Sorafenib is effective in patients with gastrointestinal stromal tumors (GIST) whose disease has progressed on imatinib and sunitinib, researchers reported at the Gastrointestinal Cancers Symposium. Twenty-six (68%) of the 38 patients enrolled in the prospective Phase II trial achieved a partial response or stable disease with sorafenib therapy.
“Prolonged disease control is possible in these refractory patients, even in those with primary sunitinib-resistance,” said lead author Nicholas P. Campbell, MD, an oncology fellow at the University of Chicago, speaking at a news conference before the meeting. “NCCN guidelines now suggest sorafenib as an option for patients with imatinib-sunitinib-resistant GIST.”
Prior research, including a retrospective patient series reported at the 2009 ASCO Annual Meeting (Abstract 10564) suggested that sorafenib may be active in imatinib- and sunitinib-resistant GIST tumors.
To test the idea in a prospective manner for the new study (Abstract 4), Dr. Campbell and colleagues enrolled patients with unresectable GIST that had progressed on imatinib (six patients) or imatinib and sunitinib (32 patients) between 2006 and 2009 at six centers in the United States.
Patients received 400 mg sorafenib twice daily in 28-day cycles and underwent CT scans after every two cycles.
Five patients (13%) had a partial response to sorafenib therapy, including one who was imatinib resistant and four who were resistant to both imatinib and sorafenib. An additional 21 patients (55%) had stable disease, including three imatinib-resistant patients and 18 imatinib-sunitinib-resistant patients.
Median progression-free survival was 5.2 months for the entire study population and 3.4 and 5.2 months for the imatinib- and imatinib-sunitinib-resistant patients, respectively.
The median overall survival time was 11.6 months, with 13.6 month and 10.5 months for the imatinib- and imatinib-sunitinib-resistant patients, respectively. The median duration of therapy was 4 cycles, with a range of 1 to 40.
Dr. Campbell said that the drug was relatively well tolerated, although 63% of patients required dose reductions. The most common Grade 3 toxicities were hand-foot syndrome, with 45% of patients affected, and hypertension, with 21% of patients affected.
“Our patients with metastatic GIST do very well,” said Jennifer C. Obel, MD, Attending Physician and Assistant Professor at the NorthShore University Health System in Evanston, Illinois, who moderated the news conference. “They live, on average, four years after diagnosis.
“But unfortunately many patients have limited options at some point during their illness. This presentation demonstrates that additional treatments may be on the horizon.”
She noted, however, that the trial was a small study. Therefore, while oncologists may consider sorafenib an option for these patients, they should also consider clinical trial participation for these dual-refractory individuals.
Finally, Dr. Campbell noted that the NCI-sponsored trial includes molecular analyses to look for correlates of response to sorafenib. That portion of the study is still under way, with only 26 samples analyzed thus far. He declined to provide any information about what the team has seen, saying, “There is really not much to make of it right now.”
The Gastrointestinal Cancers Symposium is cosponsored by the American Society of Clinical Oncology, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology