Sorafenib Offers Alternative Treatment for Drug-resistant GIST

Two-thirds of patients achieved stable disease with sorafenib after resistance to imatinib and sunitinib treatment for gastrointestinal stromal tumors (GIST), according to a phase 2 trial to be presented at the Gastrointestinal Cancers Symposium.

 

Based on a previous preclinical study that showed sorafenib—an inhibitor of KIT, VEGFR, PDGFR-β, and BRAF kinases—to have activity against several imatinib- and sunitinib-resistant tumors, researchers treated KIT-expressing GIST patients with sorafenib 400 mg orally twice daily. The study was initiated before sunitinib approval for imatinib-resistant GIST, but was amended afterward; therefore, of 38 patients, six were imatinib-resistant and 32 were imatinib/sunitinib-resistant.

 

With a median follow-up of 31 months, 13% achieved partial response and 55% stable disease. Median progression-free survival was 5.2 months (95% confidence interval [CI], 3.4-7.4); median overall survival was 11.6 months (95% CI, 8.8-18.0). Fifty percent of patients were alive at 1 year; 29% at 2 years. Three patients remain on study. The drug was well tolerated, with grade 3/4 hand-foot syndrome (45%) and hypertension (21%) of most significance.

 

Based on their results, the researchers concluded that more investigation into sorafenib in the treatment of GIST is warranted.