AYVAKYT (avapritinib)

Key points

Favourable opinion for reimbursement as monotherapy for the treatment of adult patients with unresectable or metastatic gastrointestinal stromal tumours (GIST) harbouring the platelet-derived growth factor receptor alpha (PDGFRA) D842V mutation. Maintenance of this opinion is subject to submission of the results of the phase 3 BLU-285-1303 study comparing avapritinib with regorafenib and data from the registry of patients treated in France; the Committee will conduct a revaluation within a maximum period of 3 years.

What therapeutic improvement?

No clinical added value on the basis of currently available data.

Role in the care pathway?

The current care pathway for gastrointestinal stromal tumours (GIST) depends on the disease stage; it differs depending on whether these tumours are localised (around 85% of cases) or otherwise (locally advanced or unresectable metastatic tumours, 10 to 15% of GIST cases). Complete surgical resection of the tumour is the standard treatment for localised forms.

Genetic analysis (molecular biology testing for mutations) of these tumours is also essential: the presence of a mutation and the mutation type are important prognostic factors and influence the efficacy of treatment, particularly in metastatic situations, with, in particular, testing for KIT or PDGFRA mutations.

The management of patients with GIST with the PDGFRA/D842V mutation requires:

• the opinion of a regional reference centre with expertise in the treatment of sarcomas and connective tissue tumours, particularly for atypical or difficult-to-treat cases or patients that could be included in a clinical study; 
• a multidisciplinary team (MDT) meeting for therapeutic decisions for patients with locally advanced or metastatic GIST (with PDGFRA/D842V mutation) in accordance with the NETSARC soft tissue sarcomas management network.

ESMO 2018 guidelines considered that there was no recommended treatment for these patients.

Role of the medicinal product in the care pathway

AYVAKYT (avapritinib), a type 1 kinase inhibitor, is a first-line medicinal product in the care pathway for patients with GIST harbouring the platelet-derived growth factor receptor alpha (PDGFRA) D842V mutation.

The decision to initiate treatment with AYVAKYT (avapritinib) should be taken after a documented proposal resulting from a treatment review meeting with a reference centre with expertise in the treatment of sarcomas and connective tissue tumours.

In particular, it is necessary to take into account the specific notable neurological toxicity of this medicinal product (unexplained to date) involving two phenomena: rare intracranial haemorrhages not found with other TKIs and cognitive disorders of varying severity leading to a reduction in the dose or the temporary suspension of treatment. The efficacy and safety data are very limited at this stage.

Special recommendations

Due to the complexity of management of these rare tumours, the decision to prescribe AYVAKYT (avapritinib), assessed for each GIST patient with a D842V/PDGFRA mutation, should be taken following a documented proposal based on a treatment review meeting with a reference centre with expertise in the treatment of sarcomas and connective tissue tumours.

Treatment should be initiated and monitored by the reference centre.