Addition of Bevacizumab to Standard Chemotherapy Does Not Improve Overall Survival in Newly Diagnosed Ovarian Cancer
Final overall survival results of the phase III ICON7 trial reported in The Lancet Oncology by Oza et al indicate no significant increase with the addition of bevacizumab (Avastin) to standard chemotherapy in women with newly diagnosed ovarian cancer. However, overall survival benefit of bevacizumab was observed among women with high-risk disease. ICON7 had shown that bevacizumab improved progression-free survival, the primary endpoint, with the largest benefit in high-risk disease.
Study Details
In the open-label ICON7 trial, 1,528 women were randomly assigned between December 2006 and February 2009 to receive chemotherapy (n = 764; six 3-weekly cycles of carboplatin at AUC 5 or 6 and paclitaxel at 175 mg/m²) or the same regimen plus bevacizumab at 7.5 mg/kg every 3 weeks given concurrently and continued with up to 12 additional 3-weekly cycles of maintenance therapy (n = 764).
Patients had to have newly diagnosed epithelial ovarian, fallopian tube, or primary peritoneal cancer, Eastern Cooperative Oncology Group performance status of 0 to 2, International Federation of Gynecology and Obstetrics (FIGO) 1988 stage IIb to IV or high-risk (grade 3 or clear cell histology) stage I to IIa disease, and had to have undergone debulking cytoreductive surgery or, in advanced disease, a biopsy with no further surgery planned.
In total, 254 patients in the chemotherapy group and 248 in the bevacizumab group were categorized as at high risk of progression due to stage IV disease, inoperable stage III disease, or suboptimally debulked (> 1 cm) stage III disease.
Overall Survival
Median follow-up was 48.9 months. Median overall survival was 58.0 months (95% confidence interval [CI] = 52.4–66.9 months) in the bevacizumab group vs 58.6 months (95% CI =53.5–67.5 months) in the chemotherapy group, with median overall survival among 502 patients with poor-prognosis disease being 39.7 vs 30.2 months.
Since the results showed evidence of nonproportional hazards, difference in restricted mean survival time was used as the primary estimate of effect. On this analysis, no benefit of bevacizumab was observed among all patients (restricted mean survival = 45.5 vs 44.6 months, P = .85). However, a significant benefit was observed among the 502 patients with poor-prognosis disease (restricted mean survival time = 39.3 vs 34.5 months (P = .03). No difference was observed among the patients without poor-prognosis disease (48.4 vs 49.7 months, P = .20).
In the primary progression-free survival analysis, reported at 759 events, restricted mean progression-free survival was 21.8 months in the bevacizumab group vs 20.3 months in the chemotherapy group (hazard ratio = 0.81, P = .004). In the current updated analysis, at 1,080 events, there was no longer a significant benefit of bevacizumab (restricted mean survival = 29.2 vs 27.7 months, P = .25), although a significant benefit was observed among high-risk patients (20.0 vs 15.9 months , P = .001).
The investigators concluded: “Bevacizumab, added to platinum-based chemotherapy, did not increase overall survival in the study population as a whole. However, an overall survival benefit was recorded in poor-prognosis patients, which is concordant with the progression-free survival results from ICON7 and GOG-218, and provides further evidence towards the optimum use of bevacizumab in the treatment of ovarian cancer.”
Adrian D. Cook, MSc, of the Medical Research Council Clinical Trials Unit at University College London, is the corresponding author for the Lancet Oncology article.
The study was funded by The National Institute for Health Research through the UK National Cancer Research Network, Medical Research Council, and Roche. For full disclosures of the study authors, visit www.thelancet.com.
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