Efficacy of sorafenib in patients with gastrointestinal stromal tumors in the third- or fourth-line treatment: A retrospective multicenter experience

Abstract

Sorafenib is a multi-targeted tyrosine kinase receptor inhibitor used to treat patients with advanced gastrointestinal stromal tumors (GISTs). The present study evaluated the efficacy and tolerability of sorafenib therapy for patients with GISTs. Between January 2001 and November 2012, 25 patients, from multiple centers, who had received sorafenib as the third- or fourth-line treatment for GISTs were investigated retrospectively. In total, 17 patients were male and eight were female. The median age was 54.0 years (range, 16–82 years). From the patients, 21 received imatinib for longer than six months and four received it for less than six months. The clinical benefit rate of sorafenib was 40.0%. Treatment-related adverse events were reported in 72% of patients. These adverse events were generally mild to moderate in intensity. The median progression-free survival (PFS) and overall survival (OS) times of the patients who received sorafenib were 7.2 and 15.2 months, respectively. The duration of imatinib usage was an independent prognostic factor for PFS and OS. Sorafenib is an effective treatment in patients with GISTs showing a clinical benefit rate of 40.0% and an acceptable tolerability.

The analysis of the long-term outcomes of sorafenib therapy in routine practice in imatinib and sunitinib resistant gastrointestinal stromal tumors (GIST)*

“…In in vitro studies Heinrich et al determined that sorafenib inhibited imatinib-resistant mutations in exons encoding the ATP/drug-binding pocket (exon 11 + 13 and exon 11 + 14) and in exons encoding the activation loop (exon 17 and 18), with the exception of substitutions at KIT codon D816 and PDGFRA codon 842 [ 18 ]. Until now it has been studied in two small phase II trials and two retrospective series (smaller one center and larger multicenter with short follow-up) [ 10 – 12 , 20 , 21 ]. Two single-arm phase II clinical trials ( n = 38 and n = 31 patients) have demonstrated activity in patients with GIST after progression to at least imatinib and sunitinib, with an clinical benefit rate exceeding 60% and disease control rate at 24 weeks > 30%.…”

“…A retrospective analysis of sorafenib as 3 rd or 4 th line treatment in 124 patients with advanced GIST showed median PFS of 6.4 months and median OS identical to our study – 13.5 months [ 20 ]. Another multicenter study on 25 patients showed median PFS 7.2 months and median OS 15.2 months as the 3 rd - or 4 th -line treatment for GISTs [ 21 ]. Toxicity of sorafenib in our study was mostly manageable and comparable to those observed in other multikinase inhibitors [ 5 , 6 ].…”

Gastrointestinal Stromal Tumors, Version 2.2014

“…The most common treatmentrelated adverse events (≥ grade 3) were hypertension (23%), hand-foot skin reaction (20%), and diarrhea (5%). Sorafenib, [30][31][32][33] nilotinib, [34][35][36][37][38] dasatinib, 39,40 and pazopanib 41 have also shown activity in patients with GIST resistant to imatinib and sunitinib. Much of the data on these TKIs are from phase II studies and retrospective analyses involving small numbers of patients.…”

“…45 Regorafenib (category 1) is recommended for patients experiencing disease progression on imatinib and sunitinib. 29 Based on the limited data, [30][31][32][33][34][35][36][37][38][39][40] the NCCN Guidelines have also included sorafenib, dasatinib, and nilotinib as additional options for patients who are no longer receiving clinical benefit from imatinib, sunitinib, or regorafenib (see SARC-E, page 858), although all data regarding the potential benefit of these agents are from the preregorafenib era.…”

Cancer Management by Tyrosine Kinase Inhibitors: Efficacy, Limitation, and Future Strategies

“…On the other hand, sorafenib also showed certain efficacy toward GIST. Yet its efficacy was lower than that of imatinib, and was thus only used as third/fourth line, after failure of initial therapy [97].…”