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.

Progression-free survival as a surrogate endpoint for overall survival in modern ovarian cancer trials: a meta-analysis

“…Overall, two studies 14 , 15 contained multiple comparisons among different experimental therapies and a common control arm. There were twotrials 15 , 16 of biological therapies and another two trials 17 , 18 of intraperitoneal therapy. In total, seven comparisons reported an improvement in PFS (upper limit of the 95% CI for HR <1.00 or reported p < 0.05) and four comparisons reported an improvement in OS ( Table 1 ).…”

Meeting the challenge of ascites in ovarian cancer: new avenues for therapy and research

“…However, the majority of patients relapse and the addition of a third cytotoxic drug, such as gemcitabine, topotecan, caelyx or epirubicin, to platinum and paclitaxel has yielded disappointing results 91–93 . The VEGF-binding antibody bevacizumab has been added in Phase III trials (Gynecologic Oncology Group 218 study (GOG218; clinical trial ID: NCT00262847) and ICON7 (NCT00483782)) to standard treatment during and up to 15 months after chemotherapy, with reports of improved progression-free survival 94,95 , as well as increased overall survival in high-risk subgroups (patients with stage IV disease or suboptimally debulked stage III disease) 96 . Randomized trials have indicated that bevacizumab, concurrent with and following chemotherapy, can also provide benefit in terms of delaying further recurrence in both platinum-sensitive (OCEANS trial (NCT00434642) 97 ) and platinum-resistant (AURELIA trial (NCT00976911) 98 ) disease.…”

Anti-angiogenesis therapy, synthetic lethality, and checkpoint inhibition in ovarian cancer: state of the science and novel combinations

“…ICON7, however, additionally included women from stage I, II, or III following debulking and stage IV patients. ICON7 followed a different dosage schedule (7.5 mg/kg) every three weeks versus GOG-218, which administered double the dose at 15 mg/kg every three weeks 8,9. In addition to concluding the same results as GOG-218 with regard to PFS, ICON7 also revealed an improved OS to those patients deemed to have poor prognosis or high-risk disease (stage IV disease, inoperable stage III, or suboptimally debulked stage III disease).…”