Elizabeth Mechcatie

The Food and Drug Administration has approved a portable, battery-powered device that delivers electrical fields to the brain as a treatment for adults with glioblastoma multiforme that has recurred after chemotherapy, the manufacturer and agency announced on April 15.

The approval of the NovoTTF-100A System (NovoTTF), manufactured by Israel-based Novocure, was based on the results of a randomized company-sponsored study of 237 patients with glioblastoma multiforme (GBM) that had recurred or progressed after surgical, radiation, and chemotherapy treatments.

Photo credit: Novocure

In the study, overall survival rates were "comparable," between patients treated with the device and those given best available chemotherapy, according to the FDA. Median overall survival had been reported as 6.3 months and 6.4 months, respectively.

The agency cited evidence suggesting that quality of life improved among those treated with the device, compared with those on chemotherapy. While the incidence of convulsions, headaches, and other neurologic side effects were slightly increased among those treated with the device, they did not experience chemotherapy-related side effects, the agency noted.

The device, which weighs about 6 pounds, is intended to be worn about 20 hours per day. It can run on batteries or be plugged into an electric outlet.

When using the device, the device’s electrodes are placed on the patient’s scalp, "to deliver low-intensity, changing electrical fields called "tumor treatment fields" (TTFs) to the tumor site," the FDA statement said: "The unique shape and electrical characteristics of dividing tumor cells make them susceptible to damage when exposed to TTF, which could stop tumor growth."

The most common treatment-associated adverse event reported was mild to moderate rash under the electrodes. The FDA said it should not be used in patients who "have an implanted medical device or a skull defect, or have a known sensitivity to conductive hydrogels, such as those used with electrocardiograms."

The company press release characterized the device as an alternative to chemotherapy, but the agency announcement stressed that it should not be used with other treatments. Rather the agency said "the device should only be used after other treatments have failed."

At a meeting in March, the majority of the FDA’s Neurological Devices Advisory Panel voted that the benefits of treatment with the device exceeded its risks when used as monotherapy in adults who have exhausted surgical and radiation treatment options for histologically or radiologically confirmed recurrent GBM.

Although the study was designed as a superiority study and failed to show treatment with the device was superior to chemotherapy, panelists said that because of its safety profile and evidence of benefit in some patients, they supported approval.

Novocure is conducting a study of the device in patients with newly diagnosed GBM tumors.

The device has been approved in the European Union as a treatment for newly diagnosed and recurrent GBM and for the treatment of non–small cell lung cancer.

The Food and Drug Administration has approved a portable, battery-powered device that delivers electrical fields to the brain as a treatment for adults with glioblastoma multiforme that has recurred after chemotherapy, the manufacturer and agency announced on April 15.

The approval of the NovoTTF-100A System (NovoTTF), manufactured by Israel-based Novocure, was based on the results of a randomized company-sponsored study of 237 patients with glioblastoma multiforme (GBM) that had recurred or progressed after surgical, radiation, and chemotherapy treatments.

Photo credit: Novocure

In the study, overall survival rates were "comparable," between patients treated with the device and those given best available chemotherapy, according to the FDA. Median overall survival had been reported as 6.3 months and 6.4 months, respectively.

The agency cited evidence suggesting that quality of life improved among those treated with the device, compared with those on chemotherapy. While the incidence of convulsions, headaches, and other neurologic side effects were slightly increased among those treated with the device, they did not experience chemotherapy-related side effects, the agency noted.

The device, which weighs about 6 pounds, is intended to be worn about 20 hours per day. It can run on batteries or be plugged into an electric outlet.

When using the device, the device’s electrodes are placed on the patient’s scalp, "to deliver low-intensity, changing electrical fields called "tumor treatment fields" (TTFs) to the tumor site," the FDA statement said: "The unique shape and electrical characteristics of dividing tumor cells make them susceptible to damage when exposed to TTF, which could stop tumor growth."

The most common treatment-associated adverse event reported was mild to moderate rash under the electrodes. The FDA said it should not be used in patients who "have an implanted medical device or a skull defect, or have a known sensitivity to conductive hydrogels, such as those used with electrocardiograms."

The company press release characterized the device as an alternative to chemotherapy, but the agency announcement stressed that it should not be used with other treatments. Rather the agency said "the device should only be used after other treatments have failed."

At a meeting in March, the majority of the FDA’s Neurological Devices Advisory Panel voted that the benefits of treatment with the device exceeded its risks when used as monotherapy in adults who have exhausted surgical and radiation treatment options for histologically or radiologically confirmed recurrent GBM.

Although the study was designed as a superiority study and failed to show treatment with the device was superior to chemotherapy, panelists said that because of its safety profile and evidence of benefit in some patients, they supported approval.

Novocure is conducting a study of the device in patients with newly diagnosed GBM tumors.

The device has been approved in the European Union as a treatment for newly diagnosed and recurrent GBM and for the treatment of non–small cell lung cancer.

The Food and Drug Administration has approved a portable, battery-powered device that delivers electrical fields to the brain as a treatment for adults with glioblastoma multiforme that has recurred after chemotherapy, the manufacturer and agency announced on April 15.

The approval of the NovoTTF-100A System (NovoTTF), manufactured by Israel-based Novocure, was based on the results of a randomized company-sponsored study of 237 patients with glioblastoma multiforme (GBM) that had recurred or progressed after surgical, radiation, and chemotherapy treatments.

Photo credit: Novocure

In the study, overall survival rates were "comparable," between patients treated with the device and those given best available chemotherapy, according to the FDA. Median overall survival had been reported as 6.3 months and 6.4 months, respectively.

The agency cited evidence suggesting that quality of life improved among those treated with the device, compared with those on chemotherapy. While the incidence of convulsions, headaches, and other neurologic side effects were slightly increased among those treated with the device, they did not experience chemotherapy-related side effects, the agency noted.

The device, which weighs about 6 pounds, is intended to be worn about 20 hours per day. It can run on batteries or be plugged into an electric outlet.

When using the device, the device’s electrodes are placed on the patient’s scalp, "to deliver low-intensity, changing electrical fields called "tumor treatment fields" (TTFs) to the tumor site," the FDA statement said: "The unique shape and electrical characteristics of dividing tumor cells make them susceptible to damage when exposed to TTF, which could stop tumor growth."

The most common treatment-associated adverse event reported was mild to moderate rash under the electrodes. The FDA said it should not be used in patients who "have an implanted medical device or a skull defect, or have a known sensitivity to conductive hydrogels, such as those used with electrocardiograms."

The company press release characterized the device as an alternative to chemotherapy, but the agency announcement stressed that it should not be used with other treatments. Rather the agency said "the device should only be used after other treatments have failed."

At a meeting in March, the majority of the FDA’s Neurological Devices Advisory Panel voted that the benefits of treatment with the device exceeded its risks when used as monotherapy in adults who have exhausted surgical and radiation treatment options for histologically or radiologically confirmed recurrent GBM.

Although the study was designed as a superiority study and failed to show treatment with the device was superior to chemotherapy, panelists said that because of its safety profile and evidence of benefit in some patients, they supported approval.

Novocure is conducting a study of the device in patients with newly diagnosed GBM tumors.

The device has been approved in the European Union as a treatment for newly diagnosed and recurrent GBM and for the treatment of non–small cell lung cancer.

The Food and Drug Administration has approved a portable, battery-powered device that delivers electrical fields to the brain as a treatment for adults with glioblastoma multiforme that has recurred after chemotherapy, the manufacturer and agency announced on April 15.

The approval of the NovoTTF-100A System (NovoTTF), manufactured by Israel-based Novocure, was based on the results of a randomized company-sponsored study of 237 patients with glioblastoma multiforme (GBM) that had recurred or progressed after surgical, radiation, and chemotherapy treatments.

Photo credit: Novocure

In the study, overall survival rates were "comparable," between patients treated with the device and those given best available chemotherapy, according to the FDA. Median overall survival had been reported as 6.3 months and 6.4 months, respectively.

The agency cited evidence suggesting that quality of life improved among those treated with the device, compared with those on chemotherapy. While the incidence of convulsions, headaches, and other neurologic side effects were slightly increased among those treated with the device, they did not experience chemotherapy-related side effects, the agency noted.

The device, which weighs about 6 pounds, is intended to be worn about 20 hours per day. It can run on batteries or be plugged into an electric outlet.

