User login
Idle hands
If you consider yourself a busy pediatrician and haven’t seen a Fidget Spinner, you are either a neonatologist or have been on maternity leave for the last 3 months. Because I no longer see patients, my introduction to Fidget Spinners came via my 10-year-old grandson, Peter. Last week, I was tasked with meeting him after school and accompanying him on his bike ride to our house. Instead of a hi-grampy-smile he shouted, “Look what Jonah gave me!”
Peter held in his hand a collection of stainless steel nuts, a bolt, and a pair of roller blade wheel bearings that had been epoxified together so that they would spin with the flick of a finger. This was a homemade Fidget. This wasn’t a “gadget,” a term that would imply to me that it might have some function. No, this was a Fidget, and its sole purpose was to keep the user’s hands busy, usually by spinning it.
Of course ,within days of my enlightening, I discovered articles about the Fidget tsunami in several national newspapers. The most complete chronology of the Fidget’s trajectory from its unheralded birth in the 1990s to its explosive entry on grade school scene in the last 6 months appeared in the New York Times. (Alex Williams. “How Fidget Spinners Became the Hula-Hoop for Generation Z.” May 6, 2017).
For a brief period of time, Fidget Spinners were touted by some “experts” as calming devices for both adults and children who have been labeled with ADHD. I assume this unsubstantiated benefit was in part based on the aphorism attributed to St. Jerome that “idle hands are the Devil’s workshop.” However, when Fidgets escaped from their niche for the distractable and inattentive and entered the mainstream, educators and school administrators quickly realized that, what might have been a cure for some students, can become an intolerable distraction for the entire classroom. Not surprisingly, hastily enacted rules and restrictions have only made the spinners even more popular, must-have items.
While Fidget Spinners are the latest rage for the grade-school crowd, the attraction between palm-sized objects and young children has probably existed since the first Neanderthal infant picked up a shiny stream-polished pebble or a dried seed pod that rattled. I suspect that, if you begin keeping a record, you will discover that, on an average day, at least half of your patients under the age of 4 years have arrived with some temporarily treasured object clutched in their hands – a smooth stone, a matchbox truck, or a Lego or Playmobil figure. These treasures are not to be confused with the plushy and soft security or transition objects that are primarily sleep associated.
What I’m talking about are the recently found items that fulfill a primordial need of little hands to hold something ... anything. For the most part, they are ephemeral and will be replaced in a day or a week with another palm-sized tactile companion.
This compulsion to hold something seems to persist longer in boys and becomes stronger when they are exposed to objects that spin, roll, or make noise. Even Peter, at age 10, invariably shows up at a restaurant with a fidgetable item in his hand to help him endure the interminable wait for his pasta or pizza to arrive at the table. As distracting as it may be to his fellow diners, it certainly beats the alternative of kicking his sister under the table.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].
If you consider yourself a busy pediatrician and haven’t seen a Fidget Spinner, you are either a neonatologist or have been on maternity leave for the last 3 months. Because I no longer see patients, my introduction to Fidget Spinners came via my 10-year-old grandson, Peter. Last week, I was tasked with meeting him after school and accompanying him on his bike ride to our house. Instead of a hi-grampy-smile he shouted, “Look what Jonah gave me!”
Peter held in his hand a collection of stainless steel nuts, a bolt, and a pair of roller blade wheel bearings that had been epoxified together so that they would spin with the flick of a finger. This was a homemade Fidget. This wasn’t a “gadget,” a term that would imply to me that it might have some function. No, this was a Fidget, and its sole purpose was to keep the user’s hands busy, usually by spinning it.
Of course ,within days of my enlightening, I discovered articles about the Fidget tsunami in several national newspapers. The most complete chronology of the Fidget’s trajectory from its unheralded birth in the 1990s to its explosive entry on grade school scene in the last 6 months appeared in the New York Times. (Alex Williams. “How Fidget Spinners Became the Hula-Hoop for Generation Z.” May 6, 2017).
For a brief period of time, Fidget Spinners were touted by some “experts” as calming devices for both adults and children who have been labeled with ADHD. I assume this unsubstantiated benefit was in part based on the aphorism attributed to St. Jerome that “idle hands are the Devil’s workshop.” However, when Fidgets escaped from their niche for the distractable and inattentive and entered the mainstream, educators and school administrators quickly realized that, what might have been a cure for some students, can become an intolerable distraction for the entire classroom. Not surprisingly, hastily enacted rules and restrictions have only made the spinners even more popular, must-have items.
While Fidget Spinners are the latest rage for the grade-school crowd, the attraction between palm-sized objects and young children has probably existed since the first Neanderthal infant picked up a shiny stream-polished pebble or a dried seed pod that rattled. I suspect that, if you begin keeping a record, you will discover that, on an average day, at least half of your patients under the age of 4 years have arrived with some temporarily treasured object clutched in their hands – a smooth stone, a matchbox truck, or a Lego or Playmobil figure. These treasures are not to be confused with the plushy and soft security or transition objects that are primarily sleep associated.
What I’m talking about are the recently found items that fulfill a primordial need of little hands to hold something ... anything. For the most part, they are ephemeral and will be replaced in a day or a week with another palm-sized tactile companion.
This compulsion to hold something seems to persist longer in boys and becomes stronger when they are exposed to objects that spin, roll, or make noise. Even Peter, at age 10, invariably shows up at a restaurant with a fidgetable item in his hand to help him endure the interminable wait for his pasta or pizza to arrive at the table. As distracting as it may be to his fellow diners, it certainly beats the alternative of kicking his sister under the table.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].
If you consider yourself a busy pediatrician and haven’t seen a Fidget Spinner, you are either a neonatologist or have been on maternity leave for the last 3 months. Because I no longer see patients, my introduction to Fidget Spinners came via my 10-year-old grandson, Peter. Last week, I was tasked with meeting him after school and accompanying him on his bike ride to our house. Instead of a hi-grampy-smile he shouted, “Look what Jonah gave me!”
Peter held in his hand a collection of stainless steel nuts, a bolt, and a pair of roller blade wheel bearings that had been epoxified together so that they would spin with the flick of a finger. This was a homemade Fidget. This wasn’t a “gadget,” a term that would imply to me that it might have some function. No, this was a Fidget, and its sole purpose was to keep the user’s hands busy, usually by spinning it.
Of course ,within days of my enlightening, I discovered articles about the Fidget tsunami in several national newspapers. The most complete chronology of the Fidget’s trajectory from its unheralded birth in the 1990s to its explosive entry on grade school scene in the last 6 months appeared in the New York Times. (Alex Williams. “How Fidget Spinners Became the Hula-Hoop for Generation Z.” May 6, 2017).
For a brief period of time, Fidget Spinners were touted by some “experts” as calming devices for both adults and children who have been labeled with ADHD. I assume this unsubstantiated benefit was in part based on the aphorism attributed to St. Jerome that “idle hands are the Devil’s workshop.” However, when Fidgets escaped from their niche for the distractable and inattentive and entered the mainstream, educators and school administrators quickly realized that, what might have been a cure for some students, can become an intolerable distraction for the entire classroom. Not surprisingly, hastily enacted rules and restrictions have only made the spinners even more popular, must-have items.
While Fidget Spinners are the latest rage for the grade-school crowd, the attraction between palm-sized objects and young children has probably existed since the first Neanderthal infant picked up a shiny stream-polished pebble or a dried seed pod that rattled. I suspect that, if you begin keeping a record, you will discover that, on an average day, at least half of your patients under the age of 4 years have arrived with some temporarily treasured object clutched in their hands – a smooth stone, a matchbox truck, or a Lego or Playmobil figure. These treasures are not to be confused with the plushy and soft security or transition objects that are primarily sleep associated.
What I’m talking about are the recently found items that fulfill a primordial need of little hands to hold something ... anything. For the most part, they are ephemeral and will be replaced in a day or a week with another palm-sized tactile companion.
This compulsion to hold something seems to persist longer in boys and becomes stronger when they are exposed to objects that spin, roll, or make noise. Even Peter, at age 10, invariably shows up at a restaurant with a fidgetable item in his hand to help him endure the interminable wait for his pasta or pizza to arrive at the table. As distracting as it may be to his fellow diners, it certainly beats the alternative of kicking his sister under the table.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].
Meningococcal B, C vaccines together lead to adequate immune response
and it demonstrated adequate immune response to MenB, according to Marco Aurelio P. Safadi, MD, of Santa Casa de São Paulo (Brazil) School of Medical Sciences, and his associates.
