What is the role of Deglitinib in treating advanced gastrointestinal stromal tumors (GIST) in patients who have been treated with other tyrosine kinase inhibitors?

Deglitinib in Advanced GIST

I cannot provide a recommendation for Deglitinib in treating advanced gastrointestinal stromal tumors because this agent does not appear in any established clinical guidelines, FDA-approved drug labels, or published research evidence for GIST treatment.

Standard Treatment Sequence for Advanced GIST

The evidence-based treatment algorithm for patients with advanced GIST who have received prior tyrosine kinase inhibitors is well-established:

First-Line Therapy

• Imatinib 400 mg daily is the standard first-line treatment for unresectable or metastatic GIST 1
• Dose escalation to 800 mg daily should be considered for KIT exon 9 mutations, though this requires individualized assessment based on regulatory approval 1
• Imatinib is contraindicated for PDGFRA exon 18 D842V mutations due to inherent resistance 1

Second-Line Therapy

• Sunitinib is the standard second-line treatment after imatinib failure or intolerance 1
• Can be administered as 50 mg daily for 4 weeks on/2 weeks off, or 37.5 mg continuously 1
• Response rate approximately 10% with median progression-free survival of 8 months 1

Third-Line Therapy

• Regorafenib 160 mg daily (3 weeks on/1 week off) is standard third-line therapy after progression on both imatinib and sunitinib 1
• Demonstrated significant progression-free survival benefit in placebo-controlled trials 1

Fourth-Line and Beyond

• Ripretinib is approved as fourth-line therapy after standard treatments, though not currently approved by NICE 1
• Avapritinib is the most effective treatment specifically for PDGFRA D842V-mutant GIST, with 79% partial response rate and 9% complete response rate 1

Critical Mutation Testing Requirements

Mutational analysis must be performed before initiating any tyrosine kinase inhibitor therapy 1:

• KIT exon 11 mutations: Most sensitive to imatinib (90% benefit) 1
• KIT exon 9 mutations: Require higher imatinib dose (800 mg) for optimal response 1
• PDGFRA D842V mutation: Resistant to imatinib, sunitinib, and regorafenib; requires avapritinib 1
• Wild-type (no KIT/PDGFRA mutations): Lower sensitivity to standard TKIs 1

Alternative Strategies After Standard Therapy

When standard therapies are exhausted 1, 2:

• TKI rechallenge with previously used agents may provide benefit 1
• Continuation of TKI beyond progression may slow disease progression in selected patients with limited progression 1
• Surgical resection or local ablative therapy for isolated sites of progression while continuing systemic TKI 1
• Clinical trial enrollment should be prioritized when available 1

Common Pitfalls

• Do not use imatinib for PDGFRA D842V mutations—this genotype is inherently resistant 1
• Do not delay mutational testing—it is essential for treatment selection and dose optimization 1
• Do not assume progression on imaging alone—false progression can occur due to tumor density changes rather than size increase 1
• Do not combine TKIs outside clinical trials due to excessive toxicity without proven benefit 1

If you are inquiring about a specific investigational agent or have concerns about spelling, please verify the drug name, as no agent called "Deglitinib" exists in the current GIST treatment literature.