Regulatory Outlook and Later-Line Sequencing in KIT-Mutant GIST

This segment covers the panelists' discussion of regulatory status and practical implications in KIT-mutant gastrointestinal stromal tumor (GIST), where the currently approved agents, imatinib, sunitinib, regorafenib, and ripretinib, were all approved as sequential monotherapies. They explain that bezuclastinib plus sunitinib remains investigational and under regulatory review after breakthrough therapy designation, with access at some centers through an expanded access program, and anticipate a regimen that would slot into the existing sequence rather than displace it, leaving regorafenib and ripretinib in their current later-line positions. The panelists emphasize sending mutation testing before starting systemic therapy and considering circulating tumor DNA at progression to capture secondary mutations across multiple sites. They acknowledge that resistance mechanisms emerging after the combination are unknown, discuss rescanning sooner than usual after a switch, and encourage cycling patients through all available agents.