Clinical trialPhase 3Ovarian cancer

Incorporation of Bevacizumab in the Primary Treatment of Ovarian Cancer

N Engl J Med · 20111873 women

Burger RA, Brady MF, Bookman MA, Fleming GF, Monk BJ, Huang H, et al. N Engl J Med. 2011. 365:2473-2483

Study type: Clinical trial
Study name: GOG-0218
Phase: Phase 3
Design: Randomised, double-blind, placebo-controlled trial with three treatment groups
Sample size: 1873 women
Source: N Engl J Med · 2011
Trial registration: NCT00262847

In plain words

In this large study, women with advanced ovarian cancer who had had surgery were given the drug bevacizumab or a placebo in addition to standard chemotherapy. When bevacizumab was given with chemotherapy and then continued, the time without the disease getting worse was about 4 months longer. At the time of the analysis, no difference in overall length of life was seen between the groups. This drug can cause side effects such as high blood pressure and, rarely, damage to the wall of the bowel; the decision to use it should be made with the treating doctor.

Key results

10.3 months

Median PFS — control group

11.2 months

Median PFS — bevacizumab-initiation group

14.1 months

Median PFS — bevacizumab-throughout group

0.908 (95% CI 0.795–1.040)

HR for progression or death: bevacizumab initiation vs control

P=0.16

0.717 (95% CI 0.625–0.824)

HR for progression or death: bevacizumab throughout vs control

P<0.001

76.3% of patients were alive at the time of analysis

Overall survival

No significant difference between the three groups

Drugs in this study:Bevacizumab (Avastin)Carboplatin (Paraplatin)Paclitaxel (Taxol)

Dose and schedule cards

Carboplatin + paclitaxel + bevacizumab, then maintenance bevacizumab (GOG-0218, ICON7)

Stage III–IV after primary surgery (greater benefit in patients at high risk of progression)Cycle length: Every 21 daysOn the page “Ovarian cancer” · First line: chemotherapy and surgery

Stage III–IV after primary surgery (greater benefit in patients at high risk of progression)

Drug	Dose	Route	Schedule
Cycles 1 to 6
Carboplatin + paclitaxel	AUC 6 + 175 mg/m²	IV	Day 1
From cycle 2
Bevacizumab	15 mg/kg	IV	Day 1
Maintenance
Bevacizumab	15 mg/kg	IV	Day 1, up to a total of 22 cycles

Cycle length: Every 21 days
Duration: Bevacizumab up to a total of 22 cycles or until progression (label regimen, GOG-0218); in ICON7: bevacizumab 7.5 mg/kg with 5 or 6 cycles of chemotherapy, then 12 more cycles

In GOG-0218, bevacizumab was started from cycle 2 because of the required interval after surgery. If maintenance olaparib is planned, bevacizumab 15 mg/kg for a total of 15 months (PAOLA-1 regimen).

On the page “Ovarian cancer” · First line: chemotherapy and surgery

Stage III or IV ovarian cancer after initial surgery (GOG-0218)

Epithelial ovarian, fallopian tube or primary peritoneal cancerCycle length: Every 21 daysOn the page “Bevacizumab (Avastin)” · Dosing in gynaecological cancers: cervix and ovary (FDA label)

Epithelial ovarian, fallopian tube or primary peritoneal cancer

Drug	Dose	Route	Schedule
Up to 6 cycles
Bevacizumab	15 mg/kg	IV	Day 1
6 cycles
Carboplatin + paclitaxel	AUC 6 + 175 mg/m²	IV	Day 1
Maintenance
Bevacizumab	15 mg/kg	IV	Every 3 weeks

Cycle length: Every 21 days
Duration: Up to 22 cycles in total or until progression (whichever comes first)

In GOG-0218, bevacizumab was started with chemotherapy cycle 2.

On the page “Bevacizumab (Avastin)” · Dosing in gynaecological cancers: cervix and ovary (FDA label)

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1Control group

IV chemotherapy with paclitaxel 175 mg/m² plus carboplatin AUC 6 in cycles 1 to 6, with placebo in cycles 2 to 22 (each cycle 3 weeks).

2Bevacizumab-initiation group

The same chemotherapy (paclitaxel 175 mg/m² + carboplatin AUC 6 in cycles 1 to 6), plus bevacizumab 15 mg/kg in cycles 2 to 6, then placebo in cycles 7 to 22 (each cycle 3 weeks).

3Bevacizumab-throughout group

The same chemotherapy (paclitaxel 175 mg/m² + carboplatin AUC 6 in cycles 1 to 6), plus bevacizumab 15 mg/kg in cycles 2 to 22 (each cycle 3 weeks).

Source of the regimen details: Abstract of the paper

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Women with newly diagnosed stage 3 (incompletely resectable) or stage 4 epithelial ovarian cancer who had undergone debulking surgery.

Endpoints

Primary endpoint: progression-free survival (PFS). The abstract also reports overall survival and adverse events (hypertension requiring medical therapy and gastrointestinal wall disruption requiring medical intervention).

Safety and side effects

Hypertension requiring medical therapy: 7.2% in the control group, 16.5% in the bevacizumab-initiation group and 22.9% in the bevacizumab-throughout group. Gastrointestinal wall disruption requiring medical intervention: 1.2% in the control group, 2.8% in the bevacizumab-initiation group and 2.6% in the bevacizumab-throughout group.

Clinical significance and place in guidelines

Based on the abstract, adding bevacizumab to carboplatin and paclitaxel and continuing it for up to 10 months after chemotherapy improved progression-free survival in advanced epithelial ovarian cancer by about 4 months, with no significant difference in overall survival at the time of analysis. Starting bevacizumab without continuing it did not significantly improve PFS. The status of drug approvals and current guideline recommendations should be checked separately, as they are not given in the abstract.

Limitations

At the time of the analysis reported in the abstract, there was no significant difference in overall survival between the groups. The primary endpoint was progression-free survival. Hypertension and gastrointestinal wall disruption were more frequent in the bevacizumab groups. Other limitations should be checked in the full text of the paper.

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.