Economic Evaluation of Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer in the United States

Figures & data

Figure 1 The decision tree and partitioned survival model structure overview for HER2-low breast cancer patients. Group 1 represents overall patients, which includes HR-positive and HR-negative patients. Group 2 represents the HR-positive patients. The intervention and comparator of each group is T-DXd and chemotherapy, respectively. The PartSA containes three health states: progression-free, progressed disease and death.

Abbreviations: PartSA, partitioned survival approach; HR+, hormone receptor–positive; T-DXd, trastuzumab deruxtecan.

Table 1 Key Clinical Data

Parameter		Values	Range	Distribution
All patients: Projected PFS curve based on Weibull distribution in the chemotherapy arm		Shape=1.124 Scale=11.089	–	–
All patients: Projected OS curve based on Weibull distribution in the chemotherapy arm		Shape=1.458 Scale=31.481	–	–
HR-positive subgroup: Projected PFS curve based on Weibull distribution in the chemotherapy arm		Shape=1.144 Scale=11.776	–	–
HR-positive subgroup: Projected OS curve based on Weibull distribution in the chemotherapy arm		Shape=1.455 Scale=33.953	–	–
All patients: Hazard ratio of T-DXd vs chemotherapy arm for PFS		0.5	0.4–0.63	Lognormal
All patients: Hazard ratio of T-DXd vs chemotherapy arm for OS		0.64	0.49–0.84	Lognormal
HR-positive subgroup: Hazard ratio of T-DXd vs chemotherapy arm for PFS		0.51	0.4–0.64	Lognormal
HR-positive subgroup: Hazard ratio of T-DXd vs chemotherapy arm for OS		0.64	0.48–0.86	Lognormal
Grade 3 and more AEs in the chemotherapy arm		Incidence	Range	Distribution
Neutropenia		40.7%	30.53% to 50.88%	Beta
Anemia		4.7%	3.53% to 5.88%	Beta
Thrombocytopenia		0.6%	0.45% to 0.75%	Beta
Leukopenia		19.2%	14.4% to 24%	Beta
Nausea		0%	NA	Beta
Fatigue		4.7%	3.53% to 5.88%	Beta
Grade 3 and more AEs in the T-DXd arm
Neutropenia		13.7%	10.28% to 17.13%	Beta
Anemia		8.1%	6.08% to 10.13%	Beta
Thrombocytopenia		5.1%	3.83% to 6.38%	Beta
Leukopenia		6.5%	4.88% to 8.13%	Beta
Nausea		4.6%	3.45% to 5.75%	Beta
Fatigue		7.5%	5.63% to 9.38%	Beta

Abbreviations: PFS, progression-free survival; HR, hormone-receptor; OS, overall survival; AEs, adverse events; T-DXd, trastuzumab deruxtecan.

Table 2 Model Costs, Utility Estimates and Other Parameters

Parameter	Distribution	Values (Range), USD	Reference
Treatment costs
T-DXd (per 100 mg)	Gamma	2613.56 (1960.17–3266.95)	[18]
Eribulin (per 0.1 mg)	Gamma	132.803 (99.602–166.004)	[17]
Capecitabine (per 500 mg)	Gamma	0.805 (0.604–1.006)	[17]
Nab-paclitaxel (per 1 mg)	Gamma	14.693 (11.020–18.366)	[17]
Gemcitabine (per 200 mg)	Gamma	3.764 (2.823–4.705)	[17]
Paclitaxel (per 1 mg)	Gamma	0.124 (0.093–0.155)	[17]
Administration (first hour)	Gamma	148.3 (111.23–185.38)	[20]
Administration (additional hour)	Gamma	31.4 (23.55–39.25)	[20]
Follow-up (per cycle)	Gamma	931.44 (698.58–1164.3)	[21]
Best supportive care (per cycle)	Gamma	3750.14 (2812.61–4687.68)	[21]
Palliative care	Gamma	9787.97 (7340.98–12,234.96)	[22]
Expenditure of AEs management
Neutropenia	Gamma	4804.04 (3603.03–6005.05)	[22]
Anemia	Gamma	14,092.64 (10,569.48–17,615.8)	[23]
Thrombocytopenia	Gamma	12,794.98 (9596.24–15,993.73)	[24]
Leukopenia	Gamma	12,749.06 (9561.80–15,936.33)	[24]
Nausea	Gamma	8341.60 (6256.2–10,427)	[23]
Fatigue	Gamma	13,088.35 (9816.26–16,360.44)	[23]
Utility estimates
Progression-Free Disease	Beta	0.85 (0.64, 1.00)	[22]
Progressive Disease	Beta	0.52 (0.39, 0.65)	[22]
Other parameters
Body surface area, m^2	Normal	1.86 (1.40–2.33)	[19]