Of 117 healthy infants who received 4CMenB concomitantly with MenC CRM and 111 who received MenC CRM alone, 99%-100% of infants had serum bactericidal antibody assay using human complement (hSBA) titres 1:8 or greater against MenC after the second vaccination of the primary series (3 months, 5 months, and 12 months of age), and 100% of infants reached these titres after the booster vaccination.
There were more local reactions, such as tenderness, with the combination MenB and MenC vaccinations than with the MenC vaccine alone, as well as systemic adverse reactions such as unusual crying and fever.
Read more in the journal Vaccine (2017 Apr 11;35[16]:2052-9).
and it demonstrated adequate immune response to MenB, according to Marco Aurelio P. Safadi, MD, of Santa Casa de São Paulo (Brazil) School of Medical Sciences, and his associates.
Of 117 healthy infants who received 4CMenB concomitantly with MenC CRM and 111 who received MenC CRM alone, 99%-100% of infants had serum bactericidal antibody assay using human complement (hSBA) titres 1:8 or greater against MenC after the second vaccination of the primary series (3 months, 5 months, and 12 months of age), and 100% of infants reached these titres after the booster vaccination.
There were more local reactions, such as tenderness, with the combination MenB and MenC vaccinations than with the MenC vaccine alone, as well as systemic adverse reactions such as unusual crying and fever.
Read more in the journal Vaccine (2017 Apr 11;35[16]:2052-9).
and it demonstrated adequate immune response to MenB, according to Marco Aurelio P. Safadi, MD, of Santa Casa de São Paulo (Brazil) School of Medical Sciences, and his associates.
Of 117 healthy infants who received 4CMenB concomitantly with MenC CRM and 111 who received MenC CRM alone, 99%-100% of infants had serum bactericidal antibody assay using human complement (hSBA) titres 1:8 or greater against MenC after the second vaccination of the primary series (3 months, 5 months, and 12 months of age), and 100% of infants reached these titres after the booster vaccination.
There were more local reactions, such as tenderness, with the combination MenB and MenC vaccinations than with the MenC vaccine alone, as well as systemic adverse reactions such as unusual crying and fever.
Read more in the journal Vaccine (2017 Apr 11;35[16]:2052-9).
FROM VACCINE
Children’s asthma risk reduced with prenatal vitamin D supplementation
SAN FRANCISCO – Vitamin D supplementation during pregnancy may reduce the incidence of asthma or allergies in children at high risk for atopic disease, a study showed.
At age 3 years, asthma or recurrent wheeze occurred in 24% of children born to mothers with substantial vitamin D3 supplementation in pregnancy, compared with 30% of children whose mothers took a placebo during pregnancy.
However, observational study findings on vitamin D deficiency in pregnancy and asthma risk have been mixed, with no effect seen in research using measurements of 25OHD levels, despite protective effects seen in studies estimating vitamin D intake based on diet. Dr. Litonjua, therefore, led a randomized, controlled trial at three clinical centers to test whether vitamin D supplementation in pregnancy could prevent children at high risk of asthma from developing the condition. High-risk status was based on the presence of maternal and/or paternal asthma, allergic rhinitis, or eczema.
The 881 initial participants, enrolled between October 2009 and January 2015, were randomized to receive either 4,000 IU daily of vitamin D3 (440 women) or a placebo daily (436 women). Both groups took a multivitamin that contained 400 IU of vitamin D3. The participants included 43% black women, 26% white women, 14% Hispanic women, and 17% of other races/ethnicities.
The researchers collected maternal blood at the start of the study, between 32 and 38 weeks’ post partum, and at 1-year post partum. They collected cord blood at birth and then children’s blood at 1, 3, and 6 years old. At the third trimester, 87% of the women in the intervention group and 72% of the control group women had at least 50 nmol/L of 25OHD. Levels of at least 75 nmol/L were present in 75% of the intervention group and 35% of the control group in the third trimester.
Primary follow-up occurred at 3 years old with continuing follow-up through 6 years old, but data also were collected every 3 months regarding asthma and allergy symptoms and environmental exposures and diet. Stool was collected for microbiome analysis at 6 months, 1 year, and 3 years, and then annually after age 3 years. Children’s lung function was assessed with impulse oscillometry annually starting at age 4 years, with spirometry annually starting at age 5 years, and with bronchodilator response at age 6 years, Dr. Litonjua reported at the Pediatric Academic Societies meeting.
Just over one-quarter (27%) of the 806 children included in the final analysis had parental report of either an asthma diagnosis or recurrent wheeze, defined using any of five criteria involving multiple wheeze reports and/or use of an asthma controller. Rates of asthma or wheeze were significantly lower in children of women supplemented with 4,400 IU of vitamin D than in those born to women in the control group.
At age 1 year, the rate of asthma or wheeze among children from the intervention group was 9 percentage points lower than that of children from the control group, a 36% reduction. By age 2 years, the rate difference was 7%, a 25% reduced risk for intervention children, compared with control children. Children from the intervention group had a 20% lower risk of asthma or wheeze at age 3 years than those from the control group, with a rate difference of 6% (P = .051).
“Both maternal baseline 25OHD levels and third-trimester 25OHD levels were inversely associated with asthma/recurrent wheeze by age 3 years,” Dr. Litonjua reported, and relative risk at age 3 years was identical in black and white children. Maternal levels of 25OHD in the first trimester, however, “modified the effects of supplementation such that children born to women with higher levels and [who] were in the treatment arm had lowest risks for asthma/recurrent wheeze,” he said.
The greater reduction among women with higher baseline levels and supplementation suggests that higher levels than 30 ng/mL may be necessary for the prevention of asthma or allergies, Dr. Litonjua said. Personalized dosing or earlier supplementation may, therefore, be needed, he said.
“One of the main findings from our trial was that there were no serious adverse effects,” he said. Other trials, however, have found concerns with vitamin D toxicity. One challenge in the study was very low adherence: Only about half the women regularly took their vitamin D supplements at first, Dr. Litonjua said, although they were eventually able to raise adherence to around 80%.
The research was funded by the National Heart, Lung, and Blood Institute. Dr. Litonjua reported royalties from UpToDate and Springer Humana Press and consultation fees from AstraZeneca.
SAN FRANCISCO – Vitamin D supplementation during pregnancy may reduce the incidence of asthma or allergies in children at high risk for atopic disease, a study showed.
At age 3 years, asthma or recurrent wheeze occurred in 24% of children born to mothers with substantial vitamin D3 supplementation in pregnancy, compared with 30% of children whose mothers took a placebo during pregnancy.
However, observational study findings on vitamin D deficiency in pregnancy and asthma risk have been mixed, with no effect seen in research using measurements of 25OHD levels, despite protective effects seen in studies estimating vitamin D intake based on diet. Dr. Litonjua, therefore, led a randomized, controlled trial at three clinical centers to test whether vitamin D supplementation in pregnancy could prevent children at high risk of asthma from developing the condition. High-risk status was based on the presence of maternal and/or paternal asthma, allergic rhinitis, or eczema.
The 881 initial participants, enrolled between October 2009 and January 2015, were randomized to receive either 4,000 IU daily of vitamin D3 (440 women) or a placebo daily (436 women). Both groups took a multivitamin that contained 400 IU of vitamin D3. The participants included 43% black women, 26% white women, 14% Hispanic women, and 17% of other races/ethnicities.
The researchers collected maternal blood at the start of the study, between 32 and 38 weeks’ post partum, and at 1-year post partum. They collected cord blood at birth and then children’s blood at 1, 3, and 6 years old. At the third trimester, 87% of the women in the intervention group and 72% of the control group women had at least 50 nmol/L of 25OHD. Levels of at least 75 nmol/L were present in 75% of the intervention group and 35% of the control group in the third trimester.
Primary follow-up occurred at 3 years old with continuing follow-up through 6 years old, but data also were collected every 3 months regarding asthma and allergy symptoms and environmental exposures and diet. Stool was collected for microbiome analysis at 6 months, 1 year, and 3 years, and then annually after age 3 years. Children’s lung function was assessed with impulse oscillometry annually starting at age 4 years, with spirometry annually starting at age 5 years, and with bronchodilator response at age 6 years, Dr. Litonjua reported at the Pediatric Academic Societies meeting.