When using the device, the device’s electrodes are placed on the patient’s scalp, "to deliver low-intensity, changing electrical fields called "tumor treatment fields" (TTFs) to the tumor site," the FDA statement said: "The unique shape and electrical characteristics of dividing tumor cells make them susceptible to damage when exposed to TTF, which could stop tumor growth."

The most common treatment-associated adverse event reported was mild to moderate rash under the electrodes. The FDA said it should not be used in patients who "have an implanted medical device or a skull defect, or have a known sensitivity to conductive hydrogels, such as those used with electrocardiograms."

The company press release characterized the device as an alternative to chemotherapy, but the agency announcement stressed that it should not be used with other treatments. Rather the agency said "the device should only be used after other treatments have failed."

At a meeting in March, the majority of the FDA’s Neurological Devices Advisory Panel voted that the benefits of treatment with the device exceeded its risks when used as monotherapy in adults who have exhausted surgical and radiation treatment options for histologically or radiologically confirmed recurrent GBM.

Although the study was designed as a superiority study and failed to show treatment with the device was superior to chemotherapy, panelists said that because of its safety profile and evidence of benefit in some patients, they supported approval.

Novocure is conducting a study of the device in patients with newly diagnosed GBM tumors.

The device has been approved in the European Union as a treatment for newly diagnosed and recurrent GBM and for the treatment of non–small cell lung cancer.

The Food and Drug Administration has approved a portable, battery-powered device that delivers electrical fields to the brain as a treatment for adults with glioblastoma multiforme that has recurred after chemotherapy, the manufacturer and agency announced on April 15.

The approval of the NovoTTF-100A System (NovoTTF), manufactured by Israel-based Novocure, was based on the results of a randomized company-sponsored study of 237 patients with glioblastoma multiforme (GBM) that had recurred or progressed after surgical, radiation, and chemotherapy treatments.

Photo credit: Novocure

In the study, overall survival rates were "comparable," between patients treated with the device and those given best available chemotherapy, according to the FDA. Median overall survival had been reported as 6.3 months and 6.4 months, respectively.

The agency cited evidence suggesting that quality of life improved among those treated with the device, compared with those on chemotherapy. While the incidence of convulsions, headaches, and other neurologic side effects were slightly increased among those treated with the device, they did not experience chemotherapy-related side effects, the agency noted.

The device, which weighs about 6 pounds, is intended to be worn about 20 hours per day. It can run on batteries or be plugged into an electric outlet.

When using the device, the device’s electrodes are placed on the patient’s scalp, "to deliver low-intensity, changing electrical fields called "tumor treatment fields" (TTFs) to the tumor site," the FDA statement said: "The unique shape and electrical characteristics of dividing tumor cells make them susceptible to damage when exposed to TTF, which could stop tumor growth."

The most common treatment-associated adverse event reported was mild to moderate rash under the electrodes. The FDA said it should not be used in patients who "have an implanted medical device or a skull defect, or have a known sensitivity to conductive hydrogels, such as those used with electrocardiograms."

The company press release characterized the device as an alternative to chemotherapy, but the agency announcement stressed that it should not be used with other treatments. Rather the agency said "the device should only be used after other treatments have failed."

At a meeting in March, the majority of the FDA’s Neurological Devices Advisory Panel voted that the benefits of treatment with the device exceeded its risks when used as monotherapy in adults who have exhausted surgical and radiation treatment options for histologically or radiologically confirmed recurrent GBM.

Although the study was designed as a superiority study and failed to show treatment with the device was superior to chemotherapy, panelists said that because of its safety profile and evidence of benefit in some patients, they supported approval.

Novocure is conducting a study of the device in patients with newly diagnosed GBM tumors.

The device has been approved in the European Union as a treatment for newly diagnosed and recurrent GBM and for the treatment of non–small cell lung cancer.

The Food and Drug Administration has approved a portable, battery-powered device that delivers electrical fields to the brain as a treatment for adults with glioblastoma multiforme that has recurred after chemotherapy, the manufacturer and agency announced on April 15.

The approval of the NovoTTF-100A System (NovoTTF), manufactured by Israel-based Novocure, was based on the results of a randomized company-sponsored study of 237 patients with glioblastoma multiforme (GBM) that had recurred or progressed after surgical, radiation, and chemotherapy treatments.

Photo credit: Novocure

In the study, overall survival rates were "comparable," between patients treated with the device and those given best available chemotherapy, according to the FDA. Median overall survival had been reported as 6.3 months and 6.4 months, respectively.

The agency cited evidence suggesting that quality of life improved among those treated with the device, compared with those on chemotherapy. While the incidence of convulsions, headaches, and other neurologic side effects were slightly increased among those treated with the device, they did not experience chemotherapy-related side effects, the agency noted.

The device, which weighs about 6 pounds, is intended to be worn about 20 hours per day. It can run on batteries or be plugged into an electric outlet.

When using the device, the device’s electrodes are placed on the patient’s scalp, "to deliver low-intensity, changing electrical fields called "tumor treatment fields" (TTFs) to the tumor site," the FDA statement said: "The unique shape and electrical characteristics of dividing tumor cells make them susceptible to damage when exposed to TTF, which could stop tumor growth."

The most common treatment-associated adverse event reported was mild to moderate rash under the electrodes. The FDA said it should not be used in patients who "have an implanted medical device or a skull defect, or have a known sensitivity to conductive hydrogels, such as those used with electrocardiograms."

The company press release characterized the device as an alternative to chemotherapy, but the agency announcement stressed that it should not be used with other treatments. Rather the agency said "the device should only be used after other treatments have failed."

At a meeting in March, the majority of the FDA’s Neurological Devices Advisory Panel voted that the benefits of treatment with the device exceeded its risks when used as monotherapy in adults who have exhausted surgical and radiation treatment options for histologically or radiologically confirmed recurrent GBM.

Although the study was designed as a superiority study and failed to show treatment with the device was superior to chemotherapy, panelists said that because of its safety profile and evidence of benefit in some patients, they supported approval.

Novocure is conducting a study of the device in patients with newly diagnosed GBM tumors.

The device has been approved in the European Union as a treatment for newly diagnosed and recurrent GBM and for the treatment of non–small cell lung cancer.

The Food and Drug Administration has approved a portable, battery-powered device that delivers electrical fields to the brain as a treatment for adults with glioblastoma multiforme that has recurred after chemotherapy, the manufacturer and agency announced on April 15.

The approval of the NovoTTF-100A System (NovoTTF), manufactured by Israel-based Novocure, was based on the results of a randomized company-sponsored study of 237 patients with glioblastoma multiforme (GBM) that had recurred or progressed after surgical, radiation, and chemotherapy treatments.

Photo credit: Novocure

In the study, overall survival rates were "comparable," between patients treated with the device and those given best available chemotherapy, according to the FDA. Median overall survival had been reported as 6.3 months and 6.4 months, respectively.

The agency cited evidence suggesting that quality of life improved among those treated with the device, compared with those on chemotherapy. While the incidence of convulsions, headaches, and other neurologic side effects were slightly increased among those treated with the device, they did not experience chemotherapy-related side effects, the agency noted.

The device, which weighs about 6 pounds, is intended to be worn about 20 hours per day. It can run on batteries or be plugged into an electric outlet.

When using the device, the device’s electrodes are placed on the patient’s scalp, "to deliver low-intensity, changing electrical fields called "tumor treatment fields" (TTFs) to the tumor site," the FDA statement said: "The unique shape and electrical characteristics of dividing tumor cells make them susceptible to damage when exposed to TTF, which could stop tumor growth."

The most common treatment-associated adverse event reported was mild to moderate rash under the electrodes. The FDA said it should not be used in patients who "have an implanted medical device or a skull defect, or have a known sensitivity to conductive hydrogels, such as those used with electrocardiograms."

The company press release characterized the device as an alternative to chemotherapy, but the agency announcement stressed that it should not be used with other treatments. Rather the agency said "the device should only be used after other treatments have failed."

At a meeting in March, the majority of the FDA’s Neurological Devices Advisory Panel voted that the benefits of treatment with the device exceeded its risks when used as monotherapy in adults who have exhausted surgical and radiation treatment options for histologically or radiologically confirmed recurrent GBM.

Although the study was designed as a superiority study and failed to show treatment with the device was superior to chemotherapy, panelists said that because of its safety profile and evidence of benefit in some patients, they supported approval.

