FDA Approves Sutent (sunitinib malate) for Adjuvant Treatment of Adult Patients at High Risk of Recurrent Renal Cell Carcinoma

In continuation of my update on Sunitib

The U.S. Food and Drug Administration today approved Sutent (sunitinib malate) for the adjuvant treatment of adult patients who are at a high risk of kidney cancer (renal cell carcinoma) returning after a kidney has been removed (nephrectomy). Adjuvant treatment is a form of therapy that is taken after an initial surgical removal to lower the risk of the cancer coming back.

“This is the first adjuvant treatment approved for patients with renal cell carcinoma, which is significant because patients with this disease who have a nephrectomy are often at high risk of the cancer returning,” said Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “There is now an approved therapy for patients who previously did not have options to potentially reduce cancer recurrence.”

The National Cancer Institute (NCI) at the National Institutes of Health estimates approximately 63,990 patients will be diagnosed with kidney and renal cell pelvis cancer this year, and 14,440 will die of the disease.

Sutent is a kinase inhibitor that works by blocking several enzymes that promote cell growth. Sutent was first approved in 2006 for the treatment of certain patients with gastrointestinal stromal tumors and advanced renal cell carcinoma. It is also approved for patients with a certain type of pancreatic cancer.

The approval of Sutent for the adjuvant treatment of renal cell carcinoma was based on a randomized trial of 615 patients with high risk of recurrent renal cell carcinoma following nephrectomy. The study measured the amount of time after the start of the trial that it took for the cancer to come back, for the patient to develop another unrelated cancer, or for death to occur from any cause (disease-free survival). After five years, 59.3 percent of patients treated with Sutent had not experienced cancer recurrence or death compared with 51.3 percent of patients receiving placebo.

Common side effects of Sutent include fatigue, diarrhea, inflammation of the mucous membranes and inside the mouth (mucositis/stomatitis), nausea, decreased appetite/anorexia, vomiting, abdominal pain, skin reactions on the hands and feet (hand-foot syndrome), high blood pressure (hypertension), bleeding events, altered taste (dysgeusia), indigestion (dyspepsia) and low levels of blood platelets (thrombocytopenia).

Severe side effects of Sutent include severe liver damage (hepatotoxicity), heart failure (low left ventricular ejection fraction), heart attack (myocardial ischemia/infarction), abnormal health rhythm (prolonged QT intervals/Torsade de Pointes), hypertension, bleeding (hemorrhagic events), metabolic abnormalities due to breakdown of the tumor (tumor lysis syndrome), blood vessel abnormalities leading to blood clots in the small blood vessels resulting in low platelet counts and organ dysfunction (thrombotic microangiopathy, including thrombotic thrombocytopenic purpura and hemolytic uremic syndrome), high levels of protein in the urine (proteinuria), thyroid dysfunction, low blood sugar (hypoglycemia), breakdown of the bone of the jaw due to loss of blood supply (osteonecrosis), and wound healing complications. Patients should stop taking Sutent if serious skin reactions occur (necrotizing fasciitis, erythema multiforme, Stevens-Johnson syndrome or toxic epidermal necrolysis). Women who are pregnant should not take Sutent because it may cause harm to a developing fetus.

The labeling for Sutent contains a boxed warning to alert healthcare professionals and patients about the risk of severe liver damage (hepatoxicity), which may result in liver failure or death.

FDA Approves Sutent (sunitinib malate) for Adjuvant Treatment of Adult Patients at High Risk of Recurrent Renal Cell Carcinoma

FDA panel votes in favour of Sunitib (Sutent) for pancreatic tumors....

In continuation of my update on sutent/sunitib....

 Pfizer Inc. announced this Tuesday that its oral multi-kinase inhibitor "Sutent" (see structure)  was determined as having a favourable benefit-risk profile by an oncology advisory committee of the FDA for the treatment of unresectable pancreatic neuroendocrine tumors. The panel voted 8-2 in favour of Sutent – generically called Sunitib malate.

Advanced pancreatic neuroendocrine tumour or NET, is a rare, life-threatening and difficult-to-treat form of cancer that accounts for approximately 22-28 percent of all neuroendocrine tumours. Nearly 90 percent of patients are initially diagnosed with locally advanced or metastatic disease, or cancer that has spread to other organs. An unresectable tumour is one that cannot be removed or resected by surgery.

 More...

Sutent or sunitinib malate targets vascular endothelial growth factor receptor or VEGFR and platelet-derived growth factor receptor or PDGFR, both of which are expressed by many types of solid tumours. The two targets are involved in tumours acquiring blood vessels, oxygen and nutrients needed for growth. 

Sunitinib was approved in 2006 in the United States for treating locally advanced or metastatic renal cell carcinoma and for imatinib-refractory or -intolerant gastrointestinal stromal tumour (GIST). It was approved for treating PNET in 2010 in Europe. A decision on approval is expected by the end of 2011, according to a company spokesperson....

Sunitinib (Sutent) May Spare Some Kidney Cancer Patients From Organ Removal

In continuation of my update on Sunitinib (Sutent)

Many people with advanced kidney cancer might not need to have their kidneys removed during treatment, something that until now has been standard practice.

Patients who only received a targeted drug for their kidney cancer survived just as well as those who had their cancerous organ removed before drug therapy, according to a new clinical trial.

