Avapritinib in unresectable or metastatic gastrointestinal stromal tumor with PDGFRA exon 18 mutation: safety and efficacy

ABSTRACT

Introduction

Avapritinib (formerly known as BLU-285) is an orally available type I tyrosine kinase inhibitor that, in 2020, obtained regulatory approval for the treatment of patients with gastrointestinal stromal tumors (GISTs) harboring a primary mutation in PDGFRA exon 18, including the PDGFRA D842V mutation.

Areas covered

Herein, we comprehensively review the available efficacy and safety data on avapritinib, with the final goal of providing practical knowledge to both sarcoma and community-based oncologists for the correct management of this rare GIST subpopulation with this novel therapy.

Expert opinion

The approval of avapritinib in GIST is a milestone in precision oncology, as this is the first agent ever demonstrating unequivocal antitumoral activity in GIST driven by the multi-resistant PDGFRA D842V mutation. The safety profile is manageable and tolerability-guided dose adjustment is recommended to manage treatment-related adverse events without compromising efficacy. Based on its unprecedented activity, avapritinib should be considered as first-line therapy for GIST patients harboring this mutation. We strongly recommend to determine KIT/PDGFRA genotype in order to identify the different GIST molecular subtypes and guide treatment decision.

KEYWORDS:

• Avapritinib
• BLU-285
• GIST
• imatinib
• PDGFRA
• sarcoma
• treatment
• tyrosine kinase inhibitor

Article highlights

• Avapritinib is the first agent ever displaying unequivocal activity in locally-advanced or metastatic GIST patients harboring a primary mutation in PDFRA exon 18 D842V.

• Virtually all patients with this mutation achieve tumor reduction with avapritinib treatment, and therefore it is advised to use it as front line.

• Avapritinib toxicity profile is derived from on-target KIT and PDGFRA inhibition, being mostly grade 1 or 2 and manageable. Early recognition of cognitive effects is essential to maintain patients’ quality of life.

Declaration of interest

C Serrano has received research funding (institution) from Karyopharm, Pfizer, Inc, Deciphera Pharmaceuticals, and Bayer AG; consulting fees (advisory role) from Immunicum AB, Deciphera Pharmaceuticals and Blueprint Medicines; payment for lectures from Bayer AG and Blueprint Medicines; and travel grants from Pharmamar, Pfizer, Bayer AG, Novartis and Lilly. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper received no funding.