Although the survival advantage of intraperitoneal chemotherapy observed in GOG protocol 172 was consistent with the results of two previous phase III trials, intraperitoneal administration was associated with more severe adverse events and lower QOL during treatment, raising serious concerns.3-5
Our study suggests that when compared with standard outpatient carboplatin and paclitaxel, the costs and effects on QOL of inpatient intraperitoneal chemotherapy also need to be considered. We found that extending the survival curves over a longer time horizon (11.5 years and over a lifetime) improved the cost effectiveness of IP-CIS/PAC compared with IV-CARBO/PAC. However, incorporation of time horizons beyond 7 years required use of data from GOG-114 and United States life-tables, with inherent uncertainty in such projections. As expected, if the survival benefit that existed at 7 years was assumed to persist over these extended time horizons, IP-CIS/PAC retained a more favorable cost effectiveness profile.
A recently published cost-effectiveness analysis reported that IP-CIS/PAC was potentially cost effective compared with IV-CARBO/PAC, with an ICER of $37,454 per QALY.7
This is considerably lower than our estimate of $180,022 at a 7-year time horizon. While the prior study used median survival times, we used a Markov model and obtained survival from trial data at 6-month intervals, with calculation of mean survival times as a measure of effectiveness. The Markov model format allowed us to evaluate the economic impact of the chemotherapy regimens at several time horizons. Unlike the prior study, we obtained costs from Medicare reimbursement data and a large national database rather than local hospital charges. The prior study calculated the costs of each chemotherapy regimen based on the number of patients who completed intended cycles of treatments; patients not completing six cycles of intraperitoneal treatment were assigned costs of outpatient IV regimens to fill the balance of chemotherapy cycles.7,8
This results in a lower cost estimate for the intraperitoneal regimen. We assigned each patient the full cost of six cycles of the assigned chemotherapy regimen. To assess for bias, we performed the alternative method of chemotherapy cost calculations without significant change in results. Finally, we incorporated the costs of all severe toxicities whose rates differed significantly between regimens, incorporating both inpatient and outpatient costs in cases of hematologic toxicity.
The relatively high ICER of $180,022 for IP-CIS/PAC compared with IV-CARBO/PAC at 7 years appears to be driven by the higher costs of inpatient chemotherapy. Many oncologists who administer intraperitoneal chemotherapy may choose to modify IV paclitaxel to a 3-hour infusion, which is now standard practice for outpatient IV-CARBO/PAC. In our sensitivity analysis, IP-CIS/PAC administered outpatient had a favorable ICER compared with IV-CARBO/PAC. However, acceptance of the cost effectiveness of outpatient IP-CIS/PAC with costs adjusted as such requires the assumption that 3-hour and 24-hour paclitaxel infusions result in regimens of equivalent effectiveness. While the effectiveness of paclitaxel infusions of different durations is likely similar, there is relatively limited phase III data to support the assumption that they are equivalent.22,23
One potential limitation of our study is the use of survival data from two separate phase III trials. When comparing the raw survival data from both GOG-158 and GOG-172, we incorporated the IV-CIS/PAC arm data from each trial with nearly identical results and no difference in the ordering of strategies, suggesting that regimens from the two trials can be compared.
We used estimates for QOL-related utilities to compare chemotherapy regimens using QALYs. Women in the intraperitoneal arm of GOG-172 had significantly lower FACT-O QOL, pain, and neurotoxicity scores during treatment and 6 weeks post-treatment; neurotoxicity scores remained lower 1 year after treatment.3,4
As there is no validated method to directly convert the FACT-O score into a utility ratio to apply to the model,24
we applied a method for calculation of utilities from QOL scores reported by Bristow et al to report results in QALYs.11,12
This may introduce error but does allow us to account for the impact of QOL on cost-effectiveness assessments. Further validated sets of ovarian cancer-specific utilities are needed to accurately assess the impact of treatments.
The treatment of patients with advanced ovarian cancer requires consideration of both the likelihood that each therapy will be effective and the patient's expected QOL during and after treatment. While it is attractive to suppose that the treatment resulting in the highest survival should become the gold standard, the costs of treatment and adverse events, both in dollars spent and in treatment-related reduction in QOL, must be taken into account. Our study suggests that an intraperitoneal inpatient chemotherapy regimen is only cost effective over a longer time horizon or if we assume that a survival advantage persists. If intraperitoneal chemotherapy can be conducted on an outpatient basis with a comparable and lasting survival advantage, this regimen has an attractive ICER compared with IV carboplatin and paclitaxel. Consideration should be given to a two-arm clinical trial of inpatient IP-CIS/PAC versus an outpatient intraperitoneal platinum-taxane chemotherapy regimen to identify the most effective treatment with the most acceptable adverse effects and costs.