[Report: circulating tumour DNA (liquid biopsy)-based EGFR exon 20 T790M mutation detection in advanced non-small cell lung cancer after previous EGFR-directed therapy]

Tchekanda E, Mortier T
Record ID 32018002362
Original Title: Avis: Détection de la mutation T790M de l’exon 20 du gène EGFR dans le cancer du poumon résistant aux inhibiteurs de l’EGFR sur ADN tumoral circulant (biopsie liquide)
Authors' objectives: Approximately 60% of NSCLC patients treated with a 1st- or 2nd generation TKI will develop the EGFR-T790M resistance mutation and require a change in therapy. Although a test used to detect this mutation from a tissue biopsy is listed in the Répertoire québécois et système de mesure des procédures de biologie médicale (hereinafter the "Répertoire"), the present request concerns the detection of the EGFRT790M mutation in samples obtained by liquid biopsy, an alternative specimen collection method that enables the patient to avoid a tissue biopsy and the associated risks, and to obtain a change in therapy more quickly.
Authors' results and conclusions: RESULTS: (1.Diagnostic performance): According to the Health Quality Ontario assessment report published in 2020, the concordance rate for EGFR-T790M mutation detection results between liquid biopsy and tissue biopsy ranges from 50% to 96%. The sensitivity and specificity, negative predictive value (NPV) and positive predictive value (PPV) are 68% [46%-88%], 86% [62%-99%], 61% and 89%, respectively. The use of droplet digital PCR (ddPCR) appears to increase the rate of positive detection of the EGFR-T790M mutation by liquid biopsy. (2. Patient perspective) : According to the HQO report, patients perceived liquid biopsy as a faster and more convenient approach because they would not have to wait several weeks to get an appointment for a tissue biopsy, which could require a trip to a specialized centre that might be further away. They also expressed fear and even panic about the tissue sample collection procedure, in which a large-gauge needle is used. (3. Economic evaluation ): Liquid biopsy as a triage test is less expensive and more effective than tissue biopsy in detecting the EGFR-T790M mutation. However, when the clinical benefits and costs of the subsequent treatments are factored in, the incremental cost-utility ratio is high, in part because of osimertinib's non-cost-effectiveness. Since the listing of this drug as a 1st-line therapy in the formularies, the liquid biopsy-eligible population has been steadily decreasing. The current number of people receiving 1st- or 2nd-generation TKIs was estimated to be 32, based on RAMQ data, and 40 if patients with private insurance are included. These analyses estimate the laboratory savings at $460, but they anticipate that 5 additional patients could receive osimertinib, for a net budget impact of approximately $537,000 over the next 3 years. (4. Position of the experts consulted): The experts consulted support the use of liquid biopsy in the context defined by the requester. They did not raise any specific issues, apart from the limited relevance of this test, given the recent listing of osimertinib as a 1st-line therapy. The rapid emergence of a large number of indications for liquid biopsy appears to be imminent and would constitute a technological and oncologic revolution.
Authors' recommendations: Based on the deliberation, by the CSABM’s members, of all the evidence, including the perspective of the experts consulted, INESSS recommends that circulating tumour DNA-based EGFR-T790M mutation detection be included in the Répertoire.
Authors' methods: The assessment process included a rapid review of the scientific and grey literature, and consultations with experts and other stakeholders. An assessment report on the relevance of using liquid biopsy in the same context as this request was published by Health Quality Ontario (HQO) in March 2020. The report includes an assessment of its diagnostic performance, clinical utility, safety, cost-effectiveness and budget impact, and an assessment of patient preferences and values. The HQO report was deemed to be of good methodological quality and is the main source of data for the present assessment.
Project Status: Completed
Year Published: 2022
Requestor: Institut universitaire de cardiologie et de pneumologie de Québec, Université Laval
English language abstract: An English language summary is available
Publication Type: Full HTA
Country: Canada
Province: Quebec
MeSH Terms
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms
  • Liquid Biopsy
  • Circulating Tumor DNA
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: Gouvernement du Québec
This is a bibliographic record of a published health technology assessment from a member of INAHTA or other HTA producer. No evaluation of the quality of this assessment has been made for the HTA database.