Trastuzumab in adjuvant breast cancer therapy. A model based cost-effectiveness analysis

Figures & data

Figure 1.  The figure shows the model. Only the cost of the prevented relapses is counted in the analysis. Adjuvant trastuzumab is calculated saving 10 or 20% from death of metastatic breast cancer (death 0.8 or 0.9). 1^st line therapy (paclitaxel/trastuzumab or docetaxel/trastuzumab) in metastatic setting was calculated administered in the time span 1–6 years following adjuvant chemotherapy (ACT) and 90% (0.9) were concluded candidates for 1^st line therapy. 2^nd line therapy (vinorelbine or vinorelbine/trastuzumab) was calculated administered in the time span 2–8 years following ACT and two-thirds (0.67) of patients undergoing 1^st line therapy was candidates for 2^nd line therapy. 3^rd line therapy (capecitabine) was calculated administered 4–10 years following ACT and two-thirds (0.67) of patients undergoing 2^nd line therapy was candidates for 3^rd line therapy. Figure 2. The figure illustrates the 10 years survival figures published by Bonadonna (CMF regimen) [13], an estimated 5% improved survival due to the FEC regimen [13], the results of the JOINT study [15] and two suggested levels (10% and 20%) of improvement (from the FEC results indicated) due to trastuzumab.

Figure 2.  The figure illustrates the 10 years survival figures published by Bonadonna (CMF regimen) [13], an estimated 5% improved survival due to the FEC regimen [13], the results of the JOINT study [15] and two suggested levels (10% and 20%) of improvement (from the FEC results indicated) due to tratuzumab.

Table I.  Effectiveness: The table illustrates the calculation of life expectancy following adjuvant chemotherapy containing trastuzumab in early breast cancer.

				Corrected^4
Age (yrs)	No BC^1	Life exp^2	LYG^3	no	LYG	LYG figure employed	3% d.r^5 LYG
20–30	16	52.4	0.44	16	0.60	0.45	0.23
30–40	101	42.6	2.24	101	3.06	2.30	1.33
40–50	391	33.2	6.75	391	9.22	6.92	4.45
50–60	769	24.3	9.72	577	9.96	7.47	5.36
60–70	646	16.1	5.41	323	3.69	2.77	2.23
	1923		24.56	1408	26.53*	20.00	13.6

¹No BC = number of breast cancers in Norway in 2003 (National Cancer Registry).

²Life exp = life expectancy. The data is from Statistics Norway and based on all women born in the time period 1956–60. The calculated life expectancy of each subgroup is indicated by in example: 20–30 years=(life exp. 20 yrs + life exp. 30 years)* 0.5

³LYG = life years gained=(no BC) * (Life exp)/1923

⁴Corrected LYG: The group 50–60 years and 60–70 years were reduced by 25 and 50%, respectively. Corrected LYG=(corrected no BC)*(life exp)/1408

⁵D.r.=discount rate. Figures employed were discounted with life expectancy in third column.

*This figure (26.53 LYG) is based on the Norwegian population¹ and possible effects as risk of death of heart disease or secondary malignancies due to therapy have to be implemented. A cautious time horizon of 20 years (25% reduction) was employed in our calculation (Figure 2).

Effectiveness: 20% improved OS = 3 LY. 3% d.r. and 20 years perspective = 2.19 LY 10% improved OS = 1.5 LY. 3% d.r. and 20 years perspective = 1.10 LY

Table II.  The costs per patient treated (in €). Only the costs and savings differing between the two adjuvant regimens (standard FEC100 and FEC100 + Trastuzumab) are included.

