LBA26 - FOXFIRE-SIRFLOX-FOXFIRE Global prospective randomised studies of first-line selective internal radiotherapy (SIRT) in patients with liver metastase...

Date 10 September 2017
Event ESMO 2017 Congress
Session Gastrointestinal tumours, colorectal
Topics Cytotoxic agents
Colon and Rectal Cancer
Gastrointestinal Cancers
Surgical oncology
Biological therapy
Radiation oncology
Presenter Harpreet Wasan
Citation Annals of Oncology (2017) 28 (suppl_5): v605-v649. 10.1093/annonc/mdx440
Authors H. Wasan1, R. Sharma2, V. Heinemann3, N. Sharma4, J. Taieb5, J. Ricke6, M. Peeters7, M. Findlay8, P.S. Virdee9, S. Love9, J. Moschandreas9, P. Dutton9, V. Gebski10, A.M. Gray11, D. Price12, G. Bower13, A. Montazeri14, P. Gibbs15, G. Van Hazel16
  • 1Medical Oncology, Imperial College London - Hammersmith Hospital, W12 0HS - London/GB
  • 2Hospitals Biomedical Research Centre, UCL - University College London, WC1E 6DD - London/GB
  • 3Department Of Internal Medicine Iii, Comprehensive Cancer Center, Ludwig-Maximilians-University of Munich, 81377 - Munich/DE
  • 4Division Of Radiation Oncology, Penn State Hershey Medical Center, 17033 - Hershey/US
  • 5Department Of Gastroenterology, European Hospital Georges Pompidou, 75015 - Paris/FR
  • 6Department Of Radiology And Nuclear Medicine, Universitätsklinikum Magdeburg - Universitätsklinik für Radiologie und Nuklearmedizin, 39120 - Magdeburg/DE
  • 7Oncology, Antwerp University Hospital, 2650 - Edegem/BE
  • 8Discipline Of Oncology, University of Auckland Faculty of Medical & Health Sciences, 1703 - Auckland/NZ
  • 9Centre For Statistics In Medicine, University of Oxford, OX3 7LD - Oxford/GB
  • 10Nhmrc Clinical Trials Centre, The University of Sydney, NSW 2050 - Camperdown/AU
  • 11Health Economics Research Centre, Nuffield Department Of Population Health, University of Oxford, OX3 7LF - Oxford/GB
  • 12Radiology, Perth Radiological Clinic, Perth/AU
  • 13Nuclear Medicine, Mount Nuclear Medicin, Perth/AU
  • 14Clinical Oncology, Clatterbridge Cancer Center, CH63 4JY - Wirral/GB
  • 15Western Hospital, Western Hospital, VICC 3011 - Footscray/AU
  • 16University Of Western Australia, University of Western Australia, WA 6000 - Perth/AU



The FOXFIRE randomised studies [FOXFIRE, SIRFLOX and FOXFIRE-Global] were designed to evaluate SIRT using yttrium-90 resin microspheres + first-line chemotherapy for unresectable metastatic colorectal cancer (mCRC). All the studies had similar designs, allowing a prospective, combined overall survival (OS) analysis. KRAS mutations are associated with poor outcomes in mCRC. Here, we report the impact of KRAS mutation status and primary tumour site on OS.


Chemotherapy-naïve mCRC patients with liver metastases not suitable for curative resection/ablation were randomised (1:1) to Control arm (standard oxaliplatin-based chemotherapy ± a biologically targeted agent) or Test arm (chemotherapy ± biological + SIRT). Patients with primary tumours in situ or limited extra-hepatic metastases were included. The primary endpoint was OS.


1103 patients (Control n = 549; Test n = 554) were enrolled; median follow-up 43.3 months (m). There was no difference in OS between the treatment arms (pooled HR 1.04; 95% CI, 0.90‒1.19; p = 0.609) or PFS (HR 0.90; 95% CI, 0.79‒1.02; p = 0.108). 182 (16.5%) patients had a KRAS mutation (MT), 279 (25.3%) had wildtype (WT) status and 642 (58.2%) had unknown (UN) status. There was no evidence that OS differed between treatment arms in patients with an MT (HR 1.03; 95% CI, 0.74–1.43; p = 0.878), WT (HR 1.10; 95% CI, 0.83–1.46; p = 0.499), or UN KRAS status (HR 1.01; 95% CI, 0.85–1.21; p = 0.878). OS in both treatment arms was lower with MT KRAS status than WT or UN status Control v SIRT: MT 19.1m v 18.7m; WT 28.3m v 24.2m; UN 23.1m v 22.6m. OS time in patients with right-side primary tumours was significantly longer in the Test than in the Control arm (22.0m v 17.1m; p = 0.007), but there was no significant OS difference between treatment arms in left-side tumours (24.6 vs. 26.6 m p = 0.279).


KRAS mutation status does not appear to be a predictive factor for survival outcome following SIRT in mCRC. OS was significantly better with the addition of SIRT in right-side primary tumours. These data suggest that primary tumour site and not KRAS status may predict for potential treatment interaction with SIRT.

Clinical trial identification

FOXFIRE has ISRCTN Registry number ISRCTN83867919. SIRFLOX and FOXFIRE-Global are registered with with registration numbers NCT00724503 and NCT01721954, respectively.

Legal entity responsible for the study

The University of Oxford, UK, Sirtex Medical Ltd (SIRFLOX and FOXFIRE-Global), Sydney, Australia


Sirtex Medical Ltd (SIRFLOX and FOXFIRE-Global) and The University of Oxford (FOXFIRE)


H. Wasan: Honoraria from Sirtex for consulting/advisory roles and giving presentations. R. Sharma: Research funding, honoraria, and consultancy fees from Sirtex Medical Ltd V. Heinemann: Honoraria from Amgen, Roche, Sanofi and Sirtex Medical Ltd for consulting roles, participation in advisory boards, and his institution has received study grants from Amgen, Merck, Roche, Sanofi and Sirtex Medical Ltd N. Sharma: Honoraria from Sirtex Medical Ltd. J. Ricke: Personal fees and grants from Sirtex Medical Ltd. M. Findlay: Grants from Sirtex Medical Ltd. P.S. Virdee: Grants from Cancer Research UK and grants and non-financial support from Sirtex Medical Ltd. S. Love, P. Dutton: Grants from Cancer Research UK and grants and non-financial support from Sirtex Medical Ltd. J. Moschandreas: Grants from Cancer Research UK and grants from and non-financial support from Sirtex Medical Ltd. V. Gebski: Compensation for participation in Advisory Committees from Sirtex Medical Ltd. A.M. Gray: Grants from Cancer Research UK. P. Gibbs: Honoraria from Sirtex for participation in advisory boards and for giving presentations. G. Van Hazel: Compensation for participation in Advisory Committees from Sirtex Medical. All other authors have declared no conflicts of interest.