Rebecca Kern

ASCO guidelines addressing the order of targeted agents in the management of patients with advanced HER2-positive breast cancer, and on the management of brain metastases, were published online May 5 in the Journal of Clinical Oncology.

Clinicians should recommend HER2-targeted therapy–based combinations for first-line treatment, except for highly selected patients with estrogen receptor–positive or progesterone receptor–positive and HER2-positive disease, for whom clinicians may use endocrine therapy alone, wrote Dr. Sharon H. Giordano and her colleagues in describing the guideline for systemic treatment (J. Clin. Oncol. 2014 May 5 [doi: 10.1200/JCO.2013.54.0948]).

A combination of trastuzumab, pertuzumab, and a taxane is recommended for first-line treatment of advanced disease. If a patient’s breast cancer has progressed during first-line HER2-targeted therapy, trastuzumab emtansine is recommended as a second-line therapy, said Dr. Giordano, of the University of Texas M.D. Anderson Cancer Center, Houston, and her colleagues.

As a third-line treatment, clinicians should prescribe other HER2-targeted therapy combinations or trastuzumab emtansine (if not previously administered) and pertuzumab (if not previously administered).

HER2-targeted therapy for those with clinical congestive heart failure or significantly compromised left-ventricular ejection fraction, should be evaluated on a case-by-case basis.

The guideline recommends chemotherapy for at least 4-6 months, but treatment can continue until time of progression or unacceptable toxicities.

The second ASCO guideline provides recommendations for management of brain metastases in patients with HER2-positive advanced breast cancer, which up to half of patients with HER2-positive metastatic breast cancer will experience over time, wrote Dr. Naren Ramakrishna, of the University of Florida Health Cancer Center at Orlando Health, and his colleagues (J. Clin. Oncol. 2014 May 5 [doi: 10.1200/JCO.2013.54.0955]).

For patients with a favorable prognosis for survival and a single brain metastasis, treatment options include surgery with postoperative radiation, stereotactic radiosurgery, whole-brain radiotherapy, and fractionated stereotactic radiotherapy, depending on metastasis size, resectability, and symptoms. After treatment, serial imaging every 2-4 months may be used to monitor for local and distant brain failure.

For patients with a favorable prognosis for survival and limited (two to four) metastases, treatment options include resection for a large symptomatic lesion(s) plus postoperative radiotherapy; stereotactic radiosurgery for additional smaller lesions; and a combination of whole-brain radiotherapy and/or stereotactic radiosurgery and fractionated stereotactic radiotherapy for other lesions, depending on resectability and symptoms.

For patients with diffuse disease or extensive metastases and a more favorable prognosis, and those with symptomatic leptomeningeal metastasis in the brain, whole-brain radiation therapy may be offered.

For patients with a poor prognosis, the guideline recommends whole-brain radiotherapy, best supportive care, clinical trial enrollment, and/or palliative care, Dr. Ramakrishna and his colleagues said.

Routine surveillance with magnetic resonance imaging is not recommended in patients without a history of or symptoms related to brain metastases or symptoms. However, clinicians should have a low threshold for diagnostic brain MRI testing in the setting of any neurologic symptoms, they said.

ASCO guidelines addressing the order of targeted agents in the management of patients with advanced HER2-positive breast cancer, and on the management of brain metastases, were published online May 5 in the Journal of Clinical Oncology.

Clinicians should recommend HER2-targeted therapy–based combinations for first-line treatment, except for highly selected patients with estrogen receptor–positive or progesterone receptor–positive and HER2-positive disease, for whom clinicians may use endocrine therapy alone, wrote Dr. Sharon H. Giordano and her colleagues in describing the guideline for systemic treatment (J. Clin. Oncol. 2014 May 5 [doi: 10.1200/JCO.2013.54.0948]).

A combination of trastuzumab, pertuzumab, and a taxane is recommended for first-line treatment of advanced disease. If a patient’s breast cancer has progressed during first-line HER2-targeted therapy, trastuzumab emtansine is recommended as a second-line therapy, said Dr. Giordano, of the University of Texas M.D. Anderson Cancer Center, Houston, and her colleagues.

As a third-line treatment, clinicians should prescribe other HER2-targeted therapy combinations or trastuzumab emtansine (if not previously administered) and pertuzumab (if not previously administered).

HER2-targeted therapy for those with clinical congestive heart failure or significantly compromised left-ventricular ejection fraction, should be evaluated on a case-by-case basis.

The guideline recommends chemotherapy for at least 4-6 months, but treatment can continue until time of progression or unacceptable toxicities.

The second ASCO guideline provides recommendations for management of brain metastases in patients with HER2-positive advanced breast cancer, which up to half of patients with HER2-positive metastatic breast cancer will experience over time, wrote Dr. Naren Ramakrishna, of the University of Florida Health Cancer Center at Orlando Health, and his colleagues (J. Clin. Oncol. 2014 May 5 [doi: 10.1200/JCO.2013.54.0955]).

For patients with a favorable prognosis for survival and a single brain metastasis, treatment options include surgery with postoperative radiation, stereotactic radiosurgery, whole-brain radiotherapy, and fractionated stereotactic radiotherapy, depending on metastasis size, resectability, and symptoms. After treatment, serial imaging every 2-4 months may be used to monitor for local and distant brain failure.

For patients with a favorable prognosis for survival and limited (two to four) metastases, treatment options include resection for a large symptomatic lesion(s) plus postoperative radiotherapy; stereotactic radiosurgery for additional smaller lesions; and a combination of whole-brain radiotherapy and/or stereotactic radiosurgery and fractionated stereotactic radiotherapy for other lesions, depending on resectability and symptoms.

For patients with diffuse disease or extensive metastases and a more favorable prognosis, and those with symptomatic leptomeningeal metastasis in the brain, whole-brain radiation therapy may be offered.

For patients with a poor prognosis, the guideline recommends whole-brain radiotherapy, best supportive care, clinical trial enrollment, and/or palliative care, Dr. Ramakrishna and his colleagues said.

Routine surveillance with magnetic resonance imaging is not recommended in patients without a history of or symptoms related to brain metastases or symptoms. However, clinicians should have a low threshold for diagnostic brain MRI testing in the setting of any neurologic symptoms, they said.

ASCO guidelines addressing the order of targeted agents in the management of patients with advanced HER2-positive breast cancer, and on the management of brain metastases, were published online May 5 in the Journal of Clinical Oncology.

Clinicians should recommend HER2-targeted therapy–based combinations for first-line treatment, except for highly selected patients with estrogen receptor–positive or progesterone receptor–positive and HER2-positive disease, for whom clinicians may use endocrine therapy alone, wrote Dr. Sharon H. Giordano and her colleagues in describing the guideline for systemic treatment (J. Clin. Oncol. 2014 May 5 [doi: 10.1200/JCO.2013.54.0948]).

A combination of trastuzumab, pertuzumab, and a taxane is recommended for first-line treatment of advanced disease. If a patient’s breast cancer has progressed during first-line HER2-targeted therapy, trastuzumab emtansine is recommended as a second-line therapy, said Dr. Giordano, of the University of Texas M.D. Anderson Cancer Center, Houston, and her colleagues.

As a third-line treatment, clinicians should prescribe other HER2-targeted therapy combinations or trastuzumab emtansine (if not previously administered) and pertuzumab (if not previously administered).

HER2-targeted therapy for those with clinical congestive heart failure or significantly compromised left-ventricular ejection fraction, should be evaluated on a case-by-case basis.

The guideline recommends chemotherapy for at least 4-6 months, but treatment can continue until time of progression or unacceptable toxicities.

The second ASCO guideline provides recommendations for management of brain metastases in patients with HER2-positive advanced breast cancer, which up to half of patients with HER2-positive metastatic breast cancer will experience over time, wrote Dr. Naren Ramakrishna, of the University of Florida Health Cancer Center at Orlando Health, and his colleagues (J. Clin. Oncol. 2014 May 5 [doi: 10.1200/JCO.2013.54.0955]).

For patients with a favorable prognosis for survival and a single brain metastasis, treatment options include surgery with postoperative radiation, stereotactic radiosurgery, whole-brain radiotherapy, and fractionated stereotactic radiotherapy, depending on metastasis size, resectability, and symptoms. After treatment, serial imaging every 2-4 months may be used to monitor for local and distant brain failure.

For patients with a favorable prognosis for survival and limited (two to four) metastases, treatment options include resection for a large symptomatic lesion(s) plus postoperative radiotherapy; stereotactic radiosurgery for additional smaller lesions; and a combination of whole-brain radiotherapy and/or stereotactic radiosurgery and fractionated stereotactic radiotherapy for other lesions, depending on resectability and symptoms.

For patients with diffuse disease or extensive metastases and a more favorable prognosis, and those with symptomatic leptomeningeal metastasis in the brain, whole-brain radiation therapy may be offered.

For patients with a poor prognosis, the guideline recommends whole-brain radiotherapy, best supportive care, clinical trial enrollment, and/or palliative care, Dr. Ramakrishna and his colleagues said.

Routine surveillance with magnetic resonance imaging is not recommended in patients without a history of or symptoms related to brain metastases or symptoms. However, clinicians should have a low threshold for diagnostic brain MRI testing in the setting of any neurologic symptoms, they said.

Physical inactivity in women aged 30 years and older has a greater impact on the risk of developing heart disease than any other major risk factor, according to an Australian study published today in the British Journal of Sports Medicine.

Wendy Brown, Ph.D., professor in the Centre for Research on Exercise, Physical Activity, and Health at the University of Queensland, Australia, and her fellow researchers, found that up to age 30 years, smoking was the most important contributor to heart disease in Australian women, but from age 30-80 years, physical inactivity was the top risk factor.

© shutterstock.com

The researchers looked at the population attributable risk of ischemic heart disease in adult Australian women. They looked at four risk factors: excess weight (high body mass index); smoking; high blood pressure, and physical inactivity.

They based their estimates on the four risk factors’ prevalence in the Australian Longitudinal Study on Women’s Health, which has tracked the long-term health of 32,154 women born in 1921-1926, 1946-1951, and 1972-1978, since 1996.

The researchers found that smoking prevalence fell from 28% in women aged 22-27 years to 5% in those aged 73-78 years. However, the prevalence of inactivity and high blood pressure increased from age 22-90 years, and weight gain increased from age 22-64 years, but dropped in older age (Br. J. Sports Med. 2014 May 8 [doi:10.1136/bjsports-2013-093090]).

The researchers used a mathematical formula known as population attributable risk (PAR) to define the proportion of disease that would disappear if exposure to a specific risk factor were eliminated.

They found that relative risks for all four risk factors declined with age, but prevalence of physical inactivity, high BMI, and high blood pressure increased with age, while smoking prevalence decreased.

