Sutent Significantly Improved Progression-Free Survival For Patients With Advanced Pancreatic Islet Cell Tumours

Main Category: Cancer / Oncology
Also Included In: Clinical Trials / Drug Trials
Article Date: 01 Jul 2009 - 1:00 PDT

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Pfizer announced preliminary results from a randomized Phase 3 trial of Sutent (sunitinib malate) in patients with advanced pancreatic islet cell tumours, also known as pancreatic neuroendocrine tumours, which is a different type of cancer than the more common pancreatic adenocarcinoma. Study findings demonstrated that median progression-free survival (PFS) was 11.1 months in patients treated with Sutent compared to 5.5 months in patients treated with placebo. Researchers today presented these data at the 11th World Congress on Gastrointestinal Cancer in Barcelona, Spain. The independent Data Monitoring Committee (DMC) recommended halting the trial earlier this year because Sutent showed significant benefit and the study had met its primary endpoint. Full analysis of the data is ongoing.

"In this study, Sutent demonstrated an impressive improvement in progression-free survival for patients with pancreatic islet cell tumours," said Dr. Eric Raymond, MD, PhD, Professor of Medical Oncology and Head of University Department of Medical Oncology (Service Inter Hospitalier de Cancerologie) Bichat-Beaujon, Clichy, France, and lead investigator on this sunitinib Phase 3 study. "This is encouraging news for patients, especially given that there are limited treatment options for this type of advanced cancer."

Phase 3 Trial Results

This international, Phase 3 trial compared sunitinib to placebo in patients with progressive, well-differentiated, malignant pancreatic islet cell tumours who had progressed in the last 12 months. Patients were randomized to either the sunitinib (n=75) (37.5 mg/day, continuous daily dosing) plus best supportive care arm or the placebo plus best supportive care arm (n=79).

Results showed that median PFS was 11.1 months in patients treated with sunitinib compared to 5.5 months in patients treated in the placebo arm (Hazard ratio 0.397, p<0.001).

Adverse events were similar to those observed in other sunitinib studies. The most commonly reported grade 3-4 adverse events in the sunitinib arm were neutropenia (12.3 percent), hypertension (8.8 percent), abdominal pain (7 percent), diarrhea (7 percent), hypoglycemia (7 percent) and hand-foot syndrome (7 percent).

This trial was initiated based on the results of an earlier Phase 2 trial of 107 patients published in the Journal of Clinical Oncology (July 2008). A 16.7 percent overall objective response rate (RECIST) and 56.1 percent stable disease rate (SD ≥6 months) was seen in the 66 patients with advanced pancreatic islet cell tumours treated with sunitinib.

"The observation of substantial improvement in progression free survival in Sutent-treated patients was the basis for the independent Data Monitoring Committee's recommendation to halt accrual to the study early," said Dr. Mace Rothenberg, Senior Vice President of Clinical Development and Medical Affairs for Pfizer's Oncology Business Unit. "This is welcome news as there is currently no standard of care for patients with pancreatic islet cell tumours who progress on prior therapy."

About Pancreatic Islet Cell Tumours

In contrast to exocrine pancreatic adenocarcinoma, pancreatic islet cell tumours are rare, indolent tumours of the endocrine pancreas with an incidence of two to four people per million annually worldwide.

Pancreatic islet cell tumours include insulinomas, glucagonomas and gastrinomas. Current treatment options are limited.

About Sutent(®) (sunitinib malate)

Sutent, an oral multi-kinase inhibitor, is currently approved for both advanced renal cell carcinoma (RCC) and second-line gastrointestinal stromal tumour (GIST), based on efficacy and safety data from large, randomized Phase 3 clinical trials.

Sutent works by blocking multiple molecular targets implicated in the growth, proliferation and spread of cancer. Two important Sutent targets, vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR), are expressed by many types of solid tumours and are thought to play a crucial role in angiogenesis, the process by which tumours acquire blood vessels, oxygen and nutrients needed for growth. Sutent also inhibits other targets important to tumour growth, including KIT, FLT3 and RET.

Important Sutent(®) (sunitinib malate) Safety Information

Women of child bearing age who are (or become) pregnant during therapy should be informed of the potential for foetal harm while on Sutent.

Decreases in left ventricular ejection fraction (LVEF) to below the lower limit of normal (LLN) have been observed. Patients with concomitant cardiac conditions should be carefully monitored for clinical signs and symptoms of congestive heart failure.

Patients should be monitored for hypertension and treated as needed with standard antihypertensive therapy. Complete blood counts (CBCs) with platelet count and serum chemistries should be performed at the beginning of each treatment cycle for patients receiving treatment with Sutent.

The most common adverse reactions in advanced RCC and GIST clinical trials were fatigue, asthenia, diarrhea, nausea, mucositis/stomatitis, ONC09/010 vomiting, dyspepsia, abdominal pain, constipation, hypertension, rash, hand-foot syndrome, skin discoloration, altered taste, anorexia and bleeding.

Source
Pfizer Oncology