Authors' objectives: This health technology assessment evaluates the analytical validity, clinical validity, clinical utility, and cost-effectiveness of plasma-based comprehensive genomic profiling for non-small cell lung cancer. It also evaluates the budget impact of publicly funding liquid biopsy testing and the experiences, preferences, and values of people with non-small cell lung cancer.

Authors' results and conclusions: RESULTS We included 61 studies in the clinical evidence review. Liquid biopsy testing demonstrated a modest sensitivity in detecting actionable genomic alterations in the BRAF, EGFR, ERBB2, and KRAS genes (GRADE: Moderate to High). However, for the other genes assessed, the sensitivity was either low or uncertain (GRADE: Very Low to High). Liquid biopsy testing also showed an overall high concordance with tissue testing (GRADE: High). Further, liquid biopsy testing was found to improve partial response rates, stable disease rates, and progressive disease rates for people with NSCLC with actionable genomic alterations who were receiving matched targeted therapies (GRADE: Moderate). However, we are uncertain about the clinical validity of liquid biopsy testing in predicting prognosis with standard therapies (GRADE: Very Low). Compared with tissue testing alone, we estimate that all 4 of the potential liquid biopsy testing strategies we evaluated would be more expensive and associated with an increase in quality-adjusted life-years (QALYs). The incremental cost-effectiveness ratio (ICER) of the strategy in which liquid biopsy testing is provided only for people with insufficient tissue for tissue testing (“insufficient tissue”) was $96,738 per additional QALY; ICER estimates for the other 3 strategies (“tissue-first,” “liquid-first,” and “combined”) were all higher at $147,636, $157,267, and $173,032, respectively. All 4 potential liquid biopsy testing strategies had a chance of being cost-effective of less than 1% at a willingness-to-pay (WTP) of $50,000 per QALY gained; only the insufficient tissue strategy had a probability of being cost-effective of more than 50% at a WTP of $100,000 per QALY gained. We estimate that the 5-year budget impact of publicly funding the insufficient tissue strategy would be $13.72 million. Publicly funding the other strategies would result in a 5-year budget impact ranging from $110.13 million to $134.24 million. All interview participants viewed liquid biopsy positively. Participants perceived liquid biopsy testing as less invasive than tissue testing, and those who had undergone both tissue and liquid biopsy testing perceived that the turnaround time for results was quicker for liquid biopsy testing. Barriers to accessing liquid biopsy testing include lack of awareness, cost, and geography. CONCLUSIONS Liquid biopsy testing has moderate to high sensitivity for detecting actionable genomic alterations in the BRAF, EGFR, ERBB2, and KRAS genes (GRADE: Moderate to High) but low sensitivity for the ALK, PIK3CA, MET, RET, and ROS1 genes (GRADE: Low to High). The test has high concordance with tissue testing (87%-99%) but may miss some positive cases. We are uncertain about the clinical validity of liquid biopsy testing in predicting prognosis with standard therapies (GRADE: Very Low). However, we found that targeted therapies improve response rates (GRADE: Moderate) and survival (GRADE: Low) for people with NSCLC and actionable genomic alterations identified through liquid biopsy testing. Compared with tissue testing alone, all 4 potential liquid biopsy testing strategies that we evaluated are more costly but also associated with an increase in QALYs. We estimate that publicly funding liquid biopsy testing for people newly diagnosed with locally advanced or metastatic NSCLC (stage IIIB or IV) over 5 years would lead to an additional cost of $134.24 million for the combined strategy, $119.27 million for the liquid-first strategy, $110.13 million for the tissue-first strategy, and $13.72 million for the insufficient tissue strategy. People with NSCLC, family members, and care partners viewed liquid biopsy favourably. Those who had undergone both tissue and liquid biopsy testing perceived that the turnaround time for results was quicker for liquid biopsy testing. Current barriers to accessing liquid biopsy testing include lack of awareness, cost, and geography.

Authors' recommendations: Ontario Health, based on guidance from the Ontario Health Technology Advisory Committee, recommends publicly funding plasma-based comprehensive genomic profiling DNA assays (liquid biopsy testing) for individuals diagnosed with non–small cell lung cancer who have an insufficient tissue sample or difficult-to-reach tumour tissue and for those who are otherwise unable to undergo tissue biopsy.

Authors' methods: We performed a systematic literature search of the clinical evidence. We assessed the risk of bias of each included study using the QUADAS-2, QUADAS-C, ROBINS-I, and ROBINS-E tools and the quality of the body of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. We performed a systematic economic literature search and conducted a cost-utility analysis of 4 potential liquid biopsy testing strategies in which liquid biopsy testing was added to tissue testing in various ways; our model used a 20-year time horizon and was conducted from a public payer perspective. We also analyzed the budget impact of publicly funding liquid biopsy testing for people with NSCLC in Ontario. To contextualize the potential value of liquid biopsy testing, we spoke with people with NSCLC and family members and care partners of people with NSCLC.

Authors' identified further research: Circulating Cell-Free DNA, Comprehensive Genomic Profiling, Liquid Biopsy, Lung Neoplasms, Non-Small Cell Lung Cancer

Project Status: Completed

URL for project: https://ontariohealth.ca/system/health-innovation-pathway/reviews/hta-details?cf=plasma-genomic-profiling-dna-lung-cancer

URL for protocol: https://www.crd.york.ac.uk/PROSPERO/view/CRD42023437968

Year Published: 2024

URL for published report: https://pmc.ncbi.nlm.nih.gov/articles/PMC11650780/

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Canada

Pubmed ID: 39698418

Organisation Name: Ontario Health

Contact Address: 525 University Ave, Toronto, ON M5G 2L3

Contact Name: HealthInnovationPathway@ontariohealth.ca

Contact Email: HealthInnovationPathway@ontariohealth.ca

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