Cost–Utility Analysis of Palonosetron-Based Therapy in Preventing Emesis Among Breast Cancer Patients
We estimated the cost-utility of palonosetron-based therapy compared with generic ondansetron-based therapy throughout four cycles of anthracycline and cyclophosphamide for treating women with breast cancer. We developed a Markov model comparing six strategies in which ondansetron and palonosetron are combined with either dexamethasone alone, dexamethasone plus aprepitant following emesis, or dexamethasone plus aprepitant up front. Data on the effectiveness of antiemetics and emesis-related utility were obtained from published sources. Relative to the ondansetron-based two-drug therapy, the incremental cost–effectiveness ratios for the palonosetron-based regimens were $115,490/quality-adjusted life years (QALY) for the two-drug strategy, $199,375/QALY for the two-drug regimen plus aprepitant after emesis, and $200,526/QALY for the three-drug strategy. In sensitivity analysis, using the $100,000/QALY benchmark, the palonosetron-based two-drug strategy and the two-drug regimen plus aprepitant following emesis were shown to be cost-effective in 39% and 26% of the Monte Carlo simulations, respectively, and with changes in values for the effectiveness of antiemetics and the rate of hospitalization. The cost-utility of palonosetron-based therapy exceeds the $100,000/QALY threshold. Future research incorporating the price structure of all antiemetics following ondansetron's recent patent expiration is needed.
Three-drug prophylactic regimens
We estimated the rate of acute emesis for the three-drug regimens based on data from published studies in which either onda or palo was given in combination with dex and aprepitant on day 1 of MEC (Table 2).[5], [7] and [13] Because aprepitant was either used in combination with dexamethasone or not used on days 2−3 in the trials of palo-based three-drug therapy, we estimated the benefit of adding aprepitant alone to palo on days 2−3 by assuming that the added benefit in the delayed period would be the same as the benefit added to onda. Specifically, we obtained information on the relative risk of delayed emesis control when aprepitant is added on days 2−3 from a large clinical trial of aprepitant combined with onda and dex in breast cancer patients receiving either A or AC chemotherapy (Table 2).7
Effectiveness of antiemetics over multiple cycles of chemotherapy
The estimates of changes in the probability of emesis control over multiple cycles of chemotherapy were obtained from a RCT conducted by Herrstedt et al14 of ondansetron-based two- and three-drug regimens for prevention of chemotherapy-induced nausea and vomiting among breast cancer patients undergoing multiple cycles of AC-based chemotherapy. We assumed that changes in emesis control over four cycles of AC for the palo-based two- and three-drug regimens were similar to the observed changes for the onda-based two- and three-drug strategies, respectively.14
Resource Utilization and Cost Data
The cost of antiemetic prophylaxis was based on the 2008 Medicare Part B reimbursement rates for pharmaceuticals, which reflects the price of ondansetron following its recent patent expiration (Table 3).15 The costs of prophylaxis failures were estimated as follows. In the majority of prophylaxis failures, the only cost is the cost of rescue medication. In such cases, we obtained costs by multiplying the individual doses used for rescue treatment of breast cancer patients on AC participating in the clinical trials comparing palo 0.25 mg with single doses of onda or dolasetron by their unit costs based on the 2008 Medicare Part B reimbursement rates.[5] and [15] For the few patients who are seen in the office for uncontrolled emesis, we obtained estimates of the risk of such emesis-related office visits based on the MarketScan Health Productivity Management (HPM) database from Thomson Reuters on 707 breast cancer patients who received their first cycle of AC-based chemotherapy between 1997 and 2002 (Table 2) and its costs from the 2008 Medicare Physician Fee Schedule Reimbursement for a level III office visit (CPT 99213).[16] and [17]
| COST COMPONENT | 2008 U.S.$ (RANGES) | DATA SOURCE |
|---|---|---|
| Hospitalization | $5,237.00 ($3,921−$6,112)a | HCUP charge data18 Consumer Price Index42 Medicare cost-to-charge ratio43 |
| Level III office visit (CPT 99213) | $60.30 ($19.96–$122.46)d | 2008 Medicare Physician Fee Schedule Reimbursement17 |
| Prophylactic antiemetics | 2008 Medicare Part B reimbursement rates for pharmaceuticals15 | |
| Onda-based two-drug regimen | $49.74 | |
| Palo-based two-drug regimen | $207.20 | |
| Onda-based three-drug regimen | $324.51 | |
| Palo-based three-drug regimen | $482.46 | |
| Rescue medicinesb | $35.25 ($21.66–$48.80)c | Eisenberg et al,4 Gralla et al,5 2008 Medicare Part B reimbursement rates for pharmaceuticals15 |
AC = anthracycline and cyclophosphamide; onda = ondansetron; palo = palonosetron; HCUP = Healthcare Cost and Utilization Project
a Charges were inflated to 2008 U.S. dollars using the Consumer Price Index (CPI) for medical care and adjusted to costs using Medicare cost-to-charge ratio. The ranges were based on estimates of the 95% confidence interval.b In the randomized clinical trial directly comparing ondansetron and palonosetron, propulsives accounted for 71% of the rescue medicines used, 5-hydroxytryptamine antagonists for 20%, glucocorticoids for 7%, and aminoalkyl ethers for 2%.5c Costs for rescue medication were obtained by multiplying all drug unit costs by the individual doses used for rescue treatment of breast cancer patients on AC participating in the clinical trials comparing palo 0.25 mg with single doses of onda or dolasetron.[5] and [15] The ranges were based on estimates of the 95% confidence interval.d Ranges were based on the Medicare physician fee schedule for levels I and VI office visits.
