SUTENT® Receives U.S. FDA Approval For Advanced Pancreatic Neuroendocrine Tumors

First Anti-VEGF Therapy Approved for Patients with Advanced Pancreatic NET, A Population with Limited Treatment Options

NEW YORK--(BUSINESS WIRE)-- Pfizer Inc. announced today that the U.S. Food and Drug Administration (FDA) has approved SUTENT® (sunitinib malate) as the first anti-VEGF therapy to treat progressive, well-differentiated pancreatic neuroendocrine tumors (NET) in patients with unresectable locally advanced or metastatic disease. Pancreatic NET is a rare cancer reported in two to four people per million annually worldwide.1,2

“We are delighted that SUTENT has been granted approval by the FDA as an effective treatment option for individuals with pancreatic NET. This approval represents the third disease indication for SUTENT, which was approved by the FDA in 2006 for treatment of patients with advanced kidney cancer and imatinib-resistant or intolerant gastrointestinal stromal tumor (GIST),” said Dr. Mace Rothenberg, senior vice president of Clinical Development and Medical Affairs, Pfizer Oncology Business Unit. “Pfizer is committed to improving the lives of those with cancer. This approval is good news for the physicians, patients and caregivers who have had limited treatment options for this rare and difficult-to-treat tumor.”

The FDA approval is based on data from the SUN 1111 pivotal Phase 3 trial that demonstrated SUTENT provided a clinically significant improvement in progression-free survival (PFS) compared to placebo (10.2 versus 5.4 months, p=0.000146) in this patient population.3 Treatment with SUTENT also yielded a statistically significant improvement in tumor response, with an objective response rate (ORR) of 9.3 percent (95% CI: 3.2, 15.4, p=0.0066). No objective responses were observed with placebo. In addition, while overall survival (OS) was not mature at the time of final analysis, nine deaths were observed in patients enrolled in the SUTENT arm versus 21 deaths in patients enrolled in the placebo arm.3,4

"This approval is welcome news for physicians who have struggled to find a treatment option that shows a substantial clinical benefit in treating advanced pancreatic NET,” said Dr. Eric Raymond, professor of medical oncology and head of University Department of Medical Oncology (Service Inter Hospitalier de Cancerologie) Bichat-Beaujon, Clichy, France and principal investigator of the SUN 1111 Phase 3 trial. “Pancreatic NET is a highly vascular tumor, and as the first anti-VEGF therapy approved for this disease, SUTENT represents a treatment that attacks a key component of tumor growth.”

About the SUN 1111 Trial

SUN 1111 was a multicenter, international, randomized, double-blind, placebo-controlled Phase 3 study (n=171) evaluating single-agent SUTENT in patients with unresectable pancreatic NET, characterized by cancer that could not be surgically removed. The primary endpoint was PFS. Other endpoints included OS, ORR and safety. Use of somatostatin analogs were allowed in the study.3

The approval of SUTENT in this patient population was based on FDA assessment of PFS observed in SUN 1111. Previously reported investigator-assessed data from the trial, published in the New England Journal of Medicine, showed SUTENT more than doubled median PFS compared with placebo (11.4 versus 5.5 months, p<0.0001), which was found to be consistent in a blinded, independent central review of scans from the study (12.6 versus 5.8 months, p=0.000015).4,5 In February 2009, the independent Data Monitoring Committee for the SUN 1111 trial recommended that randomization to the study be halted early in the interest of patient safety and based on the very strong likelihood that the study would meet its primary endpoint if continued to completion. This may have led to an overestimate of the magnitude of PFS effect.

SUTENT has been approved for advanced pancreatic NET in Europe and nine additional countries. SUTENT is also approved for both gastrointestinal stromal tumors (GIST) after disease progression on or intolerance to imatinib mesylate, and advanced renal cell carcinoma (RCC) in over 100 countries and has been studied in over 10,000 patients in clinical trials. To date, with more than five years of experience, more than 100,000 patients have been treated with SUTENT worldwide.

About Pancreatic Neuroendocrine Tumors (Pancreatic NET)

Pancreatic NET is different from pancreatic adenocarcinoma, which account for about 95 percent of all pancreatic cancers.6 Pancreatic NET is a member of a broad group of cancers called neuroendocrine tumors, which arise from hormone-producing cells of the body.7,8 While neuroendocrine tumors that develop in the pancreas are known as pancreatic NET, those that arise in other areas of the body, including the lungs and gastrointestinal tract, are known as carcinoids.7 Pancreatic NET, which are mostly well-differentiated,9 account for approximately 22-28 percent of all neuroendocrine tumors.10,11 Nearly 90 percent of patients with pancreatic NET are initially diagnosed with locally advanced or metastatic disease (cancer that has spread to other organs).12 For patients with pancreatic NET that has metastasized, prognosis is poor, with a survival of only 1-3 years,13 similar to that seen with metastatic breast cancer or metastatic colon cancer.14,15

About SUTENT(®) (sunitinib malate)

SUTENT is an oral multi-kinase inhibitor that 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 tumors and are thought to play a crucial role in angiogenesis, the process by which tumors acquire blood vessels, oxygen and nutrients needed for growth. SUTENT also inhibits other targets important to tumor growth, including KIT, FLT3 and RET.

