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Becoming the Authoritative Expert on Cancer Care for Veterans
In their addresses to the assembly, both the outgoing and incoming Association of VA Hematology and Oncology (AVAHO) presidents laid out the challenges and opportunities for the growing organization. Nearly 500 people attended the meeting, which was held in Denver, Colorado September 15 to September 17. Next year the meeting will be held in the Chicago area September 28 to 30, 2018.
As Mary Thomas, MS, CNS, AOCN noted, it is a challenging time to provide care at the VA. Public scrutiny and criticism, coupled with both understaffing and difficulties in employee retention at most facilities has left many health care providers feeling overwhelmed. Amid the challenges of working within the VA and for vulnerable veteran patients AVAHO provides its members an "essential opportunity to support each other" Thomas insisted in her farewell address. "One of our strategic goals is to enhance the value of the group for our members and to broaden our base by offering other functions and activities," Thomas added. "There is something for everyone.
Over the past year AVAHO has hired a part-time executive director to focus on the business and operations of the organization, proactively hired an accounting firm to ensure that the financial processes are done properly, and developed a formal relationship with the National Association of Veterans Research to increase access to clinical trials to improve clinical research. Thomas also highlighted a new relationship between AVAHO and an organization that develops continuing education programs. These programs will be available at VA hospitals throughout the country. "As a result of these relationships," Thomas told Federal Practitioner, "we have the ability to step up to the plate to assist the VA to be a more active partner in clinical research--that's really, really exciting."
Russell "Rusty" Crawford, B Pharm, BCOP, struck an upbeat note as he closed the meeting. Noting the significant progress made during Thomas' tenure, Crawford also laid out a more ambitious goal to "make AVAHO the authoritative expert on cancer care for veterans," he said "Our patients are unique and don't fit into a National Comprehensive Cancer Network box."
Mark Klein, MD, an oncologist at the Minneapolis VA Health Care System and an assistant professor of medicine at the University of Minnesota, in Minneapolis was named president elect.
In their addresses to the assembly, both the outgoing and incoming Association of VA Hematology and Oncology (AVAHO) presidents laid out the challenges and opportunities for the growing organization. Nearly 500 people attended the meeting, which was held in Denver, Colorado September 15 to September 17. Next year the meeting will be held in the Chicago area September 28 to 30, 2018.
As Mary Thomas, MS, CNS, AOCN noted, it is a challenging time to provide care at the VA. Public scrutiny and criticism, coupled with both understaffing and difficulties in employee retention at most facilities has left many health care providers feeling overwhelmed. Amid the challenges of working within the VA and for vulnerable veteran patients AVAHO provides its members an "essential opportunity to support each other" Thomas insisted in her farewell address. "One of our strategic goals is to enhance the value of the group for our members and to broaden our base by offering other functions and activities," Thomas added. "There is something for everyone.
Over the past year AVAHO has hired a part-time executive director to focus on the business and operations of the organization, proactively hired an accounting firm to ensure that the financial processes are done properly, and developed a formal relationship with the National Association of Veterans Research to increase access to clinical trials to improve clinical research. Thomas also highlighted a new relationship between AVAHO and an organization that develops continuing education programs. These programs will be available at VA hospitals throughout the country. "As a result of these relationships," Thomas told Federal Practitioner, "we have the ability to step up to the plate to assist the VA to be a more active partner in clinical research--that's really, really exciting."
Russell "Rusty" Crawford, B Pharm, BCOP, struck an upbeat note as he closed the meeting. Noting the significant progress made during Thomas' tenure, Crawford also laid out a more ambitious goal to "make AVAHO the authoritative expert on cancer care for veterans," he said "Our patients are unique and don't fit into a National Comprehensive Cancer Network box."
Mark Klein, MD, an oncologist at the Minneapolis VA Health Care System and an assistant professor of medicine at the University of Minnesota, in Minneapolis was named president elect.
In their addresses to the assembly, both the outgoing and incoming Association of VA Hematology and Oncology (AVAHO) presidents laid out the challenges and opportunities for the growing organization. Nearly 500 people attended the meeting, which was held in Denver, Colorado September 15 to September 17. Next year the meeting will be held in the Chicago area September 28 to 30, 2018.
As Mary Thomas, MS, CNS, AOCN noted, it is a challenging time to provide care at the VA. Public scrutiny and criticism, coupled with both understaffing and difficulties in employee retention at most facilities has left many health care providers feeling overwhelmed. Amid the challenges of working within the VA and for vulnerable veteran patients AVAHO provides its members an "essential opportunity to support each other" Thomas insisted in her farewell address. "One of our strategic goals is to enhance the value of the group for our members and to broaden our base by offering other functions and activities," Thomas added. "There is something for everyone.
Over the past year AVAHO has hired a part-time executive director to focus on the business and operations of the organization, proactively hired an accounting firm to ensure that the financial processes are done properly, and developed a formal relationship with the National Association of Veterans Research to increase access to clinical trials to improve clinical research. Thomas also highlighted a new relationship between AVAHO and an organization that develops continuing education programs. These programs will be available at VA hospitals throughout the country. "As a result of these relationships," Thomas told Federal Practitioner, "we have the ability to step up to the plate to assist the VA to be a more active partner in clinical research--that's really, really exciting."
Russell "Rusty" Crawford, B Pharm, BCOP, struck an upbeat note as he closed the meeting. Noting the significant progress made during Thomas' tenure, Crawford also laid out a more ambitious goal to "make AVAHO the authoritative expert on cancer care for veterans," he said "Our patients are unique and don't fit into a National Comprehensive Cancer Network box."
Mark Klein, MD, an oncologist at the Minneapolis VA Health Care System and an assistant professor of medicine at the University of Minnesota, in Minneapolis was named president elect.
CHMP recommends approval of nilotinib for kids
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended expanding the authorized use for nilotinib (Tasigna) to include pediatric patients.
At present, nilotinib is approved for use in the European Economic Area to treat adults with chronic myeloid leukemia (CML).
The drug is used to treat adults with newly diagnosed, Philadelphia-chromosome-positive (Ph+), chronic phase CML and adults with chronic or accelerated phase, Ph+ CML with resistance or intolerance to prior therapy, including imatinib.
The CHMP has recommended expanding the marketing authorization of nilotinib to include pediatric patients with newly diagnosed, Ph+, chronic phase CML and pediatric patients with chronic phase, Ph+ CML with resistance or intolerance to prior therapy, including imatinib.
Detailed recommendations for the use of nilotinib will be described in the updated summary of product characteristics, which will be published in the revised European public assessment report. It will be available in all official European Union languages after a decision on this change to the marketing authorization has been granted by the European Commission (EC).
The EC typically adheres to the CHMP’s recommendations and delivers its final decision within 67 days of the CHMP’s recommendation.
The EC’s decision will be applicable to the entire European Economic Area—all member states of the European Union plus Iceland, Liechtenstein, and Norway. 
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended expanding the authorized use for nilotinib (Tasigna) to include pediatric patients.
At present, nilotinib is approved for use in the European Economic Area to treat adults with chronic myeloid leukemia (CML).
The drug is used to treat adults with newly diagnosed, Philadelphia-chromosome-positive (Ph+), chronic phase CML and adults with chronic or accelerated phase, Ph+ CML with resistance or intolerance to prior therapy, including imatinib.
The CHMP has recommended expanding the marketing authorization of nilotinib to include pediatric patients with newly diagnosed, Ph+, chronic phase CML and pediatric patients with chronic phase, Ph+ CML with resistance or intolerance to prior therapy, including imatinib.
Detailed recommendations for the use of nilotinib will be described in the updated summary of product characteristics, which will be published in the revised European public assessment report. It will be available in all official European Union languages after a decision on this change to the marketing authorization has been granted by the European Commission (EC).
The EC typically adheres to the CHMP’s recommendations and delivers its final decision within 67 days of the CHMP’s recommendation.
The EC’s decision will be applicable to the entire European Economic Area—all member states of the European Union plus Iceland, Liechtenstein, and Norway.
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended expanding the authorized use for nilotinib (Tasigna) to include pediatric patients.
At present, nilotinib is approved for use in the European Economic Area to treat adults with chronic myeloid leukemia (CML).
The drug is used to treat adults with newly diagnosed, Philadelphia-chromosome-positive (Ph+), chronic phase CML and adults with chronic or accelerated phase, Ph+ CML with resistance or intolerance to prior therapy, including imatinib.
The CHMP has recommended expanding the marketing authorization of nilotinib to include pediatric patients with newly diagnosed, Ph+, chronic phase CML and pediatric patients with chronic phase, Ph+ CML with resistance or intolerance to prior therapy, including imatinib.
Detailed recommendations for the use of nilotinib will be described in the updated summary of product characteristics, which will be published in the revised European public assessment report. It will be available in all official European Union languages after a decision on this change to the marketing authorization has been granted by the European Commission (EC).
The EC typically adheres to the CHMP’s recommendations and delivers its final decision within 67 days of the CHMP’s recommendation.
The EC’s decision will be applicable to the entire European Economic Area—all member states of the European Union plus Iceland, Liechtenstein, and Norway.
Suicide: A surprisingly ambivalent topic
It’s National Suicide Prevention Week (Sept. 10-16, 2017) and few psychiatrists would disagree that suicide is a bad outcome, that it is often preventable, and that the loss and pain that follow an untimely act are nothing short of tragic.
It’s also an epidemic on the rise, with more than 40,000 deaths a year, half of those by self-inflicted gunshot. Because 90% of those who suicide suffer from mental illness, one target becomes clear: We need to identify those at risk and make it easy for them to get help. Still, treatment is not a clear panacea; in the decades since selective serotonin reuptake inhibitors have become so readily available, suicide rates have risen, and many who die have gotten help of some type. The issue is a complicated one that reaches well beyond the arena of mental health.
Paul Nestadt, MD, a postdoctoral fellow in the Johns Hopkins Psychiatric Epidemiology Training Program, is a researcher on a study that correlated rural suicide rates with the availability of firearms (Am J Public Health. 2017 Oct;107[10]:1548-53). “Suicide can happen when ambivalent suicidal thoughts dip over the threshold into behavior. In those key moments, the lethality of the nearest available method may determine whether someone dies, as illustrated in the United States by the predominance of firearms in the use of completed suicides.” Yet it is not unusual for those who are against gun control to note that most firearm deaths are suicides, and therefore unlikely to be changed with gun regulation; they believe that individuals who want to die will find another way, despite research that indicates otherwise. At moments, it feels like they are saying these deaths don’t count; people who have impulses to harm themselves will do so, and gun control is not an answer. Others, like Nestadt, contend otherwise, and say that limiting access to lethal means will make a difference.
