Cost-effectiveness of enzalutamide versus apalutamide versus androgen deprivation therapy alone for the treatment of metastatic castration-sensitive prostate cancer in Canada

Figures & data

Figure 1. Markov model structure. Abbreviations. mCRPC, metastatic castration-resistant prostate cancer; mCSPC, metastatic castration-sensitive prostate cancer; PD, progressed disease.

Figure 2. Extrapolated OS across treatment arms. Extrapolation of OS was performed using parametric survival analysis, with Weibull distribution selected as the best fit. Abbreviations. ADT, androgen deprivation therapy; K-M, Kaplan–Meier; OS, overall survival.

Figure 3. Extrapolated rPFS across treatment arms. Extrapolation of PFS was performed using parametric survival analysis, with log-normal distribution selected as the best fit. Abbreviations. ADT, androgen deprivation therapy; K-M, Kaplan–Meier; PFS, progression-free survival; rPFS, radiographic progression-free survival.

Table 1. Base-case LYG in each disease state across treatment arms over a 15-year time horizon.

	Treatment arm
	Enzalutamide	ADT alone	Apalutamide
PFLYs (mCSPC)	4.945	2.111	3.982
PD1^a	0.309	1.275	0.317
PD2^a	0.226	0.312	0.228
PD3^a	2.084	1.216	1.558
Total LYGs	7.564	4.914	6.086

Abbreviations. ADT, androgen deprivation therapy; LYG, life-year gained; mCSPC, metastatic hormone-sensitive prostate cancer; OS, overall survival; PD, progressed disease; PFLY, progression-free life-year (refers to time in the mCSPC health state).

^aLYG in the PD health states were based on the probability of transitioning between the PD1–3 states (calculated using the duration of treatments at each state) and accounting for OS.

Table 2. Base-case cost-effectiveness outcomes (discounted) across treatment arms over a 15-year time horizon.

	Treatment arm
	Enzalutamide	ADT alone	Apalutamide
Total costs, CAD	349,345	162,550	294,349
Technology acquisition	206,584	11,804	169,452
Subsequent drug lines	21,573	75,444	22,204
mCSPC	34,053	3,431	27,920
mCRPC	75,552	57,906	61,430
Terminal care	11,583	13,965	13,343
Total LYGs	7.41	4.91	6.08
Total QALYs	5.62	3.61	4.59
ICERs (cost per QALY gained), CAD		92,868	53,377

Abbreviations. ADT, androgen deprivation therapy; CAD, Canadian dollars; ICER, incremental cost-effectiveness ratio; LYG, life-year gained; mCRPC, metastatic castration-resistant prostate cancer; mCSPC, metastatic castration-sensitive prostate cancer; QALY, quality-adjusted life-year.

Table 3. Summary of ICERs for enzalutamide versus ADT alone for each scenario analysis.

Model scenario	Change in settings from base-case analysis	Sequential ICER for enzalutamide, CAD^a
Alternative parametric curves for OS	Alternative parametric curves for OS: log-logistic (second-best fit)	98,269
Alternative parametric curves for rPFS	Alternative parametric curves for rPFS: gamma (second-best fit)	102,994
Shorter time horizon	Shorter time horizon: 10 years	109,055
NMA HR to model enzalutamide	NMA HR to model efficacy for enzalutamide	117,938
Base-case scenario using only ARCHES data	Base-case scenario using only ARCHES data	109,553
Canadian utility values	Utility values based on Canadian utility analysis (EQ-5D-5L)	91,202
Utility values used in published models	Utility values used in published peer-reviewed Canadian journal^19	82,196

Abbreviations. ADT, androgen deprivation therapy; CAD, Canadian dollars; EQ-5D-5L, EuroQol 5-Dimensions 5-Levels questionnaire; HR, hazard ratio; ICER, incremental cost-effectiveness ratio; NMA, network meta-analysis; OS, overall survival; rPFS, radiographic progression-free survival.

^aAcross all scenario analyses, enzalutamide and ADT alone remained on the cost-effectiveness frontier, with apalutamide extendedly dominated through ADT alone and enzalutamide. Scenario analyses were conducted probabilistically (5,000 Monte Carlo iterations for each scenario).

Figure 4. Base-case results: cost-effectiveness frontier. Abbreviations. ADT, androgen deprivation therapy; CAD, Canadian dollars; QALY, quality-adjusted life-year.

Chi KN, Agarwal N, Bjartell A, et al. Apalutamide for metastatic, castration-sensitive prostate cancer. N Engl J Med. 2019;381(1):13–24.

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