In today’s episode of OncLive On Air®, Jonathan Trent, MD, PhD, and Neeta Somaiah, MD, sat down to discuss the evolving role of circulating tumor DNA (ctDNA) testing in gastrointestinal stromal tumors (GIST), as well as the importance of identifying both initial drivers of disease and secondary resistance mechanisms when approaching frontline treatment selection and overall therapeutic sequencing.

Trent is a professor of medicine, associate director of Clinical Research, and director of the Sarcoma Medical Research Program at the University of Miami Miller School of Medicine, in Florida. Somaiah is a professor and chair of the Department of Sarcoma Medical Oncology in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center in Houston.

Drs Trent and Somaiah began their discussion by highlighting the rarity of GIST, underscoring the importance of evaluation at specialized sarcoma centers and comprehensive molecular testing to identify driver alterations.

Somaiah then reviewed the molecular landscape of GIST, noting that approximately 70% to 80% of tumors harbor activating mutations in the KIT gene, while additional cases involve rarer alterations such as BRAF or NTRK fusions. Of note, resistance to imatinib (Gleevec) frequently emerges through secondary mutations in KIT exons 13 or 17, which can influence sensitivity to subsequent TKIs.

ctDNA testing may help detect these resistance mechanisms, particularly at progression or when tissue is limited, enabling clinicians to refine sequencing strategies, both experts explained. They also discussed how mutation-informed approaches may guide treatment selection, including emerging strategies such as combining sunitinib (Sutent) with bezuclastinib to address resistant clones involving KIT exon 13 or 17 alterations.

This content is a production of OncLive; this OncLive On Air podcast episode is supported by funding, however, content is produced and independently developed by OncLive.

S16 Ep31: ctDNA Testing At Progression May Help Detect Resistance and Guide Sequencing in GIST: With Drs Jonathan Trent, MD, PhD, and Neeta Somaiah, MD