Original Title: Biomarcadores agnósticos de fusiones génicas en oncología: revisión diagnóstica y terapéutica

Authors' objectives: The objective of this report is to review the scientific literature in order to identify the best evidence on the use of IHC, FISH, RT-PCR and NGS techniques for the systematic identification of the NTRK, ALK, ROS1 and RET gene fusion biomarkers in oncology given its predictive value for a beneficial response to agnostic therapies. The effectiveness of agnostic drugs and their comparative effectiveness between this targeted therapy and standard therapy are also reviewed, in terms of health and safety results for the patient, as well as the economic implications associated with the implementation of these tests in clinical practice.

Authors' results and conclusions: CONCLUSIONS: The identification of tumor-agnostic biomarkers of NTRK, ALK, ROS1 and RET fusion genes is essential given the possibility of access to drugs directed against these genes. Diagnostic tests IHC, FISH, RT-PCR and NGS can detect fusions in these genes. For the detection of NTRK fusions, RNA-based NGS is considered the gold standard. FISH is a high Se and Sp test for the detection of fusion genes, such as ALK, ROS1 and RET. For NTRK, a FISH test is required for each gene. IHC is a valid and widely used technique due to its accessibility and ease of performance, unlike FISH, which requires experience to perform. RT-PCR and liquid biopsy are tests that are not very widespread in clinical practice. The progressive incorporation of NGS panels in laboratories, associated with a decrease in costs, could facilitate this technology becoming the test of choice for the diagnosis of NTRK fusions and ALK, ROS1 and RET rearrangements. The numerous proposals for diagnostic algorithms and/or recommendations reflect the high interest in this field of precision medicine while demonstrating the lack of a general consensus on its best use. New studies that include a larger number of cancer patients and methodologically rigorous are needed to compare the diagnostic performance of the different tests depending on the type of tumor and the biomarkers under study. It is also necessary to study the effectiveness of the drugs chosen based on the results of the diagnostic tests and their safety. It is important to include outcome variables of clinical interest but also of interest to patients, such as overall survival and quality of life. The analysis should include a medium and long-term follow-up. In addition, economic evaluation studies are necessary, with data from the diagnostic tests until the evolution of the patient after treatment. It is necessary that these results can be contextualized to the different health systems. Studies are also necessary on key organizational aspects for the implementation of the best diagnostic algorithms and the most appropriate treatments in the field of precision medicine.

Authors' methods: A review of reviews from the scientific literature has been carried out in order to synthesize and integrate all the available evidence on the diagnostic validity of the different algorithms, diagnostic proposals and recommendations for the use of the different diagnostic techniques used for the identification of agnostic biomarkers NTRK, ALK, ROS1 and RET. The studies considered to be included were the following: HTA reports, consensus documents with recommendations from the main scientific societies, expert opinions, clinical practice guidelines, systematic reviews and meta-analyses, proposals for diagnostic algorithms from groups of healthcare professionals and researchers and some narrative reviews; comparative studies between targeted drugs against these biomarkers and studies of economic evaluation related to diagnostic tests and/or agnostic treatments. The literature search was carried out in Medline, Embase, the Cochrane Library and other sources of information, collecting studies published from 2015, in English or Spanish, and that met certain selection criteria established a priori. The main characteristics and results of the selected studies have been presented.

Project Status: Completed

Year Published: 2024

URL for published report: http://hdl.handle.net/20.500.12105/19149

URL for additional information: https://redets.sanidad.gob.es/productos/buscarProductos.do?metodo=detalle&id=1214

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Spain

Organisation Name: Agencia de Evaluacion de Tecnologias Sanitarias

Contact Address: Instituto de Salud "Carlos III", Calle Sinesio Delgado 6, Pabellon 4, 28029 Madrid, Spain. Tel: +34 9 1 822 2005; Fax: +34 9 1 387 7841;

Contact Name: Esther E. García Carpintero

Contact Email: eegarcia@isciii.es

Copyright: Agencia de Evaluacion de Tecnologias Sanitarias