Let’s also consider the words we use. While the familiar term is to “commit suicide,” the current thinking is that this is stigmatizing – people “commit” crimes – and family members of survivors often prefer the phrase “died of suicide.” Is the change necessary? It is true that people commit crimes, but they also commit to relationships, and to any number of positive activities. I had not previously associated the word with criminal behavior, and the now-favored term changes suicide from an active event to a passive one. If changing the words helps lessen the pain of the survivors, then I am all in favor, but the loss and shame remain regardless of the phrasing.
Stigma may be a mixed thing when it comes to ending one’s life. We would all like to see suicidal thoughts and intentions destigmatized so that those who suffer won’t hesitate to get help. It’s not clear, however, whether stigmatizing the completed suicide might serve as a deterrent to the behavior for some. When patients talk of wanting to die and are considering a method, they often add that they could not do this to their families. If suicide is just another nonstigmatized way to die and end an individual’s suffering, perhaps even more people would choose this option? And the question moves to media portrayals where suicide is not only not stigmatized, it is sometimes glamorized, and the deceased becomes the focus of positive attention, especially for young people, and inspires copycat deaths.
Anita Everett, MD, the chief medical officer of the Substance Abuse and Mental Health Services Administration and president of the American Psychiatric Association, notes, “Suicide is a significant problem of national concern that every part of the health care system can play a part in addressing.” Yet in our societal ambivalence, the topic of physician-assisted suicide has become a subject of much contention in our state legislatures. Six states and the District of Columbia allow for “physician-assisted suicide” – also called “aid in dying” or “death with dignity” – terms that distance the association with either suicide or euthanasia. It is available for people with terminal illnesses and a projected life expectancy of less than 6 months. In this scenario, a physician prescribes a lethal dose of medication at the patient’s request, and the patient then obtains the medication and self-administers it. The death is not reported as suicide, but rather as a consequence of the underlying disease, thereby eliminating any concerns with stigma for the family survivors. While this is not obviously an issue for psychiatry, members of our profession have been outspoken about it, and in one state, the issue came to such a head that two district branches of the American Psychiatric Association with differing views could no longer continue to employ a single lobbyist.
Ambivalence is not limited to the United States. Belgium and the Netherlands have extended physician-assisted suicide to include patients with psychiatric illnesses deemed to be intractable. In these countries, the patient may choose to have a psychiatrist administer a lethal injection.
Mark Komrad, MD, is the ethicist-in-residence at Sheppard Pratt Health Systems. Earlier this month, he visited Belgium to speak on the topic. Komrad noted: “The Belgian professionals were quite aware that the majority of the world disagrees with the euthanasia of psychiatric patients. It seemed almost a point of honor that they differed in this way, as if they are on higher moral ground in a bold new era of medical ethics.” It strikes me as tragically ironic that, as we struggle to prevent the blight of suicide, we have colleagues in Europe who are ushering it along and stretching the practice of euthanasia to what many of us might classify more simply as the murder of physically healthy patients who may not have exhausted every possible psychiatric treatment, or who may spontaneously recover in the future.
Finally, I wanted to touch on a rather unusual case of two teenagers in Massachusetts. Michelle Carter was 17 years old when her boyfriend died of suicide from carbon monoxide poisoning. Sometime after the young man’s death, it was discovered that Carter, a troubled young woman with her own psychiatric illnesses, had known of his suicide plans. By text and phone call, she encouraged him to go through with it, although she was never physically present at the scene of his death. The boyfriend had been suicidal prior to meeting Carter and had spoken to her about his wishes to die. The defense contended, unsuccessfully, that the young woman was propelled to such evil because she was taking antidepressants. Carter was convicted of involuntary manslaughter in a juvenile court and sentenced to 15 months in jail for her reckless conduct that was deemed to have caused the young man’s suicide. The case was obviously quite complicated, but I found it to be one more example of our society’s ambivalence about suicide, in that a teenager would be held responsible and incarcerated for inciting another person to die with her words alone.
As suicide rates rise, we are still finding our way here. We don’t know what propels it, and we don’t know how to cure it. We vacillate between trying not to stigmatize suicide and trying not to glamorize it. And we struggle with whether it is the role of the physician to prolong life and continue to proffer hope or to end life when suffering is deemed by the individual to be unbearable.
Dr. Miller is coauthor with Annette Hanson, MD, of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016).
It’s National Suicide Prevention Week (Sept. 10-16, 2017) and few psychiatrists would disagree that suicide is a bad outcome, that it is often preventable, and that the loss and pain that follow an untimely act are nothing short of tragic.
It’s also an epidemic on the rise, with more than 40,000 deaths a year, half of those by self-inflicted gunshot. Because 90% of those who suicide suffer from mental illness, one target becomes clear: We need to identify those at risk and make it easy for them to get help. Still, treatment is not a clear panacea; in the decades since selective serotonin reuptake inhibitors have become so readily available, suicide rates have risen, and many who die have gotten help of some type. The issue is a complicated one that reaches well beyond the arena of mental health.
Paul Nestadt, MD, a postdoctoral fellow in the Johns Hopkins Psychiatric Epidemiology Training Program, is a researcher on a study that correlated rural suicide rates with the availability of firearms (Am J Public Health. 2017 Oct;107[10]:1548-53). “Suicide can happen when ambivalent suicidal thoughts dip over the threshold into behavior. In those key moments, the lethality of the nearest available method may determine whether someone dies, as illustrated in the United States by the predominance of firearms in the use of completed suicides.” Yet it is not unusual for those who are against gun control to note that most firearm deaths are suicides, and therefore unlikely to be changed with gun regulation; they believe that individuals who want to die will find another way, despite research that indicates otherwise. At moments, it feels like they are saying these deaths don’t count; people who have impulses to harm themselves will do so, and gun control is not an answer. Others, like Nestadt, contend otherwise, and say that limiting access to lethal means will make a difference.
Let’s also consider the words we use. While the familiar term is to “commit suicide,” the current thinking is that this is stigmatizing – people “commit” crimes – and family members of survivors often prefer the phrase “died of suicide.” Is the change necessary? It is true that people commit crimes, but they also commit to relationships, and to any number of positive activities. I had not previously associated the word with criminal behavior, and the now-favored term changes suicide from an active event to a passive one. If changing the words helps lessen the pain of the survivors, then I am all in favor, but the loss and shame remain regardless of the phrasing.
Stigma may be a mixed thing when it comes to ending one’s life. We would all like to see suicidal thoughts and intentions destigmatized so that those who suffer won’t hesitate to get help. It’s not clear, however, whether stigmatizing the completed suicide might serve as a deterrent to the behavior for some. When patients talk of wanting to die and are considering a method, they often add that they could not do this to their families. If suicide is just another nonstigmatized way to die and end an individual’s suffering, perhaps even more people would choose this option? And the question moves to media portrayals where suicide is not only not stigmatized, it is sometimes glamorized, and the deceased becomes the focus of positive attention, especially for young people, and inspires copycat deaths.
Anita Everett, MD, the chief medical officer of the Substance Abuse and Mental Health Services Administration and president of the American Psychiatric Association, notes, “Suicide is a significant problem of national concern that every part of the health care system can play a part in addressing.” Yet in our societal ambivalence, the topic of physician-assisted suicide has become a subject of much contention in our state legislatures. Six states and the District of Columbia allow for “physician-assisted suicide” – also called “aid in dying” or “death with dignity” – terms that distance the association with either suicide or euthanasia. It is available for people with terminal illnesses and a projected life expectancy of less than 6 months. In this scenario, a physician prescribes a lethal dose of medication at the patient’s request, and the patient then obtains the medication and self-administers it. The death is not reported as suicide, but rather as a consequence of the underlying disease, thereby eliminating any concerns with stigma for the family survivors. While this is not obviously an issue for psychiatry, members of our profession have been outspoken about it, and in one state, the issue came to such a head that two district branches of the American Psychiatric Association with differing views could no longer continue to employ a single lobbyist.
Ambivalence is not limited to the United States. Belgium and the Netherlands have extended physician-assisted suicide to include patients with psychiatric illnesses deemed to be intractable. In these countries, the patient may choose to have a psychiatrist administer a lethal injection.
Mark Komrad, MD, is the ethicist-in-residence at Sheppard Pratt Health Systems. Earlier this month, he visited Belgium to speak on the topic. Komrad noted: “The Belgian professionals were quite aware that the majority of the world disagrees with the euthanasia of psychiatric patients. It seemed almost a point of honor that they differed in this way, as if they are on higher moral ground in a bold new era of medical ethics.” It strikes me as tragically ironic that, as we struggle to prevent the blight of suicide, we have colleagues in Europe who are ushering it along and stretching the practice of euthanasia to what many of us might classify more simply as the murder of physically healthy patients who may not have exhausted every possible psychiatric treatment, or who may spontaneously recover in the future.
Finally, I wanted to touch on a rather unusual case of two teenagers in Massachusetts. Michelle Carter was 17 years old when her boyfriend died of suicide from carbon monoxide poisoning. Sometime after the young man’s death, it was discovered that Carter, a troubled young woman with her own psychiatric illnesses, had known of his suicide plans. By text and phone call, she encouraged him to go through with it, although she was never physically present at the scene of his death. The boyfriend had been suicidal prior to meeting Carter and had spoken to her about his wishes to die. The defense contended, unsuccessfully, that the young woman was propelled to such evil because she was taking antidepressants. Carter was convicted of involuntary manslaughter in a juvenile court and sentenced to 15 months in jail for her reckless conduct that was deemed to have caused the young man’s suicide. The case was obviously quite complicated, but I found it to be one more example of our society’s ambivalence about suicide, in that a teenager would be held responsible and incarcerated for inciting another person to die with her words alone.
As suicide rates rise, we are still finding our way here. We don’t know what propels it, and we don’t know how to cure it. We vacillate between trying not to stigmatize suicide and trying not to glamorize it. And we struggle with whether it is the role of the physician to prolong life and continue to proffer hope or to end life when suffering is deemed by the individual to be unbearable.
