Original Title: Panel multigène diagnostique, pronostique ou prédictif pour le carcinome pulmonaire non à petites cellules (CPNPC) par biopsie liquide (SNG)

Authors' objectives: A request to include a new assay to the Répertoire québécois et système de mesure des procédures de biologie médicale (hereinafter referred to as the Répertoire) was submitted to the Institut national d’excellence en santé et en services sociaux (INESSS) through the evaluation mechanism for new medical biology assays. The mandate aims to assess the relevance of including to the Répertoire the molecular profiling of advanced stage non-small cell lung cancers (NSCLC) from a blood sample (liquid biopsy [LB]).

Authors' results and conclusions: RESULTS: (#1 POPULATION DIMENSION): Lung cancer is the most frequently diagnosed cancer in Quebec and the leading cause of cancer mortality. NSCLC represent nearly 90% of lung cancer cases, and their diagnosis at an advanced stage in more than half of patients is associated with a 5-year survival rate of less than 20%. The diagnostic strategy for NSCLC in Quebec relies on TB to confirm the type and stage of cancer, but also to guide treatments following molecular analyses. Molecular profiling by NGS is essential to identify patients eligible for targeted therapies. In cases of confirmed genetic alterations, patients can be treated with targeted therapies that offer superior clinical benefits, safety, and quality of life compared to conventional chemotherapy and immunotherapy treatments. According to the consulted clinicians, access to molecular profiling is uneven across the province, creating inequities in therapeutic management. They believe there is a need to expand access to molecular profiling and reduce delays in the various stages of the care pathway. Patients for whom the material obtained by TB is insufficient, those with rapidly progressive disease, those in a too fragile health state, those with tumours that are difficult to access, or those living in remote areas are the ones with the most important diagnostic need. (#2 CLINICAL DIMENSION): The literature review identified 32 observational studies assessing the performance and clinical utility of molecular profiling using LB. Overall, performance data indicate that molecular profiling on LB has comparable specificity, but lower sensitivity compared to that performed on TB. The consulted clinicians believe that all negative results obtained by LB should be confirmed on TB when possible. According to the literature and consulted clinicians, clinical utility of LB is particularly pronounced in situations where tissue material is insufficient or unavailable for TB profiling. Some studies report that, when performed in addition to TB, LB could provide a diagnostic gain and increase the detection rate of actionable alterations. Given the absence of second-line targeted therapy on the Lists of Medications, clinicians estimate that the relevance of molecular profiling for patients whose disease progresses under targeted therapy is low, but that this situation could evolve with the approval of new targeted therapies. (#3 ORGANIZATIONAL DIMENSION): The diagnostic pathway involving TB mobilizes significant human and material resources in the healthcare system. The consulted clinicians indicate that the delays associated with the various stages of the current diagnostic pathway are suboptimal and heterogeneous across the province, particularly due to staff shortages. According to the literature reviewed, the LB approach could shorten the time required for molecular analyses and thus accelerate the therapeutic care of patients. The consulted clinicians estimate that a turnaround time of 10 business days to obtain molecular profiling results by LB is a realistic target if the volume of analyses aligns with projections. Considering the enthusiasm for LB in the medical community and the rapid advances in research in this field, there is a risk of use beyond the prescribed applications of the analysis, which could have repercussions on healthcare system resources. (#4 SOCIOCULTURAL DIMENSION): The current social and political context is favourable for the deployment of LB to perform molecular profiling of cancers. In its 2023-2030 action plan, the Programme québécois de cancérologie recommends its timely implementation to optimize the care trajectory for cancer patients. Furthermore, several scientific societies and expert consensuses have positioned themselves in favour of its use for NSCLC when the TB approach is not feasible. (#5 ECONOMIC DIMENSION - EFFICIENCY): The literature review identified five studies aimed at evaluating the cost effectiveness of LB as a molecular profiling tool for advanced-stage NSCLC. Overall, the results of these studies indicate that the LB approach is cost-effective in the contexts studied. Its use increases the proportion of patients who can access appropriate targeted treatment, thus generating QALY gains and, depending on the study, either cost savings or additional costs resulting in cost-utility ratios between $50,000 and $100,000 per QALY. However, due to variations in clinical and economic inputs used in these studies compared to practice in Quebec, the generalization and transferability of these results to the Quebec context are uncertain. (#5.1 ECONOMIC DIMENSION - BUDGET IMPACT ANALYSIS): A budget impact analysis considering the costs associated with adding liquid biopsy to the Répertoire and those related to the use of medications has been conducted. Costs were projected over a 3-year horizon from the perspective of the Quebec healthcare system. According to the selected scenarios, the introduction of liquid biopsy to the Répertoire as a tool for molecular profiling of advanced-stage NSCLC could result in additional costs of $2.4 million over the first three years, specifically for the completion of 2,167 tests. Sensitivity analyses were performed to account for the uncertainty surrounding certain scenarios. According to these analyses, the net impact over 3 years could vary between approximately $1.5 million and $3.7 million.