Overall, the average PAR for physical inactivity was 33% in the middle-age group and 24% in the older-age group. Specifically, the PAR for physical inactivity increased dramatically over time from 65% in women aged 73-78 years to 81% in women aged 85-90 years.

The study found that 1,261 middle-age and 9,151 older women die from heart disease every year. With increased physical activity in both age groups, the number of deaths could be reduced by 2,612 per year.

The researchers recommend to continue smoking cessation programs among younger women, and to promote physical activity in women of all ages. They also recommend at least 150 minutes of moderate activity per week for women aged 30-90 years who are currently inactive.

Dr. Carl "Chip" Lavie, medical director of cardiac rehabilitation and the exercise laboratories at the Ochsner Heart and Vascular Institute, New Orleans, says he is impressed with the study and supports its recommendations for increased physical activity.

"This is a very important study that emphasizes the fact that physical inactivity is probably the leading threat to health in the U.S. and most of the Western world, and it is clearly the case in Australia," he said.

The study was sponsored by the Australian Government Department of Health and Ageing. The investigators had no competing interests.

Physical inactivity in women aged 30 years and older has a greater impact on the risk of developing heart disease than any other major risk factor, according to an Australian study published today in the British Journal of Sports Medicine.

Wendy Brown, Ph.D., professor in the Centre for Research on Exercise, Physical Activity, and Health at the University of Queensland, Australia, and her fellow researchers, found that up to age 30 years, smoking was the most important contributor to heart disease in Australian women, but from age 30-80 years, physical inactivity was the top risk factor.

© shutterstock.com

The researchers looked at the population attributable risk of ischemic heart disease in adult Australian women. They looked at four risk factors: excess weight (high body mass index); smoking; high blood pressure, and physical inactivity.

They based their estimates on the four risk factors’ prevalence in the Australian Longitudinal Study on Women’s Health, which has tracked the long-term health of 32,154 women born in 1921-1926, 1946-1951, and 1972-1978, since 1996.

The researchers found that smoking prevalence fell from 28% in women aged 22-27 years to 5% in those aged 73-78 years. However, the prevalence of inactivity and high blood pressure increased from age 22-90 years, and weight gain increased from age 22-64 years, but dropped in older age (Br. J. Sports Med. 2014 May 8 [doi:10.1136/bjsports-2013-093090]).

The researchers used a mathematical formula known as population attributable risk (PAR) to define the proportion of disease that would disappear if exposure to a specific risk factor were eliminated.

They found that relative risks for all four risk factors declined with age, but prevalence of physical inactivity, high BMI, and high blood pressure increased with age, while smoking prevalence decreased.

Overall, the average PAR for physical inactivity was 33% in the middle-age group and 24% in the older-age group. Specifically, the PAR for physical inactivity increased dramatically over time from 65% in women aged 73-78 years to 81% in women aged 85-90 years.

The study found that 1,261 middle-age and 9,151 older women die from heart disease every year. With increased physical activity in both age groups, the number of deaths could be reduced by 2,612 per year.

The researchers recommend to continue smoking cessation programs among younger women, and to promote physical activity in women of all ages. They also recommend at least 150 minutes of moderate activity per week for women aged 30-90 years who are currently inactive.

Dr. Carl "Chip" Lavie, medical director of cardiac rehabilitation and the exercise laboratories at the Ochsner Heart and Vascular Institute, New Orleans, says he is impressed with the study and supports its recommendations for increased physical activity.

"This is a very important study that emphasizes the fact that physical inactivity is probably the leading threat to health in the U.S. and most of the Western world, and it is clearly the case in Australia," he said.

The study was sponsored by the Australian Government Department of Health and Ageing. The investigators had no competing interests.

Physical inactivity in women aged 30 years and older has a greater impact on the risk of developing heart disease than any other major risk factor, according to an Australian study published today in the British Journal of Sports Medicine.

Wendy Brown, Ph.D., professor in the Centre for Research on Exercise, Physical Activity, and Health at the University of Queensland, Australia, and her fellow researchers, found that up to age 30 years, smoking was the most important contributor to heart disease in Australian women, but from age 30-80 years, physical inactivity was the top risk factor.

© shutterstock.com

The researchers looked at the population attributable risk of ischemic heart disease in adult Australian women. They looked at four risk factors: excess weight (high body mass index); smoking; high blood pressure, and physical inactivity.

They based their estimates on the four risk factors’ prevalence in the Australian Longitudinal Study on Women’s Health, which has tracked the long-term health of 32,154 women born in 1921-1926, 1946-1951, and 1972-1978, since 1996.

The researchers found that smoking prevalence fell from 28% in women aged 22-27 years to 5% in those aged 73-78 years. However, the prevalence of inactivity and high blood pressure increased from age 22-90 years, and weight gain increased from age 22-64 years, but dropped in older age (Br. J. Sports Med. 2014 May 8 [doi:10.1136/bjsports-2013-093090]).

The researchers used a mathematical formula known as population attributable risk (PAR) to define the proportion of disease that would disappear if exposure to a specific risk factor were eliminated.

They found that relative risks for all four risk factors declined with age, but prevalence of physical inactivity, high BMI, and high blood pressure increased with age, while smoking prevalence decreased.

Overall, the average PAR for physical inactivity was 33% in the middle-age group and 24% in the older-age group. Specifically, the PAR for physical inactivity increased dramatically over time from 65% in women aged 73-78 years to 81% in women aged 85-90 years.

The study found that 1,261 middle-age and 9,151 older women die from heart disease every year. With increased physical activity in both age groups, the number of deaths could be reduced by 2,612 per year.

The researchers recommend to continue smoking cessation programs among younger women, and to promote physical activity in women of all ages. They also recommend at least 150 minutes of moderate activity per week for women aged 30-90 years who are currently inactive.

Dr. Carl "Chip" Lavie, medical director of cardiac rehabilitation and the exercise laboratories at the Ochsner Heart and Vascular Institute, New Orleans, says he is impressed with the study and supports its recommendations for increased physical activity.

"This is a very important study that emphasizes the fact that physical inactivity is probably the leading threat to health in the U.S. and most of the Western world, and it is clearly the case in Australia," he said.

The study was sponsored by the Australian Government Department of Health and Ageing. The investigators had no competing interests.

The Food and Drug Administration has approved umeclidinium as a once-daily, long-term treatment for airflow obstruction for patients with chronic obstructive pulmonary disease, GlaxoSmithKline announced April 30.

Incruse Ellipta (umeclidinium) is a long-acting muscarinic antagonist. It includes 62.5 mcg of umeclidinium delivered with the Ellipta inhaler.

Approximately 27 million people in the United States are affected by COPD, a lung disease that includes chronic bronchitis, emphysema, or both, according to the National Heart, Lung, and Blood Institute.

The phase III clinical trial for umeclidinium included seven clinical trials, which enrolled more than 2,500 COPD patients randomized to umeclidinium or placebo.

The most common adverse events with Incruse Ellipta (and placebo) were nasopharyngitis, 8% (7%); upper respiratory tract infection, 5% (4%); cough, 3% (2%); and arthralgia, 2% (1%). The drug is not recommended during rapidly deteriorating or potentially life-threatening COPD episodes, or as a rescue therapy for acute episodes of bronchospasm.

It is also recommended for the drug to be used with caution in patients with narrow-angle glaucoma and patients with urinary retention, especially prostatic hyperplasia or bladder neck obstruction.

Incruse Ellipta is currently approved in Canada and Europe, and is under review in several other countries. The firm says it plans to launch the drug in the United States in the fourth quarter of 2014.

The Food and Drug Administration has approved umeclidinium as a once-daily, long-term treatment for airflow obstruction for patients with chronic obstructive pulmonary disease, GlaxoSmithKline announced April 30.

Incruse Ellipta (umeclidinium) is a long-acting muscarinic antagonist. It includes 62.5 mcg of umeclidinium delivered with the Ellipta inhaler.

Approximately 27 million people in the United States are affected by COPD, a lung disease that includes chronic bronchitis, emphysema, or both, according to the National Heart, Lung, and Blood Institute.

The phase III clinical trial for umeclidinium included seven clinical trials, which enrolled more than 2,500 COPD patients randomized to umeclidinium or placebo.

The most common adverse events with Incruse Ellipta (and placebo) were nasopharyngitis, 8% (7%); upper respiratory tract infection, 5% (4%); cough, 3% (2%); and arthralgia, 2% (1%). The drug is not recommended during rapidly deteriorating or potentially life-threatening COPD episodes, or as a rescue therapy for acute episodes of bronchospasm.

It is also recommended for the drug to be used with caution in patients with narrow-angle glaucoma and patients with urinary retention, especially prostatic hyperplasia or bladder neck obstruction.

Incruse Ellipta is currently approved in Canada and Europe, and is under review in several other countries. The firm says it plans to launch the drug in the United States in the fourth quarter of 2014.

The Food and Drug Administration has approved umeclidinium as a once-daily, long-term treatment for airflow obstruction for patients with chronic obstructive pulmonary disease, GlaxoSmithKline announced April 30.

Incruse Ellipta (umeclidinium) is a long-acting muscarinic antagonist. It includes 62.5 mcg of umeclidinium delivered with the Ellipta inhaler.

Approximately 27 million people in the United States are affected by COPD, a lung disease that includes chronic bronchitis, emphysema, or both, according to the National Heart, Lung, and Blood Institute.

The phase III clinical trial for umeclidinium included seven clinical trials, which enrolled more than 2,500 COPD patients randomized to umeclidinium or placebo.

The most common adverse events with Incruse Ellipta (and placebo) were nasopharyngitis, 8% (7%); upper respiratory tract infection, 5% (4%); cough, 3% (2%); and arthralgia, 2% (1%). The drug is not recommended during rapidly deteriorating or potentially life-threatening COPD episodes, or as a rescue therapy for acute episodes of bronchospasm.

It is also recommended for the drug to be used with caution in patients with narrow-angle glaucoma and patients with urinary retention, especially prostatic hyperplasia or bladder neck obstruction.

Incruse Ellipta is currently approved in Canada and Europe, and is under review in several other countries. The firm says it plans to launch the drug in the United States in the fourth quarter of 2014.

Evidence is insufficient to support lung cancer screening with low-dose computed tomography in the Medicare population, members of the Medicare Evidence Development and Coverage Advisory Committee said at a meeting on April 30.

Specifically, the MEDCAC advisers said that, on average, they had low confidence there is adequate evidence that the benefits outweigh the harms of lung cancer screening with low-dose computed tomography (LDCT) in the Medicare population.

The Centers for Medicare & Medicaid Services accepted two formal requests to initiate a national coverage analysis on lung cancer screening with LDCT, which the U.S. Preventive Services Task Force gave a grade B recommendation for people at high risk for lung cancer based on age and smoking history.

"I think it’s almost impossible to extrapolate to the Medicare population the expected results that we would get when I feel it’s our obligation to first do no harm. I didn’t hear that the evidence is there to support benefit beyond harm," said Dr. Curtis Mock, national medical director of UnitedHealthcare Medicare & Retirement.

Most of the MEDCAC advisers said that they were not satisfied by the Medicare-population data in the National Lung Screening Trial (NLST). That study of more than 50,000 asymptomatic adults, aged 55-74 years, showed a 16% reduction in lung cancer mortality and a 6.7% reduction in all-cause mortality when patients were screened using LDCT (N. Engl. J. Med. 2013;368:1980-91). One cancer death was averted for every 320 patients screened, and one death from all causes was prevented in every 219 patients screened.

But Medicare-eligible patients – those aged 65-74 years – represented about 25% of patients in the trial, less than the nearly 36% NLST-eligible in the U.S. population.

"I am concerned that we don’t really have a lot of data in the Medicare population, certainly not in the 75-80 [year-old age group], particularly on the harms in the age group that was included in NLST," said Dr. Rita Redberg, MEDCAC chair and professor of medicine at the University of California, San Francisco.

Dr. Redberg also highlighted the additional health complications with Medicare-age patients.

"Surgical mortality increases as one gets older, and the benefits of early detection tend to disappear as you get older because there are more competing causes of death," she said.

The MEDCAC advisers also noted that they were not confident that the harms of lung cancer screening with LDCT (average effective dose of 1.5 mSv) would be minimized if implemented in the Medicare population.

"The harm I worry about will be the intervention of this test on people for which we know nothing about the benefits and harms," said Dr. Allan Fendrick, professor in the department of internal medicine at the University of Michigan, Ann Arbor.

Similarly, Dr. Harry Burke, associate professor at the Uniformed Services University of the Health Sciences in Bethesda, Md., said, "I think the low positive predictive value drives harm. Whether you can balance that harm with the benefit is a very difficult business."

Lastly, the advisors said that they strongly believe there are clinically significant evidence gaps when using LDCT for lung cancer screening in the Medicare population outside a clinical trial.

"The most important gap that I see is based on totality of the data – both from this large NLST trial but also high-quality publications from other trials – to be able to come up with a cohort where we would have much higher confidence that the benefits outweigh the harms than other subgroups," said MEDCAC vice chair Dr. Art Sedrakyan, director of the Patient Centered Comparative Outcomes Research Program at Cornell University, New York.

CMS will take the expert panel’s recommendations into consideration as it develops its national coverage decision for lung cancer screening with LDCT, which it plans to issue by mid-November, followed by a 30-day public comment period.

Evidence is insufficient to support lung cancer screening with low-dose computed tomography in the Medicare population, members of the Medicare Evidence Development and Coverage Advisory Committee said at a meeting on April 30.

Specifically, the MEDCAC advisers said that, on average, they had low confidence there is adequate evidence that the benefits outweigh the harms of lung cancer screening with low-dose computed tomography (LDCT) in the Medicare population.

The Centers for Medicare & Medicaid Services accepted two formal requests to initiate a national coverage analysis on lung cancer screening with LDCT, which the U.S. Preventive Services Task Force gave a grade B recommendation for people at high risk for lung cancer based on age and smoking history.

"I think it’s almost impossible to extrapolate to the Medicare population the expected results that we would get when I feel it’s our obligation to first do no harm. I didn’t hear that the evidence is there to support benefit beyond harm," said Dr. Curtis Mock, national medical director of UnitedHealthcare Medicare & Retirement.

Most of the MEDCAC advisers said that they were not satisfied by the Medicare-population data in the National Lung Screening Trial (NLST). That study of more than 50,000 asymptomatic adults, aged 55-74 years, showed a 16% reduction in lung cancer mortality and a 6.7% reduction in all-cause mortality when patients were screened using LDCT (N. Engl. J. Med. 2013;368:1980-91). One cancer death was averted for every 320 patients screened, and one death from all causes was prevented in every 219 patients screened.

But Medicare-eligible patients – those aged 65-74 years – represented about 25% of patients in the trial, less than the nearly 36% NLST-eligible in the U.S. population.

"I am concerned that we don’t really have a lot of data in the Medicare population, certainly not in the 75-80 [year-old age group], particularly on the harms in the age group that was included in NLST," said Dr. Rita Redberg, MEDCAC chair and professor of medicine at the University of California, San Francisco.

Dr. Redberg also highlighted the additional health complications with Medicare-age patients.

"Surgical mortality increases as one gets older, and the benefits of early detection tend to disappear as you get older because there are more competing causes of death," she said.

The MEDCAC advisers also noted that they were not confident that the harms of lung cancer screening with LDCT (average effective dose of 1.5 mSv) would be minimized if implemented in the Medicare population.

"The harm I worry about will be the intervention of this test on people for which we know nothing about the benefits and harms," said Dr. Allan Fendrick, professor in the department of internal medicine at the University of Michigan, Ann Arbor.

Similarly, Dr. Harry Burke, associate professor at the Uniformed Services University of the Health Sciences in Bethesda, Md., said, "I think the low positive predictive value drives harm. Whether you can balance that harm with the benefit is a very difficult business."

Lastly, the advisors said that they strongly believe there are clinically significant evidence gaps when using LDCT for lung cancer screening in the Medicare population outside a clinical trial.

"The most important gap that I see is based on totality of the data – both from this large NLST trial but also high-quality publications from other trials – to be able to come up with a cohort where we would have much higher confidence that the benefits outweigh the harms than other subgroups," said MEDCAC vice chair Dr. Art Sedrakyan, director of the Patient Centered Comparative Outcomes Research Program at Cornell University, New York.

CMS will take the expert panel’s recommendations into consideration as it develops its national coverage decision for lung cancer screening with LDCT, which it plans to issue by mid-November, followed by a 30-day public comment period.

Evidence is insufficient to support lung cancer screening with low-dose computed tomography in the Medicare population, members of the Medicare Evidence Development and Coverage Advisory Committee said at a meeting on April 30.

Specifically, the MEDCAC advisers said that, on average, they had low confidence there is adequate evidence that the benefits outweigh the harms of lung cancer screening with low-dose computed tomography (LDCT) in the Medicare population.

The Centers for Medicare & Medicaid Services accepted two formal requests to initiate a national coverage analysis on lung cancer screening with LDCT, which the U.S. Preventive Services Task Force gave a grade B recommendation for people at high risk for lung cancer based on age and smoking history.

"I think it’s almost impossible to extrapolate to the Medicare population the expected results that we would get when I feel it’s our obligation to first do no harm. I didn’t hear that the evidence is there to support benefit beyond harm," said Dr. Curtis Mock, national medical director of UnitedHealthcare Medicare & Retirement.

Most of the MEDCAC advisers said that they were not satisfied by the Medicare-population data in the National Lung Screening Trial (NLST). That study of more than 50,000 asymptomatic adults, aged 55-74 years, showed a 16% reduction in lung cancer mortality and a 6.7% reduction in all-cause mortality when patients were screened using LDCT (N. Engl. J. Med. 2013;368:1980-91). One cancer death was averted for every 320 patients screened, and one death from all causes was prevented in every 219 patients screened.

But Medicare-eligible patients – those aged 65-74 years – represented about 25% of patients in the trial, less than the nearly 36% NLST-eligible in the U.S. population.

"I am concerned that we don’t really have a lot of data in the Medicare population, certainly not in the 75-80 [year-old age group], particularly on the harms in the age group that was included in NLST," said Dr. Rita Redberg, MEDCAC chair and professor of medicine at the University of California, San Francisco.

Dr. Redberg also highlighted the additional health complications with Medicare-age patients.

"Surgical mortality increases as one gets older, and the benefits of early detection tend to disappear as you get older because there are more competing causes of death," she said.

The MEDCAC advisers also noted that they were not confident that the harms of lung cancer screening with LDCT (average effective dose of 1.5 mSv) would be minimized if implemented in the Medicare population.

"The harm I worry about will be the intervention of this test on people for which we know nothing about the benefits and harms," said Dr. Allan Fendrick, professor in the department of internal medicine at the University of Michigan, Ann Arbor.

Similarly, Dr. Harry Burke, associate professor at the Uniformed Services University of the Health Sciences in Bethesda, Md., said, "I think the low positive predictive value drives harm. Whether you can balance that harm with the benefit is a very difficult business."

Lastly, the advisors said that they strongly believe there are clinically significant evidence gaps when using LDCT for lung cancer screening in the Medicare population outside a clinical trial.

"The most important gap that I see is based on totality of the data – both from this large NLST trial but also high-quality publications from other trials – to be able to come up with a cohort where we would have much higher confidence that the benefits outweigh the harms than other subgroups," said MEDCAC vice chair Dr. Art Sedrakyan, director of the Patient Centered Comparative Outcomes Research Program at Cornell University, New York.

CMS will take the expert panel’s recommendations into consideration as it develops its national coverage decision for lung cancer screening with LDCT, which it plans to issue by mid-November, followed by a 30-day public comment period.

Should Medicare pay for low-dose computed tomography to screen certain patients for lung cancer? A panel of expert advisers will meet April 30 to review the evidence and make a recommendation.

The Centers for Medicare & Medicaid Services has accepted two formal requests to initiate a national coverage analysis on lung cancer screening with low-dose computed tomography (LDCT), which the U.S. Preventative Services Task Force gave a grade B recommendation for people at high risk for lung cancer based on age and smoking history.

©Valeriy Kirsanov/fotolia.com

CMS is specifically asking its Medicare Evidence Development & Coverage Advisory Committee (MEDCAC) to discuss:

• the evidence that identifies which Medicare patients would benefit the most from the screening.

• screening frequency and duration.

• provider characteristics that optimize benefits and minimize harm.

• criteria to identify a test as positive and the impact of false-positive results.

• follow-up tests or treatments.

The agency also seeks to know how these factors will impact patient education and informed consent in Medicare beneficiaries, including the elderly, younger disabled populations, and patients with end-stage renal disease, and on integrating smoking cessation interventions for current smokers.

In order for CMS to issue a national coverage determination for a preventive service, the following criteria must be met: reasonable and necessary for prevention or early detection of an illness or disability; an A- or B-grade recommendation from USPSTF; and appropriate for Medicare Part A or Medicare Part B beneficiaries.

