Cost-effectiveness analysis of nivolumab plus ipilimumab versus platinum-doublet chemotherapy for first-line treatment of stage IV or recurrent non-small cell lung cancer in the United States

Figures & data

Figure 1. Constructed conditional survival curve for OS in the NIVO + IPI arm. Abbreviations. CM, CheckMate; IPI, ipilimumab; NIVO, nivolumab; OS, overall survival; PFS, progression-free survival; SEER, Surveillance, Epidemiology and End Results.

Figure 2. OS and PFS in the NIVO + IPI and PDC arms, comparing trial KM data and selected parametric curves. Abbreviations. IPI, ipilimumab; KM, Kaplan–Meier; NIVO, nivolumab; OS, overall survival; PDC, platinum-doublet chemotherapy; PFS, progression-free survival.

Table 1. Scenario analyses results for NIVO + IPI versus PDC.

NIVO + IPI vs PDC	Inc. costs, $	Inc. LYs	Inc. QALYs	Inc. cost/LYG, $	Inc. cost/QALY, $	Diff. from base case, %
Base case	142 088	1.534	1.333	92 651	106 553	–
Scenario 1 (conservative NIVO + IPI OS curve [2 knots spline normal])	140 230	1.441	1.255	97 339	111 748	+5
Scenario 2 (conservative PDC OS curve [1 knot spline hazard])	142 861	1.572	1.366	90 869	104 570	–2
Scenario 3 (treatment-specific progression-based utilities)	142 088	1.534	1.214	92 651	117 076	+10
Scenario 4 (progression-based overall utility)	142 088	1.534	1.239	92 651	114 639	+8
Scenario 5 (DoT estimated with Kaplan–Meier parametric extrapolation)	132 620	1.534	1.333	86 478	99 453	–7
Scenario 6 (equal percentage of patients receiving subsequent treatments in both arms)	145 388	1.534	1.333	94 803	109 028	+2

Abbreviations. DoT, duration of treatment; IPI, ipilimumab; LYs, life-years; LYG, life-year gained; NIVO, nivolumab; OS, overall survival; PDC, platinum-doublet chemotherapy; QALY, quality-adjusted life-year.

Table 2. Model cost inputs.

Parameter	$
Disease management, PF (Q4W)^a	524
Disease management, PD (Q4W)^a	1 628
End-of-life care^b	12 303
Drug acquisition costs (per dose)^c
NIVO, 3 mg/kg Q2W	6 271
IPI, 1 mg/kg Q6W	15 765
PDC Q3W^d	5 203
Drug administration costs (per administration)
NIVO + IPI^e	208
PDC^f	259
Drug monitoring costs (per 4 weeks)^g
NIVO + IPI	182
PDC	126
Treatment-related AE costs^h
NIVO + IPI	155
PDC	4 046

^aDetailed disease management and unit cost inputs are provided in Table S4.

^bSource: Bremner, 2015 inflated to 2021 dollars using the consumer price index for all urban consumers, Medical Care in U.S, City average (CPIMEDSL)^34,49.

^cSource: Medi-Span Price Rx⁵⁰, wholesale acquisition cost.

^dPDC cost is based on the proportion of patients receiving each drug combination in Part 1 of CheckMate 227 (Table S5).

^eSource: 2022 Medicare Physician Fee Schedule⁵¹, HCPCS codes: 96413 ($140) + 96417 ($68) non-facility price.

^fSource: 2022 Medicare Physician Fee Schedule⁵¹, weighted by the mix of chemotherapy agents and their duration of administration; HCPCS codes: 2 × 96413 ($140) (to reflect the administration of gemcitabine Q2W) + 96415 ($30) (for longer infusion time of cisplatin) + 96417 ($68).

^gSource: CMS Clinical Laboratory Fee Schedule, Q1 2022⁵¹.

^hDetailed costs associated with AEs are provided in Table S1.

Abbreviations. AE, adverse event; HCPCS, Healthcare Common Procedure Coding System; IPI, ipilimumab; NIVO, nivolumab; NSCLC, non-small cell lung cancer; PD, progressed disease; PDC, platinum-doublet chemotherapy; PF, progression-free; QnW, every n weeks.

Table 3. Base-case results for NIVO + IPI versus PDC.

Incremental:	Costs, $	LYs	QALYs	Cost/LYG, $	Cost/QALY, $
NIVO + IPI vs PDC	142 088	1.53	1.33	92 651	106 553
	NIVO + IPI				PDC
Total LYs	3.53				2.00
Total QALYs	2.89				1.56
Cost breakdown, $
Disease management	58 751				43 466
Drug acquisition	191 870				44 921
Drug administration	2 655				1 408
Drug monitoring	1 452				667
AEs	155				4 045
Subsequent treatment	7 807				26 093
Total costs, $	262 689				120 601

Abbreviations. AEs, adverse events; IPI, ipilimumab; LYs, life-years; LYG, life-year gained; NIVO, nivolumab; PDC, platinum-doublet chemotherapy; QALY, quality-adjusted life-year.

Figure 3. Deterministic sensitivity analysis of NIVO + IPI versus PDC showing the 10 most impactful parameters on the model result. See Supplementary Material, Supplemental Methods, Sensitivity Analyses for details of the analysis. Abbreviations. ICER, incremental cost-effectiveness ratio; IPI, ipilimumab; NIVO, nivolumab; PDC, platinum-doublet chemotherapy; QALY, quality-adjusted life-year; TTD, time to death.

Figure 4. Cost-effectiveness acceptability curve for NIVO + IPI and PDC. See Supplementary Material, Supplemental Methods, Sensitivity Analyses for details of the analysis. Abbreviations. IPI, ipilimumab; NIVO, nivolumab; PDC, platinum-doublet chemotherapy; WTP, willingness to pay.

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Data availability statement

The analysis reported in this study uses patient-level data from the CheckMate 227 trial. The results of the trial have been reported in a number of publications¹⁸. The trial results supporting the findings of this analysis are presented graphically within the article. The survival analysis was implemented using the FlexSurv package in R.