Novocure is conducting a study of the device in patients with newly diagnosed GBM tumors.

The device has been approved in the European Union as a treatment for newly diagnosed and recurrent GBM and for the treatment of non–small cell lung cancer.

The Food and Drug Administration has approved a portable, battery-powered device that delivers electrical fields to the brain as a treatment for adults with glioblastoma multiforme that has recurred after chemotherapy, the manufacturer and agency announced on April 15.

The approval of the NovoTTF-100A System (NovoTTF), manufactured by Israel-based Novocure, was based on the results of a randomized company-sponsored study of 237 patients with glioblastoma multiforme (GBM) that had recurred or progressed after surgical, radiation, and chemotherapy treatments.

Photo credit: Novocure

In the study, overall survival rates were "comparable," between patients treated with the device and those given best available chemotherapy, according to the FDA. Median overall survival had been reported as 6.3 months and 6.4 months, respectively.

The agency cited evidence suggesting that quality of life improved among those treated with the device, compared with those on chemotherapy. While the incidence of convulsions, headaches, and other neurologic side effects were slightly increased among those treated with the device, they did not experience chemotherapy-related side effects, the agency noted.

The device, which weighs about 6 pounds, is intended to be worn about 20 hours per day. It can run on batteries or be plugged into an electric outlet.

When using the device, the device’s electrodes are placed on the patient’s scalp, "to deliver low-intensity, changing electrical fields called "tumor treatment fields" (TTFs) to the tumor site," the FDA statement said: "The unique shape and electrical characteristics of dividing tumor cells make them susceptible to damage when exposed to TTF, which could stop tumor growth."

The most common treatment-associated adverse event reported was mild to moderate rash under the electrodes. The FDA said it should not be used in patients who "have an implanted medical device or a skull defect, or have a known sensitivity to conductive hydrogels, such as those used with electrocardiograms."

The company press release characterized the device as an alternative to chemotherapy, but the agency announcement stressed that it should not be used with other treatments. Rather the agency said "the device should only be used after other treatments have failed."

At a meeting in March, the majority of the FDA’s Neurological Devices Advisory Panel voted that the benefits of treatment with the device exceeded its risks when used as monotherapy in adults who have exhausted surgical and radiation treatment options for histologically or radiologically confirmed recurrent GBM.

Although the study was designed as a superiority study and failed to show treatment with the device was superior to chemotherapy, panelists said that because of its safety profile and evidence of benefit in some patients, they supported approval.

Novocure is conducting a study of the device in patients with newly diagnosed GBM tumors.

The device has been approved in the European Union as a treatment for newly diagnosed and recurrent GBM and for the treatment of non–small cell lung cancer.

The Food and Drug Administration has approved a portable, battery-powered device that delivers electrical fields to the brain as a treatment for adults with glioblastoma multiforme that has recurred after chemotherapy, the manufacturer and agency announced on April 15.

The approval of the NovoTTF-100A System (NovoTTF), manufactured by Israel-based Novocure, was based on the results of a randomized company-sponsored study of 237 patients with glioblastoma multiforme (GBM) that had recurred or progressed after surgical, radiation, and chemotherapy treatments.

Photo credit: Novocure

In the study, overall survival rates were "comparable," between patients treated with the device and those given best available chemotherapy, according to the FDA. Median overall survival had been reported as 6.3 months and 6.4 months, respectively.

The agency cited evidence suggesting that quality of life improved among those treated with the device, compared with those on chemotherapy. While the incidence of convulsions, headaches, and other neurologic side effects were slightly increased among those treated with the device, they did not experience chemotherapy-related side effects, the agency noted.

The device, which weighs about 6 pounds, is intended to be worn about 20 hours per day. It can run on batteries or be plugged into an electric outlet.

When using the device, the device’s electrodes are placed on the patient’s scalp, "to deliver low-intensity, changing electrical fields called "tumor treatment fields" (TTFs) to the tumor site," the FDA statement said: "The unique shape and electrical characteristics of dividing tumor cells make them susceptible to damage when exposed to TTF, which could stop tumor growth."

The most common treatment-associated adverse event reported was mild to moderate rash under the electrodes. The FDA said it should not be used in patients who "have an implanted medical device or a skull defect, or have a known sensitivity to conductive hydrogels, such as those used with electrocardiograms."

The company press release characterized the device as an alternative to chemotherapy, but the agency announcement stressed that it should not be used with other treatments. Rather the agency said "the device should only be used after other treatments have failed."

At a meeting in March, the majority of the FDA’s Neurological Devices Advisory Panel voted that the benefits of treatment with the device exceeded its risks when used as monotherapy in adults who have exhausted surgical and radiation treatment options for histologically or radiologically confirmed recurrent GBM.

Although the study was designed as a superiority study and failed to show treatment with the device was superior to chemotherapy, panelists said that because of its safety profile and evidence of benefit in some patients, they supported approval.

Novocure is conducting a study of the device in patients with newly diagnosed GBM tumors.

The device has been approved in the European Union as a treatment for newly diagnosed and recurrent GBM and for the treatment of non–small cell lung cancer.

Cases of a rare, aggressive, and usually fatal lymphoma continue to be reported in people being treated with tumor necrosis factor blockers, azathioprine, and/or mercaptopurine, the Food and Drug Administration announced in an April 14 statement.

The reports of the lymphoma, hepatosplenic T-cell lymphoma (HSTCL), have primarily involved adolescents and young adults being treated with these agents for Crohn’s disease or ulcerative colitis. One patient, however, was being treated for psoriasis, and two others for rheumatoid arthritis.

Most patients were on a combination of treatments that are known to suppress the immune system, but there have been cases in patients taking azathioprine or mercaptopurine alone, the statement said.

"The risks and benefits of using TNF blockers, azathioprine, and/or mercaptopurine should be carefully weighed when prescribing these drugs to children and young adults, especially for the treatment of Crohn’s disease and ulcerative colitis," according to the FDA.

The statement recommends that health care professionals monitor patients on these treatments for malignancies and educate patients and their caregivers about the signs and symptoms of HSTCL, which can include splenomegaly, hepatomegaly, abdominal pain, persistent fever, night sweats, and weight loss.

The statement also notes that people with rheumatoid arthritis, Crohn’s, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis "may be more likely to develop lymphoma," compared with the general U.S. population, making it difficult to estimate the increased risk of malignancies associated with TNF blockers, azathioprine and/or mercaptopurine.

As of Dec. 31, 2010, the FDA’s Adverse Event Reporting System (AERS), the medical literature, and the Cancer Survivors Network had received the following unduplicated reports of HSTCL:

20 cases in patients taking infliximab (Remicade), including 18 patients also taking mercaptopurine or azathioprine.

• 1 case in a patient taking etanercept (Enbrel).

• 2 cases in patients taking adalimumab (Humira).

• 5 cases in patients taking a combination of infliximab and adalimumab (including 4 patients also taking mercaptopurine or azathioprine).

• 12 cases in patients taking azathioprine.

• 3 cases in patients taking mercaptopurine.

No cases have been reported in the TNF blockers certolizumab pegol (Cimzia) and golimumab (Simponi).

Reports of serious adverse events associated with these and other drugs should be reported online to the FDA’s MedWatch program or by phone to 800-332-1088.

Cases of a rare, aggressive, and usually fatal lymphoma continue to be reported in people being treated with tumor necrosis factor blockers, azathioprine, and/or mercaptopurine, the Food and Drug Administration announced in an April 14 statement.

The reports of the lymphoma, hepatosplenic T-cell lymphoma (HSTCL), have primarily involved adolescents and young adults being treated with these agents for Crohn’s disease or ulcerative colitis. One patient, however, was being treated for psoriasis, and two others for rheumatoid arthritis.

Most patients were on a combination of treatments that are known to suppress the immune system, but there have been cases in patients taking azathioprine or mercaptopurine alone, the statement said.

"The risks and benefits of using TNF blockers, azathioprine, and/or mercaptopurine should be carefully weighed when prescribing these drugs to children and young adults, especially for the treatment of Crohn’s disease and ulcerative colitis," according to the FDA.

The statement recommends that health care professionals monitor patients on these treatments for malignancies and educate patients and their caregivers about the signs and symptoms of HSTCL, which can include splenomegaly, hepatomegaly, abdominal pain, persistent fever, night sweats, and weight loss.

