Cost-effectiveness analysis of molecular diagnosis by next-generation sequencing versus sequential single testing in metastatic non-small cell lung cancer patients from a south Spanish hospital perspective

Figures & data

Figure 1. Diagram of the model.

Table 1. Testing and positivity rates.

	Testing rate
Biomarker	NGS	SST	Positivity rate
EGFR	100.00%	100.00%	13.60%
ALK	100.00%	100.00%	3.40%
ROS1	100.00%	100.00%	2.00%
BRAF V600	100.00%	60.00%	5.50%
NTRK	100.00%	20.00%	1.00%
HER2	100.00%	0.00%	3.80%
MET	100.00%	20.00%	4.40%
RET	100.00%	20.00%	2.10%
KRAS G12C	100.00%	20.00%	17,00%
PD-L1	100.00%	100.00%	33.00%

EGFR, epidermal growth factor receptor gene; ALK, anaplastic lymphoma receptor kinase gene; ROS1, ROS proto-oncogene 1, receptor tyrosine kinase; BRAF, B-Raf proto-oncogene, serine/threonine kinase; NTRK, neurotrophic tyrosine receptor kinase gene; HER2, human epidermal growth factor receptor 2 gene; MET, MET proto-oncogene; RET, RET proto-oncogene; KRAS, KRAS proto-oncogene; PD-L1, programmed death-ligand 1; RT-PCR, reverse transcription polymerase chain reaction; IHQ, immunohistochemistry; FISH, fluorescence in situ hybridization.

Table 2. Time spent and duration of pre-analytical and analytical phases.

	Technician time	Physician time	Shedule (day)
Pre-analytical subphase
Reception/labelling	5 min	-	Day 0
Fixation	12–16 h	-	Day 0
Macroscopic study	5–10 min	-	Day 0
Processing	12 h (overnight)	-	Day 0
Embedding	15–20 min	-	Day 1
Section cutting	20 min	-	Day 1
Staining	1.5 h	-	Day 2
Pathological diagnostic	-	20 min	Day 2
Analytical subphase
RT-PCR	2 h per sample	0.5 h per sample	Day 2+ (1–2 working days)
IHQ	2 h per sample	0.1 h per sample	Day 2+ (1 working day)
FISH	2 h per sample	0.5 h per sample	Day 2+ (2 working days)
NGS	30 min per sample	2 h per sample	Day 2+ (7 working days)

RT-PCR, real-time polymerase chain reaction; IHC, immunohistochemistry; FISH, fluorescence in situ hybridization; NGS, next-generation sequencing.

Table 3. Unit cost for NGS and SST.

Biomarker tested	Technique used	Unit cost (€)
NGS
All biomarkers	Oncomine Focus Assay	600.00
SST^a
EGFR	RT-PCR	105.00
ALK	IHC and FISH	48.40
ROS1	IHC and FISH	62.92^b
BRAFV600	RT-PCR	105.00
NTRK	IHC	96.80^c
MET	FISH	185.50^d
RET	FISH	121.00
KRAS G12C	RT-PCR	105.00
PD-L1	IHC	30.25

EGFR, epidermal growth factor receptor gene; ALK, anaplastic lymphoma receptor kinase gene; ROS1, ROS proto-oncogene 1, receptor tyrosine kinase; BRAF, B-Raf proto-oncogene, serine/threonine kinase; NTRK, neurotrophic tyrosine receptor kinase gene; MET, MET proto-oncogene; RET, RET proto-oncogene; KRAS, KRAS proto-oncogene; PD-L1, programmed death-ligand 1; RT-PCR, reverse transcription polymerase chain reaction; IHQ, immunohistochemistry; FISH, jluorescence in situ hybridization.

^aHER2 is not shown as its testing rate is 0%, as shown in Figure 1.

^bWeighted average of 80% IHC and 20% FISH.

^cWeighted average of 80% IHC and 20% FISH (three determinations for three genes, NTRK 1-2-3).

^dWeighted average of 50% FISH (amplifications) and 50% RT-PCR (MET ex14 skipping).

Figure 2. Distribution of alterations detected in hypothetical cohort.

EGFR, epidermal growth factor receptor gene; ALK, anaplastic lymphoma receptor kinase gene; ROS1, ROS proto-oncogene 1, receptor tyrosine kinase; BRAF, B-Raf proto-oncogene, serine/threonine kinase; NTRK, Neurotrophic tyrosine receptor kinase gene; HER2, human epidermal growth factor receptor 2 gene; MET, MET proto-oncogene; RET, RET proto-oncogene; KRAS, KRAS proto-oncogene; PD-L1, programmed death-ligand 1.

Table 4. Short-term cost and efficacy outcomes.

	NGS	SST	Incremental
Total diagnostic costs (€)	122,012	103,422	+18,590
Testing cost (€)	63,025	32,112	+30,913
Re-biopsy cost (€)	0	6,351	−6,351
Staff cost (€)	58,987	64,960	−5,972
peTT	53	23	+30
peCT	11	8	+3
ICER (expressed as additional € per peTT gained)			€617/peTT
ICER (expressed as additional € per peCT gained)			€6,249/peCT

NGS, next-generation sequencing; SST, sequential single testing; peTT, additional patients eligible for target therapy; peCT, additional patients eligible for enrollment in clinical trials; ICER, incremental cost–effectiveness ratio.

Figure 3. Time-to-results analysis.

NGS, next-generation sequencing; SST, sequential single testing; EGFR, epidermal growth factor receptor gene; ALK, anaplastic lymphoma receptor kinase gene; ROS1, ROS proto-oncogene 1, receptor tyrosine kinase; BRAF, B-Raf proto-oncogene, serine/threonine kinase; NTRK, neurotrophic tyrosine receptor kinase gene; MET, MET proto-oncogene; RET, RET proto-oncogene; KRAS, KRAS proto-oncogene; PD-L1, programmed death-ligand 1* HER2 is not shown as its testing rate is 0%, as shown in Table 1.

Table 5. Exploratory long-term results.

	NGS	SST	Incremental
Diagnostic costs (€)	122,012	103,422	+18,590
Treatment costs (€)	11,368,232	11,339,390	+28,843
Total overall costs (€)	11,490,245	11,442,812	+47,432
LYs	276.77	268.87	+7.90
QALYs	185.96	180.74	+5.22
ICER (expressed as additional € per LY gained)			€6,005/LY
ICUR (expressed as additional € per QALY gained)			€9,084/QALY

NGS, next-generation sequencing; SST, sequential single testing; LY, life years; QALY, quality-adjusted life years; ICER, iIncremental cost-effectiveness ratio; ICUR, incremental cost–utility ratio.

Figure 4. One-way sensitivity analysis, represented by tornado diagrams.

NGS, next-generation sequencing; SST, sequential single testing; ICER, incremental cost-effectiveness ratio; peTT, additional patients eligible for target therapy; peCT, additional patients eligible for enrollment in clinical trials.

Figure 5. PSA results, represented by a cost-effectiveness scatter plot.

NGS, next-generation sequencing; SST, sequential single testing; peTT, additional patients eligible for target therapy; peCT, additional patients eligible for enrollment in clinical trials.