The evidence supporting this protocol is provided by a phase III multicentre international randomised trial (GOG 240)r involving 452 patients studying the addition of bevacizumab to combination chemotherapy regimens (cisplatin/paclitaxel/bevacizumab or topotecan/paclitaxel/bevacizumab) as first line treatment in patients with metastatic, persistent or recurrent cervical cancer.
Between April 2009 and January 2012, using a 2-by-2 factorial design, 114 patients were randomised to receive cisplatin 50 mg/m2 plus paclitaxel 135 or 175 mg/m2, 111 patients were randomised to receive topotecan 0.75 mg/m2 days 1-3 plus paclitaxel 175 mg/m2, 115 patients were randomised to receive cisplatin 50 mg/m2 plus paclitaxel 135 or 175 mg/m2 plus bevacizumab 15 mg/kg, and 112 patients were randomised to receive topotecan 0.75 mg/m2 days 1-3 plus paclitaxel 175 mg/m2 plus bevacizumab 15 mg/kg. Each cycle was repeated every 21 days, and continued until disease progression, unacceptable toxicity or if a patient had a complete response.
The primary end points were overall survival and the frequency and severity of adverse events associated with each regimen. Secondary end points were progression free survival and response rate.
The addition of bevacizumab to combination chemotherapy in patients with recurrent, persistent or metastatic cervical cancer was associated with an improvement of 3.5 months in median overall survival.r
After a median follow up of 20.8 months, the median overall survival was 17 months in patients who received bevacizumab vs 13.3 months in patients who received chemotherapy alone (HR=0.71; CI 98% 0.54 to 0.95).r
In the final analysis of OS, chemotherapy plus bevacizumab continued to show a significant improvement compared with chemotherapy alone: 16.8 months versus 13.3 months (HR 0.77 [95% CI 0.62–0.95]; p=0.007). The survival benefit was evident when comparing the addition of bevacizumab to cisplatin/paclitaxel, but not significant when examining the addition of bevacizumab to topotecan/paclitaxel.r
Kaplan-meier analysis of overall survival (OS)
© Lancet 2017
Quality of life (QOL) data was collected using surveys, with good compliance, and balanced between treatment groups (P=0.67). Fitted mixed-model estimates for the FACT-Cx-TOI and BPI scores indicated that the addition of bevacizumab did not adversely affect health–related quality of life.r
© New England Journal of Medicine 2014
Fatal adverse events occurred in four patients (1.8%) of patients who received chemotherapy alone, and in four patients (1.8%) who received chemotherapy plus bevacizumab (P=1.0). 36 patients in the chemotherapy arm discontinued treatment due to toxicity, compared to 58 patients who received bevacizumab plus chemotherapy.r