Finally, although hospitalization for emesis is extremely rare in this population, when it occurs, it is quite expensive. For completeness, we obtained estimates of the risk of emesis-related hospitalization from the same population of breast cancer patients from whom we obtained the estimate for the risk of emesis-related office visit, whereas hospital costs were obtained from Healthcare Cost and Utilization Project (HCUP) data on 2,342 breast cancer patients who were hospitalized with a primary or admitting diagnosis of vomiting or dehydration from 1997 to 2003 ([Table 2] and [Table 3]).[16] and [18]
Of note is that since palo was only introduced into the U.S. market in 2003, we anticipated the observed risk of emesis-related office visit and hospital admission obtained from MarketScan data during the period 1997−2002 reflected the risk associated with prophylaxis with onda. As a result, given that, when compared with onda, palo has also shown superiority in reducing the severity of emetic episodes when they occur, we estimated the differential rate of health-care resource utilization for palo and onda based on Haislip et al's reported differential incidence of extreme events associated with chemotherapy-induced nausea and vomiting (CINV) experienced by community-based breast cancer patients who received either palo or onda for emesis prophylaxis following the first cycle of chemotherapy (Table 2).[5] and [19]
Utility Data
We obtained the utility weights for acute and delayed emesis from a published study of preferences elicited from ovarian cancer patients undergoing chemotherapy using a modified visual analog scale (VAS) (Table 2).20 We equally applied these emesis-related utility weights to the initial 5-day period of chemotherapy (the standard duration of follow-up in clinical trials of prophylactic antiemetics) in all six prophylactic strategies of the decision tree. Furthermore, because the risk of CINV after 5 days of chemotherapy is usually so negligible as to be unmeasured in clinical trials of antiemetics, we assumed the utility weights for the remaining 16 days of each of the chemotherapy cycles to be the same as the weight associated with complete emesis control (ie, 0.92). We subsequently converted the resulting estimates of quality-adjusted life days into quality-adjusted life years (QALY).
Analysis
We used a stepwise method to calculate the incremental cost–effectiveness ratios of the different prophylactic therapy strategies, with the generic onda-based two-drug therapy (ie, the lowest cost strategy) as the base comparator (also known as the “anchor”).21 We adopted the benchmark range of U.S. $50,000−$100,000 per QALY, which has been commonly cited for oncology-related interventions as the threshold for acceptable cost–effectiveness, and examined the robustness of the results by performing one-way sensitivity analyses of plausible ranges for the model's key parameters based on the data sources used as well as probabilistic sensitivity analysis using Monte Carlo simulation.[21] and [22]
Results
The overall rate of emesis control (on days 1−5) among breast cancer patients following a cycle of AC-based chemotherapy was estimated to be 63% (range 46%−79%) for the onda-based two-drug therapy, 74% (range 66%−85%) for the palo-based two-drug therapy, 76% (range 75%−82%) for the onda-based three-drug therapy, and 92% (range 81%−96%) for the palo-based three-drug therapy. Based on these estimates, relative to the onda-based two-drug therapy, the incremental cost–effectiveness ratios (ICERs) for the palo-based regimens were $115,490/QALY for the two-drug strategy, $199,375/QALY for the two-drug regimen plus aprepitant after emesis, and $200,526/QALY for the three-drug strategy (Table 4). The onda-based two-drug combination plus aprepitant after the onset of emesis was eliminated through extended dominance as it has a greater ICER than the next more effective therapy, the palo-based two-drug treatment strategy (Table 4). The onda-based three-drug strategy was dominated by the palo-based two-drug combination plus aprepitant after the onset of emesis as the former strategy is both less effective and more expensive than the latter (Table 4).
