Cost effectiveness of pembrolizumab plus lenvatinib compared with chemotherapy for treating previously treated advanced endometrial cancer in Sweden

Figures & data

Table 1. Model inputs.

Input	Mean value	Distribution	Source
Model settings
Time horizon (years)	40	N/A	Tandvårds- och läkemedelsförmånsverket. General guidelines for economic evaluations^9
Cycle length (weeks)	1	N/A
Discount rate (costs, outcomes), %	3	N/A
Baseline characteristics
Age (years)	63.50	Normal	KEYNOTE-775^7
Average patient weight (kg)	70.50	Log-normal
Average patient BSA (m^2)	1.77	Normal
Overall survival
PEM + LEN	KM (Wk 26)+log-logistic models	MV normal	KEYNOTE-775^13
Chemotherapy	Treatment switch adjustment HR, 0.60	Log-normal	KEYNOTE-775^13
Progression-free survival
PEM + LEN	Independent KM (Wk10)+ generalized gamma models	MV normal	KEYNOTE-775^13
Chemotherapy		MV normal	KEYNOTE-775^13
Costs (SEK)
Cost of PEM 100 mg	33,519.50	Gamma	Tandvårds- och läkemedelsförmånsverket drug price index^14
Cost of LEN 4 mg	16,180.61	Gamma
Cost of LEN 10 mg	16,180.61	Gamma
Cost of PAC 30 mg	146.25	Gamma
Cost of PAC 100 mg	386.93	Gamma
Cost of DOX 50 mg	203.50	Gamma
Cost of DOX 10 mg	67.50	Gamma
Cost of subsequent treatment upon treatment discontinuation (PEM + LEN)	66,033.88	Gamma
Cost of subsequent treatment upon treatment discontinuation (chemotherapy)	34,267.92	Gamma
Cost of IV administration	5,878.00	Gamma	Southwest region price list^15
Resource use costs/cycle (progression free)	1,121.84	Gamma	Southwest region price list^15
Resource use costs/cycle (progressed disease)	223.89	Gamma
AEs/cycle (pembrolizumab plus)	317.01	Normal	Southwest region price list^15
AEs/cycle (chemotherapy)	1,094.01	Normal
End-of-life cost upon death^a	12,165.86	Gamma	Opdivo and Yervoy submission (Tandvårds- och läkemedelsförmånsverket)^11
Utility
≥360 d	0.869	MV normal	Calculated from KEYNOTE-775^13
270–359 d	0.861	MV normal
180–269 d	0.830	MV normal
90–179 d	0.822	MV normal
30–89 d	0.772	MV normal
<30 d	0.675	MV normal

Abbreviations. AE, adverse event; BSA, body surface area; DOX, doxorubicin; HR, hazard ratio; IV, intravenous; KM, Kaplan–Meier; LEN, lenvatinib; MV, multivariate; N/A, not applicable; PAC, paclitaxel; PEM, pembrolizumab; SEK, Swedish Krona; Wk, Week.

^a The end-of life cost upon death was calculated as follows: the reported 96,000 SEK¹¹ was assumed to be the last 8 weeks of life; this value was adjusted for inflation and divided by 8 to obtain the cost in the final week of life.

Figure 1. Estimation of overall survival (A) and progression-free survival (B). Abbreviations. KM, Kaplan–Meier; LEN, lenvatinib; OS, overall survival; PEM, pembrolizumab; PFS, progression-free survival.

Table 2. Cost effectiveness of pembrolizumab plus lenvatinib compared with chemotherapy.

	Total discounted costs (SEK)	Total discounted life-years	Total discounted QALYs	Incremental			ICER (SEK per QALY)
				Discounted Costs (SEK)	Discounted life-years	Discounted QALYs
All-comers
Chemotherapy	297,904	1.70	1.44	–	–	–	–
PEM + LEN	1,484,976	3.46	2.93	1,187,073	1.76	1.49	795,712
Proficient mismatch repair
Chemotherapy	295,258	1.77	1.50	–	–	–	–
PEM + LEN	1,486,968	3.24	2.75	1,191,710	1.46	1.24	958,306

Abbreviations. ICER, incremental cost-effectiveness ratio; LEN, lenvatinib; PEM, pembrolizumab; QALY, quality-adjusted life-year; SEK, Swedish Krona.

Figure 2. Deterministic sensitivity analysis tornado plot all-comers. Increasing the hazard ratio decreased the ICER as the OS hazard ratio was entered as 1/0.06; therefore, the resulting lower bound value was greater than the upper bound value in some cases. Abbreviations. ICER, incremental cost-effectiveness ratio; LEN, lenvatinib; MRU, medical resource utilization; OS, overall survival; PEM, pembrolizumab; PFS, progression-free survival; SEK, Swedish Krona; SoC, standard of care.

Table 3. Scenario results.

Parameter	Base case setting	Scenario setting	PEM + LEN versus chemotherapy ICER (SEK)
Base case			795,712
Discount rate (costs and utilities), %	3.0	0.0	629,817
		5.0	905,944
Time horizon, years	40	30	804,026
Subsequent treatment, %	28 for PEM + LEN, 48 for chemotherapy	100	804,155
		0	801,086
Perspective	Healthcare payer	Societal	732,130
Utility	Time to death approach	Health state approach	829,651
	Sweden tariff	UK tariff	923,210
	Age-adjustment included	Age-adjustment excluded	776,341
Overall survival	Treatment switch adjustment	Separate Kaplan–Meier + log-logistic models	933,980
Progression-free survival	Separate Kaplan–Meier (Wk 10) +log-logistic models	Separate Kaplan–Meier (Wk 10) +log-normal models	791,341
		Separate Kaplan–Meier (Wk 37) +log-logistic models	808,011
		Separate one-piece log-logistic models	800,017
Time on treatment	Separate one-piece generalized gamma models	Weibull	905,130
		Progression-free survival as proxy	997,266
		Capped by progression-free survival	901,023

Abbreviations. ICER, incremental cost-effectiveness ratio; LEN, lenvatinib; PEM, pembrolizumab; SEK, Swedish Krona; UK, United Kingdom; Wk, Week.

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Data availability statement

The corresponding author has full access to all the data in the study. MSD is committed to providing qualified scientific researchers access to anonymized data and clinical study reports from the company’s clinical trials for the purpose of conducting legitimate scientific research. MSD is also obligated to protect the rights and privacy of trial participants and, as such, has a procedure in place for evaluating and fulfilling requests for sharing company clinical trial data with qualified external scientific researchers. The MSD data-sharing website (available at: http://engagezone.msd.com/ds_documentation.php) outlines the process and requirements for submitting a data request.