Adding bevacizumab to standard chemotherapy doubled progression-free survival (PFS) in a phase III randomised trial of women with platinum-resistant ovarian cancer.
“These results are very significant because the addition of bevacizumab offers a new treatment option for the 20 percent 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.”
The multi-center international randomised study evaluated bevacizumab added to chemotherapy vs. chemotherapy alone in 361 patients with epithelial ovarian, fallopian tube or primary peritoneal cancer with disease progression within six months of their last dose of platinum therapy.
All patients received one of three standard chemotherapy drugs normally offered in this setting—weekly paclitaxel, topotecan or liposomal pegylated doxorubicin. These treatments are equally effective in treatment for resistant ovarian cancer, differing only in their toxicities. The investigators selected the chemotherapy based on each patient’s previous experience with the drugs.
After a median follow-up of 13.5 months, 75 percent (135 of 179) of the patients who received bevacizumab in addition to chemotherapy had a recurrence, compared to 91 percent (166 of 182) who received chemotherapy alone.
Median PFS was 6.7 months in the combination group, compared to 3.4 months in the chemotherapy alone group. Overall survival data is not yet complete.
Adverse events were higher in the bevacizumab group. These included greater than Grade 2 hypertension (20 percent vs. 7 percent), proteinuria (11 percent vs. 1 percent), gastrointestinal perforations (2 percent vs. 0), and fistula or abscesses (2 percent vs. 0). For other adverse events greater than Grade 3, the 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 to limited the incidence of adverse events due to bevacizumab, Dr. Pujade-Lauraine said.
Previous studies have shown that bevacizumab is active in first-line and second-line treatment of ovarian cancer. Future studies are likely to test when and how long to treat the disease with this agent.
(16 May 2013)