New research: AVASTIN added to chemo increases progression-free survival in OVC

This just came out yesterday:

Bevacizumab (AVASTIN) Added to Chemotherapy Increases PFS in Ovarian, Related Cancers
Elsevier Global Medical News. 2010 Jun 7, N Osterweil


CHICAGO (EGMN) - Progression-free survival in women with advanced ovarian or related female reproductive tract cancers was increased by nearly 4 months when they received frontline therapy with standard chemotherapy and concurrent bevacizumab followed by maintenance with bevacizumab alone, reported investigators from the Gynecologic Oncology Group's GOG-0218 trial.

In a randomized, placebo-controlled, phase III trial, the addition of bevacizumab (Avastin) to chemotherapy with carboplatin and paclitaxel followed by bevacizumab monotherapy resulted in a median progression-free survival (PFS) of 14.1 months, compared with 10.3 months for women on standard chemotherapy and placebo (hazard ratio, 0.717; P less than .0001), reported lead investigator Dr. Robert A. Burger of the Fox Chase Cancer Center in Philadelphia at a session of the American Society of Clinical Oncology's 2010 annual meeting.

But bevacizumab was effective only when used both as an adjunct to chemotherapy and as maintenance therapy: Women who received the angiogenesis inhibitor with chemotherapy but got a placebo during the maintenance phase had a median progression-free survival of 11.2 months, which was not significantly better than that of women who received chemotherapy and placebo only (HR, 0.98; P=.16), Dr. Burger said.

"Bevacizumab is the first molecular-targeted and first antiangiogenic agent to demonstrate benefit in this population, and bevacizumab combined with chemotherapy followed by bevacizumab maintenance should be considered as one standard option for women with this disease," said Dr. Burger.

That recommendation may be a bit premature, however, because the data so far show an effect of bevacizumab on only progression-free survival and not on overall survival, and "we cannot infer that a progression-free survival gain will mean an overall survival gain," commented Dr. Elizabeth A. Eisenhauer, the invited discussant.

"A progression-free survival gain of only 3.8 months may not be meaningful to patients. We need the mature overall survival and quality-of-life results, and ideally the results of the other frontline trial of bevacizumab in this disease, ICON-7, to understand the full story of the impact of this advance," said Dr. Eisenhauer of the National Cancer Institute of Canada.

GOG-0218 investigators enrolled 1,873 women with stage III or IV epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer. At the time of enrollment, the patients were stratified by key prognostic factors, performance status, and a combination of tumor stage and degree of debulking, and were then randomly assigned to one of three treatment groups.

Each group received the CT regimen, consisting of 22 3-week cycles, with the first 6 cycles consisting of intravenous paclitaxel 175 mg/m² plus carboplatin at an area-under the curve of 6 mg/mL per minute. One group also received concurrent placebo followed by maintenance placebo, a second received concurrent bevacizumab plus maintenance placebo, and the third received concurrent bevacizumab and bevacizumab maintenance.

The primary end point was progression-free survival, as determined by radiographic evidence, CA 125 elevation during the maintenance phase of treatment, RECIST (Response Evaluation Criteria in Solid Tumors), or death.

Adverse events included grade 3/4 hypertension in 1.6% of patients on chemotherapy alone, in 5.4% of patients on concurrent bevacizumab, and in 10% of patients on bevacizumab maintenance. Hemorrhage or fistula occurred in 0.8%. 2.6%, and 2.3%, respectively.

The incidence of adverse events with bevacizumab was similar to that seen in other studies of the drug, Dr. Burger said.

Dr. Burger has served as an advisor/consultant to Genentech Inc. Dr. Eisenhauer reports no relevant disclosures.