Cost-effectiveness of HER2 testing and trastuzumab therapy for metastatic breast cancer

Figures & data

Table I.  Test and treatment strategies.

Strategy	First test	Second test	Treatment based on test results
1	None	None	Chemotherapy alone for all patients
2	IHC	None	Trastuzumab and chemotherapy for IHC +3 patients Chemotherapy alone for all other patients
3	IHC	None	Trastuzumab and chemotherapy for IHC +2 and +3 patients Chemotherapy alone for all other patients
4	IHC	FISH for IHC +2 and +3	Trastuzumab and chemotherapy for FISH + patients Chemotherapy alone for all other patients
5	FISH	None	Trastuzumab and chemotherapy for FISH + patients Chemotherapy alone for all other patients

Figure 1.  Markov model.

Table II.  HER2 prevalence and HER2 testing.

	Base case value	95% CI	Reference
Prevalence of HER2 positive breast cancer	0.25		4, 5
Probability of IHC score, conditional on positive FISH results^+
0, 1 +	0.079	0.025–0.134	13
2 +	0.250	0.168–0.332	13
3 +	0.671	0.547–0.795	13
Probability of IHC score, conditional on negative FISH results^+
0, 1 +	0.843	0.779–0.908	13
2 +	0.140	0.081–0.200	13
3 +	0.017	0.004–0.029	13

⁺Based on Table II from Elkin et al.

Table III.  Transition probabilities.

	Base case value	Reference
HER2 positive patients, receiving trastuzumab and chemotherapy
From stable metastatic disease to progressive metastatic disease	5.8%	7
From progressive metastatic disease to dead due to breast cancer	4.7%	*
HER2 positive patients, receiving chemotherapy
From stable metastatic disease to progressive metastatic disease	10.7%	7
From progressive metastatic disease to dead due to breast cancer	9.5%	*
HER2 negative patients
Relative reduction in risk due to lack of HER2 overexpression^+	0.75	4

* Calibration in the model, based on the median OS from the study by Marty et al.

⁺ The resulting transition probabilities are calculated by multiplying the risk reduction with the transition probabilities of HER2 positive patients, receiving chemotherapy.

Table IV.  Costs and utility weights.

	Base case value	95% CI	Reference
Utility
Metastatic breast cancer	0.685	(0.620–0.735)	26
Direct medical, informal care and palliative care costs
Outpatient visit	1 583	(1 532–1636)	22
Monthly inpatient cost for metastatic breast cancer patient	2 912	(1 860–4 564)	22
Monthly informal care cost for metastatic breast cancer patient	696	(324–1 300)	22
Monthly outpatient cost for metastatic breast cancer patient after 1^st line therapy	4 485	(4 059–4 918)	22
Cost of additional adverse events for patients receiving trastuzumab	705		7, 23, 24
Palliative care cost	63 244		3, 22
Test, drug, and monitoring costs
IHC test	1 859		25
FISH test	5 086		25
Docetaxel, 1 month	20 541		7, 10
Trastuzumab, 1 month	22 612		7, 10
Monthly outpatient drug cost after 1^st line therapy	1 868		*
Monthly heart monitoring cost for patients receiving trastuzumab	1 809		25

* Expert opinion.

Table V.  Base case cost-effectiveness analysis.

Strategy	Cost (SEK)	QALYs gained	ICER (SEK/QALY)
1. Chemotherapy alone for all patients	331 668	1.280
2. IHC test. Trastuzumab and chemotherapy for IHC 3+ patients Chemotherapy alone for all other patients	395 398	1.408	Dominated^+ +
3. IHC test. Trastuzumab and chemotherapy for IHC 2+ and 3+ patients Chemotherapy alone for all other patients	438 429	1.456	Dominated^+
4. IHC test, FISH confirmation for 2+ and 3+ Trastuzumab and chemotherapy for FISH + patients Chemotherapy alone for all other patients	416 732	1.456	485 039
5. FISH test. Trastuzumab and chemotherapy for FISH + patients Chemotherapy alone for all other patients	425 174	1.471	561 207

⁺ Dominated by simple dominance.

^+ + Dominated by extended dominance.

Table VI.  One-way sensitivity analyses, incremental cost per QALY gained.

Assumption	Strategy 4	Strategy 5
Base case	485 039	561 207
Cost
Increase outpatient visit costs with 30%	500 536	576 703
Increase inpatient and outpatient costs with 30%	531 842	608 009
Increase inpatient and outpatient cost for patients with progressive metastatic disease with 30%	511 423	587 590
Increase heart monitoring cost for trastuzumab patients with 30%	499 890	576 058
Increase adverse events costs for trastuzumab patients with 30%	485 317	561 484
Increase outpatient drug cost after 1st line therapy with 30%	494 661	570 828
Decrease the cost of Trastuzumab with 30%	421 155	497 322
Decrease the cost of IHC testing by 30%	481 859	598 280
Decrease the cost of FISH testing by 30%	482 012	495 076
Increase informal care cost by 30%	488 697	564 865
Increase palliative care cost by 30%	480 872	557 039
Transition probabilities
Increase the risk of progression for HER positive patients receiving trastuzumab by 30%	522 572	615 947
Decrease the risk of progression for HER positive patients receiving trastuzumab by 30%	443 036	502 876
Increase the risk of death due to breast cancer for HER positive patients receiving trastuzumab by 30%	574 507	671 218
Decrease the risk of death due to breast cancer for HER positive patients receiving trastuzumab by 30%	406 868	465 397
Utility
Increase the utility score for patients with metastatic breast cancer with 30%	373 107	431 698
Decrease the utility score for patients with metastatic breast cancer with 30%	692 913	801 724
Decrease the utility score for patients with progressive metastatic disease with 30%	564 607	653 269
Prevalence of HER2 amplification
Prevalence increased to 35%	480 710	515 082
Prevalence decreased to 15%	495 142	668 831

Table VII.  HER2 testing two way sensitivity analyses, incremental cost per QALY gained.

Probability of IHC score for FISH negative patients			Probability of IHC score for FISH positive patients
0, 1 +	2 +	3 +	0, 1 +	2 +	3 +	Strategy 4	Strategy 5
0.843	0.140	0.017	0.079	0.250	0.671	485 039*	561 207*
			0.020	0.130	0.850	484 196	827 244
			0.000	0.050	0.950	483 932	Dominated +
0.920	0.070	0.010	0.079	0.250	0.671	483 365	580 732
			0.020	0.130	0.850	482 622	904 368
			0.000	0.050	0.950	482 390	Dominated +

* Base case scenario.

+ By simple dominance.

Figure 2.  Acceptability curve.