The statement also notes that people with rheumatoid arthritis, Crohn’s, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis "may be more likely to develop lymphoma," compared with the general U.S. population, making it difficult to estimate the increased risk of malignancies associated with TNF blockers, azathioprine and/or mercaptopurine.

As of Dec. 31, 2010, the FDA’s Adverse Event Reporting System (AERS), the medical literature, and the Cancer Survivors Network had received the following unduplicated reports of HSTCL:

20 cases in patients taking infliximab (Remicade), including 18 patients also taking mercaptopurine or azathioprine.

• 1 case in a patient taking etanercept (Enbrel).

• 2 cases in patients taking adalimumab (Humira).

• 5 cases in patients taking a combination of infliximab and adalimumab (including 4 patients also taking mercaptopurine or azathioprine).

• 12 cases in patients taking azathioprine.

• 3 cases in patients taking mercaptopurine.

No cases have been reported in the TNF blockers certolizumab pegol (Cimzia) and golimumab (Simponi).

Reports of serious adverse events associated with these and other drugs should be reported online to the FDA’s MedWatch program or by phone to 800-332-1088.

Cases of a rare, aggressive, and usually fatal lymphoma continue to be reported in people being treated with tumor necrosis factor blockers, azathioprine, and/or mercaptopurine, the Food and Drug Administration announced in an April 14 statement.

The reports of the lymphoma, hepatosplenic T-cell lymphoma (HSTCL), have primarily involved adolescents and young adults being treated with these agents for Crohn’s disease or ulcerative colitis. One patient, however, was being treated for psoriasis, and two others for rheumatoid arthritis.

Most patients were on a combination of treatments that are known to suppress the immune system, but there have been cases in patients taking azathioprine or mercaptopurine alone, the statement said.

"The risks and benefits of using TNF blockers, azathioprine, and/or mercaptopurine should be carefully weighed when prescribing these drugs to children and young adults, especially for the treatment of Crohn’s disease and ulcerative colitis," according to the FDA.

The statement recommends that health care professionals monitor patients on these treatments for malignancies and educate patients and their caregivers about the signs and symptoms of HSTCL, which can include splenomegaly, hepatomegaly, abdominal pain, persistent fever, night sweats, and weight loss.

The statement also notes that people with rheumatoid arthritis, Crohn’s, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis "may be more likely to develop lymphoma," compared with the general U.S. population, making it difficult to estimate the increased risk of malignancies associated with TNF blockers, azathioprine and/or mercaptopurine.

As of Dec. 31, 2010, the FDA’s Adverse Event Reporting System (AERS), the medical literature, and the Cancer Survivors Network had received the following unduplicated reports of HSTCL:

20 cases in patients taking infliximab (Remicade), including 18 patients also taking mercaptopurine or azathioprine.

• 1 case in a patient taking etanercept (Enbrel).

• 2 cases in patients taking adalimumab (Humira).

• 5 cases in patients taking a combination of infliximab and adalimumab (including 4 patients also taking mercaptopurine or azathioprine).

• 12 cases in patients taking azathioprine.

• 3 cases in patients taking mercaptopurine.

No cases have been reported in the TNF blockers certolizumab pegol (Cimzia) and golimumab (Simponi).

Reports of serious adverse events associated with these and other drugs should be reported online to the FDA’s MedWatch program or by phone to 800-332-1088.

Cases of a rare, aggressive, and usually fatal lymphoma continue to be reported in people being treated with tumor necrosis factor blockers, azathioprine, and/or mercaptopurine, the Food and Drug Administration announced in an April 14 statement.

The reports of the lymphoma, hepatosplenic T-cell lymphoma (HSTCL), have primarily involved adolescents and young adults being treated with these agents for Crohn’s disease or ulcerative colitis. One patient, however, was being treated for psoriasis, and two others for rheumatoid arthritis.

Most patients were on a combination of treatments that are known to suppress the immune system, but there have been cases in patients taking azathioprine or mercaptopurine alone, the statement said.

"The risks and benefits of using TNF blockers, azathioprine, and/or mercaptopurine should be carefully weighed when prescribing these drugs to children and young adults, especially for the treatment of Crohn’s disease and ulcerative colitis," according to the FDA.

The statement recommends that health care professionals monitor patients on these treatments for malignancies and educate patients and their caregivers about the signs and symptoms of HSTCL, which can include splenomegaly, hepatomegaly, abdominal pain, persistent fever, night sweats, and weight loss.

The statement also notes that people with rheumatoid arthritis, Crohn’s, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis "may be more likely to develop lymphoma," compared with the general U.S. population, making it difficult to estimate the increased risk of malignancies associated with TNF blockers, azathioprine and/or mercaptopurine.

As of Dec. 31, 2010, the FDA’s Adverse Event Reporting System (AERS), the medical literature, and the Cancer Survivors Network had received the following unduplicated reports of HSTCL:

20 cases in patients taking infliximab (Remicade), including 18 patients also taking mercaptopurine or azathioprine.

• 1 case in a patient taking etanercept (Enbrel).

• 2 cases in patients taking adalimumab (Humira).

• 5 cases in patients taking a combination of infliximab and adalimumab (including 4 patients also taking mercaptopurine or azathioprine).

• 12 cases in patients taking azathioprine.

• 3 cases in patients taking mercaptopurine.

No cases have been reported in the TNF blockers certolizumab pegol (Cimzia) and golimumab (Simponi).

Reports of serious adverse events associated with these and other drugs should be reported online to the FDA’s MedWatch program or by phone to 800-332-1088.

Cases of a rare, aggressive, and usually fatal lymphoma continue to be reported in people being treated with tumor necrosis factor blockers, azathioprine, and/or mercaptopurine, the Food and Drug Administration announced in an April 14 statement.

The reports of the lymphoma, hepatosplenic T-cell lymphoma (HSTCL), have primarily involved adolescents and young adults being treated with these agents for Crohn’s disease or ulcerative colitis. One patient, however, was being treated for psoriasis, and two others for rheumatoid arthritis.

Most patients were on a combination of treatments that are known to suppress the immune system, but there have been cases in patients taking azathioprine or mercaptopurine alone, the statement said.

"The risks and benefits of using TNF blockers, azathioprine, and/or mercaptopurine should be carefully weighed when prescribing these drugs to children and young adults, especially for the treatment of Crohn’s disease and ulcerative colitis," according to the FDA.

The statement recommends that health care professionals monitor patients on these treatments for malignancies and educate patients and their caregivers about the signs and symptoms of HSTCL, which can include splenomegaly, hepatomegaly, abdominal pain, persistent fever, night sweats, and weight loss.

The statement also notes that people with rheumatoid arthritis, Crohn’s, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis "may be more likely to develop lymphoma," compared with the general U.S. population, making it difficult to estimate the increased risk of malignancies associated with TNF blockers, azathioprine and/or mercaptopurine.

As of Dec. 31, 2010, the FDA’s Adverse Event Reporting System (AERS), the medical literature, and the Cancer Survivors Network had received the following unduplicated reports of HSTCL:

20 cases in patients taking infliximab (Remicade), including 18 patients also taking mercaptopurine or azathioprine.

• 1 case in a patient taking etanercept (Enbrel).

• 2 cases in patients taking adalimumab (Humira).

• 5 cases in patients taking a combination of infliximab and adalimumab (including 4 patients also taking mercaptopurine or azathioprine).

• 12 cases in patients taking azathioprine.

• 3 cases in patients taking mercaptopurine.

No cases have been reported in the TNF blockers certolizumab pegol (Cimzia) and golimumab (Simponi).

Reports of serious adverse events associated with these and other drugs should be reported online to the FDA’s MedWatch program or by phone to 800-332-1088.

Cases of a rare, aggressive, and usually fatal lymphoma continue to be reported in people being treated with tumor necrosis factor blockers, azathioprine, and/or mercaptopurine, the Food and Drug Administration announced in an April 14 statement.

The reports of the lymphoma, hepatosplenic T-cell lymphoma (HSTCL), have primarily involved adolescents and young adults being treated with these agents for Crohn’s disease or ulcerative colitis. One patient, however, was being treated for psoriasis, and two others for rheumatoid arthritis.

Most patients were on a combination of treatments that are known to suppress the immune system, but there have been cases in patients taking azathioprine or mercaptopurine alone, the statement said.

