Clinical trialPhase 3Ovarian cancer

A phase 3 trial of bevacizumab in ovarian cancer

N Engl J Med · 20111528 patients

Perren TJ, Swart AM, Pfisterer J, Ledermann JA, Pujade-Lauraine E, Kristensen G, et al. N Engl J Med. 2011. 365:2484-96

Study type: Clinical trial
Study name: ICON7
Phase: Phase 3
Design: Open-label randomised trial in 11 countries (registration ISRCTN91273375)
Sample size: 1528 patients
Source: N Engl J Med · 2011

In plain words

Bevacizumab is a drug that blocks the growth of the tumour's blood vessels. In this study, adding it to standard chemotherapy slightly delayed the return of the disease, and it gave more benefit in patients with more extensive disease or disease left after surgery (high risk). This drug may raise blood pressure.

Key results

21.8 vs 20.3 months

PFS (restricted mean at 36 months)

HR 0.81 (95% CI 0.70–0.94); P=0.004

24.1 vs 22.4 months

Updated PFS (restricted mean at 42 months)

P=0.04

36.6 vs 28.8 months

Median overall survival in high-risk patients

Subgroup at high risk of progression

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

Carboplatin + paclitaxel every 3 weeks (ICON7 trial)

Initial treatment of ovarian cancer (common use outside the label wording)Cycle length: Every 21 daysOn the page “Carboplatin (Paraplatin)” · Standard dosing and combination regimens

Initial treatment of ovarian cancer (common use outside the label wording)

Drug	Dose	Route	Schedule
Carboplatin	AUC 5 or 6 (Calvert formula)	IV	Day 1
Paclitaxel	175 mg/m²	IV	Day 1

Cycle length: Every 21 days
Duration: 6 cycles

Doses from the ICON7 control arm.

On the page “Carboplatin (Paraplatin)” · Standard dosing and combination regimens

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

1Carboplatin–paclitaxel + bevacizumab

Carboplatin (AUC 5 or 6) and paclitaxel (175 mg/m²) every 3 weeks for 6 cycles, with concurrent bevacizumab 7.5 mg/kg every 3 weeks for 5 or 6 cycles, continued for 12 further cycles or until disease progression.

2Carboplatin–paclitaxel (standard)

Carboplatin (AUC 5 or 6) and paclitaxel (175 mg/m²) every 3 weeks for 6 cycles.

Source of the regimen details: Abstract and methods section of the paper (NEJM 2011)

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 ovarian cancer (90% epithelial, 69% serous); 9% high-risk early-stage disease, 30% at high risk of progression, 70% stage IIIC or IV; median age 57 years.

Endpoints

Progression-free survival (first per protocol, then updated) and interim overall survival.

Safety and side effects

Bevacizumab was associated with more toxicity, especially grade 2 or higher hypertension (18% versus 2% with chemotherapy alone).

Clinical significance and place in guidelines

Together with GOG-0218, ICON7 became the basis for adding bevacizumab to first-line chemotherapy for advanced ovarian cancer, and today bevacizumab is the backbone of the olaparib–bevacizumab regimen (PAOLA-1). ESMO guideline (Pan-Asian adapted version 2025): bevacizumab improves progression-free survival in stage III–IV disease and should be considered with paclitaxel–carboplatin [I, A]. The final overall survival analysis (Oza et al., Lancet Oncol 2015) showed no benefit in the overall population (restricted mean survival 45.5 versus 44.6 months), but in the poor-prognosis subgroup overall survival was better with bevacizumab (39.3 versus 34.5 months; log-rank p=0.03, exploratory analysis).

Limitations

Open-label design; the bevacizumab dose (7.5 mg/kg) was half the GOG-0218 dose; the overall survival benefit was seen only in the high-risk subgroup analysis; non-proportional hazards complicate interpretation.

Original article (DOI)PubMed

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.