Cost-effectiveness of Tamoxifen, Aromatase Inhibitor, and Switch Therapy (Adjuvant Endocrine Therapy) for Breast Cancer in Hormone Receptor Positive Postmenopausal Women in India

Figures & data

Figure 1 Markov model depicting the progression of early stage breast cancer patients on adjuvant endocrine therapy.

Table 1 Input Parameter: Baseline Values

Parameters	Categories	Base Value	Standard Error	Source	Distribution
Transition probability tamoxifen	PFS to LR	0.0034	0.0014	^Citation7	Beta
	PFS to CLB	0.0023	0.0016
	PFS to DM	0.0194	0.0006
	PFS to endometrial cancer	0.0016	0.0009
	PFS to osteoporosis	0.0050	0.0005
	PFS to thromboembolic event	0.0058	0.0005
	LR to DM	0.0226	0.0006
	CLR to DM	0.0226	0.0006
Transition probability aromatase inhibitor	PFS to LR	0.0023	0.0014	^Citation7	Beta
	PFS to CLB	0.0016	0.0016
	PFS to DM	0.0155	0.0006
	PFS to endometrial cancer	0.0004	0.00004
	PFS to osteoporosis	0.0067	0.0006
	PFS to thromboembolic event	0.0035	0.0003
	LR to DM	0.0176	0.0006
	CLR to DM	0.0176	0.0006
Transition probability switch therapy	PFS to LR	0.0032	0.0003	^Citation7	Beta
	PFS to CLB	0.0017	0.0001
	PFS to DM	0.0117	0.0009
	PFS to endometrial cancer	0.0005	0.00005
	PFS to osteoporosis	0.0058	0.0005
	PFS to thromboembolic event	0.0050	0.00051
	LR to DM	0.0218	0.0008
	CLR to DM	0.0218	0.0008
Mortality rates	Probability of death from distant metastasis tamoxifen	0.0114	0.0007	^Citation7	Beta
	Probability of death from distant metastasis AI	0.0093	0.0006
	Probability of death from distant metastasis switch therapy	0.0149	0.0007
	Probability of death from endometrial cancer	0.032	0.0003	^Citation62
	Probability of death from thromboembolic event	0.002	0.0002	^Citation63
Preference weights (utility)	Progression free state	0.67		Authors' calculation	Beta
	Locoregional recurrence	0.725		^Citation38
	Contralateral breast	0.725
	Distant metastasis	0.58
	Endometrial cancer	0.68		^Citation39
	Osteoporosis	0.85
	Thromboembolic event	0.58
Proportion of patient requiring management	Public sector tertiary center	0.3	0.036	^Citation43	Beta
	Private sector tertiary center	0.7	0.071	^Citation43
	LR	0.88	0.089	^Citation64
	Surgery
	Chemotherapy	0.85	0.085
	Radiotherapy	0.57	0.057
	CLB	0.88	0.089
	Surgery
	Chemotherapy	0.85	0.085
	Radiotherapy	0.57	0.057
	DM	0.19	0.019
	Surgery
	Chemotherapy	0.85	0.085
	Radiotherapy	0.36	0.036
	Proportion of endometrial cancer patient requiring Surgery	0.45	0.045	^Citation34
	Proportion of thromboembolic patient requiring surgery	0.50	0.050	^Citation65
	Proportion of patients developing osteoporosis related fracture	0.07	0.0063	^Citation66
	Tamoxifen
	Aromatase inhibitor	0.09	0.0094
	Switch therapy	0.08	0.0076

Abbreviations: PFS, progression free health state; LR, locoregional recurrence; CLB, contralateral breast; DM, distant metastasis.

Table 2 Cost Parameters

Parameter	Base Value (INR)	95%CI (INR)	Source
1. Drugs
Health system cost
Annual tamoxifen	1200	600–1800	^Citation44
Annual letrozole	3900	1950–5850	^Citation44
OOPE
Annual tamoxifen	1989	995–2984	Market rates
Annual letrozole	11,571	5785–17,356	Market rates
2. Procedures
Health system cost
Radiotherapy	18,038	9018–27,057	Authors' calculation
Chemotherapy	13,038	6519–19,556	Authors' calculation
Mastectomy	20,300	20,000–25,000	^Citation53
Hysterectomy	23,000	27,000–34,000	^Citation53
OOPE
Radiotherapy	30,160	15,080–45,240	^Citation53
Chemotherapy	14,900	7450–22,305	^Citation53
Mastectomy	25,000	12,500–37,500	Market rates
Hysterectomy	22,000	11,000–33,000	Market rates
3. Investigations
Health system
CBC	140	70–210	^Citation55
DEXA scan	3834	1917–5751	^Citation55
Chest X-ray	4475	2238–6713	^Citation55
Abdomen USG	4475	2238–6713	^Citation55
Breast USG	300	150–450	^Citation55
Mammography	220	110–330	^Citation55
PET scan	14,663	7332–21,995	^Citation55
ECG	155	78–233	^Citation55
ECHO	258	129–387	^Citation55
Biopsy	1107	554–1661	^Citation55
ER/PR/HER2	500	250–750	^Citation55
OOPE private sector
CBC	377	189–566	Market rates
DEXA scan	5100	2550–7650	Market rates
Chest X-ray	400	200–600	Market rates
Abdomen USG	470	235–705	Market rates
Breast USG	1840	920–2760	Market rates
Mammography	2100	1050–3150	Market rates
PET scan	12,000	6000–18,000	Market rates
ECG	250	125–375	Market rates
ECHO	2400	1200–3600	Market rates
Biopsy	6000	3000–9000	Market rates
ER/PR/HER2	5600	2800–8400	Market rates
5. Other
Health system
OPD consultation	364	214–563	^Citation67
Per day ward charges	1671	836–2507	^Citation67
OOPE
OPD consultation	1350	675–2025	Primary data
Per day ward charges	1800	900–2700	Authors' calculation

Abbreviations: OOPE, out-of-pocket expenditure; CBC, complete blood count; USG, ultrasonography; ECG, electrocardiography; PET, positron emission tomography; ECHO, echocardiogram; ER, estrogen receptor; PR, progesterone receptor; OPD, out patient department; INR, Indian national rupee.

