee

S.B. Love

J. Moschandreas

P. Dutton

V. Gebski

A. Gray

R. Sharma

P. Gibbs

Crossref

Overall survival in the FOXFIRE-SIRFLOX-FOXFIRE global prospective randomized studies of first-line SIRT in patients with mCRC

ORA - Oxford University Research Archive

Oxford University Research Archive

[Character count limit (title + text) = 2000; Current = 1878] [Title character count limit = 225; Current = 111] [Author number limit = 20; Current = 14] Overall survival in the FOXFIRE-SIRFLOX-FOXFIRE Global prospective randomized studies of first-line SIRT in patients with mCRC  Harpreet Wasan1, Guy van Hazel2, Volker Heinemann3, Navesh Sharma4, Julien Taieb5, Jens Ricke6, Marc Peeters7, Michael Findlay8, Pradeep S Virdee9, Sharon Love9, Joanna Moschandreas9, Peter Dutton9, Val Gebski10, Alastair Gray11, , Ricky A Sharma12,13, Peter Gibbs14 on behalf of the FOXFIRE, SIRFLOX and FOXFIRE-Global trial investigators 1Imperial College Healthcare NHS Trust & Imperial College, Hammersmith Hospital, London, UK; 2NIHR University College London Hospitals Biomedical Research Centre, UCL Cancer Institute, London, UK; 3Department of Medical Oncology and Comprehensive Cancer Centre, University of Munich, Germany; 4 Division of Radiation Oncology, Penn State Hershey Cancer Centre/School of Medicine, PA, USA; 5Sorbonne Paris Cité / Université Paris Descartes, Georges Pompidou European Hospital, Paris, France; 6Department of Radiology and Nuclear Medicine, University of Magdeburg, Germany; 7Antwerp University Hospital, Antwerp, Belgium; 8University of Auckland, Auckland, New Zealand; 9Centre for Statistics in Medicine, University of Oxford, UK; 10NHMRC Clinical Trials Centre, University of Sydney, Australia; 11University of Oxford, Health Economics Research Centre, Nuffield Department of Population Health, Oxford, UK; 12NIHR University College London Hospitals Biomedical Research Centre, UCL Cancer Institute, London, UK; 13CRUK-MRC Oxford Institute for Radiation Oncology, University of Oxford, Oxford, UK; 14Western Hospital, Footscray, Victoria, Australia   Background The FOXFIRE randomized studies [FOXFIRE, SIRFLOX and FOXFIRE-Global (FF-SF-FFG)] were designed to evaluate the efficacy and safety of selective internal radiation therapy (SIRT) using yttrium-90 resin microspheres plus first-line chemotherapy for unresectable metastatic colorectal cancer (mCRC). The design and eligibility criteria of the three studies were similar, which facilitated this prospective combined analysis of overall survival (OS). Methods Chemotherapy-naïve mCRC patients with liver metastases unsuitable for curative resection/ablation were randomized (1:1) to the Control arm with standard oxaliplatin-based chemotherapy (mFOLFOX6 or OxMdG) ± bevacizumab, or the Test arm to receive the same chemotherapy, plus a single SIRT treatment. Limited extra-hepatic metastases and primary tumor in situ were included. The primary endpoint OS was analysed on an intention-to-treat basis using individual participant data. Secondary endpoints included progression-free survival (PFS), liver PFS, response rate and adverse events (AEs). Results A total of 1103 patients (Control arm n=549; Test arm n=554) with a median age of 63 years were enrolled. Median follow-up was 43.3 months. There was no difference in median OS between the two treatment arms (pooled hazard ratio [HR] 1.04; 95% confidence interval [CI], 0.90‒1.19; p=0.609) or in median PFS (pooled HR 0.90; 95% CI, 0.79‒1.02; p=0.108). The objective response rate was higher in the SIRT arm than in the Control arm (72.2% and 63.0%, respectively, p=0.001). The risk of progression in the liver as a first event was lower in patients in the SIRT arm (pooled HR 0.51; CI 0.43‒0.62; p<0.001). There was a higher likelihood of grade 3‒5 AEs in the Test arm than in the Control arm (74.0% vs 66.5%, respectively, p=0.009). The addition of SIRT appeared to have a significant OS benefit in patients with right-sided tumors. Conclusions This combined analysis showed no improvement when SIRT is added to first-line oxaliplatin-fluorouracil chemotherapy. However, the addition of SIRT achieved higher tumor response rates and improved liver-specific PFS. The addition of SIRT appeared to have a significant OS benefit in patients with right-sided tumors. 

https://ora.ox.ac.uk/objects/uuid:407e9f83-e965-414c-97c4-b84fc94beebe/files/m2215d4acf1e597023832276061fae49a

Overall survival in the FOXFIRE-SIRFLOX-FOXFIRE Global prospective randomized studies of first-line SIRT in patients with mCRC

Abstract

Similar works

Full text

Available Versions

Oxford University Research Archive (ORA)

Crossref

ORA - Oxford University Research Archive

Oxford University Research Archive