"The risks and benefits of using TNF blockers, azathioprine, and/or mercaptopurine should be carefully weighed when prescribing these drugs to children and young adults, especially for the treatment of Crohn’s disease and ulcerative colitis," according to the FDA.

The statement recommends that health care professionals monitor patients on these treatments for malignancies and educate patients and their caregivers about the signs and symptoms of HSTCL, which can include splenomegaly, hepatomegaly, abdominal pain, persistent fever, night sweats, and weight loss.

The statement also notes that people with rheumatoid arthritis, Crohn’s, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis "may be more likely to develop lymphoma," compared with the general U.S. population, making it difficult to estimate the increased risk of malignancies associated with TNF blockers, azathioprine and/or mercaptopurine.

As of Dec. 31, 2010, the FDA’s Adverse Event Reporting System (AERS), the medical literature, and the Cancer Survivors Network had received the following unduplicated reports of HSTCL:

20 cases in patients taking infliximab (Remicade), including 18 patients also taking mercaptopurine or azathioprine.

• 1 case in a patient taking etanercept (Enbrel).

• 2 cases in patients taking adalimumab (Humira).

• 5 cases in patients taking a combination of infliximab and adalimumab (including 4 patients also taking mercaptopurine or azathioprine).

• 12 cases in patients taking azathioprine.

• 3 cases in patients taking mercaptopurine.

No cases have been reported in the TNF blockers certolizumab pegol (Cimzia) and golimumab (Simponi).

Reports of serious adverse events associated with these and other drugs should be reported online to the FDA’s MedWatch program or by phone to 800-332-1088.

SILVER SPRING, MD. – The benefits of treatment with the oral tyrosine kinase inhibitor sunitinib outweigh the risks as a treatment for patients with metastatic pancreatic neuroendocrine tumors, according to the majority of a Food and Drug Administration advisory panel.

The FDA’s Oncologic Drugs Advisory Committee voted 8 to 2 on April 12 that the drug’s risk-benefit profile was favorable for patients with this rare cancer, despite uncertainty over the magnitude of the drug’s effect on progression-free survival in a pivotal trial that was terminated early.

The panel did not vote specifically on whether to recommend approval.

Pfizer Inc. has proposed that sunitinib malate capsules, marketed as Sutent, be approved for the treatment of unresectable pancreatic neuroendocrine tumors (PNET). Panelists cited the rarity of the disease and the few treatment options available among the reasons for their positive votes on the risk-benefit question. Several noted that the drug’s labeling should indicate that most patients in the pivotal phase III study had metastatic disease, and that sunitinib should not be used to treat patients with indolent forms of the disease.

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 tumor (GIST). It was approved for treating PNET in 2010 in Europe.

The pivotal PNET trial compared 37.5 mg of sunitinib daily with placebo in patients with locally advanced or metastatic, well-differentiated, unresectable PNET with progressive disease within the past year. It was stopped early in February 2009, after benefits were identified favoring the treatment group. Based on a review of data on 154 patients, the data-safety monitoring board recommended that the study be terminated because of differences in progression-free survival events (49 on placebo vs. 24 on sunitinib), deaths (15 on placebo vs. 5 on sunitinib) and severe adverse events (28 on placebo vs. 20 on sunitinib).

In an intention-to-treat analysis of 86 patients on sunitinib and 85 patients on placebo, the median progression-free survival was 11.4 months among those on sunitinib, compared with 5.5 months among those on placebo, which represented a 68% reduction in risk, a highly statistically significant difference. Overall survival, a secondary end point, was higher among the treated patients, but the difference was not statistically significant.

There were no new or unexpected adverse events. Adverse events and toxicities associated with treatment were similar to the known safety profile of sunitinib, and included diarrhea and stomatitis. Two of the patients on sunitinib died of cardiac failure.

Panelists agreed there was evidence of benefit, but acknowledged FDA reviewers’s concerns that early termination of the study could have overestimated the magnitude of the treatment difference on progression-free survival, the primary end point of the study. FDA reviewers also raised concerns about possible unblinding because of well-known adverse effects of sunitinib, such as hypertension and changes in hair color.

A decision on approval is expected by the end of 2011, according to a company spokesperson.

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of potential conflicts of interest by the FDA prior to meetings; occasionally, the agency grants a waiver to a panelist with a conflict, but this did not occur at this meeting.

SILVER SPRING, MD. – The benefits of treatment with the oral tyrosine kinase inhibitor sunitinib outweigh the risks as a treatment for patients with metastatic pancreatic neuroendocrine tumors, according to the majority of a Food and Drug Administration advisory panel.

The FDA’s Oncologic Drugs Advisory Committee voted 8 to 2 on April 12 that the drug’s risk-benefit profile was favorable for patients with this rare cancer, despite uncertainty over the magnitude of the drug’s effect on progression-free survival in a pivotal trial that was terminated early.

The panel did not vote specifically on whether to recommend approval.

Pfizer Inc. has proposed that sunitinib malate capsules, marketed as Sutent, be approved for the treatment of unresectable pancreatic neuroendocrine tumors (PNET). Panelists cited the rarity of the disease and the few treatment options available among the reasons for their positive votes on the risk-benefit question. Several noted that the drug’s labeling should indicate that most patients in the pivotal phase III study had metastatic disease, and that sunitinib should not be used to treat patients with indolent forms of the disease.

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 tumor (GIST). It was approved for treating PNET in 2010 in Europe.

The pivotal PNET trial compared 37.5 mg of sunitinib daily with placebo in patients with locally advanced or metastatic, well-differentiated, unresectable PNET with progressive disease within the past year. It was stopped early in February 2009, after benefits were identified favoring the treatment group. Based on a review of data on 154 patients, the data-safety monitoring board recommended that the study be terminated because of differences in progression-free survival events (49 on placebo vs. 24 on sunitinib), deaths (15 on placebo vs. 5 on sunitinib) and severe adverse events (28 on placebo vs. 20 on sunitinib).

In an intention-to-treat analysis of 86 patients on sunitinib and 85 patients on placebo, the median progression-free survival was 11.4 months among those on sunitinib, compared with 5.5 months among those on placebo, which represented a 68% reduction in risk, a highly statistically significant difference. Overall survival, a secondary end point, was higher among the treated patients, but the difference was not statistically significant.

There were no new or unexpected adverse events. Adverse events and toxicities associated with treatment were similar to the known safety profile of sunitinib, and included diarrhea and stomatitis. Two of the patients on sunitinib died of cardiac failure.

Panelists agreed there was evidence of benefit, but acknowledged FDA reviewers’s concerns that early termination of the study could have overestimated the magnitude of the treatment difference on progression-free survival, the primary end point of the study. FDA reviewers also raised concerns about possible unblinding because of well-known adverse effects of sunitinib, such as hypertension and changes in hair color.

A decision on approval is expected by the end of 2011, according to a company spokesperson.

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of potential conflicts of interest by the FDA prior to meetings; occasionally, the agency grants a waiver to a panelist with a conflict, but this did not occur at this meeting.

SILVER SPRING, MD. – The benefits of treatment with the oral tyrosine kinase inhibitor sunitinib outweigh the risks as a treatment for patients with metastatic pancreatic neuroendocrine tumors, according to the majority of a Food and Drug Administration advisory panel.

The FDA’s Oncologic Drugs Advisory Committee voted 8 to 2 on April 12 that the drug’s risk-benefit profile was favorable for patients with this rare cancer, despite uncertainty over the magnitude of the drug’s effect on progression-free survival in a pivotal trial that was terminated early.

The panel did not vote specifically on whether to recommend approval.

Pfizer Inc. has proposed that sunitinib malate capsules, marketed as Sutent, be approved for the treatment of unresectable pancreatic neuroendocrine tumors (PNET). Panelists cited the rarity of the disease and the few treatment options available among the reasons for their positive votes on the risk-benefit question. Several noted that the drug’s labeling should indicate that most patients in the pivotal phase III study had metastatic disease, and that sunitinib should not be used to treat patients with indolent forms of the disease.

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 tumor (GIST). It was approved for treating PNET in 2010 in Europe.

