Bevacizumab is the first antiangiogenic agent to have demonstrated benefit as first-line and maintenance therapy in epithelial ovarian cancer (EOC), with the Gynecologic Oncology Group 218 and ICON 7 phase III trials revealing significantly prolonged progression-free survival (PFS) for carboplatin/paclitaxel plus bevacizumab followed by bevacizumab maintenance versus carboplatin/paclitaxel alone. Results are forthcoming from several phase III maintenance trials of investigational antiangiogenic agents, each evaluating PFS as the primary endpoint: AGO-OVAR12/LUME-Ovar1 (nintedanib [BIBF 1120]), AGO-OVAR16 (pazopanib), and TRINOVA-1, -2, and -3 (AMG 386). Here we review available data and ongoing clinical trials of investigational antiangiogenic agents as maintenance therapy for EOC. Current controversies, including uncertainties regarding the (1) most appropriate clinical trial endpoints, (2) optimal dosing, duration, and timing of therapy (e.g., with first-line chemotherapy and/or as maintenance monotherapy), and (3) feasibility, tolerability, and cost of adding these agents to platinum/taxane regimens are also highlighted.
Avastin as maintenance is continually being explored (if at first you don't succeed, keep trying). The ICON7 trial showed that women who continued on maintenance therapy with Avastin, following Avastin and chemotherapy, showed no worsening of their disease for an average of 14.1 months. That compares with 10.3 months for women on chemo alone. A third group of women in the study took Avastin only during chemotherapy. They lived an average of 11.2 months before their cancer progressed, a difference that was not significantly different than chemo alone.
ReplyDeleteThe results of the GOG clinical trial demonstrated an additional 3.8 months of progression-free survival when maintenance Avastin was added for about one year following treatment with standard chemotherapy drugs Carboplatin and Paclitaxel along with Avastin. Given the fact that the addition of the drug was associated with 3.8 months of additional survival without cancer, the Ohio State University Comprehensive Cancer Center set out to determine whether or not that benefit of survival was justified by the expense (and toxicity) of the drug.
Their model showed that standard chemotherapy for patients in the clinical trial would cost $2.5 million, compared to $78.3 million for patients who were treated with standard chemotherapy and Avastin, plus additional maintenance treatments of Avastin for almost one year.
Typically each treatment with Avastin costs $5,000, with most of those costs directly attributable to the cost of the drug. Effectiveness was defined as months of progression-free survival, and costs were calculated as total costs per strategy. Cost-effectiveness strategies were defined as the cost per year of progression-free survival. Incremental cost-effectiveness ratio was defined as the costs per progression-free life-year saved.
Ultimately, they found that if you reduced the drug cost to 25 percent of the baseline, it does become cost effective to treat patients with Avastin. Or, if the survival could be substantially increased above the 3.8 months of progression-free survival, that could lead to cost-effective treatment for patients with advanced ovarian cancer.