At What Cost Does a Potential Survival Advantage of Bevacizumab Make Sense for the Primary Treatment of Ovarian Cancer? A Cost-Effectiveness Analysis
ABSTRACT 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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ABSTRACT: Objective. Evaluate the cost-effectiveness of incorporating bevacizumab into the treatment regimen for recurrent, persistent, or advanced stage carcinoma of the cervix following publication of a recent phase III trial that demonstrated an overall survival (OS) benefit with the addition of bevacizumab. Methods. A cost-effectiveness decision model was constructed using recently published results from a Gynecologic Oncology Group phase III study, comparing a standard chemotherapy regimen (Chemo) to the experimental regimen (Chemo + Bev) consisting of the standard regimen + bevacizumab. Costs and adverse events were incorporated and sensitivity analyses assessed model uncertainties. Results. The cost of Chemo + Bev was $53,784 compared to $5,688 for the Chemo arm. The 3.7 month OS advantage with Chemo + Bev came at an incremental cost-effectiveness ratio (ICER) of $155K per-quality-adjusted life year (QALY). Chemo + Bev becomes cost-effective with an ICER $100K in sensitivity analysis when the cost of bevacizumab is discounted >37.5% or the dose is reduced from 15 to 7.5 mg/kg, an effective dose in ovarian cancer. Conclusions. With an ICER of $155K/QALY, the addition of bevacizumab to standard chemotherapy approaches common cost-effectiveness standards. Moderately discounting the cost of bevacizumab or using a smaller dose significantly alters its affordability. Published by Elsevier Inc.Gynecologic Oncology 11/2014; 136(1). DOI:10.1016/j.ygyno.2014.11.003 · 3.69 Impact Factor
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ABSTRACT: Bevacizumab is not cost effective in the adjuvant and maintenance treatment of advanced ovarian cancer.•Prospective collection of cost and quality of life data is critical to a well-executed cost–utility analysis.Gynecologic Oncology 10/2014; 136(2). DOI:10.1016/j.ygyno.2014.10.020 · 3.69 Impact Factor
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ABSTRACT: Ovarian cancer is the fifth most common cancer in the UK, and the fourth most common cause of cancer death. Of those people successfully treated with first-line chemotherapy, 55-75% will relapse within 2 years. At this time, it is uncertain which chemotherapy regimen is more clinically effective and cost-effective for the treatment of recurrent, advanced ovarian cancer. To determine the comparative clinical effectiveness and cost-effectiveness of topotecan (Hycamtin(®), GlaxoSmithKline), pegylated liposomal doxorubicin hydrochloride (PLDH; Caelyx(®), Schering-Plough), paclitaxel (Taxol(®), Bristol-Myers Squibb), trabectedin (Yondelis(®), PharmaMar) and gemcitabine (Gemzar(®), Eli Lilly and Company) for the treatment of advanced, recurrent ovarian cancer. Electronic databases (MEDLINE(®), EMBASE, Cochrane Central Register of Controlled Trials, Health Technology Assessment database, NHS Economic Evaluations Database) and trial registries were searched, and company submissions were reviewed. Databases were searched from inception to May 2013. A systematic review of the clinical and economic literature was carried out following standard methodological principles. Double-blind, randomised, placebo-controlled trials, evaluating topotecan, PLDH, paclitaxel, trabectedin and gemcitabine, and economic evaluations were included. A network meta-analysis (NMA) was carried out. A de novo economic model was developed. For most outcomes measuring clinical response, two networks were constructed: one evaluating platinum-based regimens and one evaluating non-platinum-based regimens. In people with platinum-sensitive disease, NMA found statistically significant benefits for PLDH plus platinum, and paclitaxel plus platinum for overall survival (OS) compared with platinum monotherapy. PLDH plus platinum significantly prolonged progression-free survival (PFS) compared with paclitaxel plus platinum. Of the non-platinum-based treatments, PLDH monotherapy and trabectedin plus PLDH were found to significantly increase OS, but not PFS, compared with topotecan monotherapy. In people with platinum-resistant/-refractory (PRR) disease, NMA found no statistically significant differences for any treatment compared with alternative regimens in OS and PFS. Economic modelling indicated that, for people with platinum-sensitive disease and receiving platinum-based therapy, the estimated probabilistic incremental cost-effectiveness ratio [ICER; incremental cost per additional quality-adjusted life-year (QALY)] for paclitaxel plus platinum compared with platinum was £24,539. Gemcitabine plus carboplatin was extendedly dominated, and PLDH plus platinum was strictly dominated. For people with platinum-sensitive disease and receiving non-platinum-based therapy, the probabilistic ICERs associated with PLDH compared with paclitaxel, and trabectedin plus PLDH compared with PLDH, were estimated to be £25,931 and £81,353, respectively. Topotecan was strictly dominated. For people with PRR disease, the probabilistic ICER associated with topotecan compared with PLDH was estimated to be £324,188. Paclitaxel was strictly dominated. As platinum- and non-platinum-based treatments were evaluated separately, the comparative clinical effectiveness and cost-effectiveness of these regimens is uncertain in patients with platinum-sensitive disease. For platinum-sensitive disease, it was not possible to compare the clinical effectiveness and cost-effectiveness of platinum-based therapies with non-platinum-based therapies. For people with platinum-sensitive disease and treated with platinum-based therapies, paclitaxel plus platinum could be considered cost-effective compared with platinum at a threshold of £30,000 per additional QALY. For people with platinum-sensitive disease and treated with non-platinum-based therapies, it is unclear whether PLDH would be considered cost-effective compared with paclitaxel at a threshold of £30,000 per additional QALY; trabectedin plus PLDH is unlikely to be considered cost-effective compared with PLDH. For patients with PRR disease, it is unlikely that topotecan would be considered cost-effective compared with PLDH. Randomised controlled trials comparing platinum with non-platinum-based treatments might help to verify the comparative effectiveness of these regimens. This study is registered as PROSPERO CRD42013003555. The National Institute for Health Research Health Technology Assessment programme.Health technology assessment (Winchester, England) 01/2015; 19(7):1-480. DOI:10.3310/hta19070 · 5.12 Impact Factor