Patients who had received prior therapy with bevacizumab or prior systemic anticancer therapy for ovarian cancer (e.g. chemotherapy, monoclonal antibody therapy, tyrosine kinase inhibitor therapy, or hormonal therapy) or previous radiotherapy to the abdomen or pelvis were excluded from the study.

A total of 1873 patients were randomised in equal proportions to the following three arms:

• CPP arm: Five cycles of placebo (started cycle 2) in combination with carboplatin (AUC 6) and paclitaxel (175 mg/m2) for 6 cycles followed by placebo alone, for a total of up to 15 months of therapy

• CPB15 arm: Five cycles of Avastin (15 mg/kg q3w started cycle 2) in combination with carboplatin (AUC 6) and paclitaxel (175 mg/m2) for 6 cycles followed by placebo alone, for a total of up to 15 months of therapy

• CPB15+ arm: Five cycles of Avastin (15 mg/kg q3w started cycle 2) in combination with carboplatin (AUC 6) and paclitaxel (175 mg/m2) for 6 cycles followed by continued use of Avastin (15 mg/kg q3w) as single agent for a total of up to 15 months of therapy.

The majority of patients included in the study were White (87% in all three arms); the median age was 60 years in CPP and CPB15 arms and 59 years in CPB15+ arm; and 29% of patients in CPP or CPB15 and 26% in CPB15+ were over 65 years of age. Overall approximately 50% of patients had a GOG PS of 0 at baseline, 43% a GOG PS score of 1, and 7% a GOG PS score of 2. Most patients had EOC (82% in CPP and CPB15, 85% in CPB15+) followed by PPC (16% in CPP, 15% in CPB15, 13% in CPB15+) and FTC (1% in CPP, 3% in CPB15, 2% in CPB15+). The majority of patients had serous adenocarcinoma histologic type (85% in CPP and CPB15, 86% in CPB15+). Overall approximately 34% of patients were FIGO Stage III optimally debulked with gross residual disease, 40% Stage III sub-optimally debulked, and 26% were Stage IV patients.

The primary endpoint was PFS based on investigator's assessment of disease progression based on radiological scans or CA 125 levels, or symptomatic deterioration per protocol. In addition, a prespecified analysis of the data censoring for CA-125 progression events was conducted, as well as an independent review of PFS as determined by radiological scans.

The trial met its primary objective of PFS improvement. Compared to patients treated with chemotherapy (carboplatin and paclitaxel) alone in the front-line setting, patients who received bevacizumab at a dose of 15 mg/kg q3w in combination with chemotherapy and continued to receive bevacizumab alone (CPB15+), had a clinically meaningful and statistically significant improvement in PFS.

In patients who only received bevacizumab in combination with chemotherapy and did not continue to receive bevacizumab alone (CPB15), no clinically meaningful benefit in PFS was observed.

The results of this study are summarised in Table 15.

Table 15 Efficacy results from study GOG-0218

Progression-free survival 1
 
  CPP

(n = 625)
 CPB15

(n = 625)
 CPB15+

(n = 623)
 
Median PFS (months)
 10.6
 11.6
 14.7
 
Hazard Ratio (95% CI) 2
    0.89

(0.78, 1.02)
  0.70

(0.61, 0.81)
 
p-value 3, 4
    0.0437
  < 0.0001
 
Objective response Rate 5
 
  CPP

(n = 396)
 CPB15

(n = 393)
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