Just over one-quarter (27%) of the 806 children included in the final analysis had parental report of either an asthma diagnosis or recurrent wheeze, defined using any of five criteria involving multiple wheeze reports and/or use of an asthma controller. Rates of asthma or wheeze were significantly lower in children of women supplemented with 4,400 IU of vitamin D than in those born to women in the control group.
At age 1 year, the rate of asthma or wheeze among children from the intervention group was 9 percentage points lower than that of children from the control group, a 36% reduction. By age 2 years, the rate difference was 7%, a 25% reduced risk for intervention children, compared with control children. Children from the intervention group had a 20% lower risk of asthma or wheeze at age 3 years than those from the control group, with a rate difference of 6% (P = .051).
“Both maternal baseline 25OHD levels and third-trimester 25OHD levels were inversely associated with asthma/recurrent wheeze by age 3 years,” Dr. Litonjua reported, and relative risk at age 3 years was identical in black and white children. Maternal levels of 25OHD in the first trimester, however, “modified the effects of supplementation such that children born to women with higher levels and [who] were in the treatment arm had lowest risks for asthma/recurrent wheeze,” he said.
The greater reduction among women with higher baseline levels and supplementation suggests that higher levels than 30 ng/mL may be necessary for the prevention of asthma or allergies, Dr. Litonjua said. Personalized dosing or earlier supplementation may, therefore, be needed, he said.
“One of the main findings from our trial was that there were no serious adverse effects,” he said. Other trials, however, have found concerns with vitamin D toxicity. One challenge in the study was very low adherence: Only about half the women regularly took their vitamin D supplements at first, Dr. Litonjua said, although they were eventually able to raise adherence to around 80%.
The research was funded by the National Heart, Lung, and Blood Institute. Dr. Litonjua reported royalties from UpToDate and Springer Humana Press and consultation fees from AstraZeneca.
SAN FRANCISCO – Vitamin D supplementation during pregnancy may reduce the incidence of asthma or allergies in children at high risk for atopic disease, a study showed.
At age 3 years, asthma or recurrent wheeze occurred in 24% of children born to mothers with substantial vitamin D3 supplementation in pregnancy, compared with 30% of children whose mothers took a placebo during pregnancy.
However, observational study findings on vitamin D deficiency in pregnancy and asthma risk have been mixed, with no effect seen in research using measurements of 25OHD levels, despite protective effects seen in studies estimating vitamin D intake based on diet. Dr. Litonjua, therefore, led a randomized, controlled trial at three clinical centers to test whether vitamin D supplementation in pregnancy could prevent children at high risk of asthma from developing the condition. High-risk status was based on the presence of maternal and/or paternal asthma, allergic rhinitis, or eczema.
The 881 initial participants, enrolled between October 2009 and January 2015, were randomized to receive either 4,000 IU daily of vitamin D3 (440 women) or a placebo daily (436 women). Both groups took a multivitamin that contained 400 IU of vitamin D3. The participants included 43% black women, 26% white women, 14% Hispanic women, and 17% of other races/ethnicities.
The researchers collected maternal blood at the start of the study, between 32 and 38 weeks’ post partum, and at 1-year post partum. They collected cord blood at birth and then children’s blood at 1, 3, and 6 years old. At the third trimester, 87% of the women in the intervention group and 72% of the control group women had at least 50 nmol/L of 25OHD. Levels of at least 75 nmol/L were present in 75% of the intervention group and 35% of the control group in the third trimester.
Primary follow-up occurred at 3 years old with continuing follow-up through 6 years old, but data also were collected every 3 months regarding asthma and allergy symptoms and environmental exposures and diet. Stool was collected for microbiome analysis at 6 months, 1 year, and 3 years, and then annually after age 3 years. Children’s lung function was assessed with impulse oscillometry annually starting at age 4 years, with spirometry annually starting at age 5 years, and with bronchodilator response at age 6 years, Dr. Litonjua reported at the Pediatric Academic Societies meeting.
Just over one-quarter (27%) of the 806 children included in the final analysis had parental report of either an asthma diagnosis or recurrent wheeze, defined using any of five criteria involving multiple wheeze reports and/or use of an asthma controller. Rates of asthma or wheeze were significantly lower in children of women supplemented with 4,400 IU of vitamin D than in those born to women in the control group.
At age 1 year, the rate of asthma or wheeze among children from the intervention group was 9 percentage points lower than that of children from the control group, a 36% reduction. By age 2 years, the rate difference was 7%, a 25% reduced risk for intervention children, compared with control children. Children from the intervention group had a 20% lower risk of asthma or wheeze at age 3 years than those from the control group, with a rate difference of 6% (P = .051).
“Both maternal baseline 25OHD levels and third-trimester 25OHD levels were inversely associated with asthma/recurrent wheeze by age 3 years,” Dr. Litonjua reported, and relative risk at age 3 years was identical in black and white children. Maternal levels of 25OHD in the first trimester, however, “modified the effects of supplementation such that children born to women with higher levels and [who] were in the treatment arm had lowest risks for asthma/recurrent wheeze,” he said.
The greater reduction among women with higher baseline levels and supplementation suggests that higher levels than 30 ng/mL may be necessary for the prevention of asthma or allergies, Dr. Litonjua said. Personalized dosing or earlier supplementation may, therefore, be needed, he said.
“One of the main findings from our trial was that there were no serious adverse effects,” he said. Other trials, however, have found concerns with vitamin D toxicity. One challenge in the study was very low adherence: Only about half the women regularly took their vitamin D supplements at first, Dr. Litonjua said, although they were eventually able to raise adherence to around 80%.
The research was funded by the National Heart, Lung, and Blood Institute. Dr. Litonjua reported royalties from UpToDate and Springer Humana Press and consultation fees from AstraZeneca.
AT PAS 2017
Key clinical point: Higher levels of vitamin D3 in pregnancy led to a reduced risk of asthma or allergies in subsequent children at high risk for the condition.
Major finding: (P = .051).
Data source: A randomized controlled trial at three clinical centers from October 2009 through January 2015, involving 881 pregnant women whose children had a high risk of asthma or allergies and 806 subsequent children.
Disclosures: The research was funded by the National Heart, Lung, and Blood Institute. Dr. Litonjua reported royalties from UpToDate and Springer Humana Press, and consultation fees from AstraZeneca.
Atezolizumab improves OS in NSCLC with brain metastases
GENEVA – Immune checkpoint inhibitors may improve survival in patients with non–small cell lung cancer (NSCLC) and brain metastases compared with chemotherapy, without adding unacceptable toxicities, pooled analyses of clinical trials suggest.
Among 1452 patients with NSCLC treated with the programmed death ligand-1 (PD-L1) inhibitor atezolizumab (Tecentriq), rates of treatment-related serious adverse events (SAEs) were similar between patients with brain metastases at baseline and those without brain metastases, reported Rimas V Lukas, MD, from the University of Chicago.
“Overall, I think that these results support the investigation of atezolizumab in non–small cell lung cancer patients with CNS metastases,” Dr. Lukas said at the European Lung Cancer Conference.
Lung cancer accounts for about 40%-50% of all cases of brain metastases, and approximately 20%-40% of patients with advanced NSCLC will develop metastases, which are associated with poor overall survival, according to Solange Peters, MD, from the Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland, the invited discussant.
To evaluate the safety and efficacy of the PD-L1 inhibitor in patients with brain metastases at baseline, Lukas et al. looked at pooled safety data on patients enrolled in one of five treatment studies with atezolizumab – PCD4989g; BIRCH, POPLAR, FIR, and OAK – and efficacy data from a subset of patients in OAK.
The pooled analysis included 1452 patients, 79 of whom (5%) had brain metastases at baseline. This analysis showed that, although there was a higher incidence of any neurological AE, treatment-related AE, or treatment–related neurologic AE among patients with brain metastases, treatment-related SAEs and treatment related neurological SAEs were similar between the two groups. The most common neurological AE was headache, reported by 8% of patients with metastases and 3% without.
The efficacy analysis, which included a cohort of the first 850 patients with or without brain metastases treated, showed a significant survival for atezolizumab in the OAK trial, with median overall survival of 20.1 months for patients with brain metastases assigned to the PD-L1 inhibitor, compared with 11.9 months for patients assigned to docetaxel. This translated into a hazard ratio for atezolizumab of 0.54 (P = .0279).
Among the 750 patients without baseline brain metastases in OAK, the respective OS rates were 13.0 months, vs. 9.4 months (HR, 0.75; P = .001).
