Sorafenib Active in GIST Resistant to Imatinib, Sunitinib and Nilotinib

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(ChemotherapyAdvisor) – Despite frequent toxicities and dose reductions, third- or fourth-line sorafenib therapy is associated with disease stabilization among patients with advanced gastrointestinal stromal tumor (GIST) who have been previously treated with imatinib, sunitinib, and nilotinib, according to a retrospective multi-institutional study published in the European Journal of Cancer.

“We conclude that sorafenib is active in GIST resistant to imatinib, sunitinib and nilotinib,”  reported lead author Michael Montemurro, MD, of the Multidisciplinary Oncology Center, University Hospital Lausanne, in Lausanne, Switzerland, and coauthors.

With a median sorafenib therapy duration was 4.5 months (0-39.7 months), a total of 12 patients (10%) exhibited partial responses to sorafenib, and 70 patients (57%) experienced disease stabilization, the authors reported.

Median progression-free survival (PFS) was 6.4 months.

“In general, sorafenib was moderately tolerated,” they wrote. “The starting dose of 400 mg twice daily was reduced in a third of patients, but this did not have an impact on PFS.”

Tyrosine kinase inhibitors improve patient outcomes in GIST, but “treatment failure is frequent, and prognosis then bleak,” Dr. Montemurro noted. “Smaller trials in this setting suggested activity for sorafenib, a multikinase inhibitor of receptor tyrosine kinases and RAF serine/theonine kinases.”

The researchers therefore assessed sorafenib efficacy in 124 patients with GIST who were treated at 13 cancer centers. All of the patients had received unsuccessful imatinib and sunitinib therapy, and 68 patients had also previously received nilotinib; 123 of the patients had WHO performance scores ≤2.

“No toxic death occurred,” they noted, but sorafenib was discontinued because of disease progression in 79 (64% of) patients, toxicities in 5 (4%), and death in 6 patients (5%), the authors wrote.

Toxicities were noted in 56% of patients, with 38% experiencing skin rash, hand-foot syndrome, or other skin reactions, fatigue and diarrhea were noted in 15% and 19% of patients, respectively, and 4% experienced hypertension. Only hand-foot-syndrome toxicities were grade 3 adverse events; the others were grade 1-2.

Dr. Montemurro disclosed receiving speaker honoraria and travel grants from Bayer.


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