At What Cost Does a Potential Survival Advantage of Bevacizumab Make Sense for the Primary Treatment of Ovarian Cancer? A Cost-Effectiveness Analysis

The Ohio State University College of Medicine, Columbus, OH, USA.
Journal of Clinical Oncology (Impact Factor: 18.43). 03/2011; 29(10):1247-51. DOI: 10.1200/JCO.2010.32.1075
Source: PubMed


To determine whether the addition of bevacizumab to paclitaxel and carboplatin for the primary treatment of advanced ovarian cancer can be cost effective.
A cost-effectiveness analysis compared the three arms of the Gynecologic Oncology Group (GOG) 218 study (paclitaxel plus carboplatin [PC], PC plus bevacizumab [PCB], and PCB plus bevacizumab maintenance [PCB+B]). Actual and estimated costs of treatment plus the potential costs of complications were established for each strategy. Progression-free survival (PFS) and bowel perforation rates were taken from recently reported results of GOG 218. Sensitivity analysis was performed for pertinent uncertainties in the model. Incremental cost-effectiveness ratios (ICERs) per progression-free life-year saved (PF-LYS) were estimated.
For the 600 patients entered onto each arm of GOG 218 at the baseline estimates of PFS and bowel perforation, the cost of PC was $2.5 million, compared with $21.4 million for PCB and $78.3 million for PCB+B. These costs led to an ICER of $479,712 per PF-LYS for PCB and $401,088 per PF-LYS for PCB+B. When the cost of bevacizumab was reduced to 25% of baseline, the ICER of PCB+B fell below $100,000 per PF-LYS. ICERs were not substantially reduced when the perforation rate was equal across all arms.
The addition of bevacizumab to standard chemotherapy in patients with advanced ovarian cancer is not cost effective. Treatment with maintenance bevacizumab leads to improved PFS but is associated with both direct and indirect costs. The cost effectiveness of bevacizumab in the adjuvant treatment of ovarian cancer is primarily dependent on drug costs.

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    • "As part of the American Recovery and Reinvestment Act of 2009, the government allocated $1.1 billion toward comparative effectiveness research, within which falls cost-effectiveness studies. In 2011, Cohn et al. conducted a costeffectiveness analysis of bevacizumab in the treatment of primary ovarian cancer using a decision analysis program [69]. In the paper the authors determined that, based on preliminary GOG 218 data, the addition of bevacizumab to the adjuvant treatment of patients with ovarian cancer was not effective, with an incremental cost-effectiveness ratio (ICER) per progression free-life year saved (PF-LYS) of $479,712 in the bevacizumab initiation arm, and $401,088 in the bevacizumab throughout arm. "
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    ABSTRACT: Despite survival gains achieved nearly two decades ago with combination platinum- and taxane-based intravenous chemotherapy, overall survival curves have remained relatively unchanged during the 21st Century using newer cytotoxic agents. Although combined intravenous-intraperitoneal (IV-IP) chemotherapy is promising, tolerability remains a significant issue. An emphasis has been placed on exploring dose dense schedules and targeted agents. Vascular endothelial growth factor (VEGF) has emerged as an important therapeutic target in several solid tumors including ovarian carcinoma. The monoclonal antibody, bevacizumab, binds VEGF, thus preventing activation of the VEGF receptor (VEGFR) leading to inhibition of tumor angiogenesis. To date eight phase 3 randomized controlled trials incorporating anti-angiogenesis therapy in the treatment of newly diagnosed and recurrent ovarian carcinoma have met their primary endpoints. Four of these trials included bevacizumab and were reported from 2010-2012. During 2013, the other four studies were reported, each studying one of the following novel anti-angiogenesis agents: pazopanib, cediranib, trabananib, and nintedanib. Importantly, none of these drugs have been approved by the United States Food and Drug Administration USFDA for the treatment of ovarian cancer. The purpose of this review will be to highlight both VEGF-dependent and non-VEGF dependent angiogenic pathways in ovarian cancer and discuss the phase 3 experiences and regulatory implications of targeting the tumor microenviroment with anti-angiogenesis therapy.
    Full-text · Article · Dec 2013 · Gynecologic Oncology
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    • "No analysis of the cost such a small increase in survival would cause was performed. US healthcare related costs are expected to account for 25% of the gross domestic product by 20147. With current governmental budgetary demands, this level of healthcare expenditure is not sustainable. "
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    ABSTRACT: Trials have demonstrated improvements in survival with adding paclitaxel (P) or topotecan (T) to cisplatin (C) for the treatment of advanced cervical cancer. We sought to evaluate the cost effectiveness of these regimens. A decision model was developed based on Gynecologic Oncology Group (GOG) protocols 169 and 179. Arm 1 is 6 cycles of cisplatin. Arm 2 is 6 cycles of CP while arm 3 is 6 cycles of CT. Parameters include overall survival (OS), cost and complications. Sensitivity analyses were performed. The incremental cost-effectiveness ratio (ICER) for C versus CP is $13,654/quality-adjusted life-year (QALY) gained. For CT compared to C, the ICER is $152,327/QALY. When compared simultaneously, CT is dominated. At a willingness to pay (WTP) threshold of $50,000/QALY, C is the preferred option but CP is acceptable. Sensitivity analyses suggest that CT would become the preferred option if it was to improve OS to 24 months (compared to 9.4 months). In this model, CP is an acceptable alternative to cisplatin for the treatment of these patients with an increase in cost of only $13,654/QALY. The addition of topotecan did not increase survival enough to justify the increased cost.
    Full-text · Article · Nov 2012 · Journal of Cancer
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    • "Arm 3 showed an improvement of 4 months in progression-free survival compared with arm 1, and demonstrated that the addition of bevacizumab showed benefit over conventional chemotherapy. Although the results may be statistically different, their clinical relevance may be tempered by the potential high costs related to bevacizumab therapy.70 In addition, there was no significant difference in overall survival between the three arms, but it should be noted that the study was not powered for overall survival.69 "
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    ABSTRACT: Epithelial ovarian cancer is typically found in its advanced stages, where a combination of surgical debulking and platinum/taxane-based chemotherapy is recommended. Although over 70%-80% of patients achieve remission, a significant proportion develop recurrence of their disease. Additional cytotoxic chemotherapy, as well as surgery, is typically used to manage disease recurrence. Therapies that target specific pathways in cancer cells are rapidly developing in the laboratory and are increasingly being studied in patients with ovarian cancer. We review the current status of novel therapies in the management of epithelial ovarian cancer.
    Preview · Article · Jul 2012 · Biologics: Targets & Therapy
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