Therapeutic Options for Progressive GIST

Patients with gastrointestinal stromal tumors (GISTs) typically receive 400 mg of imatinib as maintenance therapy, provided they are responding and tolerating initial therapy. Treatment holidays are not taken in this setting, notes Syma Iqbal, MD, since studies have shown that outcomes are worse when imatinib is temporarily discontinued. This is potentially due to a tumor flare effect, she adds, making appropriate radiologic assessment important.

The imatinib dose is typically increased from 400 mg to 800 mg for patients with progressive GIST. Approximately one third of patients may achieve disease stability from this strategy, comments Iqbal. Individuals who cannot tolerate 800 mg or have disease progression while on 800 mg should be switched to another tyrosine kinase inhibitor (TKI), such as sunitinib, which targets vascular endothelial growth factor. Regorafenib, a multi-targeted TKI, is approved in the third-line setting.

Individuals who have failed three lines of therapy should be evaluated at a high-volume sarcoma center that treats GISTs on a routine basis, since many of these centers offer clinical trials that may improve patient outcomes, states Anthony P. Conley, MD. Other available TKIs that have been approved for other indications include dasatinib, nilotinib, sorafenib, pazopanib, and axitinib. These agents may be used in GIST treatment in certain off-label situations, says Conley.