Ayvakit demonstrated more durable survival outcomes in patients with unresectable/metastatic platelet-derived growth factor receptor A D842V-mutant gastrointestinal stromal tumors than tyrosine kinase inhibitors.
The tyrosine kinase inhibitor Ayvakit (avapritinib) demonstrated better survival outcomes in patients with unresectable/metastatic platelet-derived growth factor receptor A (PDGFRA) D842V-mutant gastrointestinal stromal tumors than other tyrosine kinase inhibitors, according to data published in BMC Cancer.
“(Patients) actually had a durable response, meaning the drug shrunk the tumor, it lasted for several years for some people and patients lived longer,” said Dr. Suzanne George, medical oncologist and director of clinical research at the Sarcoma Center at the Dana-Farber Cancer Institute, and author on this study, in an interview with CURE®.. “And that's important from a patient perspective so that if somebody does have one of these unique subtypes of (gastrointestinal stromal tumors), this opens a whole new opportunity for therapy in a disease that we never had effective therapies for before,”
Tyrosine kinase inhibitors were originally developed to target pathogenic mutant kinases and has drastically changed treatment for patients with unresectable or metastatic gastrointestinal stromal tumors. Despite this, patients with PDGFRA D842V-mutant disease had poor prognosis because tyrosine kinase inhibitors lacked activity against this specific mutation. This led to the development of Ayvakit, which is an inhibitor of the kinases in question.
This study compared the efficacy of Ayvakit in 56 patients enrolled in a previously conducted phase 1 trial with 19 patients enrolled in a previously conducted study who received other tyrosine kinase inhibitors. The primary factor of interest was overall survival, and the secondary factor of interest was progression-free survival.
Of the 56 patients treated with Ayvakit, researchers also analyzed a subgroup of 38 patients treated with either 300 mg (the recommended phase 2 dose) or 400 mg (the maximum tolerated dose).
Regardless of dose, the median overall survival in the Ayvakit group was not reached, meaning that more than half of patients were alive when this was assessed. For patients in the other tyrosine kinase inhibitor group, their median overall survival was 12.6 months. Overall survival rate at six months was 100% in the Avyakit group and 56% in the other tyrosine kinase inhibitor group; at 48 months, it was 63% and 17%, respectively.
Patients who took a 300-mg dose of Ayvakit had an adjusted overall survival rate of 100% at six months and 73% at 36 months. In contrast, those who took a 400-mg dose had an adjusted overall survival rate of 68% at six months and 20% at 26 months.
Progression-free survival was 29.5 months in the Ayvakit group compared with 3.4 months in the other tyrosine kinase inhibitor group.
“Historically, D842V mutant (gastrointestinal stromal tumor)was a very stubborn disease, and one for which we did not have effective therapies, but with the introduction and development of (Ayvakit), we now have an option that can help improve disease control and can help patients live longer that have this particular mutation,” said George.
“It is important to note that (Ayvakit) is currently approved for unresectable/metastatic PDGFRA D842V-mutant (gastrointestinal stromal tumors) regardless of the line of therapy,” the study authors wrote. “In real-world clinical practice, (Ayvakit) is expected to be used as a first-line (tyrosine kinase inhibitor) for this indication, hence, it will be crucial to collect and publish data evaluating (Ayvakit) in the first-line setting for unresectable/metastatic PDGFRA D842V-mutant (gastrointestinal stromal tumors).”
George concluded that the only way this study and others are done is through patient participation, and that it is so critical, particularly in this rare tumor population. “It's that blending of research and patient participation that has allowed this study to move forward. And I just think it's a wonderful example of really how patients drive everything we do. Without the patient community, and without patient involvement and commitment to research, we wouldn't be where we are today,” she said.
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