Dr. Miller is coauthor with Annette Hanson, MD, of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016).
It’s National Suicide Prevention Week (Sept. 10-16, 2017) and few psychiatrists would disagree that suicide is a bad outcome, that it is often preventable, and that the loss and pain that follow an untimely act are nothing short of tragic.
It’s also an epidemic on the rise, with more than 40,000 deaths a year, half of those by self-inflicted gunshot. Because 90% of those who suicide suffer from mental illness, one target becomes clear: We need to identify those at risk and make it easy for them to get help. Still, treatment is not a clear panacea; in the decades since selective serotonin reuptake inhibitors have become so readily available, suicide rates have risen, and many who die have gotten help of some type. The issue is a complicated one that reaches well beyond the arena of mental health.
Paul Nestadt, MD, a postdoctoral fellow in the Johns Hopkins Psychiatric Epidemiology Training Program, is a researcher on a study that correlated rural suicide rates with the availability of firearms (Am J Public Health. 2017 Oct;107[10]:1548-53). “Suicide can happen when ambivalent suicidal thoughts dip over the threshold into behavior. In those key moments, the lethality of the nearest available method may determine whether someone dies, as illustrated in the United States by the predominance of firearms in the use of completed suicides.” Yet it is not unusual for those who are against gun control to note that most firearm deaths are suicides, and therefore unlikely to be changed with gun regulation; they believe that individuals who want to die will find another way, despite research that indicates otherwise. At moments, it feels like they are saying these deaths don’t count; people who have impulses to harm themselves will do so, and gun control is not an answer. Others, like Nestadt, contend otherwise, and say that limiting access to lethal means will make a difference.
Let’s also consider the words we use. While the familiar term is to “commit suicide,” the current thinking is that this is stigmatizing – people “commit” crimes – and family members of survivors often prefer the phrase “died of suicide.” Is the change necessary? It is true that people commit crimes, but they also commit to relationships, and to any number of positive activities. I had not previously associated the word with criminal behavior, and the now-favored term changes suicide from an active event to a passive one. If changing the words helps lessen the pain of the survivors, then I am all in favor, but the loss and shame remain regardless of the phrasing.
Stigma may be a mixed thing when it comes to ending one’s life. We would all like to see suicidal thoughts and intentions destigmatized so that those who suffer won’t hesitate to get help. It’s not clear, however, whether stigmatizing the completed suicide might serve as a deterrent to the behavior for some. When patients talk of wanting to die and are considering a method, they often add that they could not do this to their families. If suicide is just another nonstigmatized way to die and end an individual’s suffering, perhaps even more people would choose this option? And the question moves to media portrayals where suicide is not only not stigmatized, it is sometimes glamorized, and the deceased becomes the focus of positive attention, especially for young people, and inspires copycat deaths.
Anita Everett, MD, the chief medical officer of the Substance Abuse and Mental Health Services Administration and president of the American Psychiatric Association, notes, “Suicide is a significant problem of national concern that every part of the health care system can play a part in addressing.” Yet in our societal ambivalence, the topic of physician-assisted suicide has become a subject of much contention in our state legislatures. Six states and the District of Columbia allow for “physician-assisted suicide” – also called “aid in dying” or “death with dignity” – terms that distance the association with either suicide or euthanasia. It is available for people with terminal illnesses and a projected life expectancy of less than 6 months. In this scenario, a physician prescribes a lethal dose of medication at the patient’s request, and the patient then obtains the medication and self-administers it. The death is not reported as suicide, but rather as a consequence of the underlying disease, thereby eliminating any concerns with stigma for the family survivors. While this is not obviously an issue for psychiatry, members of our profession have been outspoken about it, and in one state, the issue came to such a head that two district branches of the American Psychiatric Association with differing views could no longer continue to employ a single lobbyist.
Ambivalence is not limited to the United States. Belgium and the Netherlands have extended physician-assisted suicide to include patients with psychiatric illnesses deemed to be intractable. In these countries, the patient may choose to have a psychiatrist administer a lethal injection.
Mark Komrad, MD, is the ethicist-in-residence at Sheppard Pratt Health Systems. Earlier this month, he visited Belgium to speak on the topic. Komrad noted: “The Belgian professionals were quite aware that the majority of the world disagrees with the euthanasia of psychiatric patients. It seemed almost a point of honor that they differed in this way, as if they are on higher moral ground in a bold new era of medical ethics.” It strikes me as tragically ironic that, as we struggle to prevent the blight of suicide, we have colleagues in Europe who are ushering it along and stretching the practice of euthanasia to what many of us might classify more simply as the murder of physically healthy patients who may not have exhausted every possible psychiatric treatment, or who may spontaneously recover in the future.
Finally, I wanted to touch on a rather unusual case of two teenagers in Massachusetts. Michelle Carter was 17 years old when her boyfriend died of suicide from carbon monoxide poisoning. Sometime after the young man’s death, it was discovered that Carter, a troubled young woman with her own psychiatric illnesses, had known of his suicide plans. By text and phone call, she encouraged him to go through with it, although she was never physically present at the scene of his death. The boyfriend had been suicidal prior to meeting Carter and had spoken to her about his wishes to die. The defense contended, unsuccessfully, that the young woman was propelled to such evil because she was taking antidepressants. Carter was convicted of involuntary manslaughter in a juvenile court and sentenced to 15 months in jail for her reckless conduct that was deemed to have caused the young man’s suicide. The case was obviously quite complicated, but I found it to be one more example of our society’s ambivalence about suicide, in that a teenager would be held responsible and incarcerated for inciting another person to die with her words alone.
As suicide rates rise, we are still finding our way here. We don’t know what propels it, and we don’t know how to cure it. We vacillate between trying not to stigmatize suicide and trying not to glamorize it. And we struggle with whether it is the role of the physician to prolong life and continue to proffer hope or to end life when suffering is deemed by the individual to be unbearable.
Dr. Miller is coauthor with Annette Hanson, MD, of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016).
FDA gives nod to first mobile app for substance use disorders
The Food and Drug Administration has permitted marketing of the first mobile medical application aimed at helping to treat substance use disorders (SUDs) in adults, the agency announced Sept. 14.
“This is an example of how innovative digital technologies can help provide patients access to additional tools during their treatment,” said Carlos Peña, PhD, director of the division of neurological and physical medicine devices in the FDA’s Center for Devices and Radiological Health, in a statement.
“More therapy tools means a greater potential to help improve outcomes ... for patients with substance use disorder,” Dr. Peña added.
The agency’s permission is based on data reviewed from a multisite, unblinded 12-week clinical trial sponsored by the National Institute on Drug Abuse of 399 patients who received either standard treatment or standard treatment with the addition of a desktop-based version of reSET. According to the data, adherence to abstinence for patients with alcohol, cocaine, marijuana, and stimulant SUD who used reSET increased 40.3%, compared with an increase of 17.6% in adherence to abstinence for patients who did not use the system.
No side effects are associated with the reSET application. Adverse events reported in clinical trials were in line with those found in patients with SUD, including cardiovascular disease, gastrointestinal events, depression, mania, suicidal behavior and ideation, and suicide attempts.
Edward V. Nunes, MD, said in a statement issued by the company that developed reSET, Pear Therapeutics, that the clinical outcomes found in the pivotal study were remarkable. “Clinically validated digital therapeutics may become a cornerstone of future treatment,” said Dr. Nunes, lead investigator in the study submitted to the FDA and a professor of psychiatry at Columbia University in New York.
For more information about the reSET medical application system, click here.
acruz@frontlinemedcom.com
On Twitter @abbbbeeeyyy
The Food and Drug Administration has permitted marketing of the first mobile medical application aimed at helping to treat substance use disorders (SUDs) in adults, the agency announced Sept. 14.
“This is an example of how innovative digital technologies can help provide patients access to additional tools during their treatment,” said Carlos Peña, PhD, director of the division of neurological and physical medicine devices in the FDA’s Center for Devices and Radiological Health, in a statement.
“More therapy tools means a greater potential to help improve outcomes ... for patients with substance use disorder,” Dr. Peña added.
The agency’s permission is based on data reviewed from a multisite, unblinded 12-week clinical trial sponsored by the National Institute on Drug Abuse of 399 patients who received either standard treatment or standard treatment with the addition of a desktop-based version of reSET. According to the data, adherence to abstinence for patients with alcohol, cocaine, marijuana, and stimulant SUD who used reSET increased 40.3%, compared with an increase of 17.6% in adherence to abstinence for patients who did not use the system.
No side effects are associated with the reSET application. Adverse events reported in clinical trials were in line with those found in patients with SUD, including cardiovascular disease, gastrointestinal events, depression, mania, suicidal behavior and ideation, and suicide attempts.
Edward V. Nunes, MD, said in a statement issued by the company that developed reSET, Pear Therapeutics, that the clinical outcomes found in the pivotal study were remarkable. “Clinically validated digital therapeutics may become a cornerstone of future treatment,” said Dr. Nunes, lead investigator in the study submitted to the FDA and a professor of psychiatry at Columbia University in New York.
For more information about the reSET medical application system, click here.
acruz@frontlinemedcom.com
On Twitter @abbbbeeeyyy
The Food and Drug Administration has permitted marketing of the first mobile medical application aimed at helping to treat substance use disorders (SUDs) in adults, the agency announced Sept. 14.
“This is an example of how innovative digital technologies can help provide patients access to additional tools during their treatment,” said Carlos Peña, PhD, director of the division of neurological and physical medicine devices in the FDA’s Center for Devices and Radiological Health, in a statement.
“More therapy tools means a greater potential to help improve outcomes ... for patients with substance use disorder,” Dr. Peña added.
The agency’s permission is based on data reviewed from a multisite, unblinded 12-week clinical trial sponsored by the National Institute on Drug Abuse of 399 patients who received either standard treatment or standard treatment with the addition of a desktop-based version of reSET. According to the data, adherence to abstinence for patients with alcohol, cocaine, marijuana, and stimulant SUD who used reSET increased 40.3%, compared with an increase of 17.6% in adherence to abstinence for patients who did not use the system.
No side effects are associated with the reSET application. Adverse events reported in clinical trials were in line with those found in patients with SUD, including cardiovascular disease, gastrointestinal events, depression, mania, suicidal behavior and ideation, and suicide attempts.