The pivotal PNET trial compared 37.5 mg of sunitinib daily with placebo in patients with locally advanced or metastatic, well-differentiated, unresectable PNET with progressive disease within the past year. It was stopped early in February 2009, after benefits were identified favoring the treatment group. Based on a review of data on 154 patients, the data-safety monitoring board recommended that the study be terminated because of differences in progression-free survival events (49 on placebo vs. 24 on sunitinib), deaths (15 on placebo vs. 5 on sunitinib) and severe adverse events (28 on placebo vs. 20 on sunitinib).

In an intention-to-treat analysis of 86 patients on sunitinib and 85 patients on placebo, the median progression-free survival was 11.4 months among those on sunitinib, compared with 5.5 months among those on placebo, which represented a 68% reduction in risk, a highly statistically significant difference. Overall survival, a secondary end point, was higher among the treated patients, but the difference was not statistically significant.

There were no new or unexpected adverse events. Adverse events and toxicities associated with treatment were similar to the known safety profile of sunitinib, and included diarrhea and stomatitis. Two of the patients on sunitinib died of cardiac failure.

Panelists agreed there was evidence of benefit, but acknowledged FDA reviewers’s concerns that early termination of the study could have overestimated the magnitude of the treatment difference on progression-free survival, the primary end point of the study. FDA reviewers also raised concerns about possible unblinding because of well-known adverse effects of sunitinib, such as hypertension and changes in hair color.

A decision on approval is expected by the end of 2011, according to a company spokesperson.

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of potential conflicts of interest by the FDA prior to meetings; occasionally, the agency grants a waiver to a panelist with a conflict, but this did not occur at this meeting.

SILVER SPRING, MD. – The benefits of treatment with the oral tyrosine kinase inhibitor sunitinib outweigh the risks as a treatment for patients with metastatic pancreatic neuroendocrine tumors, according to the majority of a Food and Drug Administration advisory panel.

The FDA’s Oncologic Drugs Advisory Committee voted 8 to 2 on April 12 that the drug’s risk-benefit profile was favorable for patients with this rare cancer, despite uncertainty over the magnitude of the drug’s effect on progression-free survival in a pivotal trial that was terminated early.

The panel did not vote specifically on whether to recommend approval.

Pfizer Inc. has proposed that sunitinib malate capsules, marketed as Sutent, be approved for the treatment of unresectable pancreatic neuroendocrine tumors (PNET). Panelists cited the rarity of the disease and the few treatment options available among the reasons for their positive votes on the risk-benefit question. Several noted that the drug’s labeling should indicate that most patients in the pivotal phase III study had metastatic disease, and that sunitinib should not be used to treat patients with indolent forms of the disease.

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 tumor (GIST). It was approved for treating PNET in 2010 in Europe.

The pivotal PNET trial compared 37.5 mg of sunitinib daily with placebo in patients with locally advanced or metastatic, well-differentiated, unresectable PNET with progressive disease within the past year. It was stopped early in February 2009, after benefits were identified favoring the treatment group. Based on a review of data on 154 patients, the data-safety monitoring board recommended that the study be terminated because of differences in progression-free survival events (49 on placebo vs. 24 on sunitinib), deaths (15 on placebo vs. 5 on sunitinib) and severe adverse events (28 on placebo vs. 20 on sunitinib).

In an intention-to-treat analysis of 86 patients on sunitinib and 85 patients on placebo, the median progression-free survival was 11.4 months among those on sunitinib, compared with 5.5 months among those on placebo, which represented a 68% reduction in risk, a highly statistically significant difference. Overall survival, a secondary end point, was higher among the treated patients, but the difference was not statistically significant.

There were no new or unexpected adverse events. Adverse events and toxicities associated with treatment were similar to the known safety profile of sunitinib, and included diarrhea and stomatitis. Two of the patients on sunitinib died of cardiac failure.

Panelists agreed there was evidence of benefit, but acknowledged FDA reviewers’s concerns that early termination of the study could have overestimated the magnitude of the treatment difference on progression-free survival, the primary end point of the study. FDA reviewers also raised concerns about possible unblinding because of well-known adverse effects of sunitinib, such as hypertension and changes in hair color.

A decision on approval is expected by the end of 2011, according to a company spokesperson.

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of potential conflicts of interest by the FDA prior to meetings; occasionally, the agency grants a waiver to a panelist with a conflict, but this did not occur at this meeting.

SILVER SPRING, MD. – The benefits of treatment with the oral tyrosine kinase inhibitor sunitinib outweigh the risks as a treatment for patients with metastatic pancreatic neuroendocrine tumors, according to the majority of a Food and Drug Administration advisory panel.

The FDA’s Oncologic Drugs Advisory Committee voted 8 to 2 on April 12 that the drug’s risk-benefit profile was favorable for patients with this rare cancer, despite uncertainty over the magnitude of the drug’s effect on progression-free survival in a pivotal trial that was terminated early.

The panel did not vote specifically on whether to recommend approval.

Pfizer Inc. has proposed that sunitinib malate capsules, marketed as Sutent, be approved for the treatment of unresectable pancreatic neuroendocrine tumors (PNET). Panelists cited the rarity of the disease and the few treatment options available among the reasons for their positive votes on the risk-benefit question. Several noted that the drug’s labeling should indicate that most patients in the pivotal phase III study had metastatic disease, and that sunitinib should not be used to treat patients with indolent forms of the disease.

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 tumor (GIST). It was approved for treating PNET in 2010 in Europe.

The pivotal PNET trial compared 37.5 mg of sunitinib daily with placebo in patients with locally advanced or metastatic, well-differentiated, unresectable PNET with progressive disease within the past year. It was stopped early in February 2009, after benefits were identified favoring the treatment group. Based on a review of data on 154 patients, the data-safety monitoring board recommended that the study be terminated because of differences in progression-free survival events (49 on placebo vs. 24 on sunitinib), deaths (15 on placebo vs. 5 on sunitinib) and severe adverse events (28 on placebo vs. 20 on sunitinib).

In an intention-to-treat analysis of 86 patients on sunitinib and 85 patients on placebo, the median progression-free survival was 11.4 months among those on sunitinib, compared with 5.5 months among those on placebo, which represented a 68% reduction in risk, a highly statistically significant difference. Overall survival, a secondary end point, was higher among the treated patients, but the difference was not statistically significant.

There were no new or unexpected adverse events. Adverse events and toxicities associated with treatment were similar to the known safety profile of sunitinib, and included diarrhea and stomatitis. Two of the patients on sunitinib died of cardiac failure.

Panelists agreed there was evidence of benefit, but acknowledged FDA reviewers’s concerns that early termination of the study could have overestimated the magnitude of the treatment difference on progression-free survival, the primary end point of the study. FDA reviewers also raised concerns about possible unblinding because of well-known adverse effects of sunitinib, such as hypertension and changes in hair color.

A decision on approval is expected by the end of 2011, according to a company spokesperson.

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of potential conflicts of interest by the FDA prior to meetings; occasionally, the agency grants a waiver to a panelist with a conflict, but this did not occur at this meeting.

SILVER SPRING, MD. – The benefits of treatment with the oral tyrosine kinase inhibitor sunitinib outweigh the risks as a treatment for patients with metastatic pancreatic neuroendocrine tumors, according to the majority of a Food and Drug Administration advisory panel.

The FDA’s Oncologic Drugs Advisory Committee voted 8 to 2 on April 12 that the drug’s risk-benefit profile was favorable for patients with this rare cancer, despite uncertainty over the magnitude of the drug’s effect on progression-free survival in a pivotal trial that was terminated early.

The panel did not vote specifically on whether to recommend approval.

Pfizer Inc. has proposed that sunitinib malate capsules, marketed as Sutent, be approved for the treatment of unresectable pancreatic neuroendocrine tumors (PNET). Panelists cited the rarity of the disease and the few treatment options available among the reasons for their positive votes on the risk-benefit question. Several noted that the drug’s labeling should indicate that most patients in the pivotal phase III study had metastatic disease, and that sunitinib should not be used to treat patients with indolent forms of the disease.

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 tumor (GIST). It was approved for treating PNET in 2010 in Europe.

The pivotal PNET trial compared 37.5 mg of sunitinib daily with placebo in patients with locally advanced or metastatic, well-differentiated, unresectable PNET with progressive disease within the past year. It was stopped early in February 2009, after benefits were identified favoring the treatment group. Based on a review of data on 154 patients, the data-safety monitoring board recommended that the study be terminated because of differences in progression-free survival events (49 on placebo vs. 24 on sunitinib), deaths (15 on placebo vs. 5 on sunitinib) and severe adverse events (28 on placebo vs. 20 on sunitinib).