CMS has asked the panel to vote on whether there is adequate evidence to determine if the benefits of lung cancer screening with LDCT outweigh the harms. The agency will specifically ask if there is adequate evidence to determine if LDCT improves health outcomes: in asymptomatic, high-risk adults over 74 years old; with more than three annual LDCT screens; and if the screening program is implemented outside a clinical study.

The agency is also asking for panel input on the harms of lung cancer screening with LDCT in the Medicare population, specifically harms from the scan itself (an average dose of 1.5 mSv), harms from follow-up evaluation of findings in and outside the lungs, and harms from treatment as a result of positive and false-positive results.

CMS will also ask the panel to identify and discuss any clinically significant evidence gaps regarding the use of LDCT in lung cancer screening outside of a clinical trial.

Last December, the USPSTF recommended annual screening for lung cancer with LDCT in adults aged 55- 80 years who have a 30-pack-year smoking history and currently smoke or have quit in the past 15 years. The recommendation states that screening should be stopped once a person has stopped smoking for 15 years or develops a health problem limiting life expectancy or the ability to have curative lung surgery.

The USPSTF’s recommendations were based largely on a systematic review of several randomized, controlled trials published between 2000 and 2013, including the National Lung Screening Trial. That study of more than 50,000 asymptomatic adults, aged 55-74 years, showed a 16% reduction in lung cancer mortality and a 6.7% reduction in all-cause mortality when patients were screened using LDCT. One cancer death was averted for every 320 patients screened, and one death from all causes was prevented in every 219 patients screened.

Under the Affordable Care Act, insurers are required to cover, with no copay requirements, preventative care and screening services that receive a grade A or grade B recommendation from USPSTF.

Should Medicare pay for low-dose computed tomography to screen certain patients for lung cancer? A panel of expert advisers will meet April 30 to review the evidence and make a recommendation.

The Centers for Medicare & Medicaid Services has accepted two formal requests to initiate a national coverage analysis on lung cancer screening with low-dose computed tomography (LDCT), which the U.S. Preventative Services Task Force gave a grade B recommendation for people at high risk for lung cancer based on age and smoking history.

©Valeriy Kirsanov/fotolia.com

CMS is specifically asking its Medicare Evidence Development & Coverage Advisory Committee (MEDCAC) to discuss:

• the evidence that identifies which Medicare patients would benefit the most from the screening.

• screening frequency and duration.

• provider characteristics that optimize benefits and minimize harm.

• criteria to identify a test as positive and the impact of false-positive results.

• follow-up tests or treatments.

The agency also seeks to know how these factors will impact patient education and informed consent in Medicare beneficiaries, including the elderly, younger disabled populations, and patients with end-stage renal disease, and on integrating smoking cessation interventions for current smokers.

In order for CMS to issue a national coverage determination for a preventive service, the following criteria must be met: reasonable and necessary for prevention or early detection of an illness or disability; an A- or B-grade recommendation from USPSTF; and appropriate for Medicare Part A or Medicare Part B beneficiaries.

CMS has asked the panel to vote on whether there is adequate evidence to determine if the benefits of lung cancer screening with LDCT outweigh the harms. The agency will specifically ask if there is adequate evidence to determine if LDCT improves health outcomes: in asymptomatic, high-risk adults over 74 years old; with more than three annual LDCT screens; and if the screening program is implemented outside a clinical study.

The agency is also asking for panel input on the harms of lung cancer screening with LDCT in the Medicare population, specifically harms from the scan itself (an average dose of 1.5 mSv), harms from follow-up evaluation of findings in and outside the lungs, and harms from treatment as a result of positive and false-positive results.

CMS will also ask the panel to identify and discuss any clinically significant evidence gaps regarding the use of LDCT in lung cancer screening outside of a clinical trial.

Last December, the USPSTF recommended annual screening for lung cancer with LDCT in adults aged 55- 80 years who have a 30-pack-year smoking history and currently smoke or have quit in the past 15 years. The recommendation states that screening should be stopped once a person has stopped smoking for 15 years or develops a health problem limiting life expectancy or the ability to have curative lung surgery.

The USPSTF’s recommendations were based largely on a systematic review of several randomized, controlled trials published between 2000 and 2013, including the National Lung Screening Trial. That study of more than 50,000 asymptomatic adults, aged 55-74 years, showed a 16% reduction in lung cancer mortality and a 6.7% reduction in all-cause mortality when patients were screened using LDCT. One cancer death was averted for every 320 patients screened, and one death from all causes was prevented in every 219 patients screened.

Under the Affordable Care Act, insurers are required to cover, with no copay requirements, preventative care and screening services that receive a grade A or grade B recommendation from USPSTF.

Should Medicare pay for low-dose computed tomography to screen certain patients for lung cancer? A panel of expert advisers will meet April 30 to review the evidence and make a recommendation.

The Centers for Medicare & Medicaid Services has accepted two formal requests to initiate a national coverage analysis on lung cancer screening with low-dose computed tomography (LDCT), which the U.S. Preventative Services Task Force gave a grade B recommendation for people at high risk for lung cancer based on age and smoking history.

©Valeriy Kirsanov/fotolia.com

CMS is specifically asking its Medicare Evidence Development & Coverage Advisory Committee (MEDCAC) to discuss:

• the evidence that identifies which Medicare patients would benefit the most from the screening.

• screening frequency and duration.

• provider characteristics that optimize benefits and minimize harm.

• criteria to identify a test as positive and the impact of false-positive results.

• follow-up tests or treatments.

The agency also seeks to know how these factors will impact patient education and informed consent in Medicare beneficiaries, including the elderly, younger disabled populations, and patients with end-stage renal disease, and on integrating smoking cessation interventions for current smokers.

In order for CMS to issue a national coverage determination for a preventive service, the following criteria must be met: reasonable and necessary for prevention or early detection of an illness or disability; an A- or B-grade recommendation from USPSTF; and appropriate for Medicare Part A or Medicare Part B beneficiaries.

CMS has asked the panel to vote on whether there is adequate evidence to determine if the benefits of lung cancer screening with LDCT outweigh the harms. The agency will specifically ask if there is adequate evidence to determine if LDCT improves health outcomes: in asymptomatic, high-risk adults over 74 years old; with more than three annual LDCT screens; and if the screening program is implemented outside a clinical study.

The agency is also asking for panel input on the harms of lung cancer screening with LDCT in the Medicare population, specifically harms from the scan itself (an average dose of 1.5 mSv), harms from follow-up evaluation of findings in and outside the lungs, and harms from treatment as a result of positive and false-positive results.

CMS will also ask the panel to identify and discuss any clinically significant evidence gaps regarding the use of LDCT in lung cancer screening outside of a clinical trial.

Last December, the USPSTF recommended annual screening for lung cancer with LDCT in adults aged 55- 80 years who have a 30-pack-year smoking history and currently smoke or have quit in the past 15 years. The recommendation states that screening should be stopped once a person has stopped smoking for 15 years or develops a health problem limiting life expectancy or the ability to have curative lung surgery.

The USPSTF’s recommendations were based largely on a systematic review of several randomized, controlled trials published between 2000 and 2013, including the National Lung Screening Trial. That study of more than 50,000 asymptomatic adults, aged 55-74 years, showed a 16% reduction in lung cancer mortality and a 6.7% reduction in all-cause mortality when patients were screened using LDCT. One cancer death was averted for every 320 patients screened, and one death from all causes was prevented in every 219 patients screened.

Under the Affordable Care Act, insurers are required to cover, with no copay requirements, preventative care and screening services that receive a grade A or grade B recommendation from USPSTF.

A case of non–islet cell tumor hypoglycemia caused by recurrent renal cell carcinoma as a result of the production of high-molecular-weight insulinlike growth factor–2 was reported online in the Journal of Clinical Oncology.

Malignant fibrous histiocytoma is the most common origin of non–islet cell tumor hypoglycemia (NICTH), while NICTH caused by renal cell carcinoma is rare, Dr. Shingo Kimura of the Tohoku University, Sendai, Japan, and associates reported (J. Clin. Oncology 2014 April [doi:10.1200/JCO.2013.49.5374]).

The 60-year-old male patient had a history of radial nephrectomy for a left renal tumor 17 years earlier, but no recurrence had been observed as of the 10-year postoperative follow-up. Computed tomography found a relatively homogeneous, hypervascular 20-cm tumor in the left retroperitoneal space. It was widely adherent to the stomach, pancreas, and colon.

Once the tumor was removed, hypoglycemia disappeared immediately, and the patient has remained free from hypoglycemia and tumor recurrence for 1 year postoperatively.

Hypoglycemia can be induced by several different tumors, including islet cell and non–islet cell tumors, the researchers noted. The most common cause of NICTH is the overproduction of the proprotein insulinlike growth factor–2 (IGF-2) because of its high molecular weight. The structure and function of IGF-2 are similar to those of insulin, and the protein may interfere with the insulin receptor and lead to hypoglycemia.

In the patient, there were strongly positive indications of IGF-2 in both the primary renal tumor and the retroperitoneal tumor; however, hypoglycemia had not been observed in the primary renal tumor. While NICTH originating from renal cell carcinoma is rare, three cases have been reported. However, this is the first case of recurrent renal cell carcinoma that led to NICTH, the researchers said.

The authors reported no financial conflicts of interest.

A case of non–islet cell tumor hypoglycemia caused by recurrent renal cell carcinoma as a result of the production of high-molecular-weight insulinlike growth factor–2 was reported online in the Journal of Clinical Oncology.

Malignant fibrous histiocytoma is the most common origin of non–islet cell tumor hypoglycemia (NICTH), while NICTH caused by renal cell carcinoma is rare, Dr. Shingo Kimura of the Tohoku University, Sendai, Japan, and associates reported (J. Clin. Oncology 2014 April [doi:10.1200/JCO.2013.49.5374]).

The 60-year-old male patient had a history of radial nephrectomy for a left renal tumor 17 years earlier, but no recurrence had been observed as of the 10-year postoperative follow-up. Computed tomography found a relatively homogeneous, hypervascular 20-cm tumor in the left retroperitoneal space. It was widely adherent to the stomach, pancreas, and colon.

Once the tumor was removed, hypoglycemia disappeared immediately, and the patient has remained free from hypoglycemia and tumor recurrence for 1 year postoperatively.

Hypoglycemia can be induced by several different tumors, including islet cell and non–islet cell tumors, the researchers noted. The most common cause of NICTH is the overproduction of the proprotein insulinlike growth factor–2 (IGF-2) because of its high molecular weight. The structure and function of IGF-2 are similar to those of insulin, and the protein may interfere with the insulin receptor and lead to hypoglycemia.

In the patient, there were strongly positive indications of IGF-2 in both the primary renal tumor and the retroperitoneal tumor; however, hypoglycemia had not been observed in the primary renal tumor. While NICTH originating from renal cell carcinoma is rare, three cases have been reported. However, this is the first case of recurrent renal cell carcinoma that led to NICTH, the researchers said.

