Updated efficacy and safety results from a multicenter international phase III trial indicate that compared to placebo, sunitinib (Sutent) provides significantly longer progression-free survival for patients with advanced, progressive, and well-differentiated pancreatic neuroendocrine tumors, according to a presentation at the 2010 ASCO Annual Meeting. In the trial, patients on sunitinib had a median progression-free survival of 11.4 months vs 5.5 months in the placebo group (HR = 0.418, P = .0001). The trial closed early because of more serious adverse events and deaths in the placebo arm, so Kaplan-Meier analysis of one of the planned endpoints, overall survival, was not possible. Yet after a median follow-up of just under a year, there were 9 deaths in the sunitinib group and 21 in the placebo arm, as well as a trend toward improved overall survival in those who received sunitinib, with a hazard ratio of 0.409 (P = .0204), said lead investigator Patricia Niccoli, MD, who presented the results at the Annual Meeting.

Significant New Finding

"This is a significant new finding and an advance for patients with low-grade and intermediate-grade neuroendocrine tumors. As well as achieving increased progression-free survival across all the subgroups in the trial, sunitinib was fairly well tolerated, and the findings in this study may soon be applied to patients we see in our practices," said James L. Abbruzzese, MD, Professor of Medicine, and Chairman of the Department of Gastrointestinal Medical Oncology at The University of Texas M. D. Anderson Cancer Center. Dr. Abbruzzese presented the study's results at the Best of ASCO Meeting in San Francisco.¹

Researchers with the sunitinib trial planned to accrue 340 patients with advanced pancreatic endocrine tumors, who had experienced disease progression in the last 12 months, and were not amenable to curative treatment. When the trial closed in April 2009, 171 patients had been randomly assigned to receive either 37.5 mg daily of sunitinib or placebo. Most patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and many had nonfunctioning tumors (48.4% in the sunitinib arm and 51.8% in the placebo group). Numerous patients had distant metastases, primarily in the liver. Yet patients in the placebo group were more heavily pretreated and the median time since their diagnosis was longer than in the sunitinib group.

Along with the trial's premature closure, these factors made it difficult to reach definitive conclusions about the true efficacy of sunitinib, said Kjell Oberg, MD, PhD, the discussant at the Annual Meeting. But the trial suggests that sunitinib "offers us a new possibility for treating pancreatic tumors," he said.

Key Results

In the trial, the objective response rate was 9% and there were no objective responses in the placebo group. After closure of the trial, patients in the placebo group became candidates for open-label sunitinib, Dr. Niccoli said.

The most frequent grade 3 or 4 events on sunitinib were neutropenia, hypertension, and hand-foot syndrome, which affected 12%, 9.6%, and 6% of patients who received the medication, respectively. "Most of the toxicities were manageable," said Dr. Abbruzzese. He also noted that almost a third of patients on both arms of the study were receiving somatostatin analogs concurrently, which did not seem to add to toxicities.

Dr. Abbruzzese noted that most of the patients in the trial did not have high-grade tumors. And for patients with low- to intermediate-grade tumors, who are often asymptomatic, it may be challenging to make the decision of whether or not-and at what point- to introduce a treatment like sunitinib that has some toxicity, Dr. Abbruzzese said. "The fact that there's a survival benefit does give me some comfort about introducing this agent earlier rather than later," he said. "Yet I think it's going to take a little time and perhaps some additional studies to understand the best timing for intervention with an agent like sunitinib," he added. ■

Reference

1. Niccoli P, Raoul J, Bang Y, et al: Updated safety and efficacy results of the phase III trial of sunitib versus placebo for treatment of pancreatic neuroendocrine tumors. Best of ASCO Meeting San Francisco. Abstract 4000. Presented July 17, 2010, by James L. Abbruzzese, MD.