Cost-effectiveness analysis of pembrolizumab monotherapy versus chemotherapy for previously untreated advanced non-small cell lung cancer

Figures & data

Figure 1. Partitioned survival model health state transitions. Abbreviations: PF: progression-free; PD: progressed disease.

Figure 2. Kaplan Meier survival curves for overall survival (A) and progression-free survival (B).

Table 1. Key input data for base-case analysis.

Model parameters	Base-case		Range			Distribution for PSA	Source
Clinical inputs
Overall survival (Updated analysis)	Exponential					Normal	Extrapolated from published KM curves from KEYNOTE-024 study^5^,^6
Pembrolizumab	Intercept = 5.285		Standard error: 0.164
Chemotherapy	Intercept = 4.701		Standard error: 0.149
Overall survival (Interim analysis)	Exponential					Normal	Extrapolated from published KM curves from KEYNOTE-024 study^5^,^6
Pembrolizumab	Intercept = 5.319		Standard error: 0.354
Chemotherapy	Intercept = 4.540		Standard error: 0.277
Progression-free survival	Weibull			Cholesky matrix		Multi-variate normal	Extrapolated from published KM curves from KEYNOTE-024 study^5^,^6
				Intercept	Log (scale)
Pembrolizumab	Intercept = 4.946 Log (scale) = 0.394		Intercept Log (scale)	0.326894 0.102399	0 0.111895
Chemotherapy	Intercept = 3.3549 Log (scale) =-0.206		Intercept Log (scale)	0.092845 0.004419	0 0.096256
Quality-of-life inputs
First-line PF	0.71		0.67–0.76			Beta	Chouaid et al.^11
Second-line PF	0.67		0.59–0.75			Beta	Chouaid et al.^11
Second-line PD	0.59		0.42–0.77			Beta	Chouaid et al.^11
Utility decrement for any grade 3 and above adverse events	0.070		0.030–0.110			Beta	Reported in NICE TA447^15
Mean duration of adverse events	31.5 days		–			–	Reported in NICE TA447^15
Incidence rates of grade 3 and above adverse events			–			–	Reported in NICE TA447^15
Pembrolizumab	26.6%
Chemotherapy	53.3%
Cost inputs (SGD)^a
Cost of medication per 3 week cycle		–				–	Local hospital, 2019 data
Pembrolizumab	$10,540
Chemotherapy	$731
Cost of chemotherapy administration		–				–	Local hospital, 2019 data
Facility fee	$272.20
Chemotherapy preparation fee	$52.80
Cost of events (one-time)		–				–	MOH Casemix & Subvention data 2017
Neutropenia	$4,983
Pneumonitis	$13,432
Severe skin reaction	$8,695
Cost of disease management		–				–	Local hospital, 2019 data
Specialist consult	$75
CT scan	$940
Liver function test	$71
Full blood count	$26
Renal panel test	$63
Thyroid function test	$226
Cost of terminal care	$3,211		–			–	Local hospital, 2019 data

Abbreviations. CT, computerized tomography; PD, progressed disease; PF, progression free; PSA, probabilistic sensitivity analyses.

^aCost inputs were not included in the probabilistic sensitivity analyses as they were considered to be fixed with no uncertainty.

Table 2. Results of base-case and scenario analyses.

Base-case results
	Pembrolizumab	Chemotherapy	Incremental
Benefits
Progression-free LYs	2.1099	0.5233	1.5866
Post-progression LYs	0.8108	1.2498	−0.439
Total LYs	2.9207	1.7731	1.1476
Total QALYs	1.9983	1.1317	0.8666
Costs (SGD)
Drug costs	$197,677	$59,899	$137,778
Management costs	$14,629	$6,995	$7,634
Terminal care costs	$2,767	$3,025	-$258
AE costs	$688	$525	$163
Total costs	$215,761	$70,444	$145,317
Scenario analysis
Scenarios	Incremental costs (SGD)	Incremental QALYs	ICER per QALY gained (SGD)
Base-case*	$145,317	0.8666	$167,692
Survival curves
OS curves from interim analysis	$146,596	1.0056	$145,774
Two-piece fitting at week 23 on OS curves	$145,337	0.8680	$167,437
Two-piece fitting at week 43 on OS curves	$144,768	0.8060	$179,608
Weibull distribution for OS curves	$145,740	0.9191	$158,574
Pembrolizumab treatment effect
Limit to only 2 years	$142,331	0.4173	$341,073
Limit to only 5 years	$144,498	0.7207	$200,510
Utility weights reference source
Utilities from KEYNOTE-024/010 (PF and PD health states)	$145,317	0.9340	$155,577
Utilities from KEYNOTE-024 (Time to death classification)	$145,317	0.9254	$157,025
Simulation of reduction of pembrolizumab selling price
20% reduction	$118,378	0.8666	$136,605
30% reduction	$104,908	0.8666	$121,062
40% reduction	$91,439	0.8666	$105,518
50% reduction	$77,969	0.8666	$89,975
60% reduction	$64,500	0.8666	$74,431
70% reduction	$51,030	0.8666	$58,888

Abbreviations. AE, adverse events; LY, life-year; QALY, quality-adjusted life-year; SGD, Singapore dollars.

*Base-case analysis: •Two-piece fitting for OS and PFS of both pembrolizumab and chemotherapy (OS: exponential fitting, PFS: Weibull fitting). •OS curves from final analysis of KEYNOTE-024 study⁶ (25.2 months median follow-up). •Pembrolizumab treatment effect assumed to continue throughout time horizon. •Utility weights obtained from Chouaid et al.¹¹.

Figure 3. One-way sensitivity analysis tornado diagram for pembrolizumab versus chemotherapy (base-case ICER: SGD167,692 per QALY). Abbreviations: ICER, incremental cost-effectiveness ratio; QALY, Quality-adjusted life-years; SGD, Singapore dollars; 1L, first-line; 2L, second line; AE, adverse events.

Figure 4. Cost-effectiveness acceptability curve showing the likelihood of pembrolizumab being cost-effective compared to platinum-based chemotherapy across different willingness-to-pay thresholds.

Reck M, Rodriguez-Abreu D, Robinson AG, et al. Pembrolizumab versus chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2016;375(19):1823–1833.

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