Although it was not statistically significant, the risk for developing new central nervous system lesions also appeared to be lower with atezolizumab than with docetaxel, with a median time to new lesions not reached, vs. 9.5 months with docetaxel (HR, 0.42; 95% confidence interval, 0.15-1.18).
Among patients without baseline brain metastases, there was also a hint that atezolizumab could delay onset of CNS metastases, although the trend was not significant, the investigators found.
In her commentary on the study, Dr. Peters said that “checkpoint inhibitors demonstrate activity in the brain that remains to be quantified and prospectively compared to systemic activity in larger series, and these are very small series.”
“Limitations in duration and level of activity might exist, however, related to the blood brain barrier and the brain immune system characteristics,” she added.
The study was supported by F. Hoffmann-La Roche/Genentech, a member of the Roche Group. Dr. Lukas disclosed serving on advisory boards for AstraZeneca and Novocure and receiving honoraria from AbbVie. Two coauthors are employees of Genentech, and two are employed by Roche. The remaining author had no disclosures. Dr. Peters reported relationships with Bristol-Myers Squibb, F. Hoffmann-La Roche, Eli Lilly, AstraZeneca, Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, Morphotek, Merrimack, Merck Sharp and Dohme, and Merck Serono.
GENEVA – Immune checkpoint inhibitors may improve survival in patients with non–small cell lung cancer (NSCLC) and brain metastases compared with chemotherapy, without adding unacceptable toxicities, pooled analyses of clinical trials suggest.
Among 1452 patients with NSCLC treated with the programmed death ligand-1 (PD-L1) inhibitor atezolizumab (Tecentriq), rates of treatment-related serious adverse events (SAEs) were similar between patients with brain metastases at baseline and those without brain metastases, reported Rimas V Lukas, MD, from the University of Chicago.
“Overall, I think that these results support the investigation of atezolizumab in non–small cell lung cancer patients with CNS metastases,” Dr. Lukas said at the European Lung Cancer Conference.
Lung cancer accounts for about 40%-50% of all cases of brain metastases, and approximately 20%-40% of patients with advanced NSCLC will develop metastases, which are associated with poor overall survival, according to Solange Peters, MD, from the Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland, the invited discussant.
To evaluate the safety and efficacy of the PD-L1 inhibitor in patients with brain metastases at baseline, Lukas et al. looked at pooled safety data on patients enrolled in one of five treatment studies with atezolizumab – PCD4989g; BIRCH, POPLAR, FIR, and OAK – and efficacy data from a subset of patients in OAK.
The pooled analysis included 1452 patients, 79 of whom (5%) had brain metastases at baseline. This analysis showed that, although there was a higher incidence of any neurological AE, treatment-related AE, or treatment–related neurologic AE among patients with brain metastases, treatment-related SAEs and treatment related neurological SAEs were similar between the two groups. The most common neurological AE was headache, reported by 8% of patients with metastases and 3% without.
The efficacy analysis, which included a cohort of the first 850 patients with or without brain metastases treated, showed a significant survival for atezolizumab in the OAK trial, with median overall survival of 20.1 months for patients with brain metastases assigned to the PD-L1 inhibitor, compared with 11.9 months for patients assigned to docetaxel. This translated into a hazard ratio for atezolizumab of 0.54 (P = .0279).
Among the 750 patients without baseline brain metastases in OAK, the respective OS rates were 13.0 months, vs. 9.4 months (HR, 0.75; P = .001).
Although it was not statistically significant, the risk for developing new central nervous system lesions also appeared to be lower with atezolizumab than with docetaxel, with a median time to new lesions not reached, vs. 9.5 months with docetaxel (HR, 0.42; 95% confidence interval, 0.15-1.18).
Among patients without baseline brain metastases, there was also a hint that atezolizumab could delay onset of CNS metastases, although the trend was not significant, the investigators found.
In her commentary on the study, Dr. Peters said that “checkpoint inhibitors demonstrate activity in the brain that remains to be quantified and prospectively compared to systemic activity in larger series, and these are very small series.”
“Limitations in duration and level of activity might exist, however, related to the blood brain barrier and the brain immune system characteristics,” she added.
The study was supported by F. Hoffmann-La Roche/Genentech, a member of the Roche Group. Dr. Lukas disclosed serving on advisory boards for AstraZeneca and Novocure and receiving honoraria from AbbVie. Two coauthors are employees of Genentech, and two are employed by Roche. The remaining author had no disclosures. Dr. Peters reported relationships with Bristol-Myers Squibb, F. Hoffmann-La Roche, Eli Lilly, AstraZeneca, Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, Morphotek, Merrimack, Merck Sharp and Dohme, and Merck Serono.
GENEVA – Immune checkpoint inhibitors may improve survival in patients with non–small cell lung cancer (NSCLC) and brain metastases compared with chemotherapy, without adding unacceptable toxicities, pooled analyses of clinical trials suggest.
Among 1452 patients with NSCLC treated with the programmed death ligand-1 (PD-L1) inhibitor atezolizumab (Tecentriq), rates of treatment-related serious adverse events (SAEs) were similar between patients with brain metastases at baseline and those without brain metastases, reported Rimas V Lukas, MD, from the University of Chicago.
“Overall, I think that these results support the investigation of atezolizumab in non–small cell lung cancer patients with CNS metastases,” Dr. Lukas said at the European Lung Cancer Conference.
Lung cancer accounts for about 40%-50% of all cases of brain metastases, and approximately 20%-40% of patients with advanced NSCLC will develop metastases, which are associated with poor overall survival, according to Solange Peters, MD, from the Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland, the invited discussant.
To evaluate the safety and efficacy of the PD-L1 inhibitor in patients with brain metastases at baseline, Lukas et al. looked at pooled safety data on patients enrolled in one of five treatment studies with atezolizumab – PCD4989g; BIRCH, POPLAR, FIR, and OAK – and efficacy data from a subset of patients in OAK.
The pooled analysis included 1452 patients, 79 of whom (5%) had brain metastases at baseline. This analysis showed that, although there was a higher incidence of any neurological AE, treatment-related AE, or treatment–related neurologic AE among patients with brain metastases, treatment-related SAEs and treatment related neurological SAEs were similar between the two groups. The most common neurological AE was headache, reported by 8% of patients with metastases and 3% without.
The efficacy analysis, which included a cohort of the first 850 patients with or without brain metastases treated, showed a significant survival for atezolizumab in the OAK trial, with median overall survival of 20.1 months for patients with brain metastases assigned to the PD-L1 inhibitor, compared with 11.9 months for patients assigned to docetaxel. This translated into a hazard ratio for atezolizumab of 0.54 (P = .0279).
Among the 750 patients without baseline brain metastases in OAK, the respective OS rates were 13.0 months, vs. 9.4 months (HR, 0.75; P = .001).
Although it was not statistically significant, the risk for developing new central nervous system lesions also appeared to be lower with atezolizumab than with docetaxel, with a median time to new lesions not reached, vs. 9.5 months with docetaxel (HR, 0.42; 95% confidence interval, 0.15-1.18).
Among patients without baseline brain metastases, there was also a hint that atezolizumab could delay onset of CNS metastases, although the trend was not significant, the investigators found.
In her commentary on the study, Dr. Peters said that “checkpoint inhibitors demonstrate activity in the brain that remains to be quantified and prospectively compared to systemic activity in larger series, and these are very small series.”
“Limitations in duration and level of activity might exist, however, related to the blood brain barrier and the brain immune system characteristics,” she added.
The study was supported by F. Hoffmann-La Roche/Genentech, a member of the Roche Group. Dr. Lukas disclosed serving on advisory boards for AstraZeneca and Novocure and receiving honoraria from AbbVie. Two coauthors are employees of Genentech, and two are employed by Roche. The remaining author had no disclosures. Dr. Peters reported relationships with Bristol-Myers Squibb, F. Hoffmann-La Roche, Eli Lilly, AstraZeneca, Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, Morphotek, Merrimack, Merck Sharp and Dohme, and Merck Serono.
Key clinical point: The PD-L1 inhibitor atezolizumab improved overall survival, vs. docetaxel, in patients with non–small cell lung cancer and brain metastases.
Major finding: The hazard ratio for overall survival was 0.54 for patients assigned to atezolizumab, vs. docetaxel, in the OAK trial.
Data source: Pooled safety analysis of 1452 patients and efficacy analysis of 850 patients with NSCLC with or without brain metastases.
