Research

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

Publish date: January 25, 2011

Figure 1.

Markov Model Comparing Palo-Based Therapy vs Onda-Based Therapy for Prophylaxis of Chemotherapy-Induced Emesis in Breast Cancer Patients Receiving Four Cycles of AC-Based Chemotherapy (1) Onda (32 mg intravenously) + dex (8 mg intravenously) on day 1, followed by dex (4 mg orally twice a day) on days 2−5. (2) Onda (32 mg intravenously) + dex (8 mg intravenously) on day 1, followed by dex (4 mg orally twice a day) on days 2−5 and aprepitant in the subsequent cycles following the occurrence of emesis (ie, onda 16 mg orally + aprepitant 125 mg orally + dex 12 mg orally on day 1 followed by aprepitant 80 mg orally on days 2−3). (3) Palo (0.25 mg intravenously) + dex (8 mg intravenously) on day 1, followed by dex (4 mg orally twice a day) on days 2−5. (4) Palo (0.25 mg intravenously) + dex (8 mg intravenously) on day 1, followed by dex (4 mg orally twice a day) on days 2−5 and aprepitant in the subsequent cycles following the occurrence of emesis (ie, palo 0.25 mg intravenously + aprepitant 125 mg orally + dex 12 mg orally on day 1 followed by aprepitant 80 mg orally on days 2−3). (5) Onda (16 mg orally) + aprepitant (125 mg orally) + dex (12 mg orally) on day 1 followed by aprepitant (80 mg orally) on days 2−3. (6) Palo (0.25 mg intravenously) + aprepitant (125 mg orally) + dex (12 mg orally) on day 1 followed by aprepitant (80 mg orally) on days 2−3. Palo = palonosetron; onda = ondansetron; AC = anthracycline and cyclophosphamide; dex, dexamethasone

We modeled emesis-related outcomes and direct medical costs (from a third-party payer perspective within the context of the U.S. health-care system) over a total of four cycles of chemotherapy as patients receiving AC-based regimens usually undergo at least four cycles of AC.¹⁰ We performed all analyses using TreeAge Pro 2009 Suite (Decision Analysis; TreeAge Software, Williamstown, MA). The study was submitted to our institutional review board and was determined to be exempt from review.

Probability Data

Two-drug prophylactic regimens

We estimated the effectiveness of the 5-HT₃ antagonists based on secondary analysis of the raw data from the randomized clinical trial (RCT) directly comparing onda and palo when used alone for prevention of emesis associated with MEC, including 90 breast cancer patients from the palo 0.25-mg arm and 82 from the onda 32-mg arm who received AC-based chemotherapy (Table 1).⁵ Effectiveness estimates for palo 0.25 mg were augmented by data on 117 breast cancer patients on AC-based chemotherapy participating in a multicenter RCT comparing palo with dolasetron (Table 1).⁴ We assumed that dex adds the same relative benefit to either first- or second-generation 5-HT₃ antagonists and obtained the expected additional benefit of dex in preventing acute emesis based on the results of an RCT comparing a single-dose of granisetron in combination with dex vs granisetron given alone to patients undergoing MEC (Table 2).¹¹ Since in the aforementioned study dex was only given on day 1 of chemotherapy, the estimated additional benefit of adding dex to a 5-HT₃ inhibitor on the delayed period was obtained from another RCT; this study, conducted by the Italian Group for Antiemetic Research, compared dex alone, dex plus onda, or placebo on days 2−5 of MEC.¹²

Table 1. Emesis Control During the Initial 5-Day Period Following Administration of AC-Based Chemotherapy to Patients with Breast Cancer

From Eisenberg et al ⁴ and Gralla et al ⁵

EMESIS CONTROL	PALO (0.25 MG)^[4]^and ^[5] (n = 207), % PATIENTS (95% CI)	ONDA (32 MG)⁵ (n = 82), % PATIENTS (95% CI)	P
Acute (day 1)	0.70 (0.63−0.76)	0.61 (0.50−0.71)	0.14
Delayed (days 2−5)	0.65 (0.58−0.71)	0.50 (0.39−0.61)	0.02
Overall (days 1−5)	0.55 (0.48−0.62)	0.40 (0.30−0.52)	0.02

AC = anthracycline and cyclophosphamide; palo = palonosetron; onda = ondansetron; CI = confidence interval