Edward V. Nunes, MD, said in a statement issued by the company that developed reSET, Pear Therapeutics, that the clinical outcomes found in the pivotal study were remarkable. “Clinically validated digital therapeutics may become a cornerstone of future treatment,” said Dr. Nunes, lead investigator in the study submitted to the FDA and a professor of psychiatry at Columbia University in New York.
For more information about the reSET medical application system, click here.
acruz@frontlinemedcom.com
On Twitter @abbbbeeeyyy
LORELEI sings praises of neoadjuvant taselisib/letrozole in ER+/HER2– breast cancer
MADRID – Adding the investigational PI3K inhibitor taselisib to letrozole (Femara) significantly improved overall response rates, compared with neoadjuvant letrozole alone, in postmenopausal women with early estrogen receptor–positive, human epidermal growth factor receptor 2–negative (ER+/HER2–) breast cancer, results of the LORELEI trial show.
In this phase 2 trial, the overall response rate (ORR), the primary endpoint, was 50% for 166 patients assigned to letrozole plus taselisib, compared with 39.3% for 168 patients assigned to letrozole plus placebo, reported Cristina Saura, MD, of Vall d’Hebron University Hospital in Barcelona.
Although the pathologic complete rate (pCR) was low in each study arm, this was not unexpected, due to the short course (4 months) of endocrine-based therapy, she said.
Taselisib is a selective inhibitor of phosphatidylinositol 3-kinase (PI3K), with enhanced activity against the mutation isoform of the protein, labeled p110a. The PI3K alpha isoform, Taselisib degrades p110a by a mechanism of action that is different from other PI3K inhibitors, Dr. Saura said.
As monotherapy and in combination with endocrine therapy agents in phase 1 trials, taselisib elicited partial responses in patients with PIK3CA-mutated metastatic breast cancer, she noted.
In LORELEI, 334 postmenopausal women with previously untreated ER+/HER2– stage I-III operable breast cancer with tumors of 2 cm or greater on MRI were enrolled. The patients were stratified by tumor size and nodal status and then randomly assigned to letrozole 2.5 mg daily plus taselisib 4 mg taken in 2 mg doses twice daily for 5 days each week for 16 weeks, or letrozole plus placebo. Patients then went on to surgery, were followed for safety for 30 days, and then had adjuvant therapy consisting of endocrine therapy and/or chemotherapy and/or radiation therapy.
As noted, the ORR for patients assigned to the combination was 50%, consisting of 4.8% CR, and 45.2% partial responses (PR). Additionally, 40.4% of patients assigned to the taselisib arm had stable disease. The corresponding response rates for patients assigned to the letrozole/placebo arm were 1.8%, 37.5%, and 51.2%.
The odds ratio favoring the combination was 1.55 (P = .049).
For the subset of patients with PIK3CA-mutated tumors, the ORR was 56.2% for 73 patients in the taselisib arm, vs. 38% for 79 patients in the placebo arm (OR, 2.03; P = .033).
The pCRs in the overall population were 1.8% with taselisib vs. 0.6% with placebo. The corresponding pCRs in the PIK3CA-mutated population were 1.4% and 0%. None of the differences were statistically significant.
In all, 11.4% of patients assigned to taselisib required dose reductions, and 10.8% had to discontinue the drug.
The incidence of adverse events of any grade was 91% with letrozole/taselisib, and 83.2% with letrozole placebo.
Taselisib was associated with higher rates of gastrointestinal side effects, skin and subcutaneous disorders, metabolic and nutritional side effects and respiratory, thoracic, and mediastinal disorders. Patients in the taselisib arm had a lower incidence of musculoskeletal/connective tissue problems, vascular disorders, and psychiatric complaints.
The toxicities were generally manageable and consistent with that of other PI3K inhibitors, Dr. Saura said.
She said that although taselisib is more selective than other PI3K inhibitors and has a somewhat lower incidence of GI toxicities, “it’s still difficult to manage as a drug in the clinic, but I think if we can tell a patient there is a selection criterion which is a PIK3CA mutation, then patients are more willing and we as therapists are more willing to give those drugs.”
LORELEI provides the first clinical proof of efficacy of a specific PI3K inhibitor in early breast cancer, and “results of confirmatory phase 3 trials in metastatic breast cancer are eagerly awaited,” Dr. Harbeck added.
The study was supported by Genentech/F. Hoffman–La Roche. Dr. Saura disclosed consulting fees and institutional funding from Roche. Dr. Harbeck reported no disclosures relevant to the study.
MADRID – Adding the investigational PI3K inhibitor taselisib to letrozole (Femara) significantly improved overall response rates, compared with neoadjuvant letrozole alone, in postmenopausal women with early estrogen receptor–positive, human epidermal growth factor receptor 2–negative (ER+/HER2–) breast cancer, results of the LORELEI trial show.
In this phase 2 trial, the overall response rate (ORR), the primary endpoint, was 50% for 166 patients assigned to letrozole plus taselisib, compared with 39.3% for 168 patients assigned to letrozole plus placebo, reported Cristina Saura, MD, of Vall d’Hebron University Hospital in Barcelona.
Although the pathologic complete rate (pCR) was low in each study arm, this was not unexpected, due to the short course (4 months) of endocrine-based therapy, she said.
Taselisib is a selective inhibitor of phosphatidylinositol 3-kinase (PI3K), with enhanced activity against the mutation isoform of the protein, labeled p110a. The PI3K alpha isoform, Taselisib degrades p110a by a mechanism of action that is different from other PI3K inhibitors, Dr. Saura said.
As monotherapy and in combination with endocrine therapy agents in phase 1 trials, taselisib elicited partial responses in patients with PIK3CA-mutated metastatic breast cancer, she noted.
In LORELEI, 334 postmenopausal women with previously untreated ER+/HER2– stage I-III operable breast cancer with tumors of 2 cm or greater on MRI were enrolled. The patients were stratified by tumor size and nodal status and then randomly assigned to letrozole 2.5 mg daily plus taselisib 4 mg taken in 2 mg doses twice daily for 5 days each week for 16 weeks, or letrozole plus placebo. Patients then went on to surgery, were followed for safety for 30 days, and then had adjuvant therapy consisting of endocrine therapy and/or chemotherapy and/or radiation therapy.
As noted, the ORR for patients assigned to the combination was 50%, consisting of 4.8% CR, and 45.2% partial responses (PR). Additionally, 40.4% of patients assigned to the taselisib arm had stable disease. The corresponding response rates for patients assigned to the letrozole/placebo arm were 1.8%, 37.5%, and 51.2%.
The odds ratio favoring the combination was 1.55 (P = .049).
For the subset of patients with PIK3CA-mutated tumors, the ORR was 56.2% for 73 patients in the taselisib arm, vs. 38% for 79 patients in the placebo arm (OR, 2.03; P = .033).
The pCRs in the overall population were 1.8% with taselisib vs. 0.6% with placebo. The corresponding pCRs in the PIK3CA-mutated population were 1.4% and 0%. None of the differences were statistically significant.
In all, 11.4% of patients assigned to taselisib required dose reductions, and 10.8% had to discontinue the drug.
The incidence of adverse events of any grade was 91% with letrozole/taselisib, and 83.2% with letrozole placebo.
Taselisib was associated with higher rates of gastrointestinal side effects, skin and subcutaneous disorders, metabolic and nutritional side effects and respiratory, thoracic, and mediastinal disorders. Patients in the taselisib arm had a lower incidence of musculoskeletal/connective tissue problems, vascular disorders, and psychiatric complaints.
The toxicities were generally manageable and consistent with that of other PI3K inhibitors, Dr. Saura said.
She said that although taselisib is more selective than other PI3K inhibitors and has a somewhat lower incidence of GI toxicities, “it’s still difficult to manage as a drug in the clinic, but I think if we can tell a patient there is a selection criterion which is a PIK3CA mutation, then patients are more willing and we as therapists are more willing to give those drugs.”
LORELEI provides the first clinical proof of efficacy of a specific PI3K inhibitor in early breast cancer, and “results of confirmatory phase 3 trials in metastatic breast cancer are eagerly awaited,” Dr. Harbeck added.
The study was supported by Genentech/F. Hoffman–La Roche. Dr. Saura disclosed consulting fees and institutional funding from Roche. Dr. Harbeck reported no disclosures relevant to the study.
MADRID – Adding the investigational PI3K inhibitor taselisib to letrozole (Femara) significantly improved overall response rates, compared with neoadjuvant letrozole alone, in postmenopausal women with early estrogen receptor–positive, human epidermal growth factor receptor 2–negative (ER+/HER2–) breast cancer, results of the LORELEI trial show.
In this phase 2 trial, the overall response rate (ORR), the primary endpoint, was 50% for 166 patients assigned to letrozole plus taselisib, compared with 39.3% for 168 patients assigned to letrozole plus placebo, reported Cristina Saura, MD, of Vall d’Hebron University Hospital in Barcelona.
Although the pathologic complete rate (pCR) was low in each study arm, this was not unexpected, due to the short course (4 months) of endocrine-based therapy, she said.
Taselisib is a selective inhibitor of phosphatidylinositol 3-kinase (PI3K), with enhanced activity against the mutation isoform of the protein, labeled p110a. The PI3K alpha isoform, Taselisib degrades p110a by a mechanism of action that is different from other PI3K inhibitors, Dr. Saura said.
As monotherapy and in combination with endocrine therapy agents in phase 1 trials, taselisib elicited partial responses in patients with PIK3CA-mutated metastatic breast cancer, she noted.
In LORELEI, 334 postmenopausal women with previously untreated ER+/HER2– stage I-III operable breast cancer with tumors of 2 cm or greater on MRI were enrolled. The patients were stratified by tumor size and nodal status and then randomly assigned to letrozole 2.5 mg daily plus taselisib 4 mg taken in 2 mg doses twice daily for 5 days each week for 16 weeks, or letrozole plus placebo. Patients then went on to surgery, were followed for safety for 30 days, and then had adjuvant therapy consisting of endocrine therapy and/or chemotherapy and/or radiation therapy.
As noted, the ORR for patients assigned to the combination was 50%, consisting of 4.8% CR, and 45.2% partial responses (PR). Additionally, 40.4% of patients assigned to the taselisib arm had stable disease. The corresponding response rates for patients assigned to the letrozole/placebo arm were 1.8%, 37.5%, and 51.2%.
The odds ratio favoring the combination was 1.55 (P = .049).
