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CHICAGO -- Women with recurrent platinum-sensitive ovarian cancer had a 50% improvement in progression-free survival when bevacizumab (Avastin) was added to chemotherapy, results of a multicenter randomized trial showed.

The median progression-free survival increased from 8.4 months with chemotherapy alone to 12.4 months with concurrent bevacizumab followed by bevacizumab maintenance.

The addition of the angiogenesis inhibitor significantly improved the objective response rate and duration of response. Data for overall survival have yet to reach the maturity required for a definitive analysis, according to a presentation here at the American Society of Clinical Oncology meeting.

"Bevacizumab plus carboplatin and gemcitabine followed by bevacizumab until progression provides a clinically meaningful benefit over chemotherapy alone in recurrent ovarian cancer," Carol Aghajanian, MD, of Memorial Sloan-Kettering Cancer Center in New York City, said during a press briefing.

"This [bevacizumab] regimen should be considered a new option for recurrent platinum-sensitive ovarian cancer," she added.

The findings came from a trial involving two therapies with proven activity in platinum-sensitive ovarian cancer. Single-arm studies of bevacizumab and randomized studies of carboplatin plus gemcitabine had demonstrated significant improvement in progression-free survival, said Aghajanian.

To examine the potential benefits of combining the regimens, investigators enrolled almost 500 patients with recurrent, platinum-sensitive ovarian cancer.

The patients had received one prior chemotherapy regimen for primary disease, no prior chemotherapy for recurrent disease, and no prior exposure to bevacizumab.

All patients received six cycles of carboplatin-gemcitabine chemotherapy and were randomized to concurrent bevacizumab or placebo, followed by bevacizumab or placebo maintenance therapy until progression.

The primary endpoint of the trial was progression-free survival, and key secondary endpoints included objective response rate, duration of response, overall survival, and safety.

The trial had the statistical power to detect a 27% reduction in the hazard for progression or death with the bevacizumab arm versus chemotherapy alone.

The patients had a mean age of about 60, and 35% to 40% were 65 or older. About 80% of the tumors had serous histology. Aghajanian said that about 40% of patients had platinum-free intervals of six to 12 months and the remaining patients had longer platinum-free intervals.

The primary analysis showed that the difference in progression-free survival translated into a 52% reduction in the hazard ratio for progression or death in the bevacizumab arm (HR 0.48, P<0.0001).

Subgroup analysis showed a consistent benefit for the addition of bevacizumab to chemotherapy, irrespective of age, platinum-free interval, cytoreductive surgery for recurrent disease (versus none), or baseline performance status.

Patients in the bevacizumab arm had an objective response rate of 78.5% compared with 57.4% for chemotherapy alone (P<0.0001).

The median duration of response was 10.4 months with chemotherapy plus bevacizumab and 7.4 months with chemotherapy, a difference that resulted in a 47% reduction in the hazard in favor of the bevacizumab arm (HR 0.53, P<0.0001).

Analysis of median overall survival revealed a trend in favor of bevacizumab (35.5 versus 29.9 months), but the difference did not reach statistical significance after a median follow-up of 24 months.

About 90% of patients had discontinued therapy at the interim analysis. Two-thirds in the placebo group discontinued because of disease progression compared with 40% of the bevacizumab arm.

Adverse event rates were similar in the treatment groups, although bevacizumab was associated with a higher incidence of serious adverse events (35% versus 25%).

Among adverse events of special interest, grade 3+ hypertension occurred in 17% of bevacizumab-treated patients versus <1% of the placebo arm, and grade 3+ proteinuria occurred in 9% and 1% of patients in the bevacizumab and control arms, respectively.

"In advanced ovarian cancer there is often the opportunity to intervene with main lines of chemotherapy. There are many chapters in this story, so to speak," said Andrew Seidman, MD, also of Memorial Sloan-Kettering, who moderated the press briefing.

"The ability to prolong each and every chapter in this disease will, in my estimation, make the story longer and ultimately improve survival. These trial results are certainly an important step in that direction."

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