Costs of biomarker testing in advanced non-small cell lung cancer: a global study comparing next-generation sequencing and single-gene testing

Abstract

Current European/US guidelines recommend that molecular testing in advanced non-small cell lung cancer (aNSCLC) be performed using next-generation sequencing (NGS). However, the global uptake of NGS is limited, largely owing to reimbursement constraints. We compared real-world costs of NGS and single-gene testing (SGT) in nonsquamous aNSCLC. This observational study was conducted across 10 pathology centers in 10 different countries worldwide. Biomarker data collected via structured questionnaires (1 January-31 December 2021) were used to feed micro-costing analyses for three scenarios ['Starting Point' (SP; 2021-2022), 'Current Practice' (CP; 2023-2024), and 'Future Horizons' (FH; 2025-2028)] in both a real-world model, comprising all biomarkers tested by each center, and a standardized model, comprising the same sets of biomarkers across centers. Testing costs (including retesting) encompassed personnel costs, consumables, equipment, and overheads. Overall, 4,491 patients with aNSCLC were evaluated. Mean per-patient costs decreased for NGS relative to SGT over time, with real-world model costs 18% lower for NGS than for SGT in the SP scenario, and 26% lower for NGS than for SGT in the CP scenario. Mean per-biomarker costs also decreased over time for NGS relative to SGT. In the standardized model, the tipping point for the minimum number of biomarkers required for NGS to result in cost savings (per patient) was 10 and 12 in the SP and CP scenarios, respectively. Retesting had a negligible impact on cost analyses, and results were robust to variation in cost parameters. This study provides robust real-world global evidence for cost savings with NGS-based panels over SGT to evaluate predictive biomarkers in nonsquamous aNSCLC when the number of biomarkers to be tested exceeds 10. Widespread adoption of NGS may enable more efficient use of limited healthcare resources.

Keywords: NSCLC; cost comparison; next‐generation sequencing; precision medicine; predictive biomarker; single‐gene testing.

Figure 1

Study design. Map created using Power‐user SAS. ^aCenter 6 used NGS partially since 2015. ^bCenter 7 used NGS for predictive testing (for all cancer types) since 2002, as well as for diagnostic testing since 2013. ^cBiomarkers included in the standardized model were the same across centers; biomarkers included in the real‐world model differed between centers. AKT, protein kinase B; ALK, anaplastic lymphoma kinase; BRAF, v‐raf murine sarcoma viral oncogene homolog B1; BRCA, BReast CAncer gene; CGP, comprehensive genomic profiling; CP, Current Practice; DDR, DNA damage response; EGFR, epidermal growth factor receptor; ERBB2, erb‐b2 receptor tyrosine kinase 2; FGFR, fibroblast growth factor receptor; FH, Future Horizons; FISH, fluorescence in situ hybridization; HER2, human epidermal growth factor receptor 2; HRAS, Harvey rat sarcoma viral oncogene homolog; IHC, immunohistochemistry; ISH, in situ hybridization; JAK, Janus kinase; KEAP1, Kelch‐like ECH‐associated protein 1; KRAS, Kirsten rat sarcoma viral oncogene homologue; MET, mesenchymal epithelial transition factor receptor; MMR, mismatch repair; MSI, microsatellite instability; NA, not available; NGS, next‐generation sequencing; NRAS, neuroblastoma RAS viral oncogene homolog; NRG1, neuregulin 1; NTRK, neurotrophic tyrosine receptor kinase; PCR, polymerase chain reaction; PD‐L1, programmed cell death ligand 1; PIK3CA, phosphatidylinositol‐4,5‐bisphosphate 3‐kinase, catalytic subunit alpha; RET, rearranged during transfection; ROS1, c‐ros oncogene 1; RT, real‐time; SGT, single‐gene testing; SP, Starting Point; STK11, serine/threonine kinase 11; TP53, tumor protein p53.

Figure 2

Mean cost per patient for SGT and NGS in the real‐world model. CP, Current Practice; FH, Future Horizons; NGS, next‐generation sequencing; SGT, single‐gene testing, SP, Starting Point.

Figure 3

Mean cost per patient for SGT and NGS in the standardized model. CP, Current Practice; FH, Future Horizons; NGS, next‐generation sequencing; SGT, single‐gene testing; SP, Starting Point.