Ayvakit (avapritinib)

For therapeutic categories, performance reached 0.84 for avapritinib sensitivity, 0.81 for imatinib sensitivity. DL applied to WSIs enables prediction of molecular alterations, treatment sensitivity, and RFS in GIST, performing comparably to established risk scores across international cohorts, providing a baseline for future multimodal predictors. Deep learning on histology predicts KIT and PDGFRA mutations in a large international cohort of GISTs from multiple centers Whole-slide image models stratify recurrence-free survival comparable to pathology-based risk scores Prognostic value of deep learning is preserved in adjuvant therapy subgroups, supporting treatment duration decisions.

Targeted tyrosine kinase inhibitors (TKIs) have transformed GIST management, with imatinib as the foundational first-line therapy and subsequent agents, sunitinib, regorafenib, avapritinib, and ripretinib, addressing primary or secondary resistance driven by diverse mutational patterns. Emerging therapeutic directions include next-generation kinase inhibitors, heat shock protein inhibitors, immunotherapy, metabolic and epigenetic targeting, and biomarker-driven individualized treatment strategies. This review synthesizes contemporary advances in the histopathological, molecular, and therapeutic landscape of GISTs, emphasizing an integrated diagnostic approach and highlighting ongoing efforts to overcome therapeutic resistance and optimize personalized care.

Eleven (10%) patients experienced TEAEs leading to death, of which 1 was deemed related to avapritinib by the principal investigator. With 4-year follow-up, avapritinib-treated patients with AdvSM experienced deep and durable responses and a favorable benefit-risk profile.

Targeted therapy with avapritinib and ruxolitinib was initiated but yielded limited response. Given the consistent co-occurrence of KIT mutations in previously reported similar cases, we propose the recognition of a distinct disease entity: ovarian germ cell tumor/mastocytosis with KIT mutations. This report emphasizes the importance of early genetic profiling and multidisciplinary collaboration in diagnosing and managing rare, genetically unified malignancies in pediatric oncology.

P1/2, N=29, Completed, Blueprint Medicines Corporation | Active, not recruiting --> Completed

P=N/A, N=80, Recruiting, Blueprint Medicines Corporation | Not yet recruiting --> Recruiting

While imatinib revolutionized first-line therapy, resistance and specific mutation profiles necessitate subsequent generations of tyrosine kinase inhibitors (TKIs). Second- and third-generation TKIs have transformed the management of advanced GIST, extending survival and offering mutation-specific precision therapy. Ongoing research into resistance mechanisms, combination strategies, and novel inhibitors promises further optimization of patient-centered care.

It suggests that avapritinib may bridge therapeutic gaps for atypical KIT-mutant systemic mastocytosis with associated hematologic neoplasm (SM-AHN) that is ineligible for Allo-HSCT or relapsed. Prospective trials are warranted to validate its efficacy, optimize dosing, and explore synergies with Allo-HSCT, offering new strategies for these high-risk patients.

Notably, 47% of patients received previous midostaurin. AdvSM subtype, the presence and number of additional comutated genes beyond KIT D816V, BM mast cell burden, and KIT D816V variant allele fraction were associated with the presence and/or number of WHO/mIWG organ damage findings. Our study provides a snapshot of the correlates of organ damage in patients enrolled in clinical trials of avapritinib and identifies a key association between molecular profile and burden of organ damage.

P=N/A, N=80, Not yet recruiting, Blueprint Medicines Corporation

P1/2, N=37, Active, not recruiting, Blueprint Medicines Corporation | Trial primary completion date: Feb 2025 --> Nov 2025

Both patients underwent allogeneic hematopoietic stem cell transplantation, but subsequently developed refractory disease progression unresponsive to multiple salvage regiments. Strikingly, avapritinib intervention achieved unprecedented clinical responses in these complex cases.