Next generation sequencing gene panel for gastrointestinal stromal tumour care

Aim

The objective of this assessment was to determine the benefit of using a next generation sequencing (NGS) gene panel for the clinical management of gastrointestinal stromal tumour (GIST) patients in routine clinical practice. The aim was to assess the clinical utility of this procedure, the molecular alterations of specific interest and to define the role of this procedure in the therapeutic care of GIST patients.  

Conclusions and results

The assessment of the evidence and data demonstrated that next generation sequencing gene panel testing indicates:

• superior diagnostic performances for KIT and PDGFRA molecular alteration detection compared to Sanger sequencing;
• superior diagnostic performances for NTRK 1/2/3 fusion detection compared to immunohistochemistry;
• evidence of the clinical utility of the targeted gene panel considering the benefits provided by targeted therapies.

Recommendations

The French National Authority for Health deems that funding the next generation sequencing gene panel procedure for gastrointestinal stromal tumour patients is justified in the following situations:

• for KIT and PDGFRA gene sequencing and analysis:
  • in cases of locally advanced or metastatic gastrointestinal stromal tumours at an intermediate risk or high risk of recurrence
  • in cases of suspected gastrointestinal stromal tumour in a patient whose histology has been inconclusive in establishing a diagnosis (complex cases)
• for NTRK1/2/3 (RNA) gene sequencing and analysis:
  • in cases of refractory or relapsed locally advanced or metastatic paediatric wild-type gastrointestinal stromal tumours.

The French National Authority for Health deems that next generation sequencing should be carried out on a tissue biopsy or surgical specimen where applicable.

Methods

The method used for this assessment was based on (1) a critical analysis of the systematic reviews and meta-analyses and clinical practice guidelines identified by a systematic search based on PICO criteria; (2) the identification (a) of the level of evidence of molecular alteration clinical actionability as set out by the European Society for Medical Oncology Scale (ESCAT), (b) of targeted therapies included on the list of reimbursable drugs assessed by the Transparency Committee of the French National Authority of Health or drugs that have compassionate use authorisations issued by the French National Agency for Medicines and Health Products Safety (ANSM); and (3) stakeholder consultations (relevant professional bodies and patient and user organisations), as well as observations by public health institutions.

Further research/reviews required

The French National Authority for Health points out that the composition of the next generation sequencing gene panel may be subject to change, in accordance with favourable assessments of new gene alterations. These new assessments shall be conducted in a dynamic manner in response to developments in scientific knowledge (identification of new relevant evidence and/or publication of new French National Authority for Health Transparency Committee advice and/or, compassionate use by the French National Agency for Medicines and Health Products Safety).