Cost-effectiveness analysis of cabozantinib compared with everolimus, axitinib, and nivolumab in subsequent line advanced renal cell carcinoma in Japan

Figures & data

Figure 1. Model structure. Abbreviations. OS, Overall survival; PFS, Progression-free survival.

Table 1. Clinical inputs.

Parameter		DSA		PSA
	Base Case*	Lower Bound	Upper Bound	Distribution	SE
PFS – cabozantinib and everolimus
Log-logistic - intercept	1.523	1.414	1.632	Normal	0.057
Log-logistic – scale	0.533	0.490	0.576	Normal	0.035
Log-logistic - cabozantinib	0.567	0.413	0.720	Normal	0.081
PFS – relative efficacy
HR – axitinib vs. cabozantinib	1.695	1.075	2.632	Log-normal	0.170
HR – nivolumab vs. cabozantinib	1.613	1.235	2.128	Log-normal	0.161
OS – cabozantinib and everolimus
Log-logistic - intercept	2.853	2.744	2.962	Normal	0.059
Log-logistic – scale	0.597	0.554	0.640	Normal	0.025
Log-logistic - cabozantinib	0.293	0.140	0.446	Normal	0.083
OS – relative efficacy
HR – axitinib vs. cabozantinib	1.786	0.625	5.000	Log-normal	0.179
HR – nivolumab vs. cabozantinib	1.042	0.813	1.333	Log-normal	0.104
TTD – cabozantinib and everolimus
Log-normal - intercept	1.612	1.504	1.721	Normal	0.053
Log-normal – scale	0.945	0.902	0.989	Normal	0.028
Log-normal - cabozantinib	0.626	0.473	0.779	Normal	0.074
TTD – axitinib and nivolumab
Exponential – intercept, axitinib	2.312	2.205	2.420	Normal	0.003
Exponential – intercept, nivolumab	2.155	2.048	2.261	Normal	0.003

*The inverse of the HRs are currently reported, as cabozantinib was treated as the reference arm in the cost-effectiveness model. For observed HR and additional information of parameterization of survival functions, please see the supplementary appendix.

Abbreviations. DSA, Deterministic sensitivity analysis; HR, Hazard ratio; OS, Overall survival; PFS, Progression-free survival; PSA, Probabilistic sensitivity analysis; SE, Standard error; TTD, Time-to-treatment discontinuation.

Table 2. Direct Medical cost and utility inputs.

Parameter		DSA		PSA
	Base Case	Lower Bound	Upper Bound	Distribution	SE
Health state utilities
Progression-free	0.756	0.747	0.765	Beta	0.005
Post-progression	0.717	0.706	0.729	Beta	0.006
Disutility due to Aes
Cabozantinib	0.0027	0.0022	0.0033	Beta	0.00027
Everolimus	0.0017	0.0014	0.0021	Beta	0.00017
Axitinib	0.0022	0.0018	0.0027	Beta	0.00022
Nivolumab	0.0004	0.0003	0.0005	Beta	0.00004
Total subsequent treatment cost
Following cabozantinib	¥ 2,125,251	¥ 1,700,201	¥ 2,550,302	Gamma	¥ 216,862
Following everolimus	¥ 2,365,196	¥ 1,892,156	¥ 2,838,235	Gamma	¥ 241,346
Following axitinib	¥ 2,435,136	¥ 1,948,109	¥ 2,922,163	Gamma	¥ 248,483
Following nivolumab	¥ 2,987,660	¥ 2,390,128	¥ 3,585,192	Gamma	¥ 304,863
One-time cost at end-of-life	¥ 1,431,661	¥ 1,145,329	¥ 1,717,994	Gamma	¥ 146,088
Disease management cost per cycle
Cabozantinib, everolimus, and axitinib	¥ 18,560	¥ 14,848	¥ 22,272	Gamma	¥ 1,894
Nivolumab	¥ 19,730	¥ 15,784	¥ 23,676	Gamma	¥ 2,013
AE management costs per cycle
Cabozantinib	¥ 1,249	¥ 999	¥ 1,499	Gamma	¥ 127
Everolimus	¥ 266	¥ 213	¥ 319	Gamma	¥ 27
Axitinib	¥ 1,174	¥ 939	¥ 1,409	Gamma	¥ 120
Nivolumab	¥ 39	¥ 31	¥ 47	Gamma	¥ 4

Abbreviations. AE, Adverse event; DSA, Deterministic sensitivity analysis; PSA, Probabilistic sensitivity analysis; SE, Standard error.