In an intention-to-treat analysis of 86 patients on sunitinib and 85 patients on placebo, the median progression-free survival was 11.4 months among those on sunitinib, compared with 5.5 months among those on placebo, which represented a 68% reduction in risk, a highly statistically significant difference. Overall survival, a secondary end point, was higher among the treated patients, but the difference was not statistically significant.

There were no new or unexpected adverse events. Adverse events and toxicities associated with treatment were similar to the known safety profile of sunitinib, and included diarrhea and stomatitis. Two of the patients on sunitinib died of cardiac failure.

Panelists agreed there was evidence of benefit, but acknowledged FDA reviewers’s concerns that early termination of the study could have overestimated the magnitude of the treatment difference on progression-free survival, the primary end point of the study. FDA reviewers also raised concerns about possible unblinding because of well-known adverse effects of sunitinib, such as hypertension and changes in hair color.

A decision on approval is expected by the end of 2011, according to a company spokesperson.

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of potential conflicts of interest by the FDA prior to meetings; occasionally, the agency grants a waiver to a panelist with a conflict, but this did not occur at this meeting.

SILVER SPRING, MD. – A Food and Drug Administration advisory panel voted 10-0 that everolimus had a favorable risk-benefit profile when used to treat people with advanced pancreatic neuroendocrine tumors, but cautioned that it should not be used in all patients with this diagnosis.

At their April 12 meeting, members of the FDA’s Oncologic Drugs Advisory Committee cited the unmet need for treatments for this rare disease and evidence that everolimus (Afinitor) is effective in some patients with more aggressive disease.

They cautioned, however, that it should not be used in every patient with advanced pancreatic neuroendocrine tumors (PNET). The disease can be indolent, they noted, and there was evidence that everolimus has a more favorable risk-benefit profile in patients with progressive disease.

The panel members recommended that more work be done to identify the subset of patients with the disease who can benefit most from treatment with everolimus. They also recommended that it not be used to treat patients with carcinoid tumors because it has not been shown to be effective and may be harmful in this population.

Novartis Pharmaceuticals Corp., which markets Afinitor, has proposed that it be approved for the treatment of patients with advanced PNET. Everolimus is an inhibitor of the mammalian target of rapamycin (mTOR), a key protein kinase that regulates cell growth, proliferation, and survival. It was approved in the United States in 2009 for treating advanced renal cell carcinoma and in 2010 for subependymal giant cell astrocytoma.

In the pivotal, double-blind, placebo-controlled phase III study, in patients with unresectable or metastatic biopsy-proven PNET, 207 patients treated with 10 mg of everolimus daily plus best supportive care were compared with 203 patients on placebo and best supportive care. Almost all patients enrolled had metastatic disease.

The primary end point, median progression-free survival as determined by the investigators, was 11 months in the everolimus arm, compared with 4.6 months in the placebo arm, a reduced risk of 65% that was statistically significant. There was no difference in overall survival between the two groups.

There were 12 deaths in the treatment group: 5 due to disease progression and 7 due to an adverse event related to treatment. In the placebo group, there were 4 deaths, 3 due to disease progression. Sixty-two percent of those on everolimus had a grade 3/4 adverse event, compared with 40% of those on placebo. Pneumonitis, opportunistic infections, and renal failure were among the significant adverse events associated with everolimus therapy.

The incidence of pancreatic neuroendocrine tumors is about 3 per million people a year, according to Novartis. A decision on approval is expected in the second quarter of this year, according to a Novartis spokesperson.

The FDA usually follows the recommendations of its advisory panels. Panel members are cleared of potential conflicts of interest by the FDA prior to meetings; occasionally, the FDA grants a waiver to a panelist with a conflict, but that did not occur at this meeting.

SILVER SPRING, MD. – A Food and Drug Administration advisory panel voted 10-0 that everolimus had a favorable risk-benefit profile when used to treat people with advanced pancreatic neuroendocrine tumors, but cautioned that it should not be used in all patients with this diagnosis.

At their April 12 meeting, members of the FDA’s Oncologic Drugs Advisory Committee cited the unmet need for treatments for this rare disease and evidence that everolimus (Afinitor) is effective in some patients with more aggressive disease.

They cautioned, however, that it should not be used in every patient with advanced pancreatic neuroendocrine tumors (PNET). The disease can be indolent, they noted, and there was evidence that everolimus has a more favorable risk-benefit profile in patients with progressive disease.

The panel members recommended that more work be done to identify the subset of patients with the disease who can benefit most from treatment with everolimus. They also recommended that it not be used to treat patients with carcinoid tumors because it has not been shown to be effective and may be harmful in this population.

Novartis Pharmaceuticals Corp., which markets Afinitor, has proposed that it be approved for the treatment of patients with advanced PNET. Everolimus is an inhibitor of the mammalian target of rapamycin (mTOR), a key protein kinase that regulates cell growth, proliferation, and survival. It was approved in the United States in 2009 for treating advanced renal cell carcinoma and in 2010 for subependymal giant cell astrocytoma.

In the pivotal, double-blind, placebo-controlled phase III study, in patients with unresectable or metastatic biopsy-proven PNET, 207 patients treated with 10 mg of everolimus daily plus best supportive care were compared with 203 patients on placebo and best supportive care. Almost all patients enrolled had metastatic disease.

The primary end point, median progression-free survival as determined by the investigators, was 11 months in the everolimus arm, compared with 4.6 months in the placebo arm, a reduced risk of 65% that was statistically significant. There was no difference in overall survival between the two groups.

There were 12 deaths in the treatment group: 5 due to disease progression and 7 due to an adverse event related to treatment. In the placebo group, there were 4 deaths, 3 due to disease progression. Sixty-two percent of those on everolimus had a grade 3/4 adverse event, compared with 40% of those on placebo. Pneumonitis, opportunistic infections, and renal failure were among the significant adverse events associated with everolimus therapy.

The incidence of pancreatic neuroendocrine tumors is about 3 per million people a year, according to Novartis. A decision on approval is expected in the second quarter of this year, according to a Novartis spokesperson.

The FDA usually follows the recommendations of its advisory panels. Panel members are cleared of potential conflicts of interest by the FDA prior to meetings; occasionally, the FDA grants a waiver to a panelist with a conflict, but that did not occur at this meeting.

SILVER SPRING, MD. – A Food and Drug Administration advisory panel voted 10-0 that everolimus had a favorable risk-benefit profile when used to treat people with advanced pancreatic neuroendocrine tumors, but cautioned that it should not be used in all patients with this diagnosis.

At their April 12 meeting, members of the FDA’s Oncologic Drugs Advisory Committee cited the unmet need for treatments for this rare disease and evidence that everolimus (Afinitor) is effective in some patients with more aggressive disease.

They cautioned, however, that it should not be used in every patient with advanced pancreatic neuroendocrine tumors (PNET). The disease can be indolent, they noted, and there was evidence that everolimus has a more favorable risk-benefit profile in patients with progressive disease.

The panel members recommended that more work be done to identify the subset of patients with the disease who can benefit most from treatment with everolimus. They also recommended that it not be used to treat patients with carcinoid tumors because it has not been shown to be effective and may be harmful in this population.

Novartis Pharmaceuticals Corp., which markets Afinitor, has proposed that it be approved for the treatment of patients with advanced PNET. Everolimus is an inhibitor of the mammalian target of rapamycin (mTOR), a key protein kinase that regulates cell growth, proliferation, and survival. It was approved in the United States in 2009 for treating advanced renal cell carcinoma and in 2010 for subependymal giant cell astrocytoma.

In the pivotal, double-blind, placebo-controlled phase III study, in patients with unresectable or metastatic biopsy-proven PNET, 207 patients treated with 10 mg of everolimus daily plus best supportive care were compared with 203 patients on placebo and best supportive care. Almost all patients enrolled had metastatic disease.

The primary end point, median progression-free survival as determined by the investigators, was 11 months in the everolimus arm, compared with 4.6 months in the placebo arm, a reduced risk of 65% that was statistically significant. There was no difference in overall survival between the two groups.