The authors reported no financial conflicts of interest.

A case of non–islet cell tumor hypoglycemia caused by recurrent renal cell carcinoma as a result of the production of high-molecular-weight insulinlike growth factor–2 was reported online in the Journal of Clinical Oncology.

Malignant fibrous histiocytoma is the most common origin of non–islet cell tumor hypoglycemia (NICTH), while NICTH caused by renal cell carcinoma is rare, Dr. Shingo Kimura of the Tohoku University, Sendai, Japan, and associates reported (J. Clin. Oncology 2014 April [doi:10.1200/JCO.2013.49.5374]).

The 60-year-old male patient had a history of radial nephrectomy for a left renal tumor 17 years earlier, but no recurrence had been observed as of the 10-year postoperative follow-up. Computed tomography found a relatively homogeneous, hypervascular 20-cm tumor in the left retroperitoneal space. It was widely adherent to the stomach, pancreas, and colon.

Once the tumor was removed, hypoglycemia disappeared immediately, and the patient has remained free from hypoglycemia and tumor recurrence for 1 year postoperatively.

Hypoglycemia can be induced by several different tumors, including islet cell and non–islet cell tumors, the researchers noted. The most common cause of NICTH is the overproduction of the proprotein insulinlike growth factor–2 (IGF-2) because of its high molecular weight. The structure and function of IGF-2 are similar to those of insulin, and the protein may interfere with the insulin receptor and lead to hypoglycemia.

In the patient, there were strongly positive indications of IGF-2 in both the primary renal tumor and the retroperitoneal tumor; however, hypoglycemia had not been observed in the primary renal tumor. While NICTH originating from renal cell carcinoma is rare, three cases have been reported. However, this is the first case of recurrent renal cell carcinoma that led to NICTH, the researchers said.

The authors reported no financial conflicts of interest.

Oralair was approved April 1 by the Food and Drug Administration for the treatment of allergic rhinitis; it is the first sublingual allergen extract approved for use in the United States.

Oralair is indicated to treat allergic rhinitis with or without eye inflammation that is induced by certain grass pollens in people aged 10-65 years. The company had proposed that the treatment be approved for patients aged 5 years and older.

The treatment contains a mixture of freeze-dried extracts from the pollens of five grasses: Kentucky Blue Grass, Orchard, Perennial Rye, Sweet Vernal, and Timothy.

Once-daily Oralair is started 4 months prior to the grass-pollen season and continued throughout the season. The first dose is delivered in the doctor’s office, and the remaining doses can be self-administered at home. Manufacturer Greer Laboratories claims that Oralair may reduce grass allergy symptoms for patients within the first allergy season it is taken.

Treatment with a sublingual tablet would open up the treatment options for the approximately 30 million Americans who suffer from allergic rhinitis every year, said Dr. Linda Cox, immediate past president of the American Academy of Allergy Asthma and Immunology and a practicing allergist in Ft. Lauderdale, Fla.

She said that she sees it as a game changer for the treatment of allergic rhinitis.

"What sublingual immunotherapy offers is home treatment and easier access to care because its safety profile is so good," Dr. Cox said in an interview. "That could potentially open up this treatment for the 90% or so of patients who are not receiving anything and are just treating the symptoms."

She added that Oralair treats the underlying causes of allergic rhinitis, not just the symptoms caused by the disease. "It will bring a group of people who are just suffering through their [allergy] seasons and are getting suboptimal control with various products and give them the potential to just knock out their disease," she added.

Approval of Oralair was based on double-blind, placebo-controlled trials in the United States and Europe that enrolled more than 2,500 adults and children. To assess the treatment’s effectiveness, patients reported their symptoms and additional medications needed to cope with their allergy symptoms. During treatment for one grass-pollen season, patients taking Oralair saw a 16%-30% reduction in symptoms and the need for medications, compared with those who received a placebo.

The trials demonstrated that treatment with Oralair before and during allergy season reduced patients’ allergy symptoms and their need for symptom-relieving medication.

The most common adverse events for Oralair, reported in less than 5% of patients, were oral pruritus, throat irritation, ear pruritus, mouth edema, tongue pruritus, cough, and oropharyngeal pain, Greer Laboratories said in an April 1 statement.

Oralair was first approved in Europe in 2008, and is currently approved in 31 countries.

Oralair was approved April 1 by the Food and Drug Administration for the treatment of allergic rhinitis; it is the first sublingual allergen extract approved for use in the United States.

Oralair is indicated to treat allergic rhinitis with or without eye inflammation that is induced by certain grass pollens in people aged 10-65 years. The company had proposed that the treatment be approved for patients aged 5 years and older.

The treatment contains a mixture of freeze-dried extracts from the pollens of five grasses: Kentucky Blue Grass, Orchard, Perennial Rye, Sweet Vernal, and Timothy.

Once-daily Oralair is started 4 months prior to the grass-pollen season and continued throughout the season. The first dose is delivered in the doctor’s office, and the remaining doses can be self-administered at home. Manufacturer Greer Laboratories claims that Oralair may reduce grass allergy symptoms for patients within the first allergy season it is taken.

Treatment with a sublingual tablet would open up the treatment options for the approximately 30 million Americans who suffer from allergic rhinitis every year, said Dr. Linda Cox, immediate past president of the American Academy of Allergy Asthma and Immunology and a practicing allergist in Ft. Lauderdale, Fla.

She said that she sees it as a game changer for the treatment of allergic rhinitis.

"What sublingual immunotherapy offers is home treatment and easier access to care because its safety profile is so good," Dr. Cox said in an interview. "That could potentially open up this treatment for the 90% or so of patients who are not receiving anything and are just treating the symptoms."

She added that Oralair treats the underlying causes of allergic rhinitis, not just the symptoms caused by the disease. "It will bring a group of people who are just suffering through their [allergy] seasons and are getting suboptimal control with various products and give them the potential to just knock out their disease," she added.

Approval of Oralair was based on double-blind, placebo-controlled trials in the United States and Europe that enrolled more than 2,500 adults and children. To assess the treatment’s effectiveness, patients reported their symptoms and additional medications needed to cope with their allergy symptoms. During treatment for one grass-pollen season, patients taking Oralair saw a 16%-30% reduction in symptoms and the need for medications, compared with those who received a placebo.

The trials demonstrated that treatment with Oralair before and during allergy season reduced patients’ allergy symptoms and their need for symptom-relieving medication.

The most common adverse events for Oralair, reported in less than 5% of patients, were oral pruritus, throat irritation, ear pruritus, mouth edema, tongue pruritus, cough, and oropharyngeal pain, Greer Laboratories said in an April 1 statement.

Oralair was first approved in Europe in 2008, and is currently approved in 31 countries.

Oralair was approved April 1 by the Food and Drug Administration for the treatment of allergic rhinitis; it is the first sublingual allergen extract approved for use in the United States.

Oralair is indicated to treat allergic rhinitis with or without eye inflammation that is induced by certain grass pollens in people aged 10-65 years. The company had proposed that the treatment be approved for patients aged 5 years and older.

The treatment contains a mixture of freeze-dried extracts from the pollens of five grasses: Kentucky Blue Grass, Orchard, Perennial Rye, Sweet Vernal, and Timothy.

Once-daily Oralair is started 4 months prior to the grass-pollen season and continued throughout the season. The first dose is delivered in the doctor’s office, and the remaining doses can be self-administered at home. Manufacturer Greer Laboratories claims that Oralair may reduce grass allergy symptoms for patients within the first allergy season it is taken.

Treatment with a sublingual tablet would open up the treatment options for the approximately 30 million Americans who suffer from allergic rhinitis every year, said Dr. Linda Cox, immediate past president of the American Academy of Allergy Asthma and Immunology and a practicing allergist in Ft. Lauderdale, Fla.

She said that she sees it as a game changer for the treatment of allergic rhinitis.

"What sublingual immunotherapy offers is home treatment and easier access to care because its safety profile is so good," Dr. Cox said in an interview. "That could potentially open up this treatment for the 90% or so of patients who are not receiving anything and are just treating the symptoms."

She added that Oralair treats the underlying causes of allergic rhinitis, not just the symptoms caused by the disease. "It will bring a group of people who are just suffering through their [allergy] seasons and are getting suboptimal control with various products and give them the potential to just knock out their disease," she added.

Approval of Oralair was based on double-blind, placebo-controlled trials in the United States and Europe that enrolled more than 2,500 adults and children. To assess the treatment’s effectiveness, patients reported their symptoms and additional medications needed to cope with their allergy symptoms. During treatment for one grass-pollen season, patients taking Oralair saw a 16%-30% reduction in symptoms and the need for medications, compared with those who received a placebo.

The trials demonstrated that treatment with Oralair before and during allergy season reduced patients’ allergy symptoms and their need for symptom-relieving medication.

The most common adverse events for Oralair, reported in less than 5% of patients, were oral pruritus, throat irritation, ear pruritus, mouth edema, tongue pruritus, cough, and oropharyngeal pain, Greer Laboratories said in an April 1 statement.

Oralair was first approved in Europe in 2008, and is currently approved in 31 countries.

Oralair was approved April 1 by the Food and Drug Administration for the treatment of allergic rhinitis; it is the first sublingual allergen extract approved for use in the United States.

Oralair is indicated to treat allergic rhinitis with or without eye inflammation that is induced by certain grass pollens in people aged 10-65 years. The company had proposed that the treatment be approved for patients aged 5 years and older.

The treatment contains a mixture of freeze-dried extracts from the pollens of five grasses: Kentucky Blue Grass, Orchard, Perennial Rye, Sweet Vernal, and Timothy.

© PeskyMonkey/iStockphoto.com

Once-daily Oralair is started 4 months prior to the grass-pollen season and continued throughout the season. The first dose is delivered in the doctor’s office, and the remaining doses can be self-administered at home. Manufacturer Greer Laboratories claims that Oralair may reduce grass allergy symptoms for patients within the first allergy season it is taken.

Treatment with a sublingual tablet would open up the treatment options for the approximately 30 million Americans who suffer from allergic rhinitis every year, said Dr. Linda Cox, immediate past president of the American Academy of Allergy Asthma and Immunology and a practicing allergist in Ft. Lauderdale, Fla.

She said that she sees it as a game changer for the treatment of allergic rhinitis.

"What sublingual immunotherapy offers is home treatment and easier access to care because its safety profile is so good," Dr. Cox said in an interview. "That could potentially open up this treatment for the 90% or so of patients who are not receiving anything and are just treating the symptoms."