		Standard FEC100	FEC100+Trastuzumab	Difference 0% d.r.	3% d.r.
Cost (C) adjuvant chemotherapy
Health care (C1)
Drug (Trastuzumab)		0	42 354	42 354	42 354
Cardiac check-ups		0	330	330	330
Pharmacy administration		0	326	32	326
Out-patient clinic		98	2 192	2 094	2 094
Heart failure treatment		0	23	23	23
Patient/family (C2)	Travelling	157	1 249	1 092	1 092
Other sectors (C3)	Production losses	0	2 272	2 272	2 272
Sum cost:				48 491	48 491
Economic consequences – Savings (S).
1^stline CT (Calculated 1–6 yrs perspective, 90% undergoing chemotherapy, 90% dose intensity)
Health care (S1)
Trastuzumab		6 274	0	−6 274	−5 747
Paclitaxel		2 411	0	−2 411	−2 208
Cardiol. check-ups		77	0	−77	−71
Pharmacy adm.		264	0	−264	−242
Out-patient clinic		884	0	−884	−810
Heart failure treat.		10	0	−10	−9
CT-scans/x-rays		880	0	−880	−806
Patient/family (S2)	Travelling	506	0	−506	−463
Other sectors (S3)	Production gains	20 139	0	−20 139	−18.446
Savings due to avoided 1^stline chemotherapy in metastatic setting				−31 445	−28 802
Alternative 1^stline CT
Health care (S1a)
Trastuzumab		5 586	0	−5 586	−5 116
Docetaxel		4 306	0	4 306	−3 944
Cardiologic check and treat.		87	0	−87	−80
Pharmacy adm.		86	0	−86	−79
Out-patient clinic		288	0	−288	−264
Patient/family (S2a)	Travelling	165	0	−165	−151
Other sectors (S3a)	Production gains	20 139	0	−20 139	−18 446
Savings due to avoided alternative 1^stline regimen in metastatic setting				−30 657	−28 080
2^ndline chemotherapy (Calculated a 2–8 years perspective, 67% of 1^st line patients included)
Health care (S1)
Vinorelbine		951	0	−951	−834
Pharmacy adm.		49	0	−49	−43
Out-patient clinic		129	0	−129	−113
CT-scans		353	0	−353	−309
Patient/family (S2)	Travelling	189	0	−189	−166
Savings due to avoided 2^ndline chemotherapy				−1 671	−1 465
Alternative 2^ndline chemotherapy (Calculated a 2–8 years perspective)
Health care (S1a)
Vinorelbine		951	0	−951	−834
Trastuzumab		2 334	0	−2 334	−2 046
Pharmacy adm.		49	0	−49	−43
Out-patient clinic		129	0	−129	−113
CT-scans		353	0	−353	−309
Patient/family (S2a)	Travelling	189	0	−189	−166
Savings due to avoided alternative 2^ndline chemotherapy				−4 005	−3 511
3^rdline chemotherapy (Calculated a 4–10 years perspective, 67% of 2^nd line patients included)
Health care (S1=S1a)
Capecitabine		149	0	−149	−123
Out-patient clinic		23	0	−23	−19
CT-scans		237	0		−237
Patient/family (S2)	Travelling	51	0	−51	−42
Savings due to avoided 3^rdline chemotherapy				−460	−380

Table III.  The table shows cost-effectiveness (C/E) ratios depending on key costing assumptions and 10% or 20% improved overall survival level. Effectiveness was calculated in life years gained (LYG) or QALYs. 3% discount rate was employed.

	Costs (€)	C/E 10% LYG	C/E 10% QALYs	C/E 20% LYG	C/E 20% QALYs
Health care cost only; C1	45 127	41 212	51 515	20 606	25 757
Net health care resources; C1−S1	33 597	35 947	44 934	15 341	19 176
Health care costs + Travelling; C1+C2	46 219	42 209	52 761	21 105	26 381
Total costs; C1+C2+C3	48 491	44 284	55 355	22 142	27 678
Net costs (exclusive production gains); C1+C2+C3−S1−S2	36 290	38 713	48 391	16 571	20 713
All resource use C1+C2+C3−S1−S2−S3	17 844	30 290	37 862	8 148	10 185
E = 10% = 1.095 Life years gained (LYG). E = 20% = 2.19 LYG.
Q = 0.80. QALYs = Quality adjusted life years.
Cost effectiveness analysis (CEA): Cost/life year gained (LYG)
Discont rate = 0%
CEA^20%improved^OS=(C1 − S1)/E = €(45 127 − 10 800 − 1 482 − 449)/3 = €10 799/LYG
CEA^20%improved^OS=(C1+C2+C3−S1−S2−S3)/E = €(48 491 − 31 445 − 1 671 − 460)/3 = €4 972/LYG
CEA^10%impr.^OS=(C1 − S1)/E = €(45 127 − 5 400 − 741 − 225)/1.5 = €25 841/LYG
CEA^10%impr.^OS=(C1+C2+C3−S1−S2−S3)/E = €(48 491 − 15 723 − 836 − 230)/1.5 = €21 135/LYG

Figure 3.  The figure shows a sensitivity analysis illustrating the variables having the strongest impact on the cost-effectiveness analysis. The human capital approach (3% d.r. and 20% OS benefit (see Table II) is employed as basis (marked as 0 = €8 148, all resources use (Table III)).