Table 2. Base-Case Probabilities, Utility Weights, and Data Sources ^e

MODEL PARAMETERS	BASE-CASE VALUES (RANGES)	DATA SOURCES
Probability of acute emesis control on cycle 1 of AC:
Onda-based two-drug strategy ^c	0.84 (0.74−0.93)	Gralla et al,^a The Italian Group ^[5]^and ^[11]
Palo-based two-drug strategy ^c	0.87 (0.81−0.94)	Eisenberg et al,^a Gralla et al,^a The Italian Group ^[4]^,^[5]^and ^[11]
Onda-based three-drug strategy ^d	0.88 (0.85−0.91)	Warr et al ⁷
Palo-based three-drug strategy ^d	0.96 (0.89−0.99)	Grote et al, Grunberg et al ^[40]^and ^[41]
Probability of delayed emesis control following control of acute emesis on cycle 1 of AC ^c:
Onda-based two-drug strategy ^d	0.75 (0.62–0.85)	The Italian Group ¹²
Palo-based two-drug strategy ^c	0.85 (0.78–0.91)	Eisenberg et al,^a Gralla et al,^a The Italian Group ^[4]^,^[5]^and ^[12]
Onda-based three-drug strategy ^d	0.86 (0.82–0.90)	Warr et al ⁷
Palo-based three-drug strategy ^c	0.96 (0.91–0.97)	Eisenberg et al,^a Gralla et al,^a Warr et al ^[4]^,^[5]^and ^[7]
Probability of delayed emesis control following acute emesis on cycle 1 of AC ^c:
Onda-based two-drug strategy ^c	0.46 (0.31–0.62)	Gralla et al,^a The Italian Group ^[5]^and ^[12]
Palo-based two-drug strategy ^c	0.44 (0.27–0.59)	Eisenberg et al,^a Gralla et al,^a The Italian Group ^[4]^,^[5]^and ^[12]
Onda-based three-drug strategy ^d	0.44 (0.29–0.57)	Warr et al ⁷
Palo-based three-drug strategy ^c	0.51 (0.41–0.67)	Eisenberg et al,^a Gralla et al,^a Warr et al ^[4]^,^[5]^and ^[7]
Relative probability of emesis control in subsequent cycles of AC ^c:
Two-drug therapy	0.987 (0.970–1.0)	Herrstedt et al ¹⁴ ^e
Three-drug therapy	1.013 (1.0–1.030)	Herrstedt et al ¹⁴ ^e
Probability of hospitalization (among patients who develop emesis) per cycle of AC ^d:
Onda-based regimens	0.0035 (0.0001−0.019)	Data from Medstat MarketScan ¹⁶
Palo-based regimens	0.0017 (0.00004−0.0089)	Data from Medstat MarketScan, Haislip et al ^[16]^and ^[19]^b
Probability of office visit use (among patients who develop emesis) per cycle of AC ^d:
Onda-based regimens	0.10 (0.07−0.14)	Data from Medstat MarketScan ¹⁶
Palo-based regimens	0.05 (0.03−0.07)	Data from Medstat MarketScan, Haislip et al ^[16]^and ^[19]^b
Probability of rescue medicine utilization use (among patients who develop emesis) per cycle of AC ^d:
Onda-based regimens	0.61 (0.46−0.75)	Gralla et al ⁵ ^a
Palo-based regimens	0.56 (0.45−0.66)	Eisenberg et al, Gralla et al ^[4]^and ^[5]^a
Utility weights for emesis per cycle of AC ^f:
Acute and delayed emesis	0.15 (0.10−0.20)	Sun et al ²⁰
Acute emesis and no delayed emesis	0.76 (0.70−0.83)	Sun et al ²⁰
No acute emesis and delayed emesis	0.20 (0.14−0.26)	Sun et al ²⁰
No acute and no delayed emesis	0.92 (0.86−0.99)	Sun et al ²⁰

Full-size table

AC = anthracycline and cyclophosphamide; onda = ondansetron; palo = palonosetron.

a Included in the analysis was the subset of women with breast cancer receiving AC-based chemotherapy.b We obtained an estimate of emesis-related hospitalization and office visit utilization based on data from Medstat MarketScan, HPM subset (Medstat Group, Inc., Ann Arbor, MI) on 707 breast cancer patients who received the first cycle of AC-based chemotherapy from 1996 to 2002 and either were admitted to the hospital or had an office visit for treatment of vomiting or dehydration. Since palo was only introduced into the U.S. market in 2003, we assumed that all these breast cancer patients received onda-based antiemetic prophylaxis. As a result, we estimated the differential rate of health-care resource utilization based on Haislip et al's 19 reported differential incidence of extreme events associated with chemotherapy-induced nausea and vomiting experienced by community-based breast cancer patients who received either onda or palo for emesis prophylaxis following the first cycle of chemotherapy.c Of note is that there are two different methods for applying the benefit of adding dex and/or aprepitant to a 5-HT3 antagonist: (1) rate of emesis with 5-HT3* relative risk of emesis by adding dex and/or aprepitant and (2) rate of emesis control with 5-HT3 * relative risk of emesis control by adding dex and/or aprepitant. These produce substantially different results, with the former method skewing the results toward the least effective 5-HT3 and the latter skewing it toward the most effective one. As a result, we estimated the probability of emesis by averaging the results obtained using the two different methods. Of note is that the ranges for these effectiveness estimates were obtained by applying the two different methods to the lower and upper bounds of the 95% confidence intervals derived from the clinical trials comparing the 5-HT3 antagonists when used alone.d Ranges were obtained by constructing 95% confidence intervals for observed proportions using the normal approximation to the binomial distribution.e Ranges are based on the minimum and maximum values observed in Herrstedt et al's 14 clinical trial of multicycle chemotherapy.f Ranges are based on the estimate's actual 95% confidence intervals obtained from Sun et al's 20 data.

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

Probability Data

Two-drug prophylactic regimens

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