San Francisco, CA—Two thirds of patients with advanced gastrointestinal stromal tumor (GIST) whose disease progressed on available therapies achieved disease control with sorafenib (Nexavar), according to Nicholas P. Campbell, MD, of the University of Chicago, who reported results of a recent study presented at the 2011 Gastrointestinal Cancers Symposium.
In this study, the average patient with advanced-disease GIST survived almost 1 year after treatment with the multikinase inhibitor sorafenib, which is currently indicated by the US Food and Drug Administration (FDA) for the treatment of hepatocellular and renal-cell cancer.
On average, patients with metastatic GIST survive about 4 years after diagnosis, thanks to treatment with imatinib (Gleevec) and sunitinib (Sutent), both FDA approved agents.
Sorafenib was used in 38 patients who had previously received imatinib alone or imatinib plus sunitinib. Of the 38 patients, 5 had partial responses and 21 achieved stable disease. Median progression-free survival was 5.2 months and overall survival was 11.6 months. Some patients continued using the drug for as long as 3 years, said Dr Campbell.
Most patients had been previously treated with both available agents and were receiving sorafenib as third-line therapy. “The data demonstrate that sorafenib has definitive clinical activity in imatinib- and sunitinib-resistant GIST,” he said. “Prolonged disease control is possible in these patients with refractory disease.”
Although sorafenib is not approved for GIST, the National Comprehensive Cancer Center guidelines recommend it as an option for patients with GIST refractory to the 2 available agents. “After failure of imatinib and sunitinib, the therapeutic options are limited for patients with advanced GIST,” Dr Campbell noted.
Rates of partial response were 17% in patients treated with imatinib and 13% in those receiving both agents; stable disease was noted in approximately 50% of both groups. Altogether, 68% of all patients had disease control with sorafenib as a second- or third-line agent.
The most common grade 3 adverse events were hand–foot syndrome (45%) and hypertension (21%). Ap - proximately 60% of patients required dose reductions.
Study Limitations Commenting on the study, Peter Enzinger, MD, Director of the Gastrointestinal Cancer Treatment Center at Dana-Farber, Boston, said the response rate was indeed impressive, but “it is very difficult to interpret single-arm uncontrolled trials with tyrosine kinase inhibitors.” He proposed, however, that patients might have also responded to rechallenge with their initial drugs, and this was not tested.
Dr Enzinger noted that grade 3 hand-foot syndrome in 45% of patients is “substantial,” noting the toxicity profile of sorafenib (including diarrhea and rash) “is not inconsequential.”
“I agree with the investigators that further studies of sorafenib (and the newer multikinase inhibitor regorafenib) in GIST patients are warranted,” he said. “Patients with GIST should have access to new options, but the clinical community should support definitive phase 3 trials that allow clinicians and patients to differentiate available drugs so that best evidence can support best practices.”
The phase 3 Study of Regorafenib as a 3rd-line or Greater Treatment for GIST (GRID) is currently enrolling worldwide, he added