Disclosures: The study was supported by F. Hoffmann-La Roche/Genentech, a member of the Roche Group. Dr. Lukas disclosed serving on advisory boards for AstraZeneca and Novocure and receiving honoraria from AbbVie. Two coauthors are employees of Genentech, and two are employed by Roche. The remaining author had no disclosures. Dr. Peters reported relationships with Bristol-Myers Squibb, F. Hoffmann-La Roche, Eli Lilly, AstraZeneca, Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, Morphotek, Merrimack, Merck Sharp and Dohme, and Merck Serono.
E. Stanley Crawford Critical Issues Forum Tackles Value-Based Reimbursement
Vascular surgeons will learn how to navigate a value-based reimbursement system at the E. Stanley Crawford Critical Issues Forum on Thursday, June 1, from 10:30 a.m. to noon. This informative session, moderated by R. Clement Darling III, MD, of The Vascular Group in Albany, N.Y., will include an excellent panel of experts in the field.
“As everyone knows, the Affordable Care Act (ACA) will continue to be under serious discussion in the new administration, and we don’t know how it will affect our practices,” said Dr. Darling. “However, MACRA, MIPS, and alternative payment systems were decided on in a bipartisan fashion, so change in our reimbursement system is here to stay.”
The Forum will begin with a presentation by Michael C. Dalsing, MD, of Indiana University about “The Five Things We All Need to Know about MACRA and Alternative Payment Systems to Compete and Flourish.” MACRA – the Medicare Access and CHIP Reauthorization Act of 2015 – went into effect on January 1, 2017.
“It is extremely important for all vascular surgeons and health care professionals to participate in order to not be negatively affected by this rule,” noted Dr. Darling,
The next talk will be “Appropriate Care in Outpatient Angio Suites: How Do We Ensure the Correct Procedures Get Done on the Right Patients for the Right Reasons?” Daniel R. Gorin, MD, of Cape Cod Health Care, will cover this very important issue in current outpatient treatment of patients with venous and arterial disease. These suites have been well received by the public and third party payers; however, we may need to be involved with their accreditation to minimize the potential or perception of inappropriate indications or procedures. “A year and one-half ago,” said Dr. Darling, “Peter Lawrence talked about the increase in outpatient angio suites in his excellent SVS Presidential address.”
“I think this presentation will be absorbing and controversial for both those who are contemplating outpatient angio suites and those who are working in one,” continued Dr. Darling. “We need to police ourselves. It may be incumbent upon us to be the accreditation body that actively participates in ensuring that we are giving our patients the best and most appropriate care possible.”
An integral part of MACRA and value-based reimbursement systems is outcomes. The SVS Vascular Quality Initiative (VQI) has become a hot topic for many vascular surgeons whether they work for academic institutions, in a hospital, in multi-specialty practices, or independently.
Since MACRA and the alternative payment system include involvement with registries, the next subject will be “Outcome Registries – Necessary Evil or Useful Tool of the Future: How to Make Them Work in Your Practice” discussed by John “Jeb” Hallett, MD, of the Medical University of South Carolina. “This presentation will enlighten attendees on how to incorporate outcome registries into their daily lives,” noted Dr. Darling.
The final talk will be “Can Everyone Do It All? Regionalization and Center Accreditation: How to Make It Work for All of Us” by Anton Sidawy, MD, of GW Medical Faculty Associates and SVS Past President. “This is a fascinating topic, which should generate a fair amount of discussion,” noted Dr. Darling. “We are all aware that there is an extensive trauma center designation in this country that has helped improve mortality and patient care. Yet, for patients with vascular emergencies, recent data have shown regionalization can positively impact outcome and many patients do not suffer from transfer.” This complex problem will be analyzed from all perspectives.
“We hope that the SVS can be on the forefront of creating systems that benefit patient outcomes while maintaining excellent regional doctor/patient relationships,” stated Dr. Darling. “We will again look at the opportunity for SVS involvement in center accreditation – allowing us to maintain our preeminent position as the physicians who can best treat vascular, arterial, and venous emergencies and any vascular surgery pathology.”
The Crawford Critical Issues Forum will delve into very interesting and controversial subjects,” stated Dr. Darling. “We hope that physicians will attend the session and provide us with their input and thoughts on these critical issues.”
Dr. Darling does not have any financial conflicts of interest.
Thursday, June 1
10:30 a.m. – Noon
The E. Stanley Crawford Critical Issues Forum
Vascular surgeons will learn how to navigate a value-based reimbursement system at the E. Stanley Crawford Critical Issues Forum on Thursday, June 1, from 10:30 a.m. to noon. This informative session, moderated by R. Clement Darling III, MD, of The Vascular Group in Albany, N.Y., will include an excellent panel of experts in the field.
“As everyone knows, the Affordable Care Act (ACA) will continue to be under serious discussion in the new administration, and we don’t know how it will affect our practices,” said Dr. Darling. “However, MACRA, MIPS, and alternative payment systems were decided on in a bipartisan fashion, so change in our reimbursement system is here to stay.”
The Forum will begin with a presentation by Michael C. Dalsing, MD, of Indiana University about “The Five Things We All Need to Know about MACRA and Alternative Payment Systems to Compete and Flourish.” MACRA – the Medicare Access and CHIP Reauthorization Act of 2015 – went into effect on January 1, 2017.
“It is extremely important for all vascular surgeons and health care professionals to participate in order to not be negatively affected by this rule,” noted Dr. Darling,
The next talk will be “Appropriate Care in Outpatient Angio Suites: How Do We Ensure the Correct Procedures Get Done on the Right Patients for the Right Reasons?” Daniel R. Gorin, MD, of Cape Cod Health Care, will cover this very important issue in current outpatient treatment of patients with venous and arterial disease. These suites have been well received by the public and third party payers; however, we may need to be involved with their accreditation to minimize the potential or perception of inappropriate indications or procedures. “A year and one-half ago,” said Dr. Darling, “Peter Lawrence talked about the increase in outpatient angio suites in his excellent SVS Presidential address.”
“I think this presentation will be absorbing and controversial for both those who are contemplating outpatient angio suites and those who are working in one,” continued Dr. Darling. “We need to police ourselves. It may be incumbent upon us to be the accreditation body that actively participates in ensuring that we are giving our patients the best and most appropriate care possible.”
An integral part of MACRA and value-based reimbursement systems is outcomes. The SVS Vascular Quality Initiative (VQI) has become a hot topic for many vascular surgeons whether they work for academic institutions, in a hospital, in multi-specialty practices, or independently.
Since MACRA and the alternative payment system include involvement with registries, the next subject will be “Outcome Registries – Necessary Evil or Useful Tool of the Future: How to Make Them Work in Your Practice” discussed by John “Jeb” Hallett, MD, of the Medical University of South Carolina. “This presentation will enlighten attendees on how to incorporate outcome registries into their daily lives,” noted Dr. Darling.
The final talk will be “Can Everyone Do It All? Regionalization and Center Accreditation: How to Make It Work for All of Us” by Anton Sidawy, MD, of GW Medical Faculty Associates and SVS Past President. “This is a fascinating topic, which should generate a fair amount of discussion,” noted Dr. Darling. “We are all aware that there is an extensive trauma center designation in this country that has helped improve mortality and patient care. Yet, for patients with vascular emergencies, recent data have shown regionalization can positively impact outcome and many patients do not suffer from transfer.” This complex problem will be analyzed from all perspectives.
“We hope that the SVS can be on the forefront of creating systems that benefit patient outcomes while maintaining excellent regional doctor/patient relationships,” stated Dr. Darling. “We will again look at the opportunity for SVS involvement in center accreditation – allowing us to maintain our preeminent position as the physicians who can best treat vascular, arterial, and venous emergencies and any vascular surgery pathology.”
The Crawford Critical Issues Forum will delve into very interesting and controversial subjects,” stated Dr. Darling. “We hope that physicians will attend the session and provide us with their input and thoughts on these critical issues.”
Dr. Darling does not have any financial conflicts of interest.
Thursday, June 1
10:30 a.m. – Noon
The E. Stanley Crawford Critical Issues Forum
Vascular surgeons will learn how to navigate a value-based reimbursement system at the E. Stanley Crawford Critical Issues Forum on Thursday, June 1, from 10:30 a.m. to noon. This informative session, moderated by R. Clement Darling III, MD, of The Vascular Group in Albany, N.Y., will include an excellent panel of experts in the field.
