GOG-218: What the Ovarian Cancer Trial Found

In brief

This page explains the GOG-218 trial for people with advanced ovarian cancer and their families. The trial tested bevacizumab, a drug that blocks the blood vessels feeding a tumor. It asked whether adding it to standard chemotherapy would help. The answer, published in 2011, was split. Bevacizumab delayed cancer growth by close to four months when continued after chemotherapy. It did not help women live longer, and eight more years of follow-up did not change that.

Trial at a glance

Who took part

The trial enrolled 1,873 women with newly diagnosed epithelial ovarian, fallopian tube or primary peritoneal cancer. All had either stage III disease that surgery could not fully remove, or stage IV disease. All had already had surgery to remove as much tumor as possible. All were still reasonably active (performance status 0 to 2). Some women were excluded: anyone with a history of clinically significant vascular events, or evidence of bowel obstruction. That is because bevacizumab raises the risk of bleeding, clotting and bowel injury.

What the trial found

Everyone received six cycles of carboplatin and paclitaxel. They were split into three groups:

• One group added placebo.
• A second added bevacizumab during cycles 2 to 6 only.
• A third added bevacizumab during chemotherapy and continued it for up to 22 cycles.

Progression-free survival means the time until the cancer grew.

Median progression-free survival was 10.3 months with chemotherapy alone. It was 11.2 months with the short bevacizumab course, and 14.1 months with bevacizumab continued afterward. Only the continued group beat chemotherapy alone: hazard ratio 0.717 (95% CI, 0.625 to 0.824; P<0.001). The short course did not (hazard ratio 0.908; 95% CI, 0.795 to 1.040; P=0.16).

Overall survival is the part that matters most and the part that did not move. At the first report, 76.3% of patients were alive, with no significant differences among the three groups. The final protocol-specified analysis was published in 2019, after a median follow-up of 102.9 months. It found a hazard ratio for death of 1.06 (95% CI, 0.94 to 1.20) for the concurrent group. It was 0.96 (95% CI, 0.85 to 1.09) for the concurrent-plus-maintenance group. Disease-specific survival was not improved in any arm.

The added treatment had costs. Hypertension (high blood pressure) of grade 2 or higher occurred in 7.2%, 16.5% and 22.9% of the three groups. Gastrointestinal wall disruption occurred in 1.2%, 2.8% and 2.6%.

What changed in practice

Bevacizumab entered first-line ovarian cancer treatment on the strength of the progression-free survival result. The National Cancer Institute lists it as approved with carboplatin and paclitaxel, and then alone. This applies to patients with stage III, stage IV or recurrent disease following surgery. The European ICON7 trial landed in a similar place. Restricted mean progression-free survival at 36 months was 21.8 months with bevacizumab versus 20.3 months without (hazard ratio 0.81; 95% CI, 0.70 to 0.94; P=0.004).

What this story cannot tell you

• It cannot tell you that bevacizumab will help you live longer with advanced ovarian cancer. Across nearly nine years of follow-up, GOG-218 found no overall survival difference. A longer time before scans show growth is a real thing, but it is not the same thing.
• It does not apply to early-stage ovarian cancer or to stage III disease that surgery removed completely. It also does not apply to women with recent vascular events or bowel obstruction, who were kept out of the trial.
• A longer median survival appeared in the stage IV maintenance group (42.8 versus 32.6 months) in 2019. But that was one subgroup inside an overall negative trial. Subgroup findings raise questions rather than settle them.
• Front-line treatment has changed since 2011. The 2019 analysis found that BRCA1/2 and homologous recombination repair mutations affected prognosis. But they did not predict who benefited from bevacizumab. Its authors concluded that testing for them is essential. Decisions today involve options this trial never tested.

Questions worth asking

• Given my stage and what surgery removed, what would bevacizumab realistically change for me?
• Are we aiming to delay progression or to extend life, and which does the evidence support?
• What genomic testing should I have before we choose maintenance treatment?

Sources

This article was written from the sources below, which were checked on the source-check date shown above.

• NEJM: Incorporation of Bevacizumab in the Primary Treatment of Ovarian Cancer (GOG-218) (primary)
• JCO 2019: Final Overall Survival of a Randomized Trial of Bevacizumab for Primary Treatment of Ovarian Cancer (primary)
• ClinicalTrials.gov: NCT00262847 (registry)
• NCI: Bevacizumab (reference)
• NEJM: A Phase 3 Trial of Bevacizumab in Ovarian Cancer (ICON7) (supporting)

Related reading: ovarian cancer and its treatment.

How this article was prepared

Prepared by Cancer Explained's AI-assisted editorial system and checked against the sources listed above. This article has not been reviewed by a healthcare professional unless a named reviewer is specifically shown.

Cancer Explained is published by the National Cancer Information Foundation as a nonprofit-oriented public-interest education project. It is not a diagnostic service, does not recommend treatments, and is not for emergencies.

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