Pfizer Inc. announced that the European Commission has approved Sutent (sunitinib malate) for the treatment of unresectable or metastatic, well-differentiated pancreatic Neuro-Endocrine Tumours (NET) with disease progression in adults. Experience with Sutent as initial treatment is limited in this disease. Pancreatic NET is a rare cancer reported in two to four people per million annually worldwide. Sutent is the first treatment to be approved for patients with pancreatic NET in twenty-five years.

The approval is based on results from a randomized, Phase 3 trial that demonstrated Sutent more than doubled the time period that patients were free from disease progression or death. The Progression-Free Survival (PFS) for Sutent was 11.4 months vs. 5.5 months for placebo (p=0.0001) in 171 patients. Additionally, while the overall survival data were not mature at the time of analysis, the overall survival favoured the Sutent arm compared with placebo (9 vs. 21 deaths) (HR 0.409, p=0.0204).

“This approval represents a significant milestone in the management of pancreatic NET,” said Dr. Mace Rothenberg, senior vice president of Clinical Development and Medical Affairs, Pfizer Oncology Business Unit. “Sutent has been a standard of care for patients with advanced/metastatic Renal Cell Carcinoma (RCC) and imatinib-refractory Gastro-Intestinal Stromal Tumour (GIST) for several years, and we are proud that it is now a treatment option for patients in Europe with progressive pancreatic NET.”

Although rare, the reported incidence of pancreatic NET appears to be rising, accounting for approximately nine percent of NET. Current treatment options have limited therapeutic benefit and the prognosis is poor for patients with advanced pancreatic NET.

“As the first anti-VEGF therapy to show a substantial clinical benefit in treating progressive pancreatic NET, Sutent represents a novel therapeutic approach for this difficult-to–treat disease.” said Dr. Eric Raymond, principal investigator of the pivotal Phase 3 study that led to the approval of Sutent for pancreatic NET in Europe. "Physicians in Europe will now be able to use a therapy with proven efficacy to treat this disease.” Dr. Raymond is professor of medical oncology and head of University Department of Medical Oncology (Service Inter Hospitalier de Cancerologie) Bichat-Beaujon, Clichy, France.

Sutent is also approved for the treatment of unresectable well-differentiated advanced and/or metastatic pancreatic neuro-endocrine carcinoma in the Philippines, Switzerland, Colombia and Korea. In addition, it is under regulatory review for this indication in several other countries.

Tumours of the neuro-endocrine system are typically classified into two distinct categories: carcinoids or pancreatic neuro-endocrine tumours. Pancreatic neuro-endocrine tumours, also known as pancreatic islet cell tumours, form in the endocrine (hormone-producing) tissues of the pancreas. Subtypes include insulinomas, glucagonomas and gastrinomas. Pancreatic neuro-endocrine tumours are different from pancreatic adenocarcinoma, which account for about 95 percent of all pancreatic cancers.

Sutent is an oral multi-kinase inhibitor approved for the treatment of advanced/metastatic Renal Cell Carcinoma (RCC) and unresectable and/or metastatic malignant GIST after failure of imatinib mesilate treatment due to resistance or intolerance. In Europe, it is also indicated for the treatment of unresectable or metastatic, well-differentiated pancreatic neuroendocrine tumours with disease progression in adults. Experience with Sutent as first-line treatment is limited.

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.

Hepatotoxicity has been observed in clinical trials and post-marketing experience. Cases of hepatic failure, some with a fatal outcome, were observed in <1% of solid tumour patients treated with Sutent. It is recommended to monitor liver function tests before initiation of treatment, during each cycle of treatment, and as clinically indicated. If signs or symptoms of hepatic failure are present, sunitinib should be discontinued and appropriate supportive care should be provided.

Women of child bearing age who are (or become) pregnant during therapy should be informed of the potential for fetal 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 GIST, RCC and pancreatic NET clinical trials were diarrhoea, fatigue, asthenia, nausea, mucositis/stomatitis, anorexia, vomiting, neutropenia, hypertension, dyspepsia, abdominal pain, constipation, rash, hand-foot syndrome, skin discoloration, hair colour changes, altered taste and bleeding.

Pfizer Oncology is committed to the discovery, investigation and development of innovative treatment options to improve the outlook for cancer patients worldwide. Our strong pipeline, one of the most robust in the industry, is studied with precise focus on identifying and translating the best scientific breakthroughs into clinical application for patients across a wide range of cancers.