For the subset of patients with PIK3CA-mutated tumors, the ORR was 56.2% for 73 patients in the taselisib arm, vs. 38% for 79 patients in the placebo arm (OR, 2.03; P = .033).
The pCRs in the overall population were 1.8% with taselisib vs. 0.6% with placebo. The corresponding pCRs in the PIK3CA-mutated population were 1.4% and 0%. None of the differences were statistically significant.
In all, 11.4% of patients assigned to taselisib required dose reductions, and 10.8% had to discontinue the drug.
The incidence of adverse events of any grade was 91% with letrozole/taselisib, and 83.2% with letrozole placebo.
Taselisib was associated with higher rates of gastrointestinal side effects, skin and subcutaneous disorders, metabolic and nutritional side effects and respiratory, thoracic, and mediastinal disorders. Patients in the taselisib arm had a lower incidence of musculoskeletal/connective tissue problems, vascular disorders, and psychiatric complaints.
The toxicities were generally manageable and consistent with that of other PI3K inhibitors, Dr. Saura said.
She said that although taselisib is more selective than other PI3K inhibitors and has a somewhat lower incidence of GI toxicities, “it’s still difficult to manage as a drug in the clinic, but I think if we can tell a patient there is a selection criterion which is a PIK3CA mutation, then patients are more willing and we as therapists are more willing to give those drugs.”
LORELEI provides the first clinical proof of efficacy of a specific PI3K inhibitor in early breast cancer, and “results of confirmatory phase 3 trials in metastatic breast cancer are eagerly awaited,” Dr. Harbeck added.
The study was supported by Genentech/F. Hoffman–La Roche. Dr. Saura disclosed consulting fees and institutional funding from Roche. Dr. Harbeck reported no disclosures relevant to the study.
AT ESMO 2017
Key clinical point: Adding the PI3K inhibitor taselisib to letrozole improved response rates over letrozole alone in postmenopausal women with ER+/HER2– early breast cancer.
Major finding: The ORR was 50% for letrozole/taselisib, vs. 39.3% for letrozole/placebo (P = .049).
Data source: Randomized, double-blind phase 2 trial in 334 postmenopausal women.
Disclosures: The study was supported by Genentech/F. Hoffman–La Roche. Dr. Saura disclosed consulting fees and institutional funding from Roche. Dr. Harbeck reported no disclosures relevant to the study.
Eribulin superior to dacarbazine in advanced liposarcoma
In patients with advanced liposarcoma, eribulin was superior to dacarbazine in improving both overall and progression-free survival, investigators report.
In a phase 3 trial that included 452 patients with advanced liposarcoma (LPS), those treated with eribulin had an overall survival of 15.6 months, compared with 8.4 months with dacarbazine (hazard ratio, 0.51; 95% CI, 0.35 to 0.75; P less than .001).
Longer overall survival was also seen in all histologic subtypes of LPS and in all geographic regions included in the study.
Median progression-free survival was significantly longer among patients in the eribulin arm, compared with those who received dacarbazine, at 2.9 versus 1.7 months (HR, 0.521; 95% CI, 0.35 to 0.78; nominal P = .0015).
“Our findings demonstrate that eribulin is an important treatment option for patients with previously treated LPS, a sarcoma subtype for which limited treatment options are available,” wrote lead author George D. Demetri, MD, of the Dana-Farber Cancer Institute and Brigham and Women’s Cancer Center, both in Boston, and his colleagues (J Clin Oncol. 2017 Aug 30. doi: 10.1200/JCO.2016.71.6605).
A larger randomized, phase 3 prospective study had found that eribulin significantly improved overall survival versus dacarbazine (13.5 versus 11.5 months, respectively; HR, 0.77; 95% CI, 0.62-0.95; P = .0169) in patients with LPS and leiomyosarcoma. Toxicity was also manageable and similar to that observed when used to treat breast cancer.
However, the survival benefit with eribulin was greater in patients with LPS than those with leiomyosarcoma; on the basis of this trial, eribulin was approved in both the United States and European Union for use in advanced LPS in patients who have received a prior anthracycline-containing regimen.
The current study is a subgroup analysis of 452 patients with advanced or metastatic LPS that is dedifferentiated, myxoid/round cell, or pleomorphic and has been deemed incurable by surgery or radiotherapy; patients were randomized to receive either eribulin mesylate (1.4 mg/m2 intravenously on days 1 and 8) or dacarbazine (850, 1,000, or 1,200 mg/m2 intravenously on day 1) every 21 days.
The largest difference in overall survival for eribulin versus dacarbazine was observed in patients with pleomorphic LPS (22.2 versus 6.7 months), but there were only 23 patients (16.2%) with this disease subtype included in the study. Thus, the authors caution that this particular finding should be interpreted carefully.
All patients who received eribulin and 95.8% treated with dacarbazine experienced adverse events, with the majority being treatment related (95.7% versus 84.7% in the eribulin and dacarbazine arms, respectively).
“On the basis of its activity in patients with advanced LPS, eribulin merits further exploration in earlier lines of treatment, either alone or in combination with other therapies,” the authors concluded.
In patients with advanced liposarcoma, eribulin was superior to dacarbazine in improving both overall and progression-free survival, investigators report.
In a phase 3 trial that included 452 patients with advanced liposarcoma (LPS), those treated with eribulin had an overall survival of 15.6 months, compared with 8.4 months with dacarbazine (hazard ratio, 0.51; 95% CI, 0.35 to 0.75; P less than .001).
Longer overall survival was also seen in all histologic subtypes of LPS and in all geographic regions included in the study.
Median progression-free survival was significantly longer among patients in the eribulin arm, compared with those who received dacarbazine, at 2.9 versus 1.7 months (HR, 0.521; 95% CI, 0.35 to 0.78; nominal P = .0015).
“Our findings demonstrate that eribulin is an important treatment option for patients with previously treated LPS, a sarcoma subtype for which limited treatment options are available,” wrote lead author George D. Demetri, MD, of the Dana-Farber Cancer Institute and Brigham and Women’s Cancer Center, both in Boston, and his colleagues (J Clin Oncol. 2017 Aug 30. doi: 10.1200/JCO.2016.71.6605).
A larger randomized, phase 3 prospective study had found that eribulin significantly improved overall survival versus dacarbazine (13.5 versus 11.5 months, respectively; HR, 0.77; 95% CI, 0.62-0.95; P = .0169) in patients with LPS and leiomyosarcoma. Toxicity was also manageable and similar to that observed when used to treat breast cancer.
However, the survival benefit with eribulin was greater in patients with LPS than those with leiomyosarcoma; on the basis of this trial, eribulin was approved in both the United States and European Union for use in advanced LPS in patients who have received a prior anthracycline-containing regimen.
The current study is a subgroup analysis of 452 patients with advanced or metastatic LPS that is dedifferentiated, myxoid/round cell, or pleomorphic and has been deemed incurable by surgery or radiotherapy; patients were randomized to receive either eribulin mesylate (1.4 mg/m2 intravenously on days 1 and 8) or dacarbazine (850, 1,000, or 1,200 mg/m2 intravenously on day 1) every 21 days.
The largest difference in overall survival for eribulin versus dacarbazine was observed in patients with pleomorphic LPS (22.2 versus 6.7 months), but there were only 23 patients (16.2%) with this disease subtype included in the study. Thus, the authors caution that this particular finding should be interpreted carefully.
All patients who received eribulin and 95.8% treated with dacarbazine experienced adverse events, with the majority being treatment related (95.7% versus 84.7% in the eribulin and dacarbazine arms, respectively).
“On the basis of its activity in patients with advanced LPS, eribulin merits further exploration in earlier lines of treatment, either alone or in combination with other therapies,” the authors concluded.
In patients with advanced liposarcoma, eribulin was superior to dacarbazine in improving both overall and progression-free survival, investigators report.
In a phase 3 trial that included 452 patients with advanced liposarcoma (LPS), those treated with eribulin had an overall survival of 15.6 months, compared with 8.4 months with dacarbazine (hazard ratio, 0.51; 95% CI, 0.35 to 0.75; P less than .001).
Longer overall survival was also seen in all histologic subtypes of LPS and in all geographic regions included in the study.
Median progression-free survival was significantly longer among patients in the eribulin arm, compared with those who received dacarbazine, at 2.9 versus 1.7 months (HR, 0.521; 95% CI, 0.35 to 0.78; nominal P = .0015).
“Our findings demonstrate that eribulin is an important treatment option for patients with previously treated LPS, a sarcoma subtype for which limited treatment options are available,” wrote lead author George D. Demetri, MD, of the Dana-Farber Cancer Institute and Brigham and Women’s Cancer Center, both in Boston, and his colleagues (J Clin Oncol. 2017 Aug 30. doi: 10.1200/JCO.2016.71.6605).
A larger randomized, phase 3 prospective study had found that eribulin significantly improved overall survival versus dacarbazine (13.5 versus 11.5 months, respectively; HR, 0.77; 95% CI, 0.62-0.95; P = .0169) in patients with LPS and leiomyosarcoma. Toxicity was also manageable and similar to that observed when used to treat breast cancer.
However, the survival benefit with eribulin was greater in patients with LPS than those with leiomyosarcoma; on the basis of this trial, eribulin was approved in both the United States and European Union for use in advanced LPS in patients who have received a prior anthracycline-containing regimen.
The current study is a subgroup analysis of 452 patients with advanced or metastatic LPS that is dedifferentiated, myxoid/round cell, or pleomorphic and has been deemed incurable by surgery or radiotherapy; patients were randomized to receive either eribulin mesylate (1.4 mg/m2 intravenously on days 1 and 8) or dacarbazine (850, 1,000, or 1,200 mg/m2 intravenously on day 1) every 21 days.
The largest difference in overall survival for eribulin versus dacarbazine was observed in patients with pleomorphic LPS (22.2 versus 6.7 months), but there were only 23 patients (16.2%) with this disease subtype included in the study. Thus, the authors caution that this particular finding should be interpreted carefully.
All patients who received eribulin and 95.8% treated with dacarbazine experienced adverse events, with the majority being treatment related (95.7% versus 84.7% in the eribulin and dacarbazine arms, respectively).
“On the basis of its activity in patients with advanced LPS, eribulin merits further exploration in earlier lines of treatment, either alone or in combination with other therapies,” the authors concluded.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: Eribulin is superior to dacarbazine in improving outcomes in advanced liposarcoma.