There were 12 deaths in the treatment group: 5 due to disease progression and 7 due to an adverse event related to treatment. In the placebo group, there were 4 deaths, 3 due to disease progression. Sixty-two percent of those on everolimus had a grade 3/4 adverse event, compared with 40% of those on placebo. Pneumonitis, opportunistic infections, and renal failure were among the significant adverse events associated with everolimus therapy.

The incidence of pancreatic neuroendocrine tumors is about 3 per million people a year, according to Novartis. A decision on approval is expected in the second quarter of this year, according to a Novartis spokesperson.

The FDA usually follows the recommendations of its advisory panels. Panel members are cleared of potential conflicts of interest by the FDA prior to meetings; occasionally, the FDA grants a waiver to a panelist with a conflict, but that did not occur at this meeting.

SILVER SPRING, MD. – A Food and Drug Administration advisory panel voted 10-0 that everolimus had a favorable risk-benefit profile when used to treat people with advanced pancreatic neuroendocrine tumors, but cautioned that it should not be used in all patients with this diagnosis.

At their April 12 meeting, members of the FDA’s Oncologic Drugs Advisory Committee cited the unmet need for treatments for this rare disease and evidence that everolimus (Afinitor) is effective in some patients with more aggressive disease.

They cautioned, however, that it should not be used in every patient with advanced pancreatic neuroendocrine tumors (PNET). The disease can be indolent, they noted, and there was evidence that everolimus has a more favorable risk-benefit profile in patients with progressive disease.

The panel members recommended that more work be done to identify the subset of patients with the disease who can benefit most from treatment with everolimus. They also recommended that it not be used to treat patients with carcinoid tumors because it has not been shown to be effective and may be harmful in this population.

Novartis Pharmaceuticals Corp., which markets Afinitor, has proposed that it be approved for the treatment of patients with advanced PNET. Everolimus is an inhibitor of the mammalian target of rapamycin (mTOR), a key protein kinase that regulates cell growth, proliferation, and survival. It was approved in the United States in 2009 for treating advanced renal cell carcinoma and in 2010 for subependymal giant cell astrocytoma.

In the pivotal, double-blind, placebo-controlled phase III study, in patients with unresectable or metastatic biopsy-proven PNET, 207 patients treated with 10 mg of everolimus daily plus best supportive care were compared with 203 patients on placebo and best supportive care. Almost all patients enrolled had metastatic disease.

The primary end point, median progression-free survival as determined by the investigators, was 11 months in the everolimus arm, compared with 4.6 months in the placebo arm, a reduced risk of 65% that was statistically significant. There was no difference in overall survival between the two groups.

There were 12 deaths in the treatment group: 5 due to disease progression and 7 due to an adverse event related to treatment. In the placebo group, there were 4 deaths, 3 due to disease progression. Sixty-two percent of those on everolimus had a grade 3/4 adverse event, compared with 40% of those on placebo. Pneumonitis, opportunistic infections, and renal failure were among the significant adverse events associated with everolimus therapy.

The incidence of pancreatic neuroendocrine tumors is about 3 per million people a year, according to Novartis. A decision on approval is expected in the second quarter of this year, according to a Novartis spokesperson.

The FDA usually follows the recommendations of its advisory panels. Panel members are cleared of potential conflicts of interest by the FDA prior to meetings; occasionally, the FDA grants a waiver to a panelist with a conflict, but that did not occur at this meeting.

SILVER SPRING, MD. – A Food and Drug Administration advisory panel voted 10-0 that everolimus had a favorable risk-benefit profile when used to treat people with advanced pancreatic neuroendocrine tumors, but cautioned that it should not be used in all patients with this diagnosis.

At their April 12 meeting, members of the FDA’s Oncologic Drugs Advisory Committee cited the unmet need for treatments for this rare disease and evidence that everolimus (Afinitor) is effective in some patients with more aggressive disease.

They cautioned, however, that it should not be used in every patient with advanced pancreatic neuroendocrine tumors (PNET). The disease can be indolent, they noted, and there was evidence that everolimus has a more favorable risk-benefit profile in patients with progressive disease.

The panel members recommended that more work be done to identify the subset of patients with the disease who can benefit most from treatment with everolimus. They also recommended that it not be used to treat patients with carcinoid tumors because it has not been shown to be effective and may be harmful in this population.

Novartis Pharmaceuticals Corp., which markets Afinitor, has proposed that it be approved for the treatment of patients with advanced PNET. Everolimus is an inhibitor of the mammalian target of rapamycin (mTOR), a key protein kinase that regulates cell growth, proliferation, and survival. It was approved in the United States in 2009 for treating advanced renal cell carcinoma and in 2010 for subependymal giant cell astrocytoma.

In the pivotal, double-blind, placebo-controlled phase III study, in patients with unresectable or metastatic biopsy-proven PNET, 207 patients treated with 10 mg of everolimus daily plus best supportive care were compared with 203 patients on placebo and best supportive care. Almost all patients enrolled had metastatic disease.

The primary end point, median progression-free survival as determined by the investigators, was 11 months in the everolimus arm, compared with 4.6 months in the placebo arm, a reduced risk of 65% that was statistically significant. There was no difference in overall survival between the two groups.

There were 12 deaths in the treatment group: 5 due to disease progression and 7 due to an adverse event related to treatment. In the placebo group, there were 4 deaths, 3 due to disease progression. Sixty-two percent of those on everolimus had a grade 3/4 adverse event, compared with 40% of those on placebo. Pneumonitis, opportunistic infections, and renal failure were among the significant adverse events associated with everolimus therapy.

The incidence of pancreatic neuroendocrine tumors is about 3 per million people a year, according to Novartis. A decision on approval is expected in the second quarter of this year, according to a Novartis spokesperson.

The FDA usually follows the recommendations of its advisory panels. Panel members are cleared of potential conflicts of interest by the FDA prior to meetings; occasionally, the FDA grants a waiver to a panelist with a conflict, but that did not occur at this meeting.

SILVER SPRING, MD. – A Food and Drug Administration advisory panel voted 10-0 that everolimus had a favorable risk-benefit profile when used to treat people with advanced pancreatic neuroendocrine tumors, but cautioned that it should not be used in all patients with this diagnosis.

At their April 12 meeting, members of the FDA’s Oncologic Drugs Advisory Committee cited the unmet need for treatments for this rare disease and evidence that everolimus (Afinitor) is effective in some patients with more aggressive disease.

They cautioned, however, that it should not be used in every patient with advanced pancreatic neuroendocrine tumors (PNET). The disease can be indolent, they noted, and there was evidence that everolimus has a more favorable risk-benefit profile in patients with progressive disease.

The panel members recommended that more work be done to identify the subset of patients with the disease who can benefit most from treatment with everolimus. They also recommended that it not be used to treat patients with carcinoid tumors because it has not been shown to be effective and may be harmful in this population.

Novartis Pharmaceuticals Corp., which markets Afinitor, has proposed that it be approved for the treatment of patients with advanced PNET. Everolimus is an inhibitor of the mammalian target of rapamycin (mTOR), a key protein kinase that regulates cell growth, proliferation, and survival. It was approved in the United States in 2009 for treating advanced renal cell carcinoma and in 2010 for subependymal giant cell astrocytoma.

In the pivotal, double-blind, placebo-controlled phase III study, in patients with unresectable or metastatic biopsy-proven PNET, 207 patients treated with 10 mg of everolimus daily plus best supportive care were compared with 203 patients on placebo and best supportive care. Almost all patients enrolled had metastatic disease.

The primary end point, median progression-free survival as determined by the investigators, was 11 months in the everolimus arm, compared with 4.6 months in the placebo arm, a reduced risk of 65% that was statistically significant. There was no difference in overall survival between the two groups.

There were 12 deaths in the treatment group: 5 due to disease progression and 7 due to an adverse event related to treatment. In the placebo group, there were 4 deaths, 3 due to disease progression. Sixty-two percent of those on everolimus had a grade 3/4 adverse event, compared with 40% of those on placebo. Pneumonitis, opportunistic infections, and renal failure were among the significant adverse events associated with everolimus therapy.

The incidence of pancreatic neuroendocrine tumors is about 3 per million people a year, according to Novartis. A decision on approval is expected in the second quarter of this year, according to a Novartis spokesperson.

The FDA usually follows the recommendations of its advisory panels. Panel members are cleared of potential conflicts of interest by the FDA prior to meetings; occasionally, the FDA grants a waiver to a panelist with a conflict, but that did not occur at this meeting.