Gastrointestinal Stromal Tumors: What Is the Best Sequence of TKIs?

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Gastrointestinal stromal tumors (GIST) management relies on identifying specific mutations.
• Tyrosine kinase inhibitors (TKIs) are crucial for treating advanced, unresectable GIST.
• KIT and PDGFRA mutations are key drivers in GIST pathogenesis and treatment response.

Purpose of the Study:

• To review current management strategies for GIST based on KIT and PDGFRA mutation status.
• To outline TKI treatment sequences for advanced unresectable GIST.
• To discuss emerging therapies and their roles in different mutational contexts.

Main Methods:

• Review of existing literature and clinical practice guidelines.
• Analysis of TKI efficacy in GIST with specific mutations (KIT, PDGFRA D842V).
• Evaluation of treatment sequencing and role of novel agents like avapritinib and ripretinib.

Main Results:

• Imatinib is first-line for most GIST, with dose escalation for KIT exon 9 mutations.
• Sunitinib and regorafenib are subsequent lines of therapy after imatinib failure.
• Avapritinib shows efficacy for PDGFRA D842V mutations; ripretinib is approved for 4th-line treatment.

Conclusions:

• Mutation status is paramount for guiding TKI selection in advanced GIST.
• Treatment algorithms involve sequential TKIs, with specific agents for distinct mutations.
• Continued TKI therapy offers palliative benefits and should be maintained.