Major finding: Overall survival with eribulin was 15.6 months versus 8.4 months with dacarbazine (hazard ratio, 0.51; 95% CI, 0.35 to 0.75; P less than .001).
Data source: Phase 3 randomized, prospective clinical trial that included 452 patients with advanced liposarcoma.
Disclosures: The study was supported by Eisai. Dr. Demetri and several of the coauthors report relationships with industry including Eisai.
Doctors testify on health insurance stabilization
WASHINGTON – Physicians testifying before the Senate Health, Education, Labor & Pensions Committee offered recommendations that are generally in line with the narrow, focused legislation to stabilize the individual health insurance markets that Chairman Lamar Alexander (R-Tenn.) is hoping to introduce early in the week of Sept. 17.
Two key provisions of Chairman Alexander’s plan are extending the cost-sharing reduction (CSR) payments to insurers through the end of 2018 and providing additional flexibility to the process that allows states to come up with alternatives to the Affordable Care Act mandates.
Manny Sethi, MD, president of Healthy Tennessee, said he favored repealing and replacing the ACA but offered suggestions to fit the current legislative landscape.
“We must take three steps immediately,” Dr. Sethi, an orthopedic trauma surgeon, testified. “First, in order to stabilize the insurance markets, we must continue the cost-sharing reduction program. Premiums are rapidly rising as insurers fear they will be left bearing the cost. These soaring costs are forcing young members out, saturating the market with higher-need and higher-cost patients and further escalating prices in a troublesome cycle.
“Second, we must quickly create risk pools for those individuals with serious chronic conditions, allowing more affordable coverage options for young, healthy citizens,” Dr. Sethi continued. “Third, I believe a one-size-fits-all plan from Washington, D.C., doesn’t meet the needs of Tennesseans. Open the door for innovation, and allow more flexibility for states to create their own insurance products. For example, a catastrophic plan should be available regardless of age or income status, which is currently not the case.”
Opening the catastrophic plans to all would help bring people into the individual market, even if they don’t have access to any government subsidies, he said.
“Meeting with patients ... I do believe that creating a catastrophic plan open to all ages, all incomes, I think would bring younger folks, and people in general, into the insurance market because I think that’s the problem,” Dr. Sethi said. “You don’t want to pay more for your insurance than you do for your home mortgage. When you do that, something’s wrong.”
Susan Turney, MD, CEO of Marshfield (Wisc.) Clinic Health System, offered similar suggestions. She called for fully funding CSR payments for 2018 and beyond and also recommended creating a reinsurance program, establishing continuous coverage rules that encourage people to get and maintain coverage, enhancing risk adjustment for payments to carriers, and reinstating federal funding for outreach that was recently cut by the Trump administration.
But she also stressed a longer-term goal of how care is delivered, especially in rural areas.
“As we look at this short-term fix to a relatively small group of insured, we have to start thinking differently about how we provide care. The care delivery model needs to be above the payment system, and, once we figure out how to take care of our communities, we can then look differently at the way we support the practices who provide those services,” Dr. Turney said. “Most people don’t ask to get sick. We need to take care of them, and we need to figure out the best way to do that.”
Physicians’ organizations including the American Academy of Family Physicians, American Academy of Pediatrics, American College of Physicians, American Congress of Obstetricians and Gynecologists, American Osteopathic Association, and American Psychiatric Association, submitted a joint statement to the committee that advocated ensuring CSR funding through at least 2019, continuing reinsurance programs, continuing community outreach programs, and expanding public choice through a public option in all exchanges markets.
Chairman Alexander stressed that, in order for this narrowly focused bill to have a chance at passing, it will require a little compromise from both sides of the aisle.
“To get a result, Republicans will have to agree to something – additional funding through the Affordable Care Act – that some are reluctant to support,” he said. “And Democrats will have to agree to something – more flexibility for states – that some may be reluctant to support. I simply won’t be able to persuade the Republican majority in the Senate, the Republican majority in the House, and the Republican president to extend the cost-sharing payments without giving states meaningful flexibility.”
He stressed that the flexibility he is looking for in the 1332 waiver program will not alter consumer protections that are in place, including the ban on charging more for preexisting conditions, guaranteed issue, no annual or lifetime caps on benefits, and allowing those under 26 years of age to remain on their parent’s policy.
“Our goal is to see if we can come to a consensus by early next week so we can hand [Senate Majority Leader Mitch] McConnell and [Senate Minority Leader Chuck] Schumer an agreement that Congress can pass by the end of the month that would help limit premium increases for 18 million Americans next year and begin to lower premiums after that, and to prevent insurers from leaving the markets where those 18 million Americans buy insurance.”
WASHINGTON – Physicians testifying before the Senate Health, Education, Labor & Pensions Committee offered recommendations that are generally in line with the narrow, focused legislation to stabilize the individual health insurance markets that Chairman Lamar Alexander (R-Tenn.) is hoping to introduce early in the week of Sept. 17.
Two key provisions of Chairman Alexander’s plan are extending the cost-sharing reduction (CSR) payments to insurers through the end of 2018 and providing additional flexibility to the process that allows states to come up with alternatives to the Affordable Care Act mandates.
Manny Sethi, MD, president of Healthy Tennessee, said he favored repealing and replacing the ACA but offered suggestions to fit the current legislative landscape.
“We must take three steps immediately,” Dr. Sethi, an orthopedic trauma surgeon, testified. “First, in order to stabilize the insurance markets, we must continue the cost-sharing reduction program. Premiums are rapidly rising as insurers fear they will be left bearing the cost. These soaring costs are forcing young members out, saturating the market with higher-need and higher-cost patients and further escalating prices in a troublesome cycle.
“Second, we must quickly create risk pools for those individuals with serious chronic conditions, allowing more affordable coverage options for young, healthy citizens,” Dr. Sethi continued. “Third, I believe a one-size-fits-all plan from Washington, D.C., doesn’t meet the needs of Tennesseans. Open the door for innovation, and allow more flexibility for states to create their own insurance products. For example, a catastrophic plan should be available regardless of age or income status, which is currently not the case.”
Opening the catastrophic plans to all would help bring people into the individual market, even if they don’t have access to any government subsidies, he said.
“Meeting with patients ... I do believe that creating a catastrophic plan open to all ages, all incomes, I think would bring younger folks, and people in general, into the insurance market because I think that’s the problem,” Dr. Sethi said. “You don’t want to pay more for your insurance than you do for your home mortgage. When you do that, something’s wrong.”
Susan Turney, MD, CEO of Marshfield (Wisc.) Clinic Health System, offered similar suggestions. She called for fully funding CSR payments for 2018 and beyond and also recommended creating a reinsurance program, establishing continuous coverage rules that encourage people to get and maintain coverage, enhancing risk adjustment for payments to carriers, and reinstating federal funding for outreach that was recently cut by the Trump administration.
But she also stressed a longer-term goal of how care is delivered, especially in rural areas.
“As we look at this short-term fix to a relatively small group of insured, we have to start thinking differently about how we provide care. The care delivery model needs to be above the payment system, and, once we figure out how to take care of our communities, we can then look differently at the way we support the practices who provide those services,” Dr. Turney said. “Most people don’t ask to get sick. We need to take care of them, and we need to figure out the best way to do that.”
Physicians’ organizations including the American Academy of Family Physicians, American Academy of Pediatrics, American College of Physicians, American Congress of Obstetricians and Gynecologists, American Osteopathic Association, and American Psychiatric Association, submitted a joint statement to the committee that advocated ensuring CSR funding through at least 2019, continuing reinsurance programs, continuing community outreach programs, and expanding public choice through a public option in all exchanges markets.
Chairman Alexander stressed that, in order for this narrowly focused bill to have a chance at passing, it will require a little compromise from both sides of the aisle.
“To get a result, Republicans will have to agree to something – additional funding through the Affordable Care Act – that some are reluctant to support,” he said. “And Democrats will have to agree to something – more flexibility for states – that some may be reluctant to support. I simply won’t be able to persuade the Republican majority in the Senate, the Republican majority in the House, and the Republican president to extend the cost-sharing payments without giving states meaningful flexibility.”
He stressed that the flexibility he is looking for in the 1332 waiver program will not alter consumer protections that are in place, including the ban on charging more for preexisting conditions, guaranteed issue, no annual or lifetime caps on benefits, and allowing those under 26 years of age to remain on their parent’s policy.
“Our goal is to see if we can come to a consensus by early next week so we can hand [Senate Majority Leader Mitch] McConnell and [Senate Minority Leader Chuck] Schumer an agreement that Congress can pass by the end of the month that would help limit premium increases for 18 million Americans next year and begin to lower premiums after that, and to prevent insurers from leaving the markets where those 18 million Americans buy insurance.”
WASHINGTON – Physicians testifying before the Senate Health, Education, Labor & Pensions Committee offered recommendations that are generally in line with the narrow, focused legislation to stabilize the individual health insurance markets that Chairman Lamar Alexander (R-Tenn.) is hoping to introduce early in the week of Sept. 17.
Two key provisions of Chairman Alexander’s plan are extending the cost-sharing reduction (CSR) payments to insurers through the end of 2018 and providing additional flexibility to the process that allows states to come up with alternatives to the Affordable Care Act mandates.
Manny Sethi, MD, president of Healthy Tennessee, said he favored repealing and replacing the ACA but offered suggestions to fit the current legislative landscape.
“We must take three steps immediately,” Dr. Sethi, an orthopedic trauma surgeon, testified. “First, in order to stabilize the insurance markets, we must continue the cost-sharing reduction program. Premiums are rapidly rising as insurers fear they will be left bearing the cost. These soaring costs are forcing young members out, saturating the market with higher-need and higher-cost patients and further escalating prices in a troublesome cycle.
“Second, we must quickly create risk pools for those individuals with serious chronic conditions, allowing more affordable coverage options for young, healthy citizens,” Dr. Sethi continued. “Third, I believe a one-size-fits-all plan from Washington, D.C., doesn’t meet the needs of Tennesseans. Open the door for innovation, and allow more flexibility for states to create their own insurance products. For example, a catastrophic plan should be available regardless of age or income status, which is currently not the case.”
Opening the catastrophic plans to all would help bring people into the individual market, even if they don’t have access to any government subsidies, he said.