“As everyone knows, the Affordable Care Act (ACA) will continue to be under serious discussion in the new administration, and we don’t know how it will affect our practices,” said Dr. Darling. “However, MACRA, MIPS, and alternative payment systems were decided on in a bipartisan fashion, so change in our reimbursement system is here to stay.”
The Forum will begin with a presentation by Michael C. Dalsing, MD, of Indiana University about “The Five Things We All Need to Know about MACRA and Alternative Payment Systems to Compete and Flourish.” MACRA – the Medicare Access and CHIP Reauthorization Act of 2015 – went into effect on January 1, 2017.
“It is extremely important for all vascular surgeons and health care professionals to participate in order to not be negatively affected by this rule,” noted Dr. Darling,
The next talk will be “Appropriate Care in Outpatient Angio Suites: How Do We Ensure the Correct Procedures Get Done on the Right Patients for the Right Reasons?” Daniel R. Gorin, MD, of Cape Cod Health Care, will cover this very important issue in current outpatient treatment of patients with venous and arterial disease. These suites have been well received by the public and third party payers; however, we may need to be involved with their accreditation to minimize the potential or perception of inappropriate indications or procedures. “A year and one-half ago,” said Dr. Darling, “Peter Lawrence talked about the increase in outpatient angio suites in his excellent SVS Presidential address.”
“I think this presentation will be absorbing and controversial for both those who are contemplating outpatient angio suites and those who are working in one,” continued Dr. Darling. “We need to police ourselves. It may be incumbent upon us to be the accreditation body that actively participates in ensuring that we are giving our patients the best and most appropriate care possible.”
An integral part of MACRA and value-based reimbursement systems is outcomes. The SVS Vascular Quality Initiative (VQI) has become a hot topic for many vascular surgeons whether they work for academic institutions, in a hospital, in multi-specialty practices, or independently.
Since MACRA and the alternative payment system include involvement with registries, the next subject will be “Outcome Registries – Necessary Evil or Useful Tool of the Future: How to Make Them Work in Your Practice” discussed by John “Jeb” Hallett, MD, of the Medical University of South Carolina. “This presentation will enlighten attendees on how to incorporate outcome registries into their daily lives,” noted Dr. Darling.
The final talk will be “Can Everyone Do It All? Regionalization and Center Accreditation: How to Make It Work for All of Us” by Anton Sidawy, MD, of GW Medical Faculty Associates and SVS Past President. “This is a fascinating topic, which should generate a fair amount of discussion,” noted Dr. Darling. “We are all aware that there is an extensive trauma center designation in this country that has helped improve mortality and patient care. Yet, for patients with vascular emergencies, recent data have shown regionalization can positively impact outcome and many patients do not suffer from transfer.” This complex problem will be analyzed from all perspectives.
“We hope that the SVS can be on the forefront of creating systems that benefit patient outcomes while maintaining excellent regional doctor/patient relationships,” stated Dr. Darling. “We will again look at the opportunity for SVS involvement in center accreditation – allowing us to maintain our preeminent position as the physicians who can best treat vascular, arterial, and venous emergencies and any vascular surgery pathology.”
The Crawford Critical Issues Forum will delve into very interesting and controversial subjects,” stated Dr. Darling. “We hope that physicians will attend the session and provide us with their input and thoughts on these critical issues.”
Dr. Darling does not have any financial conflicts of interest.
Thursday, June 1
10:30 a.m. – Noon
The E. Stanley Crawford Critical Issues Forum
High allele level linked to lamotrigine-induced SCAR
, reported Byung-Keun Kim, MD, of Seoul National University and associates.
In a study of 18 Korean patients with lamotrigine-induced SCAR, a control group of Korean lamotrigine-tolerant patients, and a control group of the general Korean population, the frequency of the HLA-A*31:01 allele was significantly higher in the lamotrigine-induced SCAR patients than in the lamotrigine-tolerant patients (odds ratio, 11.43; P = .0037) or the other control group (OR, 7.27; P = .00034).
High levels of the HLA-A*31:01 allele also have been reported in Korean patients with carbamazepine-induced SCAR, suggesting an association with the HLA allele and drug-induced SCAR that is specific to ethnicity.
That idea is supported by reports that the HLA-B*15:02 allele is a well-known risk allele of carbamazepine-induced SCAR in Han Chinese and Southeast Asians and that other HLA alleles have been significantly associated with SCAR only with patients of European ancestry or only with patients of Mestizo Mexican ancestry, Dr. Kim and associates said.
The SCAR in this study were Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug rash with eosinophilia and systemic syndrome, also known as DRESS.
Read more in the Annals of Allergy, Asthma & Immunology (2017 May;118[5]:629-30).
, reported Byung-Keun Kim, MD, of Seoul National University and associates.
In a study of 18 Korean patients with lamotrigine-induced SCAR, a control group of Korean lamotrigine-tolerant patients, and a control group of the general Korean population, the frequency of the HLA-A*31:01 allele was significantly higher in the lamotrigine-induced SCAR patients than in the lamotrigine-tolerant patients (odds ratio, 11.43; P = .0037) or the other control group (OR, 7.27; P = .00034).
High levels of the HLA-A*31:01 allele also have been reported in Korean patients with carbamazepine-induced SCAR, suggesting an association with the HLA allele and drug-induced SCAR that is specific to ethnicity.
That idea is supported by reports that the HLA-B*15:02 allele is a well-known risk allele of carbamazepine-induced SCAR in Han Chinese and Southeast Asians and that other HLA alleles have been significantly associated with SCAR only with patients of European ancestry or only with patients of Mestizo Mexican ancestry, Dr. Kim and associates said.
The SCAR in this study were Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug rash with eosinophilia and systemic syndrome, also known as DRESS.
Read more in the Annals of Allergy, Asthma & Immunology (2017 May;118[5]:629-30).
, reported Byung-Keun Kim, MD, of Seoul National University and associates.
In a study of 18 Korean patients with lamotrigine-induced SCAR, a control group of Korean lamotrigine-tolerant patients, and a control group of the general Korean population, the frequency of the HLA-A*31:01 allele was significantly higher in the lamotrigine-induced SCAR patients than in the lamotrigine-tolerant patients (odds ratio, 11.43; P = .0037) or the other control group (OR, 7.27; P = .00034).
High levels of the HLA-A*31:01 allele also have been reported in Korean patients with carbamazepine-induced SCAR, suggesting an association with the HLA allele and drug-induced SCAR that is specific to ethnicity.
That idea is supported by reports that the HLA-B*15:02 allele is a well-known risk allele of carbamazepine-induced SCAR in Han Chinese and Southeast Asians and that other HLA alleles have been significantly associated with SCAR only with patients of European ancestry or only with patients of Mestizo Mexican ancestry, Dr. Kim and associates said.
The SCAR in this study were Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug rash with eosinophilia and systemic syndrome, also known as DRESS.
Read more in the Annals of Allergy, Asthma & Immunology (2017 May;118[5]:629-30).
FROM THE ANNALS OF ALLERGY, ASTHMA & IMMUNOLOGY
FDA approves pembrolizumab for first-line advanced NSCLC
The Food and Drug Administration has granted accelerated approval to checkpoint inhibitor pembrolizumab in combination with pemetrexed and carboplatin for the treatment of patients with previously untreated metastatic nonsquamous non–small cell lung cancer (NSCLC).
The immunotherapy pembrolizumab was approved as a second-line treatment for metastatic NSCLC in 2015.
First-line approval was based on an improved overall response rate (ORR) and progression-free survival (PFS) in a cohort of 123 patients within an open-label, multicohort study (KEYNOTE-21). Enrollees in cohort G1 had locally advanced or metastatic NSCLC and no prior systemic treatment for metastatic disease. They were randomized to receive either pembrolizumab, in combination with pemetrexed and carboplatin (PC) for four cycles followed by pembrolizumab for a maximum of 24 months (n = 60) or PC alone (n = 63). Randomization was stratified by PD-L1 tumor expression (tumor proportion score [TPS] less than 1% vs. TPS greater than or equal to 1%).
The hazard ratio for PFS was 0.53 (95% CI: 0.31, 0.91, P = .0205). The median PFS was 13.0 months for the pembrolizumab plus PC arm and 8.9 months for the PC-alone arm. In the TPS less than 1% subgroup, the ORR was 57% and 13% in the pembrolizumab-plus-PC and in the PC-alone arms, respectively. In the TPS greater-than-or-equal-to-1% subgroup, the ORR was 54% in the pembrolizumab-plus-PC arm and 38% in the pembrolizumab-plus-PC arm, the FDA said.