"We believe this one study will change it so that patients won't get nephrectomies [kidney removal surgery]," said Dr. Bruce Johnson, chief clinical research officer at the Dana-Farber Cancer Institute, in Boston. "If anything, it looks like it's a little bit better if you don't take it out. We think this single study will change what people do."

For about two decades, kidney removal followed by drug therapy has been the standard of care for people with advanced kidney cancer, said Johnson, who is also president of the American Society of Clinical Oncology.

"One of the things that's been odd about kidney cancer is even if you have metastatic disease, where it started in your kidney and spread through your body, there was evidence patients lived longer if you took out their kidney," Johnson said.

Cases where the cancer has spread account for about 20 percent of all kidney cancers worldwide, said study lead researcher Dr. Arnaud Mejean, a urologist with the Georges-Pompidou European Hospital at Paris Descartes University, in France.

But in the intervening years, a number of targeted therapies have been developed that attack the ability of kidney cancer to grow and spread, the researchers added.

Mejean and his colleagues set out to test whether these new targeted drugs are so powerful that they've removed the need for painful, body-wracking kidney removal surgery.

The clinical trial enrolled 450 patients with metastatic kidney cancer, and assigned them to either take the targeted drug sunitinib (Sutent) or have their kidney removed and then take sunitinib.

Sunitinib attacks blood vessel growth that allows cancer to spread throughout the body, and it also blocks other means by which kidney cancer can grow, according to the American Cancer Society.

The patients were followed for about 51 months, and during that time the researchers found that survival was not worse for patients who just took sunitinib.

Overall, survival was 18.4 months without surgery versus 13.9 months with surgery. Similar survival rates also were found in people with an intermediate or poor prognosis.

The two patient groups had a similar rate of tumor shrinkage (just over 27 percent for surgery and 29 percent for sunitinib alone), the findings showed. In addition, average time until cancer progressed was slightly longer for patients who received sunitinib alone compared with those who also had surgery (8.3 months versus 7.2 months).

People who undergo kidney removal must heal before they can start targeted cancer drugs, often losing weeks they don't have to spare, the researchers noted. In some cases, the cancer spreads so quickly during this delay that there's no time to start the drug therapy.

However, the study authors said kidney removal is still the gold standard for people who do not need targeted drug therapy, such as those whose cancer has only spread to one other organ.

Despite these findings, it's not clear that all kidney removal surgeries will end for people with advanced kidney cancer, said Dr. Daniel Cho. He's a medical oncologist at NYU Langone Health's Perlmutter Cancer Center in New York City, and was not involved with the study.

"I don't think it should be across the board a standard of care yet," Cho said.

This approach may work for patients receiving targeted drug therapies, but may not be as effective in patients who are undergoing immunotherapy -- taking drugs to boost their immune system's ability to detect and kill cancer cells, he said.

Some people believe that large kidney tumors actually suppress the immune system and are not very responsive to immunotherapy drugs, Cho said. For the best results in these patients, kidney removal may be necessary.

"There's a certain rationale to remove the primary tumor if you're planning to give immunotherapy," Cho said. "The primary tumor may be creating a more immunosuppressive environment that makes the immune therapy less effective."

On the other hand, "there are those patients who are more likely to have rapidly growing disease, and therefore would more likely benefit from immediate systemic therapy," Cho added. "I really believe we have to be thoughtful about it."

FDA approves Sutent for patients with progressive neuroendocrine cancerous tumors in pancreas

In continuation of my update on Sutent

FDA approves Sutent for patients with progressive neuroendocrine cancerous tumors in pancreas

New drug, regorafenib overcomes resistance in patients with rare sarcoma, study suggests

In continuation of my update on regorafenib

A new targeted drug demonstrated its ability to control metastatic gastrointestinal stromal tumor, an uncommon and life-threatening form of sarcoma, after the disease had become resistant to all existing therapies, report investigators at Dana-Farber Cancer Institute who led the worldwide clinical trial.

The oral drug regorafenib (see structure), which inhibits several cancer-promoting kinase enzymes, was able to control GIST for nearly four months longer than placebo in patients for whom Gleevec and Sutent were no longer effective, a result that was highly significant statistically.

"When added to best supportive care, regorafenib significantly improves disease control, as measured by progression-free survival time in patients with GIST after progression which represents failure of all other therapies," said George Demetri, MD, of Dana-Farber, principal investigator of this clinical trial.

Demonstrating the aggressive nature of this resistant disease, the study found that tumors objectively grew in less than a month, on average, in GIST patients who were initially randomized to receive a placebo. The study's "cross-over" design made it possible to treat those patients whose tumors grew, and 85 percent of the patients initially on placebo were able to receive regorafenib, which then controlled the disease in these patients as well.

Because of the study's cross-over design, Demetri said, it was not expected to prove that the patients initially randomized to receive regorafenib survived longer -- the researchers would have had to withhold the drug from the placebo patients to demonstrate that difference. "But there is no question that people are living longer" with regorafenib treatment, he said, based on the results of this trial.

An application to have regorafenib approved for use in resistant GIST is under an accelerated review by the Food and Drug Administration, Demetri said.

New drug overcomes resistance in patients with rare sarcoma, study suggests