“Meeting with patients ... I do believe that creating a catastrophic plan open to all ages, all incomes, I think would bring younger folks, and people in general, into the insurance market because I think that’s the problem,” Dr. Sethi said. “You don’t want to pay more for your insurance than you do for your home mortgage. When you do that, something’s wrong.”
Susan Turney, MD, CEO of Marshfield (Wisc.) Clinic Health System, offered similar suggestions. She called for fully funding CSR payments for 2018 and beyond and also recommended creating a reinsurance program, establishing continuous coverage rules that encourage people to get and maintain coverage, enhancing risk adjustment for payments to carriers, and reinstating federal funding for outreach that was recently cut by the Trump administration.
But she also stressed a longer-term goal of how care is delivered, especially in rural areas.
“As we look at this short-term fix to a relatively small group of insured, we have to start thinking differently about how we provide care. The care delivery model needs to be above the payment system, and, once we figure out how to take care of our communities, we can then look differently at the way we support the practices who provide those services,” Dr. Turney said. “Most people don’t ask to get sick. We need to take care of them, and we need to figure out the best way to do that.”
Physicians’ organizations including the American Academy of Family Physicians, American Academy of Pediatrics, American College of Physicians, American Congress of Obstetricians and Gynecologists, American Osteopathic Association, and American Psychiatric Association, submitted a joint statement to the committee that advocated ensuring CSR funding through at least 2019, continuing reinsurance programs, continuing community outreach programs, and expanding public choice through a public option in all exchanges markets.
Chairman Alexander stressed that, in order for this narrowly focused bill to have a chance at passing, it will require a little compromise from both sides of the aisle.
“To get a result, Republicans will have to agree to something – additional funding through the Affordable Care Act – that some are reluctant to support,” he said. “And Democrats will have to agree to something – more flexibility for states – that some may be reluctant to support. I simply won’t be able to persuade the Republican majority in the Senate, the Republican majority in the House, and the Republican president to extend the cost-sharing payments without giving states meaningful flexibility.”
He stressed that the flexibility he is looking for in the 1332 waiver program will not alter consumer protections that are in place, including the ban on charging more for preexisting conditions, guaranteed issue, no annual or lifetime caps on benefits, and allowing those under 26 years of age to remain on their parent’s policy.
“Our goal is to see if we can come to a consensus by early next week so we can hand [Senate Majority Leader Mitch] McConnell and [Senate Minority Leader Chuck] Schumer an agreement that Congress can pass by the end of the month that would help limit premium increases for 18 million Americans next year and begin to lower premiums after that, and to prevent insurers from leaving the markets where those 18 million Americans buy insurance.”
AT A SENATE HELP COMMITTEE HEARING
Alirocumab’s ODYSSEY continues: Efficacy unaffected by insulin, beats fenofibrate
LISBON – , plus it may have an edge over using older, add-on lipid-lowering therapies such as fibrates.
The findings were presented at the annual meeting of the European Association for the Study of Diabetes.
In one study involving 76 insulin-treated patients with T1DM, treatment with alirocumab (Praluent, Sanofi/Regeneron Pharmaceuticals) reduced low-density lipoprotein cholesterol levels by a mean of 47.8% versus placebo from baseline to week 24 (P less than .0001), the primary endpoint of the study.
Furthermore, in a separate study involving 413 patients with T2DM with mixed hyperlipidemia, alirocumab decreased levels of non–high-density lipoprotein cholesterol (non-HDL-C) by 33.3% compared with fenofibrate (P less than .0001).
These new results from the ODYSSEY DM-INSULIN and ODYSSEY DM-DYSLIPIDEMIA trials, respectively, add to those already presented this year at the annual scientific sessions of the American Diabetes Association.
“We have studied two groups of high- to very-high cardiovascular risk patients with diabetes mellitus: those on insulin and those with mixed dyslipidemia in whom previously only secondary data were available,” said Stefano Del Prato, MD, who presented the lipid study. “These are dedicated studies in these specific populations,” he added.
In these high-risk diabetic populations, Dr. Del Prato, professor of endocrinology and metabolism and chief of the section of diabetes, University of Pisa, Italy, observed “alirocumab was superior in lipid-lowering efficacy compared to standard care, with no specific safety issues.”
Efficacy unaffected by co-administration with insulin use
Helen Colhoun, MD, AXA chair of medical informatics and life course epidemiology at the University of Edinburgh, presented the updated findings of the ODYSSEY DM-INSULIN study, which recruited 517 patients, the majority (n = 441) of whom had T2DM.
In the study, alirocumab, a monoclonal antibody that targets proprotein convertase subtilisin–kexin type 9 (PCSK9), was compared with placebo in patients with established atherosclerotic cardiovascular disease or other cardiovascular risk factors, and in whom LDL-C was 70 mg/dL (1.8 mmol/L) or higher.
The percentage change in LDL-C from baseline to week 24 was similarly reduced in T1DM and T2DM, Dr. Colhoun observed, and commensurate with data seen across the ODYSSEY phase III trials program. Of note, the majority of type 2 (80%) and type 1 (63%) patients did not need the dose of alirocumab to be increased and remained on the starting dose of 75 mg every 2 weeks.
The results of the ODYSSEY DM-INSULIN trial, which were published online, Sept. 14, 2017, to coincide with their presentation at the meeting, also showed that the percentage change in LDL-C over time is “well sustained” and that 70% and 76% of patients with T1DM and T2DM, respectively, can achieve an LDL-C target of less than 70 mg/dL (1.8 mmol/L) and 79% and 71% can hit a non-HDL-C target of less than 100 mg/dL (2.6 mmol/L).
Other lipid parameters – including apolipoprotein (Apo) B, total cholesterol, Lp(a), and triglycerides – were also reduced to a greater extent in patients treated with alirocumab versus those given placebo. Dr. Colhoun drew attention to the reduction in Lp(a), which dropped by 23% in patients with T1DM and by 19% in patients with T2DM, as it is an important risk factor for peripheral vascular disease, and it is not affected by statin therapy.
“What this trial has told us is that coadministering alirocumab with insulin does not adversely affect its efficacy,” said Dr. Colhoun. “There’s absolutely no evidence of alirocumab altering HbA1c or fasting plasma glucose,” she added. There was also no affect on how patients were treated, either with insulin therapy or antihyperglycemic drugs.
Overall safety findings were “reassuring” and anti-drug antibodies were rare (2.1%) and did not affect the lipid-lowering effects of alirocumab.
Alirocumab beats fenofibrate as add-on lipid-lowering therapy
Presenting the ODYSSEY DM-DYSLIPIDEMIA data, which involved patients with T2DM, Dr. Del Prato observed that alirocumab was “generally well tolerated” and did not affect HbA1c or fasting plasma glucose levels.
He presented new data from a prespecified analysis that looked at the subgroup of 72 patients who were randomized into an alirocumab (n = 48) or fenofibrate (n = 24) as usual care arm. Dr. Del Prato reminded the audience that the choice of usual treatment was decided by the study investigators prior to randomizing patients, and that other usual care treatments included in the study were ezetimibe, omega-3 fatty acids, nicotinic acid, or no lipid-lowering therapy.
As in the insulin study, the majority (63.6%) of patients treated with alirocumab remained on the starting dose of 75 mg every 2 weeks and did not need up-titration.
Changes in the percentage of non-HDL-C from baseline over time were greater in the alirocumab group than in the usual care group, both in the overall population and in the fenofibrate subanalysis.
Higher percentages of patients treated with alirocumab achieved non-HDL-C compared with those given usual care (66.9% vs. 17.7% in overall population, 65.2% vs. 10.1% in fenofibrate sub-analysis) and LDL-C (70.8% vs. 16.3% and 71.9% vs. 17.5%, respectively) goals at week 24.
Alirocumab also significantly reduced levels of Apo B, total cholesterol, and Lp(a) versus the overall usual care group and also versus the fenofibrate usual care group, Dr. Del Prato said.
Taking the two studies together, he concluded: “These data support alirocumab as a treatment option in people with diabetes mellitus and hypercholesterolemia despite maximally tolerated statins,” Dr. Del Prato said.
Will the lipid-benefits translate into improved cardiovascular outcomes?
The question now is whether the lipid-lowering effects of alirocumab in patients with diabetes will translate into improved cardiovascular outcomes in patients with diabetes.
The results of the ODYSSEY OUTCOMES trial, which is evaluating cardiovascular outcomes during treatment with alirocumab after an acute coronary syndrome, are expected next year. While the trial is not being conducted specifically in patients with diabetes, it is expected that there will be subpopulations of T1DM and T2DM patients included.
Cardiovascular outcomes data on the PCSK9 inhibitor, evolocumab (Repatha, Amgen) in the FOURIER trial were published in March (N Engl J Med 2017;376:1713-22) and provide some evidence that a reduction in major cardiovascular events may be possible with these agents.
Providing independent comment on the study, Angelo Avogaro, MD, of the University of Padova, Italy, said that the additional LDL-C lowering effect of alirocumab on top of statins could theoretically halve the projected 10-year risk of cardiovascular disease using data from the two ODYSSEY studies and the UKPDS Risk Engine. Using a baseline 10-year cardiovascular risk of around 26%-28%, this could be reduced to 11%-13%, he suggested.
Of note, Dr. Avogaro said, was that, at baseline, not all patients were on high intensity statins, the majority received moderate doses, with a good number of patients taking none or who were intolerant to statins included. “This, I like,” he observed.
A reassuring point was that there was no signal of having a detrimental effect on neurocognitive dysfunction, Dr. Avogaro observed, which concurs with recent data published on evolocumab (N Engl J Med 2017; 377:633-43).
Nevertheless, longer-follow-up is needed to examine adverse effects, “especially in those insulin-treated patients experiencing severe hypoglycemic reactions.”
The ODYSSEY DM studies were funded by Sanofi and Regeneron Pharmaceuticals.
Dr. Colhoun has received research grants from AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Pfizer, Regeneron Pharmaceuticals, Roche Pharmaceuticals, and Sanofi. She has also been a consultant for Eli Lilly, Regeneron Pharmaceuticals, and Sanofi.
Dr. Del Prato has received research funding from AstraZeneca, Boehringer Ingelheim, Novartis, Merck Sharpe & Dohme, and Novo Nordisk. He is a consultant for or has received honoraria from the preceding companies, as well as from Eli Lilly, GlaxoSmithKline, Janssen Pharmaceuticals, Laboratoires Servier, Sanofi-Aventis, and Takeda Pharmaceuticals.
