June 25, 2009 — Sunitinib (Sutent) has shown a significant improvement in progression-free survival in patients with pancreatic islet cell tumors in a phase 3 trial that was halted early because of the benefit seen.
Results from the study were presented today at the World Congress on Gastrointestinal Cancer in Barcelona, Spain, by Eric Raymond, MD, head of medical oncology at the University Hospital in Bichat-Beaujon, Clichy, France.
Pancreatic islet cell tumors are rare, Dr. Raymond said, and they represent an area of unmet medical need.
Trial Accrued Only Half the Patients Planned
The results come from an analysis of 169 patients who had progressed in the previous 12 months; all were receiving the best supportive care. In the trial, they were randomized to receive either sunitinib (37.5 mg/day) or placebo.
Progression-free survival increased to 11.1 months in the sunitinib group, compared with 5.5 months in the placebo group (hazard ratio, 0.397; P < .001), an improvement that Dr. Raymond described as "impressive."
"This was a clinically meaningful improvement in progression-free survival," Dr. Raymond told Medscape Oncology. "We saw a magnitude of benefit that we did not anticipate," he said, and there was a big difference early on. He has conducted many clinical trials, but "this is a once-in-a-lifetime finding," he said.
The trial had accrued only half of the patients planned when it was stopped. Originally, it was designed to enroll 340 patients.
"This is encouraging news," Dr. Raymond said, "especially as there are limited treatment options for this type of advanced cancer."
Pressure From Patients to Use This Drug
Pancreatic islet cell tumors are a type of neuroendocrine tumor, and they are estimated to occur in about 2 to 4 people in a million. They are formed from endocrine cells, which secrete insulin and glucagons, Dr. Raymond explained. These tumors have slower proliferation and progression than the more common form of pancreatic cancer, adenocarcinoma, which affects the exocrine cells, and which is very rapidly progressing.
Currently, there is only 1 treatment for these pancreatic islet cell tumors — streptozotocin. This is a very old drug that is now only used in this type of cancer, Dr. Raymond noted. This use is based on a randomized clinical trial that was carried out more than 20 years ago, and measured only response rates, not survival.
The trial of sunitinib was investigator initiated. Dr. Raymond said he and his colleagues approached the manufacturer, Pfizer, to try the targeted drug in this patient population and the company agreed to fund the trial. "Nobody anticipated such a good result," Dr. Raymond said, but now that these data are available, he believes that the company will have discussions with regulatory authorities to obtain approval for this indication.
Sunitinib is already marketed, however, and there "will be pressure from patients to use this drug," Dr. Raymond predicted. When asked if he would use this drug in this patient population, he replied: "For sure, if I can improve the progression-free survival for several months, then I would be tempted to do so."
There are no major safety concerns with this drug, although its use needs to be supervised by medical oncologists, Dr. Raymond said.
The adverse events in this study were similar to those seen in previous sunitinib studies, he reported at the meeting. The most commonly reported grade 3/4 adverse events in the sunitinib group were neutropenia (12.3%), hypertension (8.8%), abdominal pain (7%), diarrhea (97%), hypoglycemia (7%), and hand-foot syndrome (7%).
"We have something that works, and something that is safe, and something that we can provide to our patients," Dr. Raymond concluded.
"This is a major step, but it is just the first step," said Michel Ducreux, MD, PhD, from the Institut Gustave-Roussy in Villejuif, France, who chaired the session at which the results were presented. This was proof of concept with a targeted therapy, but now there needs to be trials to see how this compares with chemotherapy, such as doxorubicin in combination with streptozotocin, and also how the 2 drug approaches work in combination, he told Medscape Oncology.
"But I am very happy with what I heard," he said. "This is a new therapeutic option for our patients. The tolerance is not too bad, and the drug is convenient, taken orally twice a day."
"The results were very clear and very positive," he said, "and I hope that this drug will be available for use in the clinic very soon, as it offers hope to our patients."
Dr. Raymond reports serving as a consultant for Pfizer, GlaxoSmithKline, Bayer, and Amgen.
World Congress on Gastrointestinal Cancers: Abstract 0-0013. Presented June 25, 2009.
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