Using the 21-gene assay to guide adjuvant chemotherapy decision-making in early-stage breast cancer: a cost-effectiveness evaluation in the German setting

Figures & data

Figure 1.  Overview of the 21-gene assay cost-effectiveness model structure. ESBC, early-stage breast cancer; ODX, 21-gene assay; M, Markov node. Squares represent decision nodes, circles represent chance nodes (or Markov nodes where designated) and triangles represent transitions to health states. Health states are designated using block capitals.

Table 1.  Changes in adjuvant therapy recommendations for breast cancer patients in Germany following 21-gene assay testing.

Patients	Chemotherapy (CT)	Pre-21-gene assay recommendation	Post-21-gene assay recommendation	Therapy administered^a	Change in chemotherapy
					n	Net^b	Relative^c
All (n = 366)	No CT	157 (42.9%)	196 (53.6%)	226 (61.7%)	69	−18.9%	−33.0%
	CT	209 (57.1%)	170 (46.4%)	140 (38.3%)
Node-negative (n = 244)	No CT	127 (52.0%)	144 (59.0%)	161 (66.0%)	34	−13.9%	−29.1%
	CT	117 (48.0%)	100 (41.0%)	83 (34.0%)
Node-positive (n = 122)	No CT	30 (24.6%)	52 (42.6%)	65 (53.3%)	35	−28.7%	−38.0%
	CT	92 (75.4%)	70 (57.4%)	57 (46.7%)
Low Recurrence Score (n = 198)	No CT	98 (49.5%)	163 (82.3%)	171 (86.4%)	73	−36.9%	−73%
	CT	100 (50.5%)	35 (17.7%)	27 (13.6%)
Intermediate Recurrence Score (n = 139)	No CT	52 (37.4%)	32 (23.0%)	54 (38.8%)	2	−1.4%	−2.3%
	CT	87 (62.6%)	107 (77.0%)	85 (61.2%)
High Recurrence Score (n = 29)	No CT	7 (24.1%)	1 (3.4%)	1 (3.4%)	6	+20.7%	+27.2%
	CT	22 (75.9%)	28 (96.6%)	28 (96.6%)

^aTherapy administered varied from post-21-gene assay recommendations as a proportion of patients chose not to follow the recommendation (most of whom decided against chemotherapy). ^b Total change in number of chemotherapies applied regardless of pre-test recommendation. ^c Number of chemotherapies applied in relation to number of patients with initial chemo recommendation.

Table 2.  Summary of mean costs of adjuvant chemotherapy per patient in breast cancer patients in Germany.

	All patients (n = 70) (€)	Node-positive (n = 40) (€)	Node-negative (n = 30) (€)
Chemotherapy medications	6444	6935	5788
Chemotherapy administration*	1007	1019	991
Supportive medications	2728	4105	893
Chemotherapy monitoring	160	156	166
Transportation	242	260	217
Management of adverse events	3082	5073	428
Absenteeism	5,600	5,600	5,600
Total cost	19,263	23,148	14,083

*Chemotherapy administration fee is based on diagnosis related group (DRG) fee for inpatient administration.

€, 2011 Euros; Mean cost per patient are presented.

Table 3.  Summary of distributions used in the probabilistic sensitivity analysis.

Parameter	Mean	Min/Alpha*	Max/Beta*	SE	Distribution
Patient characteristics
Mean age (years)	56.30	17	100	5.63	Normal
Allocation of adjuvant therapy
Net change in chemotherapy use Low RS	−20.00%	−30.00%	−10.00%	2.00%	Normal
Net change in chemotherapy use Intermediate RS	−0.50%	−0.25%	−0.75%	0.05%	Normal
Net change in chemotherapy use High RS	1.60%	0.80%	2.40%	0.16%	Normal
Event rates
Ten year endocrine therapy risk of recurrence (Low RS)	3.20%	1.60%	4.80%	1.60%	Normal
Ten year endocrine therapy risk of recurrence (Int RS)	9.10%	4.55%	13.65%	4.30%	Normal
Ten year endocrine therapy risk of recurrence (High RS)	39.50%	19.75%	59.25%	7.30%	Normal
RRR with chemotherapy for Intermediate RS	39%	19.50%	58.50%	4.43%	Normal
RRR with chemotherapy for High RS	74%	37.00%	111.00%	3.95%	Normal
Post recurrence survival	3.30	1.65	4.95	0.330	Normal
Costs
21-gene assay	3,180	100	32	318.00	Gamma
Hormone therapy (years 1–5)	302	100	3	30.20	Gamma
Hormone therapy (years 6–8)	302	100	3	30.20	Gamma
Chemotherapy	16,181	100	162	1618.10	Gamma
Endocrine therapy adverse events (years 1–5)	691	100	7	69.10	Gamma
Endocrine therapy adverse events (years 6–8)	691	100	7	69.10	Gamma
Chemotherapy adverse events	3,082	100	31	308.20	Gamma
Distant recurrence	20,955	100	210	2095.50	Gamma
Utilities
Decrement associated with chemotherapy	0.07	92.93	1234.64	0.01	Beta
One year recurrence free	0.78	111.02	31.31	0.03	Beta
One year post recurrence	0.60	220.85	147.24	0.03	Beta

*Min (minimum) and Max (maximum) were used to define the limits of the normal distributions in probabilistic sensitivity analysis, and alpha and beta parameters were used to define beta and gamma distributions. RS, Recurrence Score; RRR, relative risk reduction; Int, intermediate.

