Adding bevacizumab to standard first-line carboplatin and paclitaxel chemotherapy therapy against ovarian cancer prolonged progression-free survival in two separate, complementary, phase III clinical trials reported in the Dec. 29 issue of the New England Journal of Medicine.

Bevacizumab (Avastin) did not interfere with chemotherapy. Although it raised the rate of toxic effects, this did not impair patients’ quality of life in either study. Both trials received industry support.

The GOG Study

In the Gynecologic Oncology Group (GOG) study, 1,873 women were treated at 336 medical centers in the United States, Canada, South Korea, and Japan. All had previously untreated, incompletely resectable, stage III or stage IV epithelial ovarian, primary peritoneal, or fallopian-tube cancer, for which they had undergone debulking surgery, said Dr. Robert A. Burger of the Fox Chase Cancer Center, Philadelphia, and his associates.

The cohort as a whole had a relatively poor prognosis, and factors that could influence treatment outcome were evenly distributed among the treatment groups. Patients were randomly assigned in a double-blind fashion to one of three regimens:

• 15 mg/kg bevacizumab added to chemotherapy cycles 2-22.

• 15 mg/kg bevacizumab added only to cycles 2-6, plus placebo added to cycles 7-22.

• Placebo added to chemotherapy cycles 2-22 (the control group).

A monoclonal antibody, bevacizumab targets the vascular endothelial growth factor (VEGF), which is known to promote angiogenesis and progression of ovarian cancer.

At the primary data analysis after a median of 17.4 months of follow-up, median progression-free survival, the primary end point, was 14.1 months when bevacizumab was given throughout the chemotherapy course. This was longer than the 11.2-month median when bevacizumab was given only at the beginning of the chemotherapy course and significantly longer than the 10.3-month median when it wasn’t given at all.

Thus, the addition of bevacizumab throughout the entire chemotherapy course prolonged progression-free survival by a median of 4 months, compared with chemotherapy alone, Dr. Burger and his colleagues said (New Engl. J. Med. 2011;365:2473-83).

In a further analysis of progression-free survival "in which data for patients with increased CA-125 levels were censored, as required by regulatory agencies, the median progression-free survival was 12.0 months in the control group but 18.0 months in the bevacizumab-throughout group," they added.

This benefit in progression-free survival was consistent across all subgroups of patients, regardless of prognostic factors such as cancer stage, lesion size, the tumor’s histologic type, the patient’s performance status, or the patient’s age, the researchers noted.

There was no significant benefit in overall survival, but the ability to detect such a benefit was limited by the lack of control for subsequent treatments, including crossover to bevacizumab or other anti-VEGF agents, they noted.

Regarding adverse effects, there were no significant differences among the three groups in quality-of-life scores on the Functional Assessment of Cancer Therapy–Ovary survey.

The frequency of hypertension was significantly higher with the addition of bevacizumab, which was not unexpected. But it was easily controlled with medication and led to discontinuation of the drug in only 2.4% of affected patients.