Update on Gynecologic Oncology Group Studies in Ovarian Cancer
Faculty Disclosure: Robert F. Ozols, MD
This presentation by Dr. Ozols discusses the use of bevacizumab (Avastin), Erbitux (C225), and PS 341 for the treatment of ovarian cancer which is not approved by the FDA. Also discussed is the off label use of gefitinib (Iressa), thalidomide, and gemcitabine.
The standard of care for FIGO stage I/II ovarian cancer has evolved over the last few years based on several GOG studies. Following comprehensive staging laparotomy low risk patients have a 5-10% relapse rate, therefore no adjuvant therapy is recommended. For patients with high risk features, 2 trials have helped define the standard of care. The ICON/ACTION trial showed a 7% absolute overall survival (OS) benefit for immediate vs delayed chemotherapy. The recent GOG trial of 3 vs. 6 cycles of adjuvant chemotherapy did not show superior outcome for more chemotherapy. The standard therefore is 3 cycles of carbo/paclitaxel chemotherapy. The possible benefit of maintenance weekly paclitaxel is currently being investigated in another GOG trial.
For FIGO stage III/IV patients, the standard adjuvant chemotherapy regimen has evolved to carboplatin/paclitaxel. This is supported by the recently reported GOG 158 trial comparing cisplatin/paclitaxel to carboplatin/paclitaxel. Statistically equivalent outcomes were shown with less toxicity on the carboplatin arm. Carboplatin/paclitaxel is the accepted standard at this point.
Because of poor two year survival in advanced patients, various other strategies have been attempted. GOG 93 tested intraperitoneal (IP)32-P in patients achieving a complete remission. No OS benefit was seen with significantly increased toxicity. IP chemotherapy has been tested in the GOG 104, 114 and 172 trials. Despite promising improvements in PFS and OS, high toxicity has prevented IP chemotherapy from being adopted as the treatment standard. Maintenance therapy was tested in the GOG 178 trial of 3 vs. 12 months of monthly taxol. The trial was closed early because of improved progression free survival (PFS) in the 12 month arm. No OS data was reported. Before this can be considered the standard of care, a confimatory trial remains to be completed which will report OS data.
Newer cytotoxic agents are being evaluated in the GOG 182 trial. Standard carboplatin/paclitaxel with or without topotecan, gemcitabine or liposomal doxorubicin in various cambinations are being evaluated. Planned accrual is 4000 patients making this the largest ever ovarian cancer trial. Results will likely not be reported until 2005 at the earliest.
Various targeted biologic agents are currently under evaluation in the phase I/II setting. These include gefitinib (EGFR tyrosine kinase inhibitor), bevacizumab (anti-VEGF mAb), C225 (anti-EGFR mAb), thalidomide and PS-341 (proteosome inhibitor). Results are pending.
Future GOG ovarian cancer studies will explore biologic therapies and their integration into cytotoxic chemotherapy regimens, the OS impact of maintenance chemotherapy and the role of chemoprevention in high risk individuals. Fenretinide is currently being investigated for this use. Hopefully, these studies will improve outcomes in a disease a remains a clinical challenge.