Table 1.

Model inputs

Parameters	Patients with CPS ≥ 1 Pembrolizumab monotherapy versus cetuximab + platinum + 5-FU		Total population Pembrolizumab combination versus cetuximab + platinum + 5-FU		Estimation approach / data sources	Sensitivity analyses (PSAa distribution)
	Intervention	Comparator	Intervention	Comparator
Effectiveness					Piecewise approach using KEYNOTE-048 data: KM curve followed by parametric extrapolation	Alternative cut-off points and/or parametric distributions Survival distributional parameters (multinormal)
PFS	Week-52 cut-off followed by:
	e(− 4.73)	e(− 4.21)	e(− 4.66)	e(− 3.98)
OS	Week-80 cut-off followed by:
	ll(-0.10; 4.60)	ll(0.25; 3.75)	ln(4.87; 0.64)	ln(3.79; 0.27)
Direct medical costs, AR$					Costs sourced from different public and private Argentinian institutions The incidence of TRAE was taken from KEYNOTE-048 trial datab Drug costs are based on ex-factory public prices from AlfaBeta, schedule recommendations and KEYNOTE-048 ToT data Treatment duration caped to disease progression and pembrolizumab given for a maximum of 2 years. (Table 2)	DSA and PSA on: TRAE incidence (gamma) Resource usage (beta) Weekly resource costs (gamma) Terminal care resources (constrained beta) Patient weight and BSA (log-normal) Subsequent treatment duration (gamma) Allow for vial sharing
Weekly costs
Pre-progression, year 1	6,343.32	6,343.32	6,343.32	6,343.32
Pre-progression, after year 1	5,779.19	5,779.19	5,779.19	5,779.19
Post-progression	4,327.36	4,327.36	4,327.36	4,327.36
One-time cost
Disease progression	37,804.12	37,804.12	37,804.12	37,804.12
Terminal care	185,909.98	185,909.98	185,909.98	185,909.98
Drug administration per dose	7,877.87	18,980.95	18,980.95	18,980.95
TRAEs, weekly	11.70	633.16	767.17	633.16
1L treatment, weekly average
First 3-week cyclec	135,103.49	169,310.41	139,735.10	169,310.41
Subsequent 3-week cycles
With platinum + 5-FU	NA	141,863.06	139,735.10	141,863.06
Without platinum + 5-FUd	135,103.49	137,231.46	135,103.49	137,231.46
Subsequent treatmentse	1,076,761.67	1,691,770.64	1,316,616.83	1,578,559.19
Utilities					Utilities derived through a linear mixed regression of EQ-5D-3L scores from KEYNOTE-048 and using an Argentina algorithm	Alternative utility values DSA and PSA (normal)
Health state utilities
PFS	0.8300	0.8300	0.8300	0.8300
PD	0.7900	0.7900	0.7900	0.7900
Disutilities
TRAE Grade 3–5	0.0300	0.0300	0.0300	0.0300
Days prior to death
90–180	0.0423	0.0423	0.0423	0.0423
60–90	0.1123	0.1123	0.1123	0.1123
30–60	0.1123	0.1123	0.1123	0.1123
0–30	0.2302	0.2302	0.2302	0.2302

CPS combined positive score, EQ-5D-3L EuroQol five-dimension three-level, e exponential, ll log-logistic, ln log-normal, NA not applicable, OS overall survival, PFS progression-free survival, PSA probabilistic sensitivity analysis, ToT time-on-treatment, TRAE treatment-related adverse events, 1L first line, 5-FU 5-fluorouracil

^aThe variability of the selected distributions was based on standard errors or variance–covariance from original data sources. For costs, the standard errors were assumed to be equal to 20% of the base-case values. Other elements of the PSA (distribution) include patients age (gamma), gender distribution (beta), and survival distributional time-on-treatment parameters (multinormal)

^bTRAEs grade 3–5 occurring in at least 5% of patients (any severity) in at least one treatment arm were included

^cPatient in the comparator arm received a loading dose of cetuximab the first week. For all other drugs, the dosing regimens are equal for first and subsequent doses

^dPatients in pembrolizumab combination therapy arm or in the comparator arm received platinum (42.13% cisplatin and 57.87% carboplatin) + 5-FU for up to six 3-week cycles

^eSubsequent treatment costs are inclusive of the cost associated with the management of treatment-related adverse events AR $74 = 1 USD = 0.84 euro. Ex-factory public prices from AlfaBeta, August 28, 2020