To our knowledge, this was the first report to evaluate the cost-effectiveness of olanzapine in a four-drug antiemetic regimen. In the base-case analysis, the ICER of olanzapine added to the three-drug regimen was 5,156 USD/QALY, which was lower than the set WTP. Furthermore, the probabilistic sensitivity analysis revealed a 100% probability for the cost-effectiveness of olanzapine. These results indicated that olanzapine was cost-effective in the four-drug antiemetic regimen, with a cisplatin-containing HEC regimen. Although, it is necessary to pay attention to adverse effects such as hyperglycemia and QT prolongation. Olanzapine was recommended, not only for its antiemetic effects, but also for its cost-effectiveness.
Chanthawong et al. reported that compared to the doublet antiemetic regimen (dexamethasone plus first-generation 5-HT3 receptor antagonist), the addition of olanzapine resulted in incremental QALY of 0.0022–0.0026, with cost savings of 2.98 USD, 27.71 USD, and 52.20 USD in Thailand, Malaysia, and Indonesia, respectively . At the same time, they reported that in Singapore, switching from aprepitant to olanzapine in a triplet antiemetic regimen (dexamethasone, first-generation 5-HT3 receptor antagonist, and aprepitant) resulted in cost savings of 60.91 USD and incremental QALYs of 0.0005 . In Japan, there have been several reports examining the cost-effectiveness of aprepitant and palonosetron [12–14]. Kashiwa et al. reported the cost-effectiveness of palonosetron in cisplatin-containing HEC regimens based on the TRIPLE study results conducted in Japan [13, 21]. The calculated ICER for palonosetron compared to granisetron was 16,204,591 JPY/QALY (144,465 USD/QALY). Tsukiyama et al. reported that the cost-effectiveness of aprepitant for HEC regimens was 3,906,698 JPY/QALY (35,951 USD/QALY) in the outpatient care setting and 6,195,781 JPY/QALY (56,952 USD/QALY) in the inpatient care setting . The calculated ICER for olanzapine in our study was substantially lower than those obtained in the aforementioned studies because olanzapine cost less than antiemetics such as aprepitant and palonosetron. The one-way sensitivity analysis showed that the second most influential parameter on ICER was the drug price of olanzapine, and the cost of antiemetics was a factor that directly influenced ICER. In Japan, the cost of olanzapine (5 mg for four days) was 6.16 USD. Aprepitant for three days cost 82.11 USD, and single-dose palonosetron cost 137.04 USD. These indicated that the difference in drug cost per regimen had a significant impact on ICER.
This study had some limitations. First, this study only included cisplatin-based regimens. Navari et al. reported that the addition of 10 mg of olanzapine to a three-drug regimen significantly improved acute and delayed CINV in patients who were receiving anthracycline-cyclophosphamide (AC) or cisplatin (≥ 70 mg per square meter of body-surface area) . However, we did not use the results of Navari et al. because severe sedation occurred in 5% of patients in their study, and there was minimal opportunity to use 10 mg in Japan because of concerns about drowsiness. To the best of our knowledge, no placebo-controlled, randomized, or randomized trial has demonstrated the efficacy of olanzapine 5 mg for the AC regimen. The MASCC/ESMO stated that the clinically meaningful difference was at least 10% . In the J-FORCE study cited in our model, the CP rate in the delayed phase was 60% in the olanzapine group and 50% in the non-olanzapine group . If the same efficacy level is demonstrated in the AC regimen, olanzapine will be highly cost-effective in the AC regimen. Second, the approved palonosetron dose in Japan is 0.75 mg, which was different from other countries. ASCO, NCCN, and MASCC/ESMO guidelines recommended 0.25 mg intravenous and 0.5 mg oral palonosetron [2–4]. The dosage of palonosetron in Japan was set to 0.75 mg because a domestic phase II study on moderately emetogenic chemotherapy showed that this dosage had a higher delayed phase CR rate than 0.25 mg . Although, no statistically significant difference was observed. However, since the Navari et al. report included 75% of patients using 0.25 mg of palonosetron as a 5-HT3 receptor antagonist, the difference in palonosetron dose may have had a small effect on the results of this study. Third, this study did not take into account additional hospitalization, laboratory, and consultation costs. However, when these costs were included in the analysis, they added additional costs to the non-olanzapine group, further favoring the olanzapine group. Therefore, the omission of these costs did not affect the results and robustness of this study.
In conclusion, olanzapine was highly cost-effective in highly emetogenic cisplatin-containing risk regimens. Therefore, the use of a four-drug regimen, including olanzapine, was recommended in terms of cost-effectiveness.