There were serious adverse events in 41% of the patients in the pembrolizumab-plus-PC arm compared with 28% in the PC-alone arm. Pembrolizumab was discontinued for adverse reactions in 10% of patients, most commonly due to acute kidney injury. The most common grade 3-4 adverse reactions were fatigue, dyspnea, nausea, vomiting, diarrhea, and rash.
The FDA cautioned that immune-mediated adverse reactions can occur with pembrolizumab including pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis. Based on the severity of the adverse reaction, pembrolizumab should be withheld or discontinued and corticosteroids administered when appropriate. The recommended dose and schedule for NSCLC is 200 mg as an intravenous infusion every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
Pembrolizumab is marketed as Keytruda by Merck.
The Food and Drug Administration has granted accelerated approval to checkpoint inhibitor pembrolizumab in combination with pemetrexed and carboplatin for the treatment of patients with previously untreated metastatic nonsquamous non–small cell lung cancer (NSCLC).
The immunotherapy pembrolizumab was approved as a second-line treatment for metastatic NSCLC in 2015.
First-line approval was based on an improved overall response rate (ORR) and progression-free survival (PFS) in a cohort of 123 patients within an open-label, multicohort study (KEYNOTE-21). Enrollees in cohort G1 had locally advanced or metastatic NSCLC and no prior systemic treatment for metastatic disease. They were randomized to receive either pembrolizumab, in combination with pemetrexed and carboplatin (PC) for four cycles followed by pembrolizumab for a maximum of 24 months (n = 60) or PC alone (n = 63). Randomization was stratified by PD-L1 tumor expression (tumor proportion score [TPS] less than 1% vs. TPS greater than or equal to 1%).
The hazard ratio for PFS was 0.53 (95% CI: 0.31, 0.91, P = .0205). The median PFS was 13.0 months for the pembrolizumab plus PC arm and 8.9 months for the PC-alone arm. In the TPS less than 1% subgroup, the ORR was 57% and 13% in the pembrolizumab-plus-PC and in the PC-alone arms, respectively. In the TPS greater-than-or-equal-to-1% subgroup, the ORR was 54% in the pembrolizumab-plus-PC arm and 38% in the pembrolizumab-plus-PC arm, the FDA said.
There were serious adverse events in 41% of the patients in the pembrolizumab-plus-PC arm compared with 28% in the PC-alone arm. Pembrolizumab was discontinued for adverse reactions in 10% of patients, most commonly due to acute kidney injury. The most common grade 3-4 adverse reactions were fatigue, dyspnea, nausea, vomiting, diarrhea, and rash.
The FDA cautioned that immune-mediated adverse reactions can occur with pembrolizumab including pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis. Based on the severity of the adverse reaction, pembrolizumab should be withheld or discontinued and corticosteroids administered when appropriate. The recommended dose and schedule for NSCLC is 200 mg as an intravenous infusion every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
Pembrolizumab is marketed as Keytruda by Merck.
The Food and Drug Administration has granted accelerated approval to checkpoint inhibitor pembrolizumab in combination with pemetrexed and carboplatin for the treatment of patients with previously untreated metastatic nonsquamous non–small cell lung cancer (NSCLC).
The immunotherapy pembrolizumab was approved as a second-line treatment for metastatic NSCLC in 2015.
First-line approval was based on an improved overall response rate (ORR) and progression-free survival (PFS) in a cohort of 123 patients within an open-label, multicohort study (KEYNOTE-21). Enrollees in cohort G1 had locally advanced or metastatic NSCLC and no prior systemic treatment for metastatic disease. They were randomized to receive either pembrolizumab, in combination with pemetrexed and carboplatin (PC) for four cycles followed by pembrolizumab for a maximum of 24 months (n = 60) or PC alone (n = 63). Randomization was stratified by PD-L1 tumor expression (tumor proportion score [TPS] less than 1% vs. TPS greater than or equal to 1%).
The hazard ratio for PFS was 0.53 (95% CI: 0.31, 0.91, P = .0205). The median PFS was 13.0 months for the pembrolizumab plus PC arm and 8.9 months for the PC-alone arm. In the TPS less than 1% subgroup, the ORR was 57% and 13% in the pembrolizumab-plus-PC and in the PC-alone arms, respectively. In the TPS greater-than-or-equal-to-1% subgroup, the ORR was 54% in the pembrolizumab-plus-PC arm and 38% in the pembrolizumab-plus-PC arm, the FDA said.
There were serious adverse events in 41% of the patients in the pembrolizumab-plus-PC arm compared with 28% in the PC-alone arm. Pembrolizumab was discontinued for adverse reactions in 10% of patients, most commonly due to acute kidney injury. The most common grade 3-4 adverse reactions were fatigue, dyspnea, nausea, vomiting, diarrhea, and rash.
The FDA cautioned that immune-mediated adverse reactions can occur with pembrolizumab including pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis. Based on the severity of the adverse reaction, pembrolizumab should be withheld or discontinued and corticosteroids administered when appropriate. The recommended dose and schedule for NSCLC is 200 mg as an intravenous infusion every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
Pembrolizumab is marketed as Keytruda by Merck.
Genes may play role in breast cancer racial disparities
A new analysis of data from The Cancer Genome Atlas revealed 142 genes differentially expressed between white and African Americans that may influence breast cancer survival.
Researchers sifted through gene expression, protein expression, somatic mutations, somatic DNA copy number alteration, and DNA methylation patterns between 154 black patients of African ancestry (mean age at diagnosis, 55.66 years); and 776 white patients (mean age, 59.51) of European ancestry. They also looked at germline genetic variants for breast cancer subtypes and estimated subtype heritability.
African American patients were more likely than were whites to have basal-like breast cancer (odds ratio [OR], 3.80; 95% confidence interval [CI], 2.46-5.87; P less than .001) and HER2-enriched breast cancer (OR, 2.22; 95% CI, 1.10-4.47; P =.027).
After adjustment for subtype, 142 genes were differentially expressed between the two populations, a finding that held true after correction for testing of multiple comparisons (Bonferroni-adjusted P less than .05), reported Dezheng Huo, MD, PhD, of the department of public health sciences, University of Chicago, and his coauthors (JAMA Oncol. 2017 May 4. doi: 10.1001/jamaoncol.2017.0595).
During a median follow-up of 29 months, African Americans were more likely to experience recurrences (hazard ratio [HR], HR = 1.67, 95 CI, 1.02-2.74; P =.043). They had higher odds of basal-like breast cancer (OR, 3.80; 95% CI, 2.46-5.87; P less than .001) and human epidermal growth factor receptor 2 ERBB2 (HER2)-enriched breast cancer (OR, 2.22; 95% CI, 1.10-4.47; P =.027).
After adjusting for intrinsic subtypes, the researchers found differential expression of 16 DNA methylation probes, 4 DNA copy number segments, and 1 protein,
“If you have African ancestry, you’re more likely to have tumors that grow really fast. If we have drugs that can treat that kind of tumor, we need to find you and get you into treatment as quickly as possible,” she said.
A new analysis of data from The Cancer Genome Atlas revealed 142 genes differentially expressed between white and African Americans that may influence breast cancer survival.
Researchers sifted through gene expression, protein expression, somatic mutations, somatic DNA copy number alteration, and DNA methylation patterns between 154 black patients of African ancestry (mean age at diagnosis, 55.66 years); and 776 white patients (mean age, 59.51) of European ancestry. They also looked at germline genetic variants for breast cancer subtypes and estimated subtype heritability.
African American patients were more likely than were whites to have basal-like breast cancer (odds ratio [OR], 3.80; 95% confidence interval [CI], 2.46-5.87; P less than .001) and HER2-enriched breast cancer (OR, 2.22; 95% CI, 1.10-4.47; P =.027).
After adjustment for subtype, 142 genes were differentially expressed between the two populations, a finding that held true after correction for testing of multiple comparisons (Bonferroni-adjusted P less than .05), reported Dezheng Huo, MD, PhD, of the department of public health sciences, University of Chicago, and his coauthors (JAMA Oncol. 2017 May 4. doi: 10.1001/jamaoncol.2017.0595).
