Advanced Gastrointestinal Stromal Tumors: Historical Perspective, Future Directions - Episode 11
KIT and PDGF are pathways of interest when developing therapies for patients with gastrointestinal stromal tumors (GISTs), states Syma Iqbal, MD. Additionally, activity has been seen for agents targeting the VEGF and MAP kinase/MEK pathway. Several clinical trials are investigating the potential activity of tyrosine kinase inhibitors (TKIs) targeting these pathways, but these agents have not been compared to current standard TKI therapies, such imatinib and sunitinib.
Pazopanib, a multikinase inhibitor, has demonstrated clinically significant rates of progression-free survival (PFS) in patients with GIST who have failed imatinib and sunitinib. Phase I/II study results showed that patients who received pazopanib had a 4-month PFS rate of 46% compared with a rate of 17% in individuals who received best supportive care, says Anthony P. Conley, MD. Patients who received pazopanib also had a longer duration of stable disease, while those receiving best supportive care demonstrated nearly a two-fold increase in risk of tumor progression.
Pazopanib is moving forward for further evaluation in GISTs, notes Iqbal. A phase II study is currently assessing pazopanib with the MEK inhibitor trametinib for patients with imatinib and sunitinib-refractory or intolerant GIST. This study plans to enroll 45 patients (NCT02342600).