Table 3 Lifetime Costs, Health Outcomes, and Incremental Values per Patient in Different Treatment Arms: Tamoxifen, AI and Switch Therapy

Findings		Tamoxifen^a	Aromatase Inhibitor^a	Switch Therapy^a
LYs	• Discounted	16.74 (16.31–17.19)	16.86 (16.42–17.26)	16.78 (16.40–17.14)
	• Undiscounted	24.49 (23.54–25.54)	24.74 (23.80–25.73)	24.56 (23.70–25.43)
QALYs	• Discounted	13.12 (12.19–14.00)	13.42 (12.43–14.27)	13.32 (12.35–14.18)
	• Undiscounted	18.78 (17.23–20.27)	19.34 (17.84–20.71)	19.12 (17.65–20.51)
Health system cost in million INRs	• Discounted	0.78 (0.57–1.09)	0.70 (0.53–0.94)	0.64 (0.46–0.88)
	• Undiscounted	1.33 (0.95–1.88)	1.16 (0.86–1.59)	1.08 (0.76–1.52)
OOPE in million (INR)	• Discounted	1.23 (1.18–1.25)	1.09 (1.01–1.18)	1.08 (0.76–1.52)
	• Undiscounted	2.05 (1.88–2.25)	1.78 (1.66–1.89)	1.79 (1.65–1.88)
Total cost in million (INR)	• Discounted	1.47 (1.64–1.72)	1.37 (1.46–1.52)	1.28 (1.44–1.50)
	• Undiscounted	2.45 (2.72–2.85)	2.13 (2.3–2.5)	2.12 (2.35–2.50)
Incremental values		AI vs tamoxifen	Switch vs tamoxifen	AI vs switch
LYs	• Discounted	0.120	0.040	0.080
	• Undiscounted	0.251	0.067	0.183
QALYs	• Discounted	0.301	0.205	0.096
	• Undiscounted	0.564	0.344	0.220
Costs in million (INR)	• Discounted	−0.16	−0.190	0.025
	• Undiscounted	−0.31	−0.332	0.015

Note: ^aValues in parenthesis represent 95% confidence intervals.

Abbreviations: LYs, life years; QALYs, quality-adjusted life years; OOPE, out-of-pocket expenditure; INR, Indian national rupee.

Table 4 Cost of Management of Breast Cancer Recurrence, Contralateral Breast, Adverse Events and Hormone Therapy in Each Treatment Arm: Tamoxifen, Aromatase Inhibitor and Switch Therapy

Total Cost per Patient (INR)		Tamoxifen	Aromatase Inhibitor	Switch Therapy
Recurrence	• Discounted	12,06,411	10,89,040	10,72,997
	• Undiscounted	19,99,576	17,54,074	17,56,846
Adverse events	• Discounted	1,32,409	1,48,650	1,49,500
	• Undiscounted	2,33,239	2,67,826	2,65,831
Contralateral breast	• Discounted	1,33,216	69,105	59,315
	• Undiscounted	2,21,139	1,14,714	98,462
Hormone therapy	• Discounted	26,138	57,505	39,400
	• Undiscounted	43,650	96,034	65,798

Figure 2 Cost of management of breast cancer recurrence, contralateral breast, adverse events, and hormone therapy in each treatment arm: tamoxifen, aromatase inhibitor, and switch therapy.

Figure 3 Cost-effectiveness plane comparing three treatment arms: tamoxifen, aromatase inhibitor, and switch therapy for five years.

Figure 4 Probability of aromatase inhibitor and switch therapy being cost-effective at varying willingness to pay thresholds. ₹, Indian national rupees.

Figure 5 Price threshold analysis at different levels of aromatase inhibitor (AI) cost/year. ^aICER per QALY gained refers to ICER when AI monotherapy (five-year) is compared with switch therapy.

Table 5 Comparison of Health Outcomes and Cost from Earlier Studies and Present Evaluation

Study	Outcomes	Tamoxifen	Aromatase Inhibitor	Switch Therapy
Economic evaluation of letrozole for early breast cancer in a health resource limited country (China)^Citation18	Costs (CNY ¥)	13,613	28,797	20,061
	QALY	10.44	10.84	10.71
	Life Years	18.34	19.17	18.91
Economic evaluation of hormonal therapies for postmenopausal women with estrogen receptor–positive early breast cancer in Canada^Citation17	Costs (CA$)	19,534	19,359	18,953
	QALYs	8.86	9.06	9.05
	Life Years	17.93	18.33	18.32
Present study	Costs (INR)	14,72,037	13,06,795	12,81,811
	QALYs	13.12	13.42	13.32
	Life Years	16.74	16.86	16.78

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