Important SUTENT(®) (sunitinib malate) Safety Information

Hepatotoxicity has been observed in clinical trials and post-marketing experience. This hepatotoxicity may be severe, and deaths have been reported. It is recommended to monitor liver function tests before initiation of treatment, during each cycle of treatment, and as clinically indicated. SUTENT should be interrupted for Grade 3 or 4 drug-related hepatic adverse events and discontinued if there is no resolution. SUTENT should not be restarted if patients subsequently experience severe changes in liver function tests or have other signs and symptoms of liver failure.

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) and cardiac failure, including death, 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 diarrhea, fatigue, asthenia, nausea, mucositis/stomatitis, anorexia, vomiting, neutropenia, hypertension, dyspepsia, abdominal pain, constipation, rash, hand-foot syndrome, skin discoloration, hair color changes, altered taste and bleeding.

For more information on SUTENT, including full prescribing information for SUTENT (sunitinib malate), please visit www.pfizer.com [http://www.pfizer.com].

About Pfizer Oncology

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. Pfizer Oncology has biologics and small molecules in clinical development and more than 100 clinical trials underway. By working collaboratively with academic institutions, individual researchers, cooperative research groups, governments, and licensing partners, Pfizer Oncology strives to cure or control cancer with breakthrough medicines, to deliver the right drug for each patient at the right time. For more information please visit www.Pfizer.com.

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1 Ramage JK, Davies AHG, Ardill et al. Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours. Gut. 2005;54:iv1–16

2 Halfdanarson TR, Rabe KG, Rubin J et al. Pancreatic neuroendocrine tumors (PNETs): incidence, prognosis and recent trend toward improved survival. Ann Oncol. 2008;19:1727–33.

3 SUTENT [Package Insert]. New York, NY: Pfizer, Inc. 2011.

4 Raymond E, et al. Sunitinib Malate for the Treatment of Pancreatic Neuroendocrine Tumors. N Engl J Med 2011; 334: 501-13.

5 ASCO GI Abstract #249. Evaluation of Progression Free Survival by Blinded Independent Central Review in Patients With Progressive, Well-Differentiated Pancreatic Neuroendocrine Tumors Treated With Sunitinib or Placebo. E. Van Cutsem - Presenter. 8th Annual Gastrointestinal (GI) Cancers Symposium, San Francisco, CA, January 20-22, 2011.

6 American Cancer Society. What is cancer of the pancreas? Available at: http://www.cancer.org/Cancer/PancreaticCancer/DetailedGuide/pancreatic-cancer-what-is-pancreatic-cancer. Accessed March 1, 2011

7 National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology - Neuroendocrine Tumors. Version 1.2011: National Comprehensive Cancer Network, Inc.; 2011.

8 Cancer.net. Neuroendocrine Tumor. Available at: http://www.cancer.net/patient/Cancer+Types/Neuroendocrine+Tumor. Accessed May 6, 2011.

9 Choi I, Estecio M, et al. Hypomethylation of LINE-1 and Alu in well-differentiated neuroendocrine tumors (pancreatic endocrine tumors and carcinoid tumors). Modern Pathology. 2007; 20:802–810.

10 Pape UF, Berndt U, Muller-Nordhorn J et al. Prognostic factors for long-term outcome in gastroenteropancreatic neuroendocrine tumors. Endocrine-Related Cancers; 15: 1083-97, 2008.

11 Ter-Minassian M, Frauenhoffer CS, Hooshmand SM et al. Prospective analysis of clinical outcomes and prognostic factors in patients with Neuroendocrine tumors (NETs). ASCO Meeting Abstracts; Jun 14; 4044, 2010.

12 Yao JC, Hassan M, Phan A, et al. One hundred years after “Carcinoid”: epidemiology of and prognostic factors for Neuroendocrine tumors in 35,825 cases in the United States. J Clin ONcol; 26 (18): 3063-72, 2008.

13 Yao JC, et al. Population-based study of islet cell carcinoma. Ann Surg Oncol. 2007;14(12):3492–3500

14 Pal SK, et al "Lack of survival benefit in metastatic breast cancer with newer chemotherapy agents: The City of Hope cancer experience" ASCO Breast 2008; Abstract 95.

15 Kopetz S, Chang G, et al. Improved Survival in Metastatic Colorectal Cancer is Associated With Adoption of Hepatic Resection and Improved Chemotherapy. J Clin Oncol. 2009; 7:3677-3683.



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