Research

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.



 

Original research

Cost–Utility Analysis of Palonosetron-Based Therapy in Preventing Emesis Among Breast Cancer Patients

Elenir B.C. Avritscher MD, PhD, MBA/MHA

, a,
, Ya-Chen T. Shih PhDa, Charlotte C. Sun DrPHa, Richard J. Gralla MDa, Steven M. Grunberg MDa, Ying Xu MD, MSa and Linda S. Elting DrPHa

a Division of Quantitative Sciences, Department of Gynecologic Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas; The Monter Cancer Center, North Shore-Long Island Jewish Health System, Lake Success, New York; Division of Hematology/Oncology, University of Vermont, Burlington, Vermont
Received 8 February 2010;
accepted 28 September 2010.
Available online 25 January 2011.

Abstract

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.

Article Outline

Patients and Methods
Probability Data
Two-drug prophylactic regimens
Three-drug prophylactic regimens
Effectiveness of antiemetics over multiple cycles of chemotherapy
Resource Utilization and Cost Data
Utility Data
Analysis
Results
Discussion
Conclusion
Acknowledgements
References
Over the past decade, regimens containing anthracycline and cyclophosphamide (AC) have become the mainstay of adjuvant chemotherapy for treatment of breast cancer. Although each of these agents is individually considered moderately emetogenic, the combination of the two can lead to substantial nausea and vomiting.1 Despite remarkable recent progress in antiemetic prophylaxis, chemotherapy-induced emesis continues to be a major burden for patients with breast cancer and one of the most feared side effects of cancer treatment in general.[2] and [3]

Recent advances in emesis control have been possible due to the availability of increasingly more effective antiemetic agents. During the 1990s, the development of first-generation 5-hydroxytryptamine-3 (5-HT3) antagonists (ondansetron, granisetron, tropisetron, and dolasetron) marked a significant improvement in the control of emesis induced by chemotherapy, particularly acute emesis (ie, occurring within 24 hours following chemotherapy).

More recently, two new drugs—palonosetron, a second-generation 5-HT3 antagonist, and aprepitant, a centrally acting neurokinin-1 antagonist—were added to the armamentarium of antiemetic therapy. Compared with other single-dose 5-HT3 antagonists, palonosetron has a higher 5-HT3 binding affinity and longer plasma half-life and has shown superiority in the prevention of delayed emesis (ie, occurring more than 24 hours after chemotherapy administration) following moderately emetogenic chemotherapy with methotrexate, epirubicin, or cisplatin (MEC), including AC-based regimens.[4] and [5] In a recently published clinical trial conducted by Saito et al,6 palonosetron was also shown to be superior to granisetron in preventing delayed and overall emesis when both drugs were combined with dexamethasone following chemotherapy with either AC or cisplatin. As for aprepitant, when added to the standard of a 5-HT3 antagonist and dexamethasone therapy, it has been shown to improve emesis prevention among patients receiving AC-based chemotherapy during the acute, delayed, and overall periods.7

Such benefits have led to a recent revision in the antiemetics guidelines of both the American Society of Clinical Oncology (ASCO) and the National Comprehensive Cancer Network (NCCN), incorporating both palonosetron as one of the recommended 5-HT3 antagonists and aprepitant in combination with a 5-HT3 antagonist and dexamethasone for patients receiving AC-based chemotherapy.[8] and [9] Of note is that the revised 2010 NCCN antiemetic guidelines suggest that palonosetron may be used prior to the start of multiday chemotherapy, which is more likely to cause significant delayed emesis, instead of repeated daily doses of other first-generation 5-HT3 antagonists.9

Given the multiplicity of antiemetic strategies available for prophylaxis of nausea and vomiting associated with AC-based chemotherapy with inherent variability in effectiveness and price, it is critical for existing therapies to be analyzed in terms of both their outcomes and costs. Thus, the purpose of this study is to determine, from a third-party payer perspective, the cost-utility of palonosetron-based therapy in preventing emesis among breast cancer patients receiving four cycles of AC-based chemotherapy relative to generic ondansetron-based antiemetic therapy. Due to variations in the definition of complete emetic response found across antiemetic studies, the analysis will focus on chemotherapy-induced emesis only, rather than nausea and vomiting, as vomiting can be more objectively measured than nausea and, as such, has been more consistently reported.

Patients and Methods

We developed a Markov model to estimate the costs (in 2008 U.S. dollars) and health outcomes associated with emesis among breast cancer patients receiving multiple cycles of AC-based chemotherapy under six prophylactic strategies containing either generic ondansetron (onda) or palonosetron (palo) when each is combined with either dexamethasone (dex) alone, dex plus aprepitant in the subsequent cycles following the occurrence of emesis, or dex plus aprepitant up front (Figure 1). The time horizon for the risk of chemotherapy-induced emesis during each cycle of chemotherapy was 21 days, which is the standard duration of a cycle of AC-based chemotherapy.

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