Results of ICON7: a phase III randomised Gynaecologic Cancer InterGroup trial of concurrent bevacizumab and chemotherapy followed by maintenance bevacizumab, versus chemotherapy alone in women with newly diagnosed epithelial ovarian (EOC), primary peritoneal (PPC) or fallopian tube cancer (FTC). Medical Research Council Cancer Trials Unit, presented on behalf of the GCIG ICON7 collaborators
Timothy Perren1, Jonathan Ledermann2, Charlie Gourley3, Sharadah Essapen4, Gordon Rustin5, Fiona Collinson1, Sheryl Sim1, Faisal Al-Terkait1, Clare Griffin6
1St James’s Institute of Oncology, Leeds, UK, 2UCL Cancer Institute and Cancer Research UK and UCL Cancer Trials Centre, London, UK, 3University of Edinburgh Cancer Research Centre and Western General Hospital, UK, 4Royal Surrey County Hospital, Guildford, UK, 5Mount Vernon Hospital, Northwood, UK, 6Medical Research Council Cancer Trials Unit, London, UK
17.40 - 18.00
Background
Bevacizumab is a monoclonal antibody to vascular endothelial growth factor. Evidence of activity and acceptable toxicity provided the basis for its investigation in a phase III trial.
Method
Eligible women with high-risk early (FIGO stage I or IIa (grade 3 or clear cell), capped ≤10%) or advanced (stage IIb-IV) EOC, PPC or FTC were randomised (1:1) to 6 cycles of 3 weekly chemotherapy (carboplatin AUC 6 and paclitaxel 175mg/m2) alone, or the same chemotherapy given concurrently with bevacizumab (7.5mg/kg) for 6 cycles followed by maintenance bevacizumab continued 3-weekly for 12 additional cycles or until progression, whichever was the earlier. The primary outcome measure was investigatordetermined RECIST defined progression free survival (PFS). Secondary outcome measures include response, overall survival, safety and quality of life. To show a 28% improvement in median PFS from 18 to 23 months (hazard ratio (HR) = 0.78) with a 5% significance level and 90% power) 684 progressions/deaths were required.
Results
From 12/2006 to 02/2009, 1528 women (90% with EOC) were randomised from 263 centres in 7 GCIG groups. Baseline characteristics were balanced between arms: median age (57 years); ECOG performance status 0-1 (47%); high risk early stage disease (9%); histology (69% serous, 8% endometrioid, 8% clear cell). Adverse events were consistent with previous bevacizumab studies. With 759 (50%) progressions/deaths a HR of 0.81 (95%CI 0.70, 0.94) and p-value (log-rank test) of 0.0041, favouring the bevacizumab arm, were observed. There was evidence of non-proportional hazards and other summary statistics were explored.
Conclusion
Bevacizumab improved PFS in women with EOC, PPC or FTC.
Acknowledgements
Roche supplied bevacizumab for the ICON7 Trial and funded the data collection and analysis for this academic led clinical trial.