She added that Oralair treats the underlying causes of allergic rhinitis, not just the symptoms caused by the disease. "It will bring a group of people who are just suffering through their [allergy] seasons and are getting suboptimal control with various products and give them the potential to just knock out their disease," she added.

Approval of Oralair was based on double-blind, placebo-controlled trials in the United States and Europe that enrolled more than 2,500 adults and children. To assess the treatment’s effectiveness, patients reported their symptoms and additional medications needed to cope with their allergy symptoms. During treatment for one grass-pollen season, patients taking Oralair saw a 16%-30% reduction in symptoms and the need for medications, compared with those who received a placebo.

The trials demonstrated that treatment with Oralair before and during allergy season reduced patients’ allergy symptoms and their need for symptom-relieving medication.

The most common adverse events for Oralair, reported in less than 5% of patients, were oral pruritus, throat irritation, ear pruritus, mouth edema, tongue pruritus, cough, and oropharyngeal pain, Greer Laboratories said in an April 1 statement.

Oralair was first approved in Europe in 2008, and is currently approved in 31 countries.

Oralair was approved April 1 by the Food and Drug Administration for the treatment of allergic rhinitis; it is the first sublingual allergen extract approved for use in the United States.

Oralair is indicated to treat allergic rhinitis with or without eye inflammation that is induced by certain grass pollens in people aged 10-65 years. The company had proposed that the treatment be approved for patients aged 5 years and older.

The treatment contains a mixture of freeze-dried extracts from the pollens of five grasses: Kentucky Blue Grass, Orchard, Perennial Rye, Sweet Vernal, and Timothy.

© PeskyMonkey/iStockphoto.com

Once-daily Oralair is started 4 months prior to the grass-pollen season and continued throughout the season. The first dose is delivered in the doctor’s office, and the remaining doses can be self-administered at home. Manufacturer Greer Laboratories claims that Oralair may reduce grass allergy symptoms for patients within the first allergy season it is taken.

Treatment with a sublingual tablet would open up the treatment options for the approximately 30 million Americans who suffer from allergic rhinitis every year, said Dr. Linda Cox, immediate past president of the American Academy of Allergy Asthma and Immunology and a practicing allergist in Ft. Lauderdale, Fla.

She said that she sees it as a game changer for the treatment of allergic rhinitis.

"What sublingual immunotherapy offers is home treatment and easier access to care because its safety profile is so good," Dr. Cox said in an interview. "That could potentially open up this treatment for the 90% or so of patients who are not receiving anything and are just treating the symptoms."

She added that Oralair treats the underlying causes of allergic rhinitis, not just the symptoms caused by the disease. "It will bring a group of people who are just suffering through their [allergy] seasons and are getting suboptimal control with various products and give them the potential to just knock out their disease," she added.

Approval of Oralair was based on double-blind, placebo-controlled trials in the United States and Europe that enrolled more than 2,500 adults and children. To assess the treatment’s effectiveness, patients reported their symptoms and additional medications needed to cope with their allergy symptoms. During treatment for one grass-pollen season, patients taking Oralair saw a 16%-30% reduction in symptoms and the need for medications, compared with those who received a placebo.

The trials demonstrated that treatment with Oralair before and during allergy season reduced patients’ allergy symptoms and their need for symptom-relieving medication.

The most common adverse events for Oralair, reported in less than 5% of patients, were oral pruritus, throat irritation, ear pruritus, mouth edema, tongue pruritus, cough, and oropharyngeal pain, Greer Laboratories said in an April 1 statement.

Oralair was first approved in Europe in 2008, and is currently approved in 31 countries.

Oralair was approved April 1 by the Food and Drug Administration for the treatment of allergic rhinitis; it is the first sublingual allergen extract approved for use in the United States.

Oralair is indicated to treat allergic rhinitis with or without eye inflammation that is induced by certain grass pollens in people aged 10-65 years. The company had proposed that the treatment be approved for patients aged 5 years and older.

The treatment contains a mixture of freeze-dried extracts from the pollens of five grasses: Kentucky Blue Grass, Orchard, Perennial Rye, Sweet Vernal, and Timothy.

© PeskyMonkey/iStockphoto.com

Once-daily Oralair is started 4 months prior to the grass-pollen season and continued throughout the season. The first dose is delivered in the doctor’s office, and the remaining doses can be self-administered at home. Manufacturer Greer Laboratories claims that Oralair may reduce grass allergy symptoms for patients within the first allergy season it is taken.

Treatment with a sublingual tablet would open up the treatment options for the approximately 30 million Americans who suffer from allergic rhinitis every year, said Dr. Linda Cox, immediate past president of the American Academy of Allergy Asthma and Immunology and a practicing allergist in Ft. Lauderdale, Fla.

She said that she sees it as a game changer for the treatment of allergic rhinitis.

"What sublingual immunotherapy offers is home treatment and easier access to care because its safety profile is so good," Dr. Cox said in an interview. "That could potentially open up this treatment for the 90% or so of patients who are not receiving anything and are just treating the symptoms."

She added that Oralair treats the underlying causes of allergic rhinitis, not just the symptoms caused by the disease. "It will bring a group of people who are just suffering through their [allergy] seasons and are getting suboptimal control with various products and give them the potential to just knock out their disease," she added.

Approval of Oralair was based on double-blind, placebo-controlled trials in the United States and Europe that enrolled more than 2,500 adults and children. To assess the treatment’s effectiveness, patients reported their symptoms and additional medications needed to cope with their allergy symptoms. During treatment for one grass-pollen season, patients taking Oralair saw a 16%-30% reduction in symptoms and the need for medications, compared with those who received a placebo.

The trials demonstrated that treatment with Oralair before and during allergy season reduced patients’ allergy symptoms and their need for symptom-relieving medication.

The most common adverse events for Oralair, reported in less than 5% of patients, were oral pruritus, throat irritation, ear pruritus, mouth edema, tongue pruritus, cough, and oropharyngeal pain, Greer Laboratories said in an April 1 statement.

Oralair was first approved in Europe in 2008, and is currently approved in 31 countries.

SILVER SPRING, MD. – A Food and Drug Administration advisory committee voted unanimously to support the approval of the antibacterial drug dalbavancin for the treatment of acute bacterial skin and skin structure infections.

At a March 31 meeting, the FDA Anti-Infective Drugs Advisory Committee voted 12-0 that dalbavancin (Dalvance), manufactured by Durata Therapeutics, is safe and effective for the treatment of acute bacterial skin and skin structure infections (ABSSSI). Because of its long elimination half-life, the firm is proposing a dosing regimen of 1,000 mg on day 1 and 500 mg on day 8, administered intravenously.

Durata is seeking a proposed indication for the lipoglycopeptide antibacterial drug to treat adult patients with ABSSSI caused by the following gram-positive microorganisms: Staphylococcus aureus (including methicillin-resistant isolates [MRSA]), Streptococcus pyogenes, Streptococcus agalactiae, and the Streptococcus anginosus group (including S. anginosus, S. intermedius,and S. constellatus).

The firm’s phase III data was composed of five studies: one uncomplicated skin infection study comparing dalbavancin to cefazolin/cephalexin; two complicated skin infection studies (one comparing skin infection caused by MRSA, dalbavancin to vancomycin/cephalexin; one comparing dalbavancin to linezolid) and two ABSSSI studies (DUR001-301/-302) – both comparing dalbavancin to vancomycin/linezolid.

The DUR001-301 and DUR001-302 studies were identical in design; noninferiority, double-blind, double-dummy, randomized trials comparing two weekly doses of dalbavancin (on day 1 and day 8) to vancomycin IV with the option to switch to oral linezolid in patients with ABSSSI known or suspected to be caused by gram-positive bacteria. Treatment duration lasted 10-14 days.

The primary endpoints for DUR001-301/-302 were early response (defined as cessation of spread of the lesion and absence of fever) at 48-72 hours post initiation of therapy. The noninferiority margin was 10%.

Both studies showed dalbavancin to be noninferior to the regimen of vancomycin/linezolid. Since the lower bound of the 95% confidence interval for the treatment difference was above –10% (–4.6% in DUR001-301 and –7.4% in DUR001-302), both trials met their primary endpoints.

Both studies also met the key secondary endpoint, in which clinical response is defined as a greater than or equal to 20% reduction in lesion area from baseline (no fever component).

The FDA also analyzed the sensitivity studies of additional secondary efficacy outcome measures of clinical status at the end of treatment in the intent-to-treat and clinically evaluable populations. There were inconsistencies between the two trials, with lower success rates for dalbavancin vs. the comparator in DUR001-301 and slightly higher success rates for dalbavancin in DUR001-302.

"Overall, in these sensitivity analyses success rates at [end of treatment/short-term follow-up] tended to be less favorable in both treatment arms in both trials as stricter requirements were placed on the degree of erythema necessary to be evaluated as a success," the FDA wrote in its pre–committee executive summary.

The panel members concluded that the drug was generally both safe and effective, and welcomed it as another treatment option for patients.

"This just gives that clinician who is trying to personalize medicine more tools in their toolbox," said Dr. Alan Magill, a director on malaria policy at the Bill and Melinda Gates Foundation. "I think that’s a very important consideration going forward."

Additionally, panelists suggested that the drug labeling address the major safety finding of possible dalbavancin-associated liver injury, particularly in patients with liver disease.

"I have some issues with liver function tests," said Dr. Paul G. Auwaerter, clinical director of the division of infectious diseases at the Johns Hopkins University, Baltimore. "The labeling might consider something such as preexisting liver disease, or if liver function tests are rising during the hospitalization, there could be consideration whether the second drug administration should be given."

Dr. James M. Steckelberg, professor of medicine in the Mayo Clinic’s division of infectious diseases, Rochester, Minn., noted, "If you’re going to give the second dose on day 8, I’d particularly want to check those [liver function] levels before you do that dose, and probably have the result back, rather than do that later. I would give some thought to that, especially in the labeling, about what should be done about safety monitoring for a drug that’s dosed totally differently from anything we’re doing now."

Furthermore, panelists advised the FDA and the sponsor to develop additional postmarket studies.

"I recommend that the agency work closely with the sponsor to develop some cogent and clear guidelines for follow-up and monitoring for safety before clinicians are using this drug. It’s going to be used a lot, probably in the outpatient setting, and the whole paradigm is very different from what’s currently done," Dr. Steckelberg said.

Dr. Magill also recommended that a postmarket study address pediatric patient populations.

"There are several unanswered questions about other patient populations, like pediatrics, and potential for other indications. I think what happens next is very important, whether it’s a postmarketing surveillance of some kind, required phase IV studies, or the sponsor seeking new indications with new data and a new trial," Dr. Magill said. "I’d be looking forward to see how that evolves."

