Carlos López-Jiménez, Medical Oncologist at the Sarcoma Unit of Fundación Jiménez Díaz University Hospital (Madrid) and a PhD candidate in Molecular Biosciences at Universidad Autónoma de Madrid (UAM), shared a post on LinkedIn:
“What’s new in sarcoma after ASCO 2026?
Chapter II. GIST Wars: Resistance Strikes Back
(You can access chapter one at the bottom of the publication)
Some thoughts on what ASCO2026 has brought to the GIST field:
- PEAK uses combination. StrateGIST 1, one single molecule targeting multiple mutations. Both mechanisms can be valid to surpass the polyclonality of secondary KIT-mediated resistance as they showed relevant clinical activity.
- Results form PEAK are potentially practice changing (if approved by the regulatory bodies). Phase III trials on velzatinib are in course: the results are still exploratory and small subgroup sizes limits accuracy/interpretation of the results.
- Bezuclastinib’s niche is 2L. Velzatinib may still find opportunities for development also in 1L and later lines of therapy.
- How resistance to these new agents will evolve? mPFS2 in PEAK has not yet been reached, but it does not suggest that earlier broader KIT inhibition is compromising the effectiveness of subsequent therapies. But we must wait for the data and longer follow-up. For velzatinib, it is still too early to know.
- A population difference between the two studies: PEAK does not limit treatment access according to genotype, while StrateGIST requires a confirmed KIT or PDGFRA mutation for patient enrollment.
Any conclusion?
As the GIST treatment landscape continues to expand, understanding how best to sequence these therapies may become just as important as developing them. We do not yet have post-progression data, so its impact on treatment sequencing and future resistance patterns remains an open question. ctDNA-based resistance mutational profiling is not yet validated for routine treatment selection in GIST. Still, if the INSIGHT trial demonstrates that liquid biopsy can guide second-line treatment decisions, it could represent a major step toward more personalized therapy in this disease -and a more complex sequencing and decision-taking (isn’t it exciting?).
Link for Chapter I.”