Cost-Effectiveness of Ribociclib for Hormone Receptor-Positive HER2-Negative Advanced Breast Cancer

Figures & data

Figure 1 Schematics of the decision tree and the Markov state transition model.

Notes: A network of four health states linked by transitional variables. During each 4-weeks cycle, patients either remained in their assigned health state or progressed to a new health state. It was assumed that the patients could not go back to previous health states.

Abbreviation: M, Markov node.

Table 1 Model Parameters: Baseline Values, Ranges, and Distributions for Sensitivity Analysis

Parameters	Baseline Value (Range)		Reference	Distribution
	RIB + FUL	FUL
Weibull survival model
OS of Ribociclib	Scale = 0.001327; Shape = 1.566; r^2 = 0.9967		[^Citation10]	–
OS of Placebo	Scale = 0.001579; Shape = 1.601; r^2 = 0.9922		[^Citation10]	–
PFS1 of Ribociclib	Scale = 0.040709; Shape = 0.892; r^2 = 0.9955		[^Citation10]	–
PFS1 of Placebo	Scale = 0.061186; Shape = 0.919; r^2 = 0.9997		[^Citation10]	–
PFS2 of Ribociclib	Scale = 0.005990; Shape = 1.266; r^2 = 0.9878		[^Citation10]	–
PFS2 of Placebo	Scale = 0.008061; Shape = 1.284; r^2 = 0.9972		[^Citation10]	–
Cost data, $
Ribociclib per cycle	13,835 (11,068–16,602)		[^Citation23]	γ
Fulvestrant per cycle	1129 (903–1355)		[^Citation22]	γ
Routine follow-up of patients per unit	1139 (911–1367)		[^Citation15]	γ
Best supportive care per cycle	2933 (2346–3520)		[^Citation15]	γ
End-of-life care once	9032 (7226–10,838)		[^Citation39]	γ
First subsequent treatment, $
Chemotherapy per cycle	496 (397–595)	535 (428–642)	[^Citation10,Citation22,Citation23]	C: γ, R: β
Hormone therapy per cycle	180 (144–216)	204 (163–245)	[^Citation10,Citation23]	C: γ, R: β
Targeted therapy per cycle	15 (12 −18)	16 (13–19)	[^Citation10,Citation22]	C: γ, R: β
Utility
PFS	0.715 (0.572–0.858)		[^Citation40]	β
1st PD	0.443 (0.354–0.532)		[^Citation40]	β
2nd PD	0.23 (0.18–0.276)		[^Citation41]	β
Death	0		-	-
Body weight (kg)	70 (56–84)		[^Citation19]	γ
Body surface area (meters^2)	1.79 (1.78–1.80)		[^Citation19]	γ
Discount rate	0.03		[^Citation16]	-

Abbreviations: C, cost; R, rate; OS, overall survival; PD, progression disease; PFS, progression-free survival.

Table 2 Incidence and Expenditures on Grade 3 or 4 AEs

Parameters	Baseline Value (Range)		Reference	Distribution
	RIB + FUL	FUL
AEs incidence (grade 3 or 4)
Neutropenia	0.571 (0.457–0.685)	0.008 (0.006–0.010)	[^Citation10]	β
Leukopenia	0.155 (0.124–0.186)	0	[^Citation10]	β
Infections	0.077 (0.062–0.092)	0.037 (0.030–0.044)	[^Citation10]	β
Hepatobiliary toxicity	0.137 (0.110–0.164)	0.058 (0.046–0.070)	[^Citation10]	β
QT interval prolongation	0.031 (0.025–0.037)	0.012 (0.010–0.014)	[^Citation10]	β
Rate of treatment discontinuation for AE	0.089 (0.071–0.107)	0.037 (0.030–0.044)	[^Citation10]	β
Expenditures on AEs (grade 3 or 4), $
Neutropenia per unit	17,181 (16,110–18,429)		[^Citation37]	γ
Leukopenia per unit	17,181 (16,110–18,429)		[^Citation37]	γ
Infections per unit	12,657 (10,126–15,188)		[^Citation39]	γ
Hepatobiliary toxicity per unit	5915 (4732–7098)		[^Citation38]	γ
QT interval prolongation per unit	25,236 (23,820–26,570)		[^Citation37]	γ

Abbreviations: AE, adverse event; FUL, fulvestrant; RIB, ribociclib.