Authors' recommendations: In light of the findings drawn from the five value dimensions, INESSS recommends the minister to include the molecular profiling of advanced-stage NSCLC by liquid biopsy into the Répertoire. However, molecular profiling by tissue biopsy (TB) remains the standard of practice, and the liquid biopsy (LB) approach should only be used as a second-line option. Considering the risks of use beyond recognized applications, INESSS recommends implementing the following measures to properly regulate the use of the test: • The creation of a specific code for the test specifying the intended indication, namely advanced-stage NSCLC (stages IIIB-IV). • The creation of a specific request form allowing the selection of the clinical indication eligible for the test, namely patients for whom: – biomarker analyses on tissue are insufficient or incomplete with a previous attempt or an insufficient pathology report; – no tissue material can be safely collected; – the clinical situation is progressing rapidly to the point where survival is threatened if the biomarker results are received beyond 10 business days; – the identification of resistance to a recognized targeted therapy could lead to the use of a second-line therapeutic agent if it is listed on Lists of Medications. • The inclusion of the following elements in the analysis report: – a system for classifying detected alterations based on their clinical relevance for the management of NSCLC in Quebec; and – a note intended to inform prescribers about the analytical limitations associated with the liquid biopsy approach. • Annual follow-up of test implementation to document clinical indications, response times, volumetry, and analysis costs. • Test compliance with ISO 15189 standard requirements.

Authors' methods: The evaluation process includes a review of the scientific, clinical and economic literature, a search of the gray literature, and consultations with clinicians and other stakeholders. The methodology was designed around the five dimensions of the statement of principles of INESSS’s framework for assessing the value of interventions: sociocultural, population-based, clinical, organizational, and economic. All scientific, contextual, and experiential data were interpreted and synthesized in the form of findings to guide the deliberation process of an ad hoc joint deliberative committee – Diagnostic Approaches and Screening and Reimbursement and Access, with a view to formulating recommendations.

Project Status: Completed

URL for project: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/evaluation-dun-panel-multigene-diagnostique-pronostique-ou-predictif-pour-le-carcinome-pulmonaire-non-a-petites-cellules-par-biopsie-liquide.html

Year Published: 2024

URL for published report: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/evaluation-dun-panel-multigene-diagnostique-pronostique-ou-predictif-pour-le-carcinome-pulmonaire-non-a-petites-cellules-par-biopsie-liquide.html

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Canada

Province: Quebec

Organisation Name: Institut national d'excellence en sante et en services sociaux

Contact Address: L'Institut national d'excellence en sante et en services sociaux (INESSS) , 2021, avenue Union, bureau 10.083, Montreal, Quebec, Canada, H3A 2S9;Tel: 1+514-873-2563, Fax: 1+514-873-1369

Contact Name: demande@inesss.qc.ca

Contact Email: demande@inesss.qc.ca

Copyright: L'Institut national d'excellence en sante et en services sociaux (INESSS)