Result of interim analysis of overall survival in the GCIG ICON7 phase III randomized trial of bevacizumab in women with newly diagnosed ovarian cancer.

Abstract

LBA5006 Background: ICON7 was designed to investigate safety and efficacy of adding bevacizumab to standard chemotherapy in women with newly diagnosed ovarian cancer. Analyses of mature progression-free survival (PFS) data suggest a PFS benefit from bevacizumab (p=0.0041, a 15% improvement at 12 months and 1.5 months overall), and a trend for overall survival (OS) improvement, hazard ratio (HR)=0.81, 95%CI=0.63 to 1.04, p =0.098. The final analysis of OS will be performed when 715 deaths have occurred. An interim analysis with at least 365 deaths was requested by regulatory authorities considering licensing. This was approved by the independent data monitoring and steering committees. A subgroup analysis for poor prognosis patients (FIGO III debulked to >1.0cm or FIGO IV with debulking) was performed in an exploratory manner. Methods: Eligible women with high-risk early (FIGO stage I or IIa (grade 3 or clear cell), capped ≤10%) or advanced (stage IIb-IV) epithelial ovarian, primary peritoneal or fallopian tube cancer were randomised (1:1) to 6 cycles of 3 weekly chemotherapy (carboplatin AUC 5 or 6 and paclitaxel 175mg/m2) alone, or the same chemotherapy given concurrently with bevacizumab (7.5mg/kg) for 5 or 6 cycles followed by continued 3-weekly single-agent bevacizumab for 12 additional cycles or until progression whichever was the earlier. Results: From December 2006 to February 2009, 1,528 women were randomised from 263 centres in 7 GCIG groups. Baseline characteristics were balanced between arms: median age (57 years); ECOG PS 0-1 (47%); high-risk early-stage disease (9%); poor prognosis patients (30%); histology (69% serous, 8% endometrioid, 8% clear cell). Overall OS analysis: median follow-up 28 months, 377 deaths (200 standard, 177 bevacizumab), HR=0.84, 95%CI=0.69 to 1.03, p=0.099. Exploratory subgroup analysis of poor prognosis patients: 188 deaths (109 standard, 79 bevacizumab), HR=0.64, 95%CI=0.48 to 0.85, p=0.0022 with p=0.015 for test for interaction (treatment/risk group). Conclusions: The overall trend for improvement in OS from bevacizumab continues with a numerically larger benefit in poor prognosis patients.