(CHICAGO, IL) — In women with platinum-resistant ovarian cancer, bevacizumab plus chemotherapy doubled progression-free survival (PFS) compared with chemotherapy alone, according to the results of the first randomized phase 3 trial to show a benefit with a targeted therapy and improved outcome with a combination vs. monotherapy presented at the 2012 American Society of Clinical Oncology Annual Meeting.

“These results are very significant because the addition of bevacizumab offers a new treatment option for the 20% of women who have primary platinum-resistant disease, as well as those whose disease later becomes platinum-resistant,” said lead study author Eric Pujade-Lauraine, MD, PhD, professor, Université de Paris Descartes, France, and head of the Group d’Investigateurs Nationaux pour l’Etude des Cancers Ovariens (GINECO), a clinical trials cooperative group based in France. “For the first time in platinum-resistant ovarian cancer, we have been able to significantly improve progression-free survival with a combination therapy.”

Between October 2009 and April 2011, the AURELIA trial randomly assigned 361 patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer that had progressed ≤6 months after ≥4 cycles of platinum-based therapy to one of three standard chemotherapy agents normally offered in this setting: weekly paclitaxel (n=115), topotecan (n=120) or liposomal pegylated doxorubicin (n=126) alone or with bevacizumab 15mg/kg every 3 weeks (depending on chemotherapy). Investigators selected chemotherapy based on each patient’s previous experience with the drugs. At disease progression, patients in the chemotherapy-alone arm could cross over to bevacizumab monotherapy.

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Median PFS, the primary endpoint, was 6.7 months in the bevacizumab arm vs. 3.4 months in the chemotherapy-alone arm (HR, 0.48; log-rank P<0.001). Objective response rate was 12.6% in the chemotherapy alone arm and 30.9% in the bevacizumab arm (P=0.001).

Adverse events were higher in the bevacizumab group. These included grade 2 or greater hypertension (20% vs. 7%), proteinuria (11% vs. 0.6%), gastrointestinal perforations (2% vs. 0), and fistula or abscesses (2% vs. 0). For adverse events grade 3 or greater, study arms were equivalent.

Strict patient selection — based on the absence of history of bowel obstruction/abdominal fistula or clinical/radiological evidence of rectosigmoid involvement — helped limit incidence of adverse events due to bevacizumab, Dr. Pujade-Lauraine said.

AURELIA is the first randomized phase 3 trial in platinum-resistant chemotherapy to demonstrate benefit with biologic therapy; bevacizumab combined with chemotherapy should be considered a new standard option in platinum-resistant ovarian cancer.