Cost-effectiveness of denosumab vs zoledronic acid for prevention of skeletal-related events in patients with solid tumors and bone metastases in the United States

Figures & data

Figure 1.  Depiction of Markov model states. *Not included in the base case scenario. SRE, skeletal-related event; AE, adverse event.

Table 1.  Skeletal-related event and drug discontinuation rates included in the model.

Model input	CRPC10,16		Breast cancer10,17		NSCLC10
	Dmab	ZA	Dmab	ZA	Dmab	ZA
Annual SRE rate	1.500	1.903	0.980	1.267	2.242	2.634
Annual drug discontinuation rate	0.409	0.476	0.284	0.288	0.842	1.009

SRE, skeletal-related event; CRPC, castration-resistant prostate cancer; NSCLC, non-small-cell lung cancer; Dmab, denosumab; ZA, zoledronic acid.

Table 2.  Baseline utilities and skeletal-related event QALY decrements.

	CRPC	Breast cancer	NSCLC
Baseline utility	0.680	0.660	0.560
SRE QALY decrement38
Pathologic fracture		0.070
Radiation to the bone		0.100
Surgery to the bone		0.140
Spinal cord compression^a		0.560
Weighted average SRE QALY decrement^b	0.150	0.142	0.124

^aSRE QALY decrement based on a 50:50 split between spinal cord compression with and without paralysis39.

^bDifferences in the composite SRE QALY decrement reflect differences in the distribution of the different SRE types.

SRE, skeletal-related event; QALY, quality-adjusted life year; CRPC, castration-resistant prostate cancer; NSCLC, non-small-cell lung cancer.

Table 3.  Costs of skeletal-related events (2011 USD)9.

Cost inputs	CRPC	Breast cancer	NSCLC
SRE by type
Pathologic fracture	$8382	$9854	$9118
Radiation to the bone	$9027	$11,512	$10,269
Surgery to the bone	$35,834	$29,792	$32,813
Spinal cord compression	$25,983	$22,845	$24,414

Note: No SRE costs were available for NSCLC so the average cost of CRPC and breast was used.

Costs were inflated from 2009 to 2011 prices using Medical Care Services Consumer Price Index39.

CRPC, castration-resistant prostate cancer; NSCLC, non-small-cell lung cancer; SRE, skeletal-related event.

Table 4.  Real-world skeletal-related event type distribution44,45.

	CRPC	Breast cancer	NSCLC
Pathologic fracture events	19%	29%	14%
Radiation to the bone events	68%	59%	79%
Surgery to the bone events	1%	1%	1%
Spinal cord compression events	12%	11%	6%

CRPC, castration-resistant prostate cancer; NSCLC, non-small-cell lung cancer.

Table 5.  Cost-effectiveness of denosumab vs zoledronic acid base case results.

	CRPC			Breast cancer			NSCLC
	Dmab	ZA	Diff	Dmab	ZA	Diff	Dmab	ZA	Diff
Total lifetime number of SREs	3.23	4.04	−0.81	3.56	4.55	−0.99	2.46	2.84	−0.39
Total lifetime QALYs	0.97	0.83	0.14	1.76	1.59	0.17	0.33	0.27	0.06
Total lifetime costs ($)	76,486	69,577	6910	108,538	95,087	13,451	49,068	44,993	4076
Cost per QALY gained ($)	49,405			78,915			67,931
Cost per SRE avoided ($)	8567			13,557			10,513

CRPC, castration-resistant prostate cancer; NSCLC, non-small-cell lung cancer; Dmab, denosumab; ZA, zoledronic acid; Diff, difference; SRE, skeletal-related event; QALY, quality-adjusted life year.

Table 6.  Cost-effectiveness of denosumab vs zoledronic acid scenario analyses results.