SILVER SPRING, MD. – A Food and Drug Administration advisory committee voted unanimously to support the approval of the antibacterial drug dalbavancin for the treatment of acute bacterial skin and skin structure infections.

At a March 31 meeting, the FDA Anti-Infective Drugs Advisory Committee voted 12-0 that dalbavancin (Dalvance), manufactured by Durata Therapeutics, is safe and effective for the treatment of acute bacterial skin and skin structure infections (ABSSSI). Because of its long elimination half-life, the firm is proposing a dosing regimen of 1,000 mg on day 1 and 500 mg on day 8, administered intravenously.

Durata is seeking a proposed indication for the lipoglycopeptide antibacterial drug to treat adult patients with ABSSSI caused by the following gram-positive microorganisms: Staphylococcus aureus (including methicillin-resistant isolates [MRSA]), Streptococcus pyogenes, Streptococcus agalactiae, and the Streptococcus anginosus group (including S. anginosus, S. intermedius,and S. constellatus).

The firm’s phase III data was composed of five studies: one uncomplicated skin infection study comparing dalbavancin to cefazolin/cephalexin; two complicated skin infection studies (one comparing skin infection caused by MRSA, dalbavancin to vancomycin/cephalexin; one comparing dalbavancin to linezolid) and two ABSSSI studies (DUR001-301/-302) – both comparing dalbavancin to vancomycin/linezolid.

The DUR001-301 and DUR001-302 studies were identical in design; noninferiority, double-blind, double-dummy, randomized trials comparing two weekly doses of dalbavancin (on day 1 and day 8) to vancomycin IV with the option to switch to oral linezolid in patients with ABSSSI known or suspected to be caused by gram-positive bacteria. Treatment duration lasted 10-14 days.

The primary endpoints for DUR001-301/-302 were early response (defined as cessation of spread of the lesion and absence of fever) at 48-72 hours post initiation of therapy. The noninferiority margin was 10%.

Both studies showed dalbavancin to be noninferior to the regimen of vancomycin/linezolid. Since the lower bound of the 95% confidence interval for the treatment difference was above –10% (–4.6% in DUR001-301 and –7.4% in DUR001-302), both trials met their primary endpoints.

Both studies also met the key secondary endpoint, in which clinical response is defined as a greater than or equal to 20% reduction in lesion area from baseline (no fever component).

The FDA also analyzed the sensitivity studies of additional secondary efficacy outcome measures of clinical status at the end of treatment in the intent-to-treat and clinically evaluable populations. There were inconsistencies between the two trials, with lower success rates for dalbavancin vs. the comparator in DUR001-301 and slightly higher success rates for dalbavancin in DUR001-302.

"Overall, in these sensitivity analyses success rates at [end of treatment/short-term follow-up] tended to be less favorable in both treatment arms in both trials as stricter requirements were placed on the degree of erythema necessary to be evaluated as a success," the FDA wrote in its pre–committee executive summary.

The panel members concluded that the drug was generally both safe and effective, and welcomed it as another treatment option for patients.

"This just gives that clinician who is trying to personalize medicine more tools in their toolbox," said Dr. Alan Magill, a director on malaria policy at the Bill and Melinda Gates Foundation. "I think that’s a very important consideration going forward."

Additionally, panelists suggested that the drug labeling address the major safety finding of possible dalbavancin-associated liver injury, particularly in patients with liver disease.

"I have some issues with liver function tests," said Dr. Paul G. Auwaerter, clinical director of the division of infectious diseases at the Johns Hopkins University, Baltimore. "The labeling might consider something such as preexisting liver disease, or if liver function tests are rising during the hospitalization, there could be consideration whether the second drug administration should be given."

Dr. James M. Steckelberg, professor of medicine in the Mayo Clinic’s division of infectious diseases, Rochester, Minn., noted, "If you’re going to give the second dose on day 8, I’d particularly want to check those [liver function] levels before you do that dose, and probably have the result back, rather than do that later. I would give some thought to that, especially in the labeling, about what should be done about safety monitoring for a drug that’s dosed totally differently from anything we’re doing now."

Furthermore, panelists advised the FDA and the sponsor to develop additional postmarket studies.

"I recommend that the agency work closely with the sponsor to develop some cogent and clear guidelines for follow-up and monitoring for safety before clinicians are using this drug. It’s going to be used a lot, probably in the outpatient setting, and the whole paradigm is very different from what’s currently done," Dr. Steckelberg said.

Dr. Magill also recommended that a postmarket study address pediatric patient populations.

"There are several unanswered questions about other patient populations, like pediatrics, and potential for other indications. I think what happens next is very important, whether it’s a postmarketing surveillance of some kind, required phase IV studies, or the sponsor seeking new indications with new data and a new trial," Dr. Magill said. "I’d be looking forward to see how that evolves."

SILVER SPRING, MD. – A Food and Drug Administration advisory committee voted unanimously to support the approval of the antibacterial drug dalbavancin for the treatment of acute bacterial skin and skin structure infections.

At a March 31 meeting, the FDA Anti-Infective Drugs Advisory Committee voted 12-0 that dalbavancin (Dalvance), manufactured by Durata Therapeutics, is safe and effective for the treatment of acute bacterial skin and skin structure infections (ABSSSI). Because of its long elimination half-life, the firm is proposing a dosing regimen of 1,000 mg on day 1 and 500 mg on day 8, administered intravenously.

Durata is seeking a proposed indication for the lipoglycopeptide antibacterial drug to treat adult patients with ABSSSI caused by the following gram-positive microorganisms: Staphylococcus aureus (including methicillin-resistant isolates [MRSA]), Streptococcus pyogenes, Streptococcus agalactiae, and the Streptococcus anginosus group (including S. anginosus, S. intermedius,and S. constellatus).

The firm’s phase III data was composed of five studies: one uncomplicated skin infection study comparing dalbavancin to cefazolin/cephalexin; two complicated skin infection studies (one comparing skin infection caused by MRSA, dalbavancin to vancomycin/cephalexin; one comparing dalbavancin to linezolid) and two ABSSSI studies (DUR001-301/-302) – both comparing dalbavancin to vancomycin/linezolid.

The DUR001-301 and DUR001-302 studies were identical in design; noninferiority, double-blind, double-dummy, randomized trials comparing two weekly doses of dalbavancin (on day 1 and day 8) to vancomycin IV with the option to switch to oral linezolid in patients with ABSSSI known or suspected to be caused by gram-positive bacteria. Treatment duration lasted 10-14 days.

The primary endpoints for DUR001-301/-302 were early response (defined as cessation of spread of the lesion and absence of fever) at 48-72 hours post initiation of therapy. The noninferiority margin was 10%.

Both studies showed dalbavancin to be noninferior to the regimen of vancomycin/linezolid. Since the lower bound of the 95% confidence interval for the treatment difference was above –10% (–4.6% in DUR001-301 and –7.4% in DUR001-302), both trials met their primary endpoints.

Both studies also met the key secondary endpoint, in which clinical response is defined as a greater than or equal to 20% reduction in lesion area from baseline (no fever component).

The FDA also analyzed the sensitivity studies of additional secondary efficacy outcome measures of clinical status at the end of treatment in the intent-to-treat and clinically evaluable populations. There were inconsistencies between the two trials, with lower success rates for dalbavancin vs. the comparator in DUR001-301 and slightly higher success rates for dalbavancin in DUR001-302.

"Overall, in these sensitivity analyses success rates at [end of treatment/short-term follow-up] tended to be less favorable in both treatment arms in both trials as stricter requirements were placed on the degree of erythema necessary to be evaluated as a success," the FDA wrote in its pre–committee executive summary.

The panel members concluded that the drug was generally both safe and effective, and welcomed it as another treatment option for patients.

"This just gives that clinician who is trying to personalize medicine more tools in their toolbox," said Dr. Alan Magill, a director on malaria policy at the Bill and Melinda Gates Foundation. "I think that’s a very important consideration going forward."

Additionally, panelists suggested that the drug labeling address the major safety finding of possible dalbavancin-associated liver injury, particularly in patients with liver disease.

"I have some issues with liver function tests," said Dr. Paul G. Auwaerter, clinical director of the division of infectious diseases at the Johns Hopkins University, Baltimore. "The labeling might consider something such as preexisting liver disease, or if liver function tests are rising during the hospitalization, there could be consideration whether the second drug administration should be given."

Dr. James M. Steckelberg, professor of medicine in the Mayo Clinic’s division of infectious diseases, Rochester, Minn., noted, "If you’re going to give the second dose on day 8, I’d particularly want to check those [liver function] levels before you do that dose, and probably have the result back, rather than do that later. I would give some thought to that, especially in the labeling, about what should be done about safety monitoring for a drug that’s dosed totally differently from anything we’re doing now."

Furthermore, panelists advised the FDA and the sponsor to develop additional postmarket studies.

"I recommend that the agency work closely with the sponsor to develop some cogent and clear guidelines for follow-up and monitoring for safety before clinicians are using this drug. It’s going to be used a lot, probably in the outpatient setting, and the whole paradigm is very different from what’s currently done," Dr. Steckelberg said.

Dr. Magill also recommended that a postmarket study address pediatric patient populations.

"There are several unanswered questions about other patient populations, like pediatrics, and potential for other indications. I think what happens next is very important, whether it’s a postmarketing surveillance of some kind, required phase IV studies, or the sponsor seeking new indications with new data and a new trial," Dr. Magill said. "I’d be looking forward to see how that evolves."

SILVER SPRING, MD. – A Food and Drug Administration advisory committee voted unanimously in support of the approval of the antibacterial drug tedizolid phosphate for acute bacterial skin and skin structure infections (ABSSSI).

At a March 31 meeting, the FDA Anti-Infective Drugs Advisory Committee voted 14-0 that tedizolid phosphate (Sivextro), made by Cubist Pharmaceuticals, is safe and effective for the treatment of ABSSSI caused by susceptible isolates of the designated microorganisms. Patients in the firm’s phase III study received a daily 200 mg dose of the antibacterial drug for six days either orally or intravenously.

The firm is seeking a proposed indication of ABSSSI caused by susceptible isolates of the following gram-positive microorganisms: Staphylococcus aureus (including methicillin-resistant [MRSA] and methicillin-susceptible [MSSA] variations), Streptococcus pyogenes, Staphylococcus haemolyticus, Staphylococcus lugdunensis, Streptococcus agalactiae, the Streptococcus anginosus group (including S. anginosus, S. intermedius and S. constellatus), and Enterococcus faecalis. ABSSSI also includes cellulitis/erysipelas, major cutaneous abscess with surrounding erythema, and wound infection.