Table 3 Base Case Results

	Total Cost ($)	LYs	QALYs	ICER per LY	ICER per QALY	Probability of Cost-Effectiveness
PFS stage
RIB + FUL	408,032	1.87	1.34	622,295	876,870	–
FUL	22,209	1.25	0.90	–	–	–
1st progression state
RIB + FUL	33,349	1.38	0.61	8927	19,640	–
FUL	32,367	1.27	0.56	–	–	–
2nd progression state
RIB + FUL	50,709	0.96	0.22	–	–	–
FUL	54,941	1.04	0.24	52,900	211,600	–
Total model
RIB + FUL	500,523	4.21	2.17	587,956	813,132	0
FUL	118,351	3.56	1.70	–	–	–
RIB at 50% cost + FUL	331,949	4.21	2.17	328,612	454,464	0
RIB at 20% cost + FUL	230,804	4.21	2.17	173,005	239,262	5.3%
RIB at 10% cost+ FUL	197,090	4.21	2.17	121,137	167,530	53.9%

Abbreviations: FUL, fulvestrant; ICER, incremental cost-effectiveness ratio; LY, life years; PFS, progression-free survival; QALY, quality-adjusted life years; RIB, ribociclib.

Figure 2 Tornado diagram for the one-way sensitivity analysis.

Notes: The dark blue bar represents the upper bounds and the light blue bar represents the lower bounds for each variable.

Abbreviations: FUL, fulvestrant; ICER, incremental cost-effectiveness ratio; PD, progression disease; PFS, progression-free survival; RIB, ribociclib; QALY, quality-adjusted life year.

Figure 3 Probabilistic sensitivity analysis.

Notes: (A) Cost-effectiveness acceptability curves revealed the effects of cost on the probability of being cost-effective; (B) Incremental cost-effectiveness scatterplot for 10,000 Monte Carlo simulations revealed a low probability of cost effectiveness.

Abbreviations: FUL, fulvestrant; RIB, ribociclib; QALY, quality-adjusted life year; WTP, willingness-to-pay.

Slamon DJ, Neven P, Chia S, et al. Overall survival with ribociclib plus fulvestrant in advanced breast cancer. N Engl J Med. 2020;382(6):514–524. doi:10.1056/NEJMoa191114931826360

 PubMed Web of Science ®Google Scholar

Drugs.com [online]. 2020 Available from: https://www.drugs.com/price-guide/faslodex. Accessed 513¸ 2020.

 Google Scholar

Centers for medicare and medicaid services: medicare Part B drug average sale price. 2020 Available from: https://www.cms.gov/medicare/medicare-part-b-drug-average-sales-price/2020-asp-drug-pricing-files. Accessed 516, 2020.

 Google Scholar

Zhang Y, Zeng X, Deng H, et al. Cost-effectiveness analysis of adding palbociclib as a second-line endocrine therapy for HR(+)/HER2(-) metastatic breast cancer from the US and Chinese perspectives. Clin Ther. 2019;41(6):1175–1185. doi:10.1016/j.clinthera.2019.04.03331104762

 PubMed Web of Science ®Google Scholar

Sorensen SV, Goh JW, Pan F, et al. Incidence-based cost-of-illness model for metastatic breast cancer in the United States. Int J Technol Assess Health Care. 2012;28(1):12–21. doi:10.1017/S026646231100064X22617734

 PubMed Web of Science ®Google Scholar

Lloyd A, Nafees B, Narewska J, Dewilde S, Watkins J. Health state utilities for metastatic breast cancer. Br J Cancer. 2006;95(6):683–690. doi:10.1038/sj.bjc.660332616967055

 PubMed Web of Science ®Google Scholar

Mamiya H, Tahara RK, Tolaney SM, Choudhry NK, Najafzadeh M. Cost-effectiveness of palbociclib in hormone receptor-positive advanced breast cancer. Ann Oncol. 2017;28(8):1825–1831. doi:10.1093/annonc/mdx20128472324

 PubMed Web of Science ®Google Scholar

Kohn CG, Zeichner SB, Chen Q, Montero AJ, Goldstein DA, Flowers CR. Cost-effectiveness of immune checkpoint inhibition in BRAF wild-type advanced melanoma. J Clin Oncol. 2017;35(11):1194–1202. doi:10.1200/JCO.2016.69.633628221865

 PubMed Web of Science ®Google Scholar

Huntington SF, von Keudell G, Davidoff AJ, Gross CP, Prasad SA. Cost-effectiveness analysis of brentuximab vedotin with chemotherapy in newly diagnosed stage III and IV hodgkin lymphoma. J Clin Oncol. 2018;36(33):3307.

 Web of Science ®Google Scholar

Wong W, Yim YM, Kim A, et al. Assessment of costs associated with adverse events in patients with cancer. PLoS One. 2018;13(4):e0196007. doi:10.1371/journal.pone.019600729652926

 PubMed Web of Science ®Google Scholar

Rashid N, Koh HA, Baca HC, Lin KJ, Malecha SE, Masaquel A. Economic burden related to chemotherapy-related adverse events in patients with metastatic breast cancer in an integrated health care system. Breast Cancer. 2016;8:173–181.27785099

 PubMedGoogle Scholar