Oral Presentation COSA 2015 ASM

SIRFLOX: Randomised phase III trial comparing first-line mFOLFOX6 ± bevacizumab (bev) versus mFOLFOX6 ± bev + selective internal radiation therapy (SIRT) in patients with metastatic colorectal cancer (mCRC) - analysis by presence or absence of extra-hepatic metastases, bev treatment and site of first progression (#20)

Peter Gibbs 1 , Guy A van Hazel 2 , Volker Heinemann 3 , Navesh K Sharma 4 , Michael PN Findlay 5 , Jens Ricke 6 , Marc Peeters 7 , David Perez 8 , Bridget Robinson 9 , Andrew Strickland 10 , Tom Ferguson 11 , Javier Rodrigez 12 , Hendrik Kroening 13 , Ido Wolf 14 , Vinod Ganju 15 , Euan Walpole 16 , Eveline Boucher 17 , Thomas Tichler 18 , Val Gebski 19 , Mark Van Buskirk 20
  1. Royal Melbourne hospital, Melbourne, Victoria, Australia
  2. University of Western Australia, Perth, Australia
  3. Comprehensive cancer center der LMU, Munich, Germany
  4. University of Maryland medical centre, Baltimore, Maryland, USA
  5. Cancer trials New Zealand, Auckland, New Zealand
  6. University clinic Magdeburg, Magdeburg, Germany
  7. Antwerp university hospital, Antwerp, Belgium
  8. Dunedin hospital, Dunedin, New Zealand
  9. Christchurch hospital, Christchurch, New Zealand
  10. Monash medical centre, Bentleigh, Victoria, Australia
  11. Royal Perth hospital, Perth, Western Australia, Australia
  12. Clinica universitaria de Navarra, Pamplona, Spain
  13. Schwerpunktpraxis of haematology & oncology, Magdeburg, Germany
  14. Sheba medical centre, Tel-Hashomer, Israel
  15. Frankston private hospital peninsula oncology centre, Frankston, Victoria, Australia
  16. Princess Alexandra hospital, Woolloongabba, Queensland, Australia
  17. Centre Eugéne Marquis, Hopital de Jour, Rennes, France
  18. Shaare-Zedek medical center, Jerusalem, Israel
  19. NHMRC clinical trials centre, Camperdown, New South Wales, Australia
  20. Data reduction LLC, Chester, New Jersey, USA

Background: The SIRFLOX study assessed the efficacy and safety of combining FOLFOX chemotherapy (±bev) with SIRT as first-line treatment of patients with CRC liver metastases. Planned sub-analyses analyses included ±extra-hepatic metastases, ±bev and site of first progression.

Methods: SIRFLOX was an international, multi-centre, open-label, RCT in chemotherapy-naïve patients with non-resectable, liver-only or liver-dominant mCRC. Arm A: mFOLFOX6 ±bev vs. arm B: mFOLFOX6 ±bev +SIRT using yttrium-90 resin microspheres (SIR-Spheres; Sirtex) administered once with cycle 1. The primary endpoint was overall PFS using RECIST v1.0. Stratification variables included ±extra-hepatic metastases, and ±bev. Liver PFS was assessed by Competing Risk analysis. First progression was judged by independent reader blinded to study arm.

Results: 530 patients were randomised (A, n=263; B, n=267), 212 (40%) had EHD; 292 (55%) received bev. Median follow-up was 36.1 months. Median overall PFS was 10.2 vs. 10.7 months in A vs. B, respectively (p=0.428). Median liver PFS was 12.6 vs. 20.5 months in A vs. B (p=0.002). Median Liver PFS was 12.4 vs. 21.1 months in A vs. B (p=0.003) for patients with liver-only metastases, and 12.6 vs. 16.7 months (p=0.147) for those with liver and extra-hepatic metastases. Median Liver PFS was 10.6 vs. 18.9 months in A vs. B (p=0.028) for patients with ITT -bev, and 12.7 vs. 21.0 months (p=0.018) for those with ITT +bev. The site of first progression was more frequently the liver (± other sites) in A [164/178, 92.1%] vs. B [120/166, 72.3%] (p<0.001). All-causality grade ≥3 adverse events occurred in 73.3% vs. 85.4% (NS) of patients in A vs. B.

Conclusion: In first-line treatment of patients with non-resectable CRC liver metastases, adding SIRT to FOLFOX-based chemotherapy failed to improve overall PFS. The addition of SIRT significantly extended median liver PFS and reduced the frequency that first disease progression occurred in the liver.