Pfizer Inc. announced that the US FDA Oncologic Drugs Advisory Committee (ODAC) voted 8-2 that Sutent (sunitinib malate) provides a favourable benefit-risk profile for the treatment of unresectable pancreatic Neuroendocrine Tumours (NET). The panel’s advice will be considered by the FDA when finalizing its review of Pfizer’s supplemental New Drug Application (sNDA) for sunitinib for this indication.
“We are encouraged by the panel’s favourable review of sunitinib for the treatment of unresectable pancreatic NET. Following today's discussion, we will work closely with the FDA to ensure that it has all of the information that it needs to finalize its review,” said Dr Mace Rothenberg, senior vice president of Clinical Development and Medical Affairs, Pfizer Oncology Business Unit. “If approved in the United States, sunitinib would be a major advancement in the treatment of patients with pancreatic NET, a disease for which there remains a significant unmet medical need.”
In February 2009, the independent Data Monitoring Committee for the SUN 1111 trial recommended that randomization to the study be halted 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. In the final analysis, it was demonstrated that sunitnib more than doubled median Progression-Free Survival (PFS), the primary endpoint, compared with placebo in 171 patients with progressive, well-differentiated pancreatic NET. An advantage for sunitinib was also observed in the secondary endpoints of overall survival, objective response rate and patient reported outcomes.
Adverse events observed with sunitinib were consistent with the known safety profile for the therapy.
In Europe, as of November 2010, Sutent is indicated for the treatment of unresectable or metastatic, well-differentiated pancreatic Neuroendocrine Tumours with disease progression in adults. Experience with Sutent as initial treatment in this disease is limited.
Sutent is currently approved for both Gastrointestinal Stromal Tumours (GIST) after disease progression on or intolerance to imatinib mesylate, and advanced Renal Cell Carcinoma (RCC), based on efficacy and safety data from large, randomized phase III clinical trials. It has changed the treatment landscape for patients with advanced RCC and imatinib-resistant or intolerant GIST, and is a standard of care in these indications. It is approved for these indications in over 100 countries and has been studied in over 10,000 patients in clinical trials. To date, more than 100,000 patients have been treated with Sutent worldwide.
Pancreatic Neuroendocrine Tumours are different from pancreatic adenocarcinoma, which account for about 95 percent of all pancreatic cancers. Advanced pancreatic NET is a rare, life-threatening and difficult-to-treat form of cancer reported in two to four people per million annually worldwide, and accounts for approximately 22-28 percent of all Neuroendocrine Tumours.
While pancreatic NET is typically considered an indolent disease, nearly 90 percent of patients are initially diagnosed with locally advanced or metastatic disease, or cancer that has spread to other organs. For patients with pancreatic NET that has metastasized, prognosis is poor, with a survival of only 1-3 years, similar to that seen with metastatic breast cancer or metastatic colon cancer.
Sutent is an oral multi-kinase inhibitor that works by blocking multiple molecular targets implicated in the growth, proliferation and spread of cancer. Its two important 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. 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. It 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) 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.
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