Authors' objectives: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for about 85% of all lung cancer cases. While some cases of NSCLC with actionable genomic alterations in the tumour cells may respond to standard therapies, they often show greater improvement with targeted therapies. The current standard of care in Ontario involves testing for actionable genomic alterations using both DNA and RNA panels via tissue testing alone. However, liquid biopsy testing may complement tissue testing by addressing some of its limitations. We conducted a health technology assessment of liquid biopsy testing using DNA panels for people with NSCLC, which included an evaluation of analytical validity, clinical validity, clinical utility, cost-effectiveness, the budget impact of publicly funding this technology, and patient preferences and values.

Authors' results and 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.

Project Status: Completed

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

Year Published: 2024

URL for published report: https://www.hqontario.ca/evidence-to-improve-care/health-technology-assessment/reviews-and-recommendations/plasma-based-comprehensive-genomic-profiling-dna-assays-for-non-small-cell-lung-cancer

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Canada

Province: Ontario

Organisation Name: Ontario Health

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

Contact Name: Nancy Sikich, Director Health Technology Assessment

Contact Email: oh-hqo_hta@ontariohealth.ca

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