Diagnostic and Economic Value of Biomarker Testing for Targetable Mutations in Non-Small-Cell Lung Cancer: a Literature Review

Abstract

We aimed to assess the diagnostic and economic value of next-generation sequencing (NGS) versus single-gene testing, and of liquid biopsy (LBx) versus tissue biopsy (TBx) in non-small-cell lung cancer biomarker testing through literature review. Embase and MEDLINE were searched to identify relevant studies (n = 43) from 2015 to 2020 in adults with advanced non-small-cell lung cancer. For NGS versus single-gene testing, concordance was 70–99% and sensitivity was 86–100%. For LBx versus TBx, specificity was 43–100% and sensitivity was ≥60%. Turnaround times were longer for NGS versus single-gene testing (but not vs sequential testing) and faster for LBx versus TBx. NGS was cost-effective, and LBx reduced US per-patient costs. NGS versus single-gene testing and LBx versus TBx were concordant. NGS and LBx may be cost-effective for initial screening.

An Overview of Comprehensive Genomic Profiling Technologies to Inform Cancer Care

“…40,65 One narrative review examined the economic evidence comparing NGS with single-biomarker assays (10 studies) and the evidence comparing liquid biopsies to tissue biopsies (3 studies) for NSCLC. 31 The review reported mixed findings; some studies reported cost savings with NGS compared to serial single-biomarker assays, while other studies indicated NGS may be associated with minimal cost increases. 31 The review suggested that NGS-based assays may be cost-effective compared with single-biomarker assays if they can help identify better treatments or additional people who may be eligible for targeted therapies.…”

“…7,30 However, because liquid biopsies do not directly target the primary tumour, they generally have reduced sensitivity compared with tissues samples, and, in some circumstances (e.g., certain cancer types, early-stage tumours, or patient-related factors), there may be limited ctDNA shed by tumours, which makes detection challenging. 28,31 Specificity of liquid biopsy-based tests has been reported to be high (≥ 90%) in most studies but it may still be prone to variability in different mutations and genes. 31 Sample preparation and handling of ctDNA may also affect analyses and can be prone to variability.…”

“…28,31 Specificity of liquid biopsy-based tests has been reported to be high (≥ 90%) in most studies but it may still be prone to variability in different mutations and genes. 31 Sample preparation and handling of ctDNA may also affect analyses and can be prone to variability. 30 Many researchers have stated that the future role of liquid biopsy as standard of care for many cancer types remains uncertain and requires further validation and assessment.…”

“…51 A review examining NGS technology (not specific to CGP) reported that concordance rates compared with single-gene testing were between 70% to 99% for NSCLC. 31 Evidence from primary studies and systematic reviews also indicated that although liquid-based tests can detect actionable mutations, tissue-based tests generally have higher sensitivity and detection capability. 26,29,[52][53][54][55] Tissue-based tests provide higher quality genetic signals if the tumour can be accessed appropriately.…”

“…In the absence of both elements, it will be difficult to conduct a credible cost-effectiveness analysis that will influence CGP uptake. 9 Although, the emerging economic evidence remains uncertain, we summarize some of the key findings from economic reviews 31,40,65 and budget impact studies about CGP and similar NGS technologies focused on Canadian jurisdictions. 9,27,66 Reviews have highlighted challenges in assessing the economic evidence for CGP and other NGS tests because there are varied comparators used across studies.…”