Table 4.  Summary of cost-effectiveness outcomes for the base case analysis of 21-gene assy testing vs standard care.

	21-gene assy	Standard care	Difference
Life expectancy (years)	17.01	16.94	0.06
Quality-adjusted life expectancy (QALYs)	13.19	13.12	0.06
Direct costs (€)	19,269	19,830	−561
Outcome/ICER	21-gene assy is dominant to standard care(cost and life saving)

QALY, quality-adjusted life year; €, 2011 Euros; ICER, incremental cost-effectiveness ratio.

Figure 2.  Cost-effectiveness scatterplot of the probabilistic sensitivity analysis. The cost-effectiveness scatterplot shows incremental costs vs incremental effectiveness expressed in quality-adjusted life years (QALYs) for the comparison of 21-gene assy with standard care. Each point represents one iteration of the probabilistic sensitivity analysis (with data based on sampling from distributions around clinical and cost parameters).

Figure 3.  Cost-effectiveness acceptability curve for 21-gene assay vs standard care from the probabilistic sensitivity analysis. The acceptability curve shows the percentage of points from the probabilistic sensitivity analysis (see Figure 2) that fall below a range of willingness-to-pay values from €0 to €40,000 per quality-adjusted life year gained.

Table 5.  Summary of sub-group and sensitivity analysis outcomes for 21-gene assay testing vs standard care.

	Quality-adjusted life expectancy (QALYs)			Direct costs (€)			ICER*/Outcomes
	21-gene assay	Standard care	Difference	21-gene assay	Standard care	Difference
Base case	13.19	13.12	0.06	19,269	19,830	−561	Dominant
Node-positive patients	8.76	8.70	0.06	30,848	34,529	−3680	Dominant
Node-negative patients	13.17	13.11	0.06	16,783	15,720	1062	16,667
Time horizon 10 years	8.49	8.48	0.01	18,343	18,868	−525	Dominant
Time horizon 20 years	14.01	13.97	0.04	18,947	19,501	−554	Dominant
Time horizon 40 years	17.85	17.78	0.07	19,359	19,920	−561	Dominant
Discount rate 0%	18.72	18.62	0.10	20,777	21,357	−590	Dominant
Discount rate 5%	10.82	10.77	0.05	18,519	19,066	−548	Dominant
Discount rate 7%	9.10	9.06	0.04	17,930	18,441	−537	Dominant
Discount rate 10%	7.30	7.27	0.03	17,159	17,684	−525	Dominant
Baseline age +5 years	12.22	12.17	0.06	19,077	19,634	−557	Dominant
Baseline age −5 years	13.79	13.73	0.07	19,394	19,957	−563	Dominant
Chemotherapy costs +20%	13.19	13.12	0.06	20,505	21,678	−1172	Dominant
Chemotherapy costs −20%	13.19	13.12	0.06	18,033	17,982	50	800
Including lost productivity costs for chemotherapy	13.19	13.12	0.06	22,503	21,057	−1446	Dominant
Distant recurrence costs +20%	13.19	13.12	0.06	19,633	20,217	−584	Dominant
Distant recurrence costs −20%	13.19	13.12	0.06	18,905	19,443	−538	Dominant
Disutility for chemotherapy −0.037	13.20	13.14	0.06	19,269	19,830	−561	Dominant
Disutility for chemotherapy −0.5	13.02	12.88	0.14	19,269	19,830	−561	Dominant
Utility score for recurrence 0.51	13.16	13.10	0.06	19,269	19,830	−561	Dominant
Post-recurrence survival +50%	13.26	13.20	0.06	19,269	19,830	−561	Dominant
Post recurrence survival −50%	13.11	13.04	0.07	19,269	19,830	−561	Dominant
Relative risk of recurrence 1.1% in the low RS group	13.33	13.27	0.06	18,900	19,460	−561	Dominant
Recurrence risks derived from Dowsett et al.12	12.99	12.94	0.05	19,752	20,289	−536	Dominant
Net change in chemotherapy use +10% in low RS group	13.18	13.12	0.06	21,195	19,830	1356	24,286
Net change in chemotherapy use −10% in low RS group	13.56	13.12	0.43	17,560	19,830	−2270	Dominant
Net change in chemotherapy use +10% in intermediate RS group	13.23	13.12	0.10	21,089	19,830	1258	12,544
Net change in chemotherapy use −10% in intermediate RS group	13.15	13.12	0.03	17,450	19,830	−2380	Dominant
Net change in chemotherapy use +10% in high RS group	14.45	13.12	1.33	22,087	19,830	2259	1,703
Net change in chemotherapy use −10% in high RS group	13.17	13.12	0.05	18,245	19,830	−1585	Dominant

QALY, quality-adjusted life year; €, 2011 Euros; ICER, incremental cost-effectiveness ratio; * ICERs are presented in € per QALY gained; RS, Recurrence Score.

Dowsett M, Cuzick J, Wale C, et al. Prediction of risk of distant recurrence using the 21-gene recurrence score in node-negative and node-positive postmenopausal patients with breast cancer treated with Anastrozole or Tamoxifen: A TransATAC study. J Clin Oncol 2010;28:1829-34

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