Table 3. Drug and administration costs.

Treatment	Strength per Unit	Usage	Unit Drug Price	RDI	Administration Cost per Cycle	Cost per Cycle
Cabozantinib	60 mg	60 mg once daily	¥22,333	75.25%	¥ 3,230	¥ 473,786
Everolimus	5 mg	10 mg once daily	¥10,603	83.90%	¥ 3,230	¥ 501,401
Axitinib	5 mg	5 mg twice daily	¥8,501.30	102.00%^32	¥ 3,230	¥ 488,824
Nivolumab	240 mg	240 mg, every two weeks	¥413,990	92.43%^33	¥ 13,880	¥ 779,141
Sorafenib (subsequent line only)	200 mg	400 mg twice daily	¥4,677.10	90.54%^1^,^32	¥ 3,230	¥ 486,269
Pazopanib (subsequent line only)	200 mg	800 mg once daily	¥4,142.30	86.00%^34	¥ 3,230	¥ 409,604
Sunitinib (subsequent line only)	12.5 mg	50 mg once daily for 4 weeks followed by 2 weeks off	¥ 7,613.70	87.00%^18	¥ 3,230	¥ 497,816

Abbreviation. RDI, Relative dose intensities.

Table 4. Base case (deterministic) results.

Cost and Health Outcomes	Cabozantinib	Everolimus	Axitinib	Nivolumab
Total Costs	¥ 10,163,113	¥ 7,542,119	¥ 7,978,455	¥ 11,062,991
Drug and administration	¥ 6,818,585	¥ 3,901,109	¥ 4,903,943	¥ 6,690,727
Subsequent line	¥ 1,288,455	¥ 1,724,036	¥ 1,299,677	¥ 2,303,037
AE management	¥ 1,249	¥ 266	¥ 1,174	¥ 39
Disease management	¥ 2,054,825	¥ 1,916,707	¥ 1,773,661	¥ 2,069,186
Total Lys	2.89	2.23	1.54	2.75
Progression-free Lys	0.99	0.57	0.56	0.59
Post-progression Lys	1.90	1.66	0.98	2.17
Total QALYs	2.11	1.62	1.12	2.00
Progression-free QALYs	0.75	0.43	0.42	0.44
Post-progression QALYs	1.36	1.19	0.70	1.55
Disutilities: AEs	−0.0027	−0.0017	−0.0022	−0.0004
Incremental (cabozantinib vs. comparators)
Costs	--	¥ 2,620,995	¥ 2,184,659	- ¥ 899,877
QALYs	--	0.49	0.98	0.11
Cost-effectiveness ratio	--	¥ 5,375,559	¥ 2,223,138	Dominant

Abbreviations. AE, adverse event; LY, life year; QALY, quality-adjusted life year.

Table 5. Scenario analysis results (cabozantinib vs. comparators).

Scenario	ICER (vs. everolimus)	ICER (vs. axitinib)	ICER (vs. nivolumab)
1. Axitinib and everolimus equally effective	¥ 5,375,559	¥ 3,736,376	Dominant
2. Alternative RDI for a Japanese population	¥ 889,558	¥ 353,582	Dominant
3. Cabozantinib treatment effect on OS wanes	¥ 5,963,139	¥ 2,301,145	Dominant
4. Assume treat until progression for axitinib	¥ 5,375,559	¥ 3,153,505	Dominant

Abbreviations. ICER, Incremental cost-effectiveness ratio; OS, Overall survival; RDI, Relative dose intensities.

Figure 2. Tornado ICER Results, DSA. Abbreviations. CI, Confidence interval; HR, Hazard ratio; ICER: Incremental cost-effectiveness ratio; OS, Overall survival; TTD: Time-to-treatment discontinuation; Tx, Treatment.

Figure 3. Incremental cost-effectiveness plane, PSA. Abbreviation. QALY, Quality-adjusted life year.

Figure 4. Cost-effectiveness acceptability curves, PSA. At a threshold of ¥ 7,500,000, cabozantinib had a probability of 70.1% for being cost-effective, while everolimus, axitinib, and nivolumab probabilities of 12%, 0.2%, and 17.7% for cost-effectiveness, respectively.

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Data availability statement

The authors declare that all input data to parameterize the model are available within the article and the Supplementary Material. The model can be re-built entirely based on the detailed description of the model structure and information provided.