Paclitaxel 175 mg/m2 IV over 3 hours on Day 1 and cisplatin 50 mg/m2 IV on Day 1 plus bevacizumab 15 mg/kg IV on Day 1 (q3w)

• Paclitaxel 175 mg/m2 IV over 3 hours on Day 1 and topotecan 0.75 mg/m2 IV over 30 minutes on days 1-3 (q3w)

• Paclitaxel 175 mg/m2 IV over 3 hours on Day 1 and topotecan 0.75 mg/m2 IV over 30 minutes on Days 1-3 plus bevacizumab 15 mg/kg IV on Day 1 (q3w)

Eligible patients had persistent, recurrent or metastatic squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix which was not amenable to curative treatment with surgery and/or radiation therapy and who have not received prior therapy with bevacizumab or other VEGF inhibitors or VEGF receptor–targeted agents.

The median age was 46.0 years (range: 20−83) in the Chemo alone group and 48.0 years (range: 22−85) in the Chemo+Avastin group; with 9.3% of patients in the Chemo alone group and 7.5% of patients in the Chemo+Avastin group over the age of 65 years.

Of the 452 patients randomized at baseline, the majority of patients were white (80.0% in the Chemo alone group and 75.3% in the Chemo+Avastin group), had squamous cell carcinoma (67.1% in the Chemo alone group and 69.6% in the Chemo+Avastin group), had persistent/recurrent disease (83.6% in the Chemo alone group and 82.8% in the Chemo+Avastin group), had 1-2 metastatic sites (72.0% in the Chemo alone group and 76.2% in the Chemo+Avastin group), had lymph node involvement (50.2% in the Chemo alone group and 56.4% in the Chemo+Avastin group), and had a platinum free interval ≥ 6 months (72.5% in the Chemo alone group and 64.4% in the Chemo+Avastin group).

The primary efficacy endpoint was overall survival. Secondary efficacy endpoints included progression-free survival and objective response rate. Results from the primary analysis and the follow-up analysis are presented by Avastin Treatment and by Trial Treatment in Table 23 and Table 24, respectively.

Table 23 Efficacy results from study GOG-0240 by Avastin Treatment

  Chemotherapy

(n=225)
 Chemotherapy + Avastin

(n=227)
 
Primary Endpoint
 
Overall Survival – Primary analysis6
 
Median (months)1
 12.9
 16.8
 
Hazard ratio [95% CI]
 0.74 [0.58, 0.94]

(p-value5 = 0.0132)
 
Overall Survival – Follow-up analysis7
 
Median (months)1
 13.3
 16.8
 
Hazard ratio [95% CI]
 0.76 [0.62, 0.94]

(p-value5,8 = 0.0126)
 
Secondary Endpoints
 
Progression-free survival – Primary analysis6
 
Median PFS (months)1
 6.0
 8.3
 
Hazard ratio [95% CI]
 0.66 [0.54, 0.81]

(p-value5 <0.0001)
 
Best Overall Response – Primary analysis6
 
Responders (Response rate2)
 76 (33.8 %)
 103 (45.4 %)
 
95% CI for Response Rates3
 [27.6%, 40.4%]
 [38.8%, 52.1%]
 
Difference in Response Rates
 11.60%
 
95% CI for Difference in Response Rates4
 [2.4%, 20.8%]
 
p-value (Chi-squared Test)
 0.0117
 

1 Kaplan-Meier estimates

2 Patients and percentage of patients with best overall response of confirmed CR or PR; percentage calculated on patients with measurable d