Notes: The costs of AEs in this table were presented on a per-event basis, and the costs of AEs were calculated only once at the beginning of running the analysis model. All costs reported for years prior to 2021 are updated to 2021 US dollar using the American Consumer Price Index. All costs sourced from China in this study were converted into US dollars ($1 = RMB 6.4512, Average exchange rate for 2021).

Abbreviations: AEs, adverse events; USD, US dollars; CMS, Centers for Medicare and Medicaid Services; T-DXd, trastuzumab deruxtecan.

Figure 2 Reconstructed Kaplan-Meier survival curve and the projected survival curve in different groups. (A) Output of PFS curve for all patients group; (B) Output of OS curve for all patients group; (C) Output of PFS curve for the HR+ patients group; (D) Output of OS curve for the HR+ patients group. Each cycle of the x-axis is three weeks.

Abbreviations: KM, Kaplan-Meier; PFS, progression-free survival; OS, overall survival; HR+, hormone-receptor positive; T-DXd, trastuzumab deruxtecan.

Table 3 Results of the Base-Case Analysis

Population	All Patients		HR+Subgroup
Regimen	Chemotherapy	T-DXd	Chemotherapy	T-DXd
Health-state cost
PFS state	54,431.27	211,846.28	57,654.67	217,526.78
PD state	39,123.33	38,012.22	39,123.33	38,012.22
Total cost	93,554.6	249,858.5	96,778	255,539
Difference	156,303.9		158,761
Health-state QALY
PFS state	0.519	0.948	0.548	0.974
PD state	0.517	0.539	0.563	0.607
Total QALY	1.036	1.487	1.111	1.581
Difference	0.451		0.47
ICUR($/QALY)	346,571.8		337,789.4

Abbreviations: LY, life-year; QALY, quality-adjusted life-year; ICUR, incremental cost-utility ratio; T-DXd, trastuzumab deruxtecan; HR+, hormone-receptor positive.

Figure 3 Tornado diagram of the one-way sensitivity analysis results. (A) The output of all patients group. (B) The output of HR-positive subgroup.

Abbreviations: T-DXd, trastuzumab deruxtecan; BSA, body surface area; OS, overall survival; PFS, progression-free survival; PD, progressed disease; ICUR, incremental cost-utility ratio; QALY, quality-adjusted life-year; WTP, willingness to pay; HR, hazard ratio; HR+, hormone-receptor positive;

Figure 4 The output of probabilistic sensitivity analysis. (A) The output of all patients group. (B) The output of HR-positive subgroup.

Notes: In the cost-effectiveness acceptable curve, the y-axis indicates the likelihood that a regimen is cost-effective across the willingness-to-pay threshold (x-axis). The red dashed line represents the WTP threshold; In the incremental cost-effectiveness scatter plot, each dot represents one output. The red circle is the 95% confidence ellipse. The black dashed line represents the WTP threshold.

Abbreviations: T-DXd, trastuzumab deruxtecan; QALY, quality-adjusted life-year; WTP, willingness to pay; HR+, hormone-receptor positive.

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