Jonathan C. Trent, MD, PhD, discusses why it is necessary for patients with gastrointestinal stromal tumors to have comprehensive testing to find actionable genomic alterations.
Jonathan C. Trent, MD, PhD, professor and associate director for Clinical Research at Sylvester Comprehensive Cancer Center, University of Miami Health System, discusses why it is necessary for patients with gastrointestinal stromal tumors (GIST) to have comprehensive testing to find actionable genomic alterations.
Trent says that GIST studies presented at the 2023 American Society of Clinical Oncology Annual Meeting (ASCO) emphasize the fact that patients with GIST who are treated with a tyrosine kinase inhibitor (TKI) must have testing for mutations performed, whether from biopsy or circulating tumor DNA (ctDNA), since the treatment can vary widely. He notes that a frontline patient with KIT or PDGFRA mutation would be treated with imatinib (Gleevec), but PDGFRA D842V-mutant disease is resistant to treatment except for avapritinib (Ayvakit), making this information vital to have.
Patients with RAF mutations will not benefit from KIT-directed therapies and require a targeted RAF inhibitor instead of imatinib. Those with a TRK alteration can be treated with larotrectinib [Vitrakvi] or entrectinib [Rozlytrek], which have tumor-agnostic indications for this alteration. Because of the variance in frontline treatment options, prompt testing is one of the key takeaways for oncologists who treat patients with GIST.
0:08 | The key recommendations from GIST presentations, posters, all the abstracts at ASCO this year, and for the last…15 years, is that patients with GIST who are going to be treated with a TKI must have mutation testing performed, whether that's from the original tumor surgery or biopsy block, or whether that’s ctDNA. You can't optimally treat a patient with GIST unless you know what specific mutation they have. The mutation could be a KIT or PDGFRA, which we may treat with imatinib. However, there's a PDGFRA D842V-mutant that is resistant to everything except avapritinib. That patient would have to be treated with avapritinib.
1:06 | Then there's also RAF and there's TRK and these won't benefit from the KIT-directed therapies such as imatinib. RAF-mutant [disease] you need to treat with a RAF inhibitor, and TRK should be treated with larotrectinib or entrectinib. Honestly, the mutation matters, and you have to do mutation testing in your patients with GIST if you're going to treat them.