Dr Wilky on the Role of Personalized Therapy in GIST

“You don’t want to put a patient on imatinib and tell them everything’s going to be great—you’re going to review a 90% chance of response. If you don’t [because] you have a patient who is resistant, it could totally change your therapy.”

Breelyn Wilky, MD, the director of Sarcoma Medical Oncology, The Cheryl Bennet and McNeilly Family Endowed Chair in Sarcoma Research, director of Sarcoma Medical Oncology, and deputy associate director for Clinical Research at the University of Colorado Cancer Center – Anschutz Medical Campus, detailed approaches for personalized therapy for the treatment of patients with gastrointestinal stromal tumors (GIST).

Currently, the personalized therapy approaches for the treatment of patients with GIST are still being validated through clinical trials, Wilky began. She explained that approximately 90% of patients with GIST are treated with adjuvant imatinib (Gleevec). In many of these patients, imatinib is the standard, as their tumors have exon 11 or exon 9 mutations, which are sensitive to the agent, she noted. However, the remaining 10% of the population may have mutations that are not sensitive to imatinib, including PDGFRA D842V mutations, which are entirely resistant to imatinib, Wilky added. Notably, in January 2020, the FDA approved avapritinib (Ayvakit) for the treatment of adult patients with unresectable or metastatic GIST harboring PDGFRA exon 18 mutation, including D842V mutations, particularly for this type of imatinib-resistant GIST, she emphasized. The approval of avapritinib was supported by data from the phase 1 NAVIGATOR trial (NCT02508532) that enrolled 43 patients with GIST who harbored a PDGFRA exon 18 mutation, of which 38 patients harbored PDGFRA D842V mutations.

Although this mutation is present in a smaller percentage of patients, it’s important not to tell every patient that all will be fine once they begin on imatinib therapy, Wilky advised. She noted that it’s essential to recognize the possibility of patients with imatinib-resistant disease, which could alter the trajectory of their treatment. When patients are newly diagnosed with GIST, it’s important to complete a mutation test upfront to rule out the 10% of patients who may have resistance to imatinib before starting them on the treatment, she concluded.