	CRPC	Breast cancer	NSCLC
With drug discontinuation
Cost per QALY gained	$42,526	$78,175	$49,781
Cost per SRE avoided	$7120	$13,818	$7130
With ONJ, acute phase reactions, hypocalcemia and renal toxicity considered
Cost per QALY gained	$49,428	$78,935	$67,959
Cost per SRE avoided	$8571	$13,562	$10,518

CRPC, castration-resistant prostate cancer; NSCLC, non-small-cell lung cancer; QALY, quality-adjusted life year; SRE, skeletal-related event.

Figure 2.  One-way sensitivity analyses of the effect of the input parameters on cost per QALY gained. SRE, skeletal-related events; IV, intravenous; QALY, quality-adjusted life year; SC, subcutaneous.

Figure 3.  Cost-effectiveness acceptability curves (CEACs) of denosumab vs zoledronic acid in the prevention of skeletal-related events in patients with castration-resistant prostate cancer and bone metastases. The curves illustrate the probability of denosumab being cost-effective relative to zoledronic acid and vice-versa based on different thresholds of willingness to pay. The probability of denosumab being cost-effective relative to zoledronic acid increases as the willingness to pay threshold increases. QALY, quality-adjusted life year.

Figure 4.  Cost-effectiveness of denosumab vs zoledronic acid relative to other select innovative oncology therapies58,60–62. *Costs inflated to 2010 using proportional increase in US consumer price index from 2000 to 2010 (http://www.bls.gov/data). **In patients with wild-type KRAS. ^†Costs in 2010 USD for historical data. ZA, zoledronic acid; PBO, placebo; PC, prostate cancer; CRC, colorectal cancer; ER + ve, estrogen receptor positive; BC, breast cancer; HER2 + ve, HER2-receptor positive; NSCLC, non-small-cell lung cancer; CML, chronic myeloid leukemia; CRPC, castration resistant prostate cancer; WHO, World Health Organization.

Hatoum HT, Lin SJ, Smith MR, et al. Zoledronic acid and skeletal complications in patients with solid tumors and bone metastases: analysis of a national medical claims database. Cancer 2008;113:1438-45

 PubMed Web of Science ®Google Scholar

Fizazi K, Carducci M, Smith M, et al. Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study. Lancet 2011;377:813-22

 PubMed Web of Science ®Google Scholar

Stopeck AT, Lipton A, Body JJ, et al. Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer: a randomized, double-blind study. J Clin Oncol 2010;28:5132-9

 PubMed Web of Science ®Google Scholar

Matza LS, Van Brunt K, Chung K. Health state utilities for skeletal-related events associated with bone metastases. J Clin Oncol 2011;19(suppl), Abstract e16620

 Google Scholar

Levack P, Collie D, Gibson A, et al. A prospective audit of the diagnosis, management and outcome of malignant cord compression. CRAG Report 97/08. Edinburgh: CRAG, 2001

 Google Scholar

Barlev A, Song X, Ivanov B, et al. Payer costs for inpatient treatment of pathologic fracture, surgery to bone, and spinal cord compression among patients with multiple myeloma or bone metastasis secondary to prostate or breast cancer. J Manag Care Pharm 2010;16:693-702

 PubMed Web of Science ®Google Scholar

Sathiakumar N, Delzell E, Morrisey MA, et al. Mortality following bone metastasis and skeletal-related events among women with breast cancer: a population-based analysis of U.S. Medicare beneficiaries, 1999-2006. Breast Cancer Res Treat 2012;131:231-8

 Google Scholar

Sathiakumar N, Delzell E, Morrisey MA, et al. Mortality following bone metastasis and skeletal-related events among men with prostate cancer: a population-based analysis of US Medicare beneficiaries, 1999-2006. Prostate Cancer Prostatic Dis 2011;14:177-83

 PubMed Web of Science ®Google Scholar

Nadler E, Eckert B, Neumann PJ. Do oncologists believe new cancer drugs offer good value? Oncologist 2006;11:90-5

 PubMed Web of Science ®Google Scholar