During a median follow-up of 29 months, African Americans were more likely to experience recurrences (hazard ratio [HR], HR = 1.67, 95 CI, 1.02-2.74; P =.043). They had higher odds of basal-like breast cancer (OR, 3.80; 95% CI, 2.46-5.87; P less than .001) and human epidermal growth factor receptor 2 ERBB2 (HER2)-enriched breast cancer (OR, 2.22; 95% CI, 1.10-4.47; P =.027).
After adjusting for intrinsic subtypes, the researchers found differential expression of 16 DNA methylation probes, 4 DNA copy number segments, and 1 protein,
“If you have African ancestry, you’re more likely to have tumors that grow really fast. If we have drugs that can treat that kind of tumor, we need to find you and get you into treatment as quickly as possible,” she said.
A new analysis of data from The Cancer Genome Atlas revealed 142 genes differentially expressed between white and African Americans that may influence breast cancer survival.
Researchers sifted through gene expression, protein expression, somatic mutations, somatic DNA copy number alteration, and DNA methylation patterns between 154 black patients of African ancestry (mean age at diagnosis, 55.66 years); and 776 white patients (mean age, 59.51) of European ancestry. They also looked at germline genetic variants for breast cancer subtypes and estimated subtype heritability.
African American patients were more likely than were whites to have basal-like breast cancer (odds ratio [OR], 3.80; 95% confidence interval [CI], 2.46-5.87; P less than .001) and HER2-enriched breast cancer (OR, 2.22; 95% CI, 1.10-4.47; P =.027).
After adjustment for subtype, 142 genes were differentially expressed between the two populations, a finding that held true after correction for testing of multiple comparisons (Bonferroni-adjusted P less than .05), reported Dezheng Huo, MD, PhD, of the department of public health sciences, University of Chicago, and his coauthors (JAMA Oncol. 2017 May 4. doi: 10.1001/jamaoncol.2017.0595).
During a median follow-up of 29 months, African Americans were more likely to experience recurrences (hazard ratio [HR], HR = 1.67, 95 CI, 1.02-2.74; P =.043). They had higher odds of basal-like breast cancer (OR, 3.80; 95% CI, 2.46-5.87; P less than .001) and human epidermal growth factor receptor 2 ERBB2 (HER2)-enriched breast cancer (OR, 2.22; 95% CI, 1.10-4.47; P =.027).
After adjusting for intrinsic subtypes, the researchers found differential expression of 16 DNA methylation probes, 4 DNA copy number segments, and 1 protein,
“If you have African ancestry, you’re more likely to have tumors that grow really fast. If we have drugs that can treat that kind of tumor, we need to find you and get you into treatment as quickly as possible,” she said.
FROM JAMA ONCOLOGY
Key clinical point: Genetic differences may play role in racial disparities in breast cancer outcomes.
Major finding: The Cancer Genome Atlas data show that 142 genes were differentially expressed between whites and African Americans.
Data source: Analysis of genetic and outcome data from 930 patients.
Disclosures: The study was funded by the National Cancer Institute, the Breast Cancer Research Foundation, the National Human Genome Research Institute, Susan G. Komen, and the American Cancer Society. Dr. Olopade is a cofounder of CancerIQ and Prosigna.
More pulmonary patients getting palliative care
Patients referred to palliative care are most likely to have cancer, but the proportion has gone down since 2009 as other diagnoses have increased, according to a report from the National Palliative Care Registry.
In 2015, cancer patients made up 26% of the patients referred to palliative care, compared with 35% in 2009. The situation was reversed for the next three most common diagnoses in 2015: Cardiac diagnoses rose from 5% in 2009 to 13%, pulmonary diagnoses increased from 6% to 12%, and neurologic diagnoses went from 3% to 8%, the report showed.
An increase in overall palliative care penetration was seen from 2009 to 2015, as the percentage of annual hospital admissions seen by a palliative care team increased from 2.7% to 4.8%. Over that same time period, the percentage of palliative care patients who died in the hospital decreased from 29% to 22%, according to the report.
In 2015, there were 420 palliative care programs participating in the registry, which is a joint project of the Center to Advance Palliative Care and the National Palliative Care Research Center.
Patients referred to palliative care are most likely to have cancer, but the proportion has gone down since 2009 as other diagnoses have increased, according to a report from the National Palliative Care Registry.
In 2015, cancer patients made up 26% of the patients referred to palliative care, compared with 35% in 2009. The situation was reversed for the next three most common diagnoses in 2015: Cardiac diagnoses rose from 5% in 2009 to 13%, pulmonary diagnoses increased from 6% to 12%, and neurologic diagnoses went from 3% to 8%, the report showed.
An increase in overall palliative care penetration was seen from 2009 to 2015, as the percentage of annual hospital admissions seen by a palliative care team increased from 2.7% to 4.8%. Over that same time period, the percentage of palliative care patients who died in the hospital decreased from 29% to 22%, according to the report.
In 2015, there were 420 palliative care programs participating in the registry, which is a joint project of the Center to Advance Palliative Care and the National Palliative Care Research Center.
Patients referred to palliative care are most likely to have cancer, but the proportion has gone down since 2009 as other diagnoses have increased, according to a report from the National Palliative Care Registry.
In 2015, cancer patients made up 26% of the patients referred to palliative care, compared with 35% in 2009. The situation was reversed for the next three most common diagnoses in 2015: Cardiac diagnoses rose from 5% in 2009 to 13%, pulmonary diagnoses increased from 6% to 12%, and neurologic diagnoses went from 3% to 8%, the report showed.
An increase in overall palliative care penetration was seen from 2009 to 2015, as the percentage of annual hospital admissions seen by a palliative care team increased from 2.7% to 4.8%. Over that same time period, the percentage of palliative care patients who died in the hospital decreased from 29% to 22%, according to the report.
In 2015, there were 420 palliative care programs participating in the registry, which is a joint project of the Center to Advance Palliative Care and the National Palliative Care Research Center.
More neurology patients getting palliative care
Patients referred to palliative care are most likely to have cancer, but the proportion has gone down since 2009 as other diagnoses have increased, according to a report from the National Palliative Care Registry.
In 2015, cancer patients made up 26% of the patients referred to palliative care, compared with 35% in 2009. The situation was reversed for the next three most common diagnoses in 2015: Cardiac diagnoses rose from 5% in 2009 to 13%, pulmonary diagnoses increased from 6% to 12%, and neurologic diagnoses went from 3% to 8%, the report showed.
An increase in overall palliative care penetration was seen from 2009 to 2015, as the percentage of annual hospital admissions seen by a palliative care team increased from 2.7% to 4.8%. Over that same time period, the percentage of palliative care patients who died in the hospital decreased from 29% to 22%, according to the report.
In 2015, there were 420 palliative care programs participating in the registry, which is a joint project of the Center to Advance Palliative Care and the National Palliative Care Research Center.
Patients referred to palliative care are most likely to have cancer, but the proportion has gone down since 2009 as other diagnoses have increased, according to a report from the National Palliative Care Registry.
In 2015, cancer patients made up 26% of the patients referred to palliative care, compared with 35% in 2009. The situation was reversed for the next three most common diagnoses in 2015: Cardiac diagnoses rose from 5% in 2009 to 13%, pulmonary diagnoses increased from 6% to 12%, and neurologic diagnoses went from 3% to 8%, the report showed.
An increase in overall palliative care penetration was seen from 2009 to 2015, as the percentage of annual hospital admissions seen by a palliative care team increased from 2.7% to 4.8%. Over that same time period, the percentage of palliative care patients who died in the hospital decreased from 29% to 22%, according to the report.
In 2015, there were 420 palliative care programs participating in the registry, which is a joint project of the Center to Advance Palliative Care and the National Palliative Care Research Center.
Patients referred to palliative care are most likely to have cancer, but the proportion has gone down since 2009 as other diagnoses have increased, according to a report from the National Palliative Care Registry.
In 2015, cancer patients made up 26% of the patients referred to palliative care, compared with 35% in 2009. The situation was reversed for the next three most common diagnoses in 2015: Cardiac diagnoses rose from 5% in 2009 to 13%, pulmonary diagnoses increased from 6% to 12%, and neurologic diagnoses went from 3% to 8%, the report showed.
An increase in overall palliative care penetration was seen from 2009 to 2015, as the percentage of annual hospital admissions seen by a palliative care team increased from 2.7% to 4.8%. Over that same time period, the percentage of palliative care patients who died in the hospital decreased from 29% to 22%, according to the report.
In 2015, there were 420 palliative care programs participating in the registry, which is a joint project of the Center to Advance Palliative Care and the National Palliative Care Research Center.