The phase III study consisted of two trials: study TR701-112 and study TR701-113. Both studies were global, multicenter, randomized, active-controlled, double-blind, double-dummy noninferiority trials. Subjects in both studies were stratified according to geographic region and one of three different clinical syndromes: cellulitis/erysipelas, major cutaneous abscesses, and wound infections. The first study was also stratified by the presence or absence of fever at baseline.

Study TR701-12 compared 6 days of oral tedizolid phosphate 200 mg daily with 10 days of oral linezolid 600 mg twice daily for the treatment of ABSSSI. Study TR701-113 differed in that patients were stratified either to 6 days of 200 mg IV or oral tedizolid phosphate and 10 days of twice daily 600 mg IV or oral linezolid. Subjects were required to receive at least two IV doses, and then had the option to switch to oral medication provided certain pre-specified criteria were met.

The primary endpoint of each study was the percentage of patients who responded during early clinical evaluation at the 48-72 hour visit in the intent-to-treat population. However, the two studies’ primary endpoints were measured differently because the first study protocol was designed prior to 2010 FDA draft guidance on ABSSSI drugs, and the second study protocol was designed to match the 2013 final FDA guidance.

The first study’s primary endpoint was no increase in lesion surface area from baseline and oral temperature of less than or equal to 36.7 degrees Celsius, confirmed by a second temperature measurement within 24 hours. (JAMA 2013;309:559-9 [doi:10.1001/jama.2013.241]).

The second study’s primary endpoint was greater than or equal to a 20% reduction in lesion area of erythema, edema and/or induration (length X width), compared with baseline.

In both studies, 6 days of once-daily tedizolid was noninferior to 10 days of twice-daily linezolid. Both studies also met their first secondary endpoint of clinical response at end-of-therapy visit (day 11) in the intent-to-treat population, and the second secondary endpoint of achieving investigator’s assessment of clinical success at the post therapy evaluation visit in the intent-to-treat population.

Overall, the panel found the drug to be safe and efficacious, offering clinicians another antibiotic option for patients.

"The reason I voted yes is, given the favorable comparison against the comparator linezolid, it offers the benefit of a shorter course of therapy, less frequent doses per day, and there appears to be an equivalency in the kind and the severity of side effects," said Dr. Thomas A. Moore of the department of medicine at the University of Kansas, Wichita.

In terms of labeling, the panel advised against including children aged 12-18 years in the drug’s indication, and recommended additional studies of the drug’s safety and efficacy in this population. The panel also recommended a post-market study of the long-term safety of the drug beyond 6 days of use.

Dr. Moore also recommended noting the number of gastrointestinal side effects in the trial.

"The labeling would have to address the rather frequent number of adverse effects. I was surprised to see the analysis that at least half of the patients had gastrointestinal symptoms," he said. "Nevertheless, this is a clearly effective drug and one which will add to our armamentarium against resistant organisms."

SILVER SPRING, MD. – A Food and Drug Administration advisory committee voted unanimously in support of the approval of the antibacterial drug tedizolid phosphate for acute bacterial skin and skin structure infections (ABSSSI).

At a March 31 meeting, the FDA Anti-Infective Drugs Advisory Committee voted 14-0 that tedizolid phosphate (Sivextro), made by Cubist Pharmaceuticals, is safe and effective for the treatment of ABSSSI caused by susceptible isolates of the designated microorganisms. Patients in the firm’s phase III study received a daily 200 mg dose of the antibacterial drug for six days either orally or intravenously.

The firm is seeking a proposed indication of ABSSSI caused by susceptible isolates of the following gram-positive microorganisms: Staphylococcus aureus (including methicillin-resistant [MRSA] and methicillin-susceptible [MSSA] variations), Streptococcus pyogenes, Staphylococcus haemolyticus, Staphylococcus lugdunensis, Streptococcus agalactiae, the Streptococcus anginosus group (including S. anginosus, S. intermedius and S. constellatus), and Enterococcus faecalis. ABSSSI also includes cellulitis/erysipelas, major cutaneous abscess with surrounding erythema, and wound infection.

The phase III study consisted of two trials: study TR701-112 and study TR701-113. Both studies were global, multicenter, randomized, active-controlled, double-blind, double-dummy noninferiority trials. Subjects in both studies were stratified according to geographic region and one of three different clinical syndromes: cellulitis/erysipelas, major cutaneous abscesses, and wound infections. The first study was also stratified by the presence or absence of fever at baseline.

Study TR701-12 compared 6 days of oral tedizolid phosphate 200 mg daily with 10 days of oral linezolid 600 mg twice daily for the treatment of ABSSSI. Study TR701-113 differed in that patients were stratified either to 6 days of 200 mg IV or oral tedizolid phosphate and 10 days of twice daily 600 mg IV or oral linezolid. Subjects were required to receive at least two IV doses, and then had the option to switch to oral medication provided certain pre-specified criteria were met.

The primary endpoint of each study was the percentage of patients who responded during early clinical evaluation at the 48-72 hour visit in the intent-to-treat population. However, the two studies’ primary endpoints were measured differently because the first study protocol was designed prior to 2010 FDA draft guidance on ABSSSI drugs, and the second study protocol was designed to match the 2013 final FDA guidance.

The first study’s primary endpoint was no increase in lesion surface area from baseline and oral temperature of less than or equal to 36.7 degrees Celsius, confirmed by a second temperature measurement within 24 hours. (JAMA 2013;309:559-9 [doi:10.1001/jama.2013.241]).

The second study’s primary endpoint was greater than or equal to a 20% reduction in lesion area of erythema, edema and/or induration (length X width), compared with baseline.

In both studies, 6 days of once-daily tedizolid was noninferior to 10 days of twice-daily linezolid. Both studies also met their first secondary endpoint of clinical response at end-of-therapy visit (day 11) in the intent-to-treat population, and the second secondary endpoint of achieving investigator’s assessment of clinical success at the post therapy evaluation visit in the intent-to-treat population.

Overall, the panel found the drug to be safe and efficacious, offering clinicians another antibiotic option for patients.

"The reason I voted yes is, given the favorable comparison against the comparator linezolid, it offers the benefit of a shorter course of therapy, less frequent doses per day, and there appears to be an equivalency in the kind and the severity of side effects," said Dr. Thomas A. Moore of the department of medicine at the University of Kansas, Wichita.

In terms of labeling, the panel advised against including children aged 12-18 years in the drug’s indication, and recommended additional studies of the drug’s safety and efficacy in this population. The panel also recommended a post-market study of the long-term safety of the drug beyond 6 days of use.

Dr. Moore also recommended noting the number of gastrointestinal side effects in the trial.

"The labeling would have to address the rather frequent number of adverse effects. I was surprised to see the analysis that at least half of the patients had gastrointestinal symptoms," he said. "Nevertheless, this is a clearly effective drug and one which will add to our armamentarium against resistant organisms."

SILVER SPRING, MD. – A Food and Drug Administration advisory committee voted unanimously in support of the approval of the antibacterial drug tedizolid phosphate for acute bacterial skin and skin structure infections (ABSSSI).

At a March 31 meeting, the FDA Anti-Infective Drugs Advisory Committee voted 14-0 that tedizolid phosphate (Sivextro), made by Cubist Pharmaceuticals, is safe and effective for the treatment of ABSSSI caused by susceptible isolates of the designated microorganisms. Patients in the firm’s phase III study received a daily 200 mg dose of the antibacterial drug for six days either orally or intravenously.

The firm is seeking a proposed indication of ABSSSI caused by susceptible isolates of the following gram-positive microorganisms: Staphylococcus aureus (including methicillin-resistant [MRSA] and methicillin-susceptible [MSSA] variations), Streptococcus pyogenes, Staphylococcus haemolyticus, Staphylococcus lugdunensis, Streptococcus agalactiae, the Streptococcus anginosus group (including S. anginosus, S. intermedius and S. constellatus), and Enterococcus faecalis. ABSSSI also includes cellulitis/erysipelas, major cutaneous abscess with surrounding erythema, and wound infection.

The phase III study consisted of two trials: study TR701-112 and study TR701-113. Both studies were global, multicenter, randomized, active-controlled, double-blind, double-dummy noninferiority trials. Subjects in both studies were stratified according to geographic region and one of three different clinical syndromes: cellulitis/erysipelas, major cutaneous abscesses, and wound infections. The first study was also stratified by the presence or absence of fever at baseline.

Study TR701-12 compared 6 days of oral tedizolid phosphate 200 mg daily with 10 days of oral linezolid 600 mg twice daily for the treatment of ABSSSI. Study TR701-113 differed in that patients were stratified either to 6 days of 200 mg IV or oral tedizolid phosphate and 10 days of twice daily 600 mg IV or oral linezolid. Subjects were required to receive at least two IV doses, and then had the option to switch to oral medication provided certain pre-specified criteria were met.

The primary endpoint of each study was the percentage of patients who responded during early clinical evaluation at the 48-72 hour visit in the intent-to-treat population. However, the two studies’ primary endpoints were measured differently because the first study protocol was designed prior to 2010 FDA draft guidance on ABSSSI drugs, and the second study protocol was designed to match the 2013 final FDA guidance.

The first study’s primary endpoint was no increase in lesion surface area from baseline and oral temperature of less than or equal to 36.7 degrees Celsius, confirmed by a second temperature measurement within 24 hours. (JAMA 2013;309:559-9 [doi:10.1001/jama.2013.241]).

The second study’s primary endpoint was greater than or equal to a 20% reduction in lesion area of erythema, edema and/or induration (length X width), compared with baseline.

In both studies, 6 days of once-daily tedizolid was noninferior to 10 days of twice-daily linezolid. Both studies also met their first secondary endpoint of clinical response at end-of-therapy visit (day 11) in the intent-to-treat population, and the second secondary endpoint of achieving investigator’s assessment of clinical success at the post therapy evaluation visit in the intent-to-treat population.

Overall, the panel found the drug to be safe and efficacious, offering clinicians another antibiotic option for patients.

"The reason I voted yes is, given the favorable comparison against the comparator linezolid, it offers the benefit of a shorter course of therapy, less frequent doses per day, and there appears to be an equivalency in the kind and the severity of side effects," said Dr. Thomas A. Moore of the department of medicine at the University of Kansas, Wichita.

In terms of labeling, the panel advised against including children aged 12-18 years in the drug’s indication, and recommended additional studies of the drug’s safety and efficacy in this population. The panel also recommended a post-market study of the long-term safety of the drug beyond 6 days of use.

Dr. Moore also recommended noting the number of gastrointestinal side effects in the trial.

"The labeling would have to address the rather frequent number of adverse effects. I was surprised to see the analysis that at least half of the patients had gastrointestinal symptoms," he said. "Nevertheless, this is a clearly effective drug and one which will add to our armamentarium against resistant organisms."