O-019 - SIRFLOX: Randomized trial comparing first-line mFOLFOX6 ± bevacizumab versus mFOLFOX6 + selective internal radiation therapy (SIRT) ± bevacizumab...

Date 04 July 2015
Event WorldGI 2015
Session Oral and LBA abstracts
Topics Anti-Cancer Agents & Biologic Therapy
Colon Cancer
Rectal Cancer
Surgery and/or Radiotherapy of Cancer
Presenter G.A. van Hazel
Citation Annals of Oncology (2015) 26 (suppl_4): 108-116. 10.1093/annonc/mdv235
Authors G.A. van Hazel1, J. Ricke2, V. Heinemann3, N.K. Sharma4, M.P.N. Findlay5, M. Peeters6, D. Perez7, B. Robinson8, A. Strickland9, T. Ferguson10, J. Rodrigez11, H. Kroening12, I. Wolf13, V. Ganju14, E. Walpole15, E. Boucher16, T. Tichler17, V. Gebski18, M. Van Buskirk1, P. Gibbs19
  • 1University of Western Australia, Perth/AU
  • 2University Clinic Magdeburg, Magdeburg/DE
  • 3Comprehensive Cancer Center der LMU, Munich/DE
  • 4Baltimore/US
  • 5Cancer Trials New Zealand, Auckland/NZ
  • 6Antwerp University Hospital, Antwerp/BE
  • 7Dunedin Hospital, Dunedin/NZ
  • 8Christchurch Hospital, Christchurch/NZ
  • 9Monash Medical Centre, Bentleigh/AU
  • 10Royal Perth Hospital, Perth/AU
  • 11Clinica Universitaria de Navarra, Pamplona/ES
  • 12Schwerpunktpraxis of Haematology & Oncology, Magdeburg/DE
  • 13Sheba Medical Centre, Tel-Hashomer/IL
  • 14Frankston Private Hospital Peninsula Oncology Centre, Frankston/AU
  • 15Princess Alexandra Hospital, Woolloongabba/AU
  • 16Hopital de Jour, Rennes/FR
  • 17Shaare-Zedek Medical Center, Jerusalem/IL
  • 18NHMRC Clinical Trials Centre, Camperdown/AU
  • 19Royal Melbourne Hospital, Melbourne/AU

Abstract

Background

Liver metastases are the dominant site of disease in mCRC and the dominant cause of death. The SIRFLOX study was designed to assess the efficacy and safety of combining FOLFOX chemotherapy (± bevacizumab) with SIRT using yttrium-90 (Y-90) resin microspheres as first-line treatment of patients with liver metastases from mCRC.

Methods

SIRFLOX was an international, multi-centre, open-label, RCT in chemotherapy-naïve patients with non-resectable, liver-only or liver-dominant (liver plus lung and/or lymph node metastases) mCRC. Arm A: mFOLFOX6 (± bevacizumab, at investigator discretion) was compared to arm B: mFOLFOX6 + SIRT (SIR-Spheres; Sirtex) administered once with cycle 1 (± bevacizumab, at investigator discretion) until disease progression. The primary endpoint was Progression-Free Survival (PFS) using RECIST v1.0 by independent central imaging review in the intention-to-treat (ITT) cohort. PFS in the liver, as defined by Cumulative Incidence of Liver Progression (Liver CIP), was assessed by Competing Risk analysis. Stratification variables included presence of extra-hepatic metastases (liver-only vs. liver-dominant), degree of liver involvement (≤25% vs. >25%), and ITT with bevacizumab (with vs. no bevacizumab).

Results

From October 2006 to April 2013, 530 patients were randomised (arm A, n = 263; arm B, n = 267); 212 (40%) had extra-hepatic metastases; 292 (55%) were stratified to receive bevacizumab. Median follow-up was 36.1 months. The median overall PFS was 10.2 vs. 10.7 months in arms A vs. B, respectively (hazard ratio [HR]: 0.93; 95% CI 0.77–1.12; p = 0.429) by Kaplan-Meier analysis. The median Liver PFS was 12.6 vs. 20.5 months in arm A vs. B (HR: 0.69; 95% CI 0.55–0.90; p = 0.002). Median Liver PFS was 12.4 vs. 21.1 months in arm A vs. B (HR: 0.64; 95% CI 0.48–0.86; p = 0.003) for patients with liver-only metastases, and 12.6 vs. 16.7 months (HR: 0.77, 95% CI 0.54–1.09; p = 0.147) for those with liver and extra-hepatic metastases. Median Liver PFS was 10.6 vs. 18.9 months in arm A vs. B (HR: 0.69; 95% CI 0.50–0.96; p = 0.028) for patients with ITT for no bevacizumab, and 12.7 vs. 21.0 months (HR: 0.69, 95% CI 0.50–0.94; p = 0.018) for those with ITT to receive bevacizumab. Overall response rate (partial response + complete response) was 68.1% vs. 76.4% in arm A vs. B, respectively (p = 0.113). Hepatic response rate was 68.8% vs. 78.7% in arm A vs. B (p = 0.042), including complete response rate 1.9% vs. 6.0% (p = 0.02). All-causality grade ≥3 adverse events were noted in 73.3% vs. 85.4% (not significant [NS]) of patients in arm A vs. B. Grade 5 events occurred in 1.9% vs. 3.7% (NS) in arm A vs. B. The most common grade ≥3 chemotherapy-associated toxicity was neutropenia (28.5% vs. 40.7%; p = 0.004); the most common grade ≥3 SIRT-associated event was gastric or duodenal ulcers (0.0% vs. 3.7%; p = 0.001) in treatment arms A vs. B, respectively.

Conclusion

In first-line treatment of patients with non-resectable CRC liver metastases, the addition of SIRT to a standard chemotherapy regimen failed to improve overall PFS. However, major gains in PFS in the Liver were achieved. The addition of SIRT was associated with acceptable toxicity.