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 $100,000/QALY threshold. Future research incorporating the price structure of all antiemetics following ondansetron's recent patent expiration is needed.
| STRATEGY | TOTAL COST (U.S.$) | INCREMENTAL COST (U.S.$) | EFFECTIVENESS (QALY) | INCREMENTAL EFFECTIVENESS (QALY) | INCREMENTAL COST–EFFECTIVENESS (U.S.$/QALY) |
|---|---|---|---|---|---|
| Onda-based two-drug therapy | $269 | — | 0.1989 | — | — |
| Onda-based two-drug therapy with aprepitant after emesis | $635 | $366 | 0.2010 | 0.0021 | $174, 286 Eliminated through extended dominancea |
| Palo-based two-drug therapy | $858 | $589 | 0.2040 | 0.0051 | $115,490c |
| Palo-based two-drug therapy plus aprepitant after emesis | $1,177 | $319 | 0.2056 | 0.0016 | 199,375 |
| Onda-based three-drug therapy | $1,336 | $159 | 0.205 | (0.0006) | Dominatedb |
| Palo-based three-drug therapy | $1,939 | $603 | 0.2094 | 0.0044 | $200,526d |
QALY = quality-adjusted life year; AC = anthracycline and cyclophosphamide; ICER = incremental cost–effectiveness ratio; onda = ondansetron; palo = palonosetron
a Extended dominance occurs when one of the treatment alternatives has a greater ICER than the next more effective alternative.b One intervention is said to be dominated by another when it is both less effective and more expensive than the previous less costly alternative.c Because the onda-based two-drug combination plus aprepitant after the onset of emesis was eliminated through extended dominance, the palo-based two-drug therapy was compared with the onda-based two-drug therapy.d Because the onda-based three-drug combination was dominated by the palo-based two-drug combination plus aprepitant after the onset of emesis, the palo-based three-drug therapy was compared with the latter regimen.
In sensitivity analyses using the commonly accepted cost–effectiveness benchmark range of $50,000−$100,000/QALY, the results were sensitive to changes in the overall emesis control rates for the onda-based two-drug strategy. If the probability of overall emesis control for the onda-based two-drug strategy was as low as its estimated lower bound (46%), the ICER for the palo-based two-drug treatment alternative would drop to $53,892/QALY. The results were also sensitive to changes in the effectiveness for the palo-based two-drug regimen: When its overall control rate was as high as its estimated upper bound (86%), its ICER would be $71,472. In contrast, the results were not sensitive to variations in the probability of overall emesis control for the three-drug strategies, nor were they sensitive to changes in the relative probability of emesis control in subsequent cycles of AC for either the two- or three-drug strategies.
If the probability of emesis-related hospitalization was as high as the upper limit of its 95% confidence interval (CI), the ICER for the palo-based two-drug regimen would be $97,301/QALY. However, changes in the cost of an emesis-related admission (95% CI $3,921−$6,112) did not significantly alter the results, nor did variations in office visit and rescue medicine utilization and their associated costs. The results were also not sensitive to variations in the values for the utility weights throughout their 95% CIs. We performed a threshold analysis to explore the price per dose of palo that would result in an acceptable cost–effectiveness ratio under the $100,000/QALY benchmark and found that the ICER for the palo-based two-drug treatment alternative would only fall to a $100,000/QALY threshold when the cost of palo is decreased by 11%.
Figure 2 shows the cost–effectiveness acceptability curves for each strategy, with the onda-based two-drug therapy as the base comparator. These curves show the proportion of the 100,000 simulations in which the comparing antiemetic regimen was considered more cost-effective than the base comparator at different thresholds. Using the benchmark of U.S. $100,000/QALY, the palo-based two-drug strategy and the two-drug regimen plus aprepitant following the onset of emesis were shown to be cost-effective in 39% and 26% of the simulations with the onda-based standard therapy as the baseline, respectively, whereas the palo-based and onda-based three-drug strategies and the onda-based two-drug regimen with aprepitant after emesis were cost-effective in fewer than 10% of the simulations. Of note is that the slope of the acceptability curves for the palo-based two-drug strategies are steep when willingness to pay exceeds $50,000/QALY, indicating that the greater the threshold, the greater the increase in the level of confidence that these strategies could be cost-effective. For example, the probability that the palo-based two-drug strategy is more cost-effective than the onda-based two-drug strategy rises to 51% at a threshold value of $125,000/QALY and exceeds 60% at $150,000/QALY.