LISBON – , plus it may have an edge over using older, add-on lipid-lowering therapies such as fibrates.
The findings were presented at the annual meeting of the European Association for the Study of Diabetes.
In one study involving 76 insulin-treated patients with T1DM, treatment with alirocumab (Praluent, Sanofi/Regeneron Pharmaceuticals) reduced low-density lipoprotein cholesterol levels by a mean of 47.8% versus placebo from baseline to week 24 (P less than .0001), the primary endpoint of the study.
Furthermore, in a separate study involving 413 patients with T2DM with mixed hyperlipidemia, alirocumab decreased levels of non–high-density lipoprotein cholesterol (non-HDL-C) by 33.3% compared with fenofibrate (P less than .0001).
These new results from the ODYSSEY DM-INSULIN and ODYSSEY DM-DYSLIPIDEMIA trials, respectively, add to those already presented this year at the annual scientific sessions of the American Diabetes Association.
“We have studied two groups of high- to very-high cardiovascular risk patients with diabetes mellitus: those on insulin and those with mixed dyslipidemia in whom previously only secondary data were available,” said Stefano Del Prato, MD, who presented the lipid study. “These are dedicated studies in these specific populations,” he added.
In these high-risk diabetic populations, Dr. Del Prato, professor of endocrinology and metabolism and chief of the section of diabetes, University of Pisa, Italy, observed “alirocumab was superior in lipid-lowering efficacy compared to standard care, with no specific safety issues.”
Efficacy unaffected by co-administration with insulin use
Helen Colhoun, MD, AXA chair of medical informatics and life course epidemiology at the University of Edinburgh, presented the updated findings of the ODYSSEY DM-INSULIN study, which recruited 517 patients, the majority (n = 441) of whom had T2DM.
In the study, alirocumab, a monoclonal antibody that targets proprotein convertase subtilisin–kexin type 9 (PCSK9), was compared with placebo in patients with established atherosclerotic cardiovascular disease or other cardiovascular risk factors, and in whom LDL-C was 70 mg/dL (1.8 mmol/L) or higher.
The percentage change in LDL-C from baseline to week 24 was similarly reduced in T1DM and T2DM, Dr. Colhoun observed, and commensurate with data seen across the ODYSSEY phase III trials program. Of note, the majority of type 2 (80%) and type 1 (63%) patients did not need the dose of alirocumab to be increased and remained on the starting dose of 75 mg every 2 weeks.
The results of the ODYSSEY DM-INSULIN trial, which were published online, Sept. 14, 2017, to coincide with their presentation at the meeting, also showed that the percentage change in LDL-C over time is “well sustained” and that 70% and 76% of patients with T1DM and T2DM, respectively, can achieve an LDL-C target of less than 70 mg/dL (1.8 mmol/L) and 79% and 71% can hit a non-HDL-C target of less than 100 mg/dL (2.6 mmol/L).
Other lipid parameters – including apolipoprotein (Apo) B, total cholesterol, Lp(a), and triglycerides – were also reduced to a greater extent in patients treated with alirocumab versus those given placebo. Dr. Colhoun drew attention to the reduction in Lp(a), which dropped by 23% in patients with T1DM and by 19% in patients with T2DM, as it is an important risk factor for peripheral vascular disease, and it is not affected by statin therapy.
“What this trial has told us is that coadministering alirocumab with insulin does not adversely affect its efficacy,” said Dr. Colhoun. “There’s absolutely no evidence of alirocumab altering HbA1c or fasting plasma glucose,” she added. There was also no affect on how patients were treated, either with insulin therapy or antihyperglycemic drugs.
Overall safety findings were “reassuring” and anti-drug antibodies were rare (2.1%) and did not affect the lipid-lowering effects of alirocumab.
Alirocumab beats fenofibrate as add-on lipid-lowering therapy
Presenting the ODYSSEY DM-DYSLIPIDEMIA data, which involved patients with T2DM, Dr. Del Prato observed that alirocumab was “generally well tolerated” and did not affect HbA1c or fasting plasma glucose levels.
He presented new data from a prespecified analysis that looked at the subgroup of 72 patients who were randomized into an alirocumab (n = 48) or fenofibrate (n = 24) as usual care arm. Dr. Del Prato reminded the audience that the choice of usual treatment was decided by the study investigators prior to randomizing patients, and that other usual care treatments included in the study were ezetimibe, omega-3 fatty acids, nicotinic acid, or no lipid-lowering therapy.
As in the insulin study, the majority (63.6%) of patients treated with alirocumab remained on the starting dose of 75 mg every 2 weeks and did not need up-titration.
Changes in the percentage of non-HDL-C from baseline over time were greater in the alirocumab group than in the usual care group, both in the overall population and in the fenofibrate subanalysis.
Higher percentages of patients treated with alirocumab achieved non-HDL-C compared with those given usual care (66.9% vs. 17.7% in overall population, 65.2% vs. 10.1% in fenofibrate sub-analysis) and LDL-C (70.8% vs. 16.3% and 71.9% vs. 17.5%, respectively) goals at week 24.
Alirocumab also significantly reduced levels of Apo B, total cholesterol, and Lp(a) versus the overall usual care group and also versus the fenofibrate usual care group, Dr. Del Prato said.
Taking the two studies together, he concluded: “These data support alirocumab as a treatment option in people with diabetes mellitus and hypercholesterolemia despite maximally tolerated statins,” Dr. Del Prato said.
Will the lipid-benefits translate into improved cardiovascular outcomes?
The question now is whether the lipid-lowering effects of alirocumab in patients with diabetes will translate into improved cardiovascular outcomes in patients with diabetes.
The results of the ODYSSEY OUTCOMES trial, which is evaluating cardiovascular outcomes during treatment with alirocumab after an acute coronary syndrome, are expected next year. While the trial is not being conducted specifically in patients with diabetes, it is expected that there will be subpopulations of T1DM and T2DM patients included.
Cardiovascular outcomes data on the PCSK9 inhibitor, evolocumab (Repatha, Amgen) in the FOURIER trial were published in March (N Engl J Med 2017;376:1713-22) and provide some evidence that a reduction in major cardiovascular events may be possible with these agents.
Providing independent comment on the study, Angelo Avogaro, MD, of the University of Padova, Italy, said that the additional LDL-C lowering effect of alirocumab on top of statins could theoretically halve the projected 10-year risk of cardiovascular disease using data from the two ODYSSEY studies and the UKPDS Risk Engine. Using a baseline 10-year cardiovascular risk of around 26%-28%, this could be reduced to 11%-13%, he suggested.
Of note, Dr. Avogaro said, was that, at baseline, not all patients were on high intensity statins, the majority received moderate doses, with a good number of patients taking none or who were intolerant to statins included. “This, I like,” he observed.
A reassuring point was that there was no signal of having a detrimental effect on neurocognitive dysfunction, Dr. Avogaro observed, which concurs with recent data published on evolocumab (N Engl J Med 2017; 377:633-43).
Nevertheless, longer-follow-up is needed to examine adverse effects, “especially in those insulin-treated patients experiencing severe hypoglycemic reactions.”
The ODYSSEY DM studies were funded by Sanofi and Regeneron Pharmaceuticals.
Dr. Colhoun has received research grants from AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Pfizer, Regeneron Pharmaceuticals, Roche Pharmaceuticals, and Sanofi. She has also been a consultant for Eli Lilly, Regeneron Pharmaceuticals, and Sanofi.
Dr. Del Prato has received research funding from AstraZeneca, Boehringer Ingelheim, Novartis, Merck Sharpe & Dohme, and Novo Nordisk. He is a consultant for or has received honoraria from the preceding companies, as well as from Eli Lilly, GlaxoSmithKline, Janssen Pharmaceuticals, Laboratoires Servier, Sanofi-Aventis, and Takeda Pharmaceuticals.
LISBON – , plus it may have an edge over using older, add-on lipid-lowering therapies such as fibrates.
The findings were presented at the annual meeting of the European Association for the Study of Diabetes.
In one study involving 76 insulin-treated patients with T1DM, treatment with alirocumab (Praluent, Sanofi/Regeneron Pharmaceuticals) reduced low-density lipoprotein cholesterol levels by a mean of 47.8% versus placebo from baseline to week 24 (P less than .0001), the primary endpoint of the study.
Furthermore, in a separate study involving 413 patients with T2DM with mixed hyperlipidemia, alirocumab decreased levels of non–high-density lipoprotein cholesterol (non-HDL-C) by 33.3% compared with fenofibrate (P less than .0001).
These new results from the ODYSSEY DM-INSULIN and ODYSSEY DM-DYSLIPIDEMIA trials, respectively, add to those already presented this year at the annual scientific sessions of the American Diabetes Association.
“We have studied two groups of high- to very-high cardiovascular risk patients with diabetes mellitus: those on insulin and those with mixed dyslipidemia in whom previously only secondary data were available,” said Stefano Del Prato, MD, who presented the lipid study. “These are dedicated studies in these specific populations,” he added.
In these high-risk diabetic populations, Dr. Del Prato, professor of endocrinology and metabolism and chief of the section of diabetes, University of Pisa, Italy, observed “alirocumab was superior in lipid-lowering efficacy compared to standard care, with no specific safety issues.”
Efficacy unaffected by co-administration with insulin use
Helen Colhoun, MD, AXA chair of medical informatics and life course epidemiology at the University of Edinburgh, presented the updated findings of the ODYSSEY DM-INSULIN study, which recruited 517 patients, the majority (n = 441) of whom had T2DM.
In the study, alirocumab, a monoclonal antibody that targets proprotein convertase subtilisin–kexin type 9 (PCSK9), was compared with placebo in patients with established atherosclerotic cardiovascular disease or other cardiovascular risk factors, and in whom LDL-C was 70 mg/dL (1.8 mmol/L) or higher.
The percentage change in LDL-C from baseline to week 24 was similarly reduced in T1DM and T2DM, Dr. Colhoun observed, and commensurate with data seen across the ODYSSEY phase III trials program. Of note, the majority of type 2 (80%) and type 1 (63%) patients did not need the dose of alirocumab to be increased and remained on the starting dose of 75 mg every 2 weeks.
The results of the ODYSSEY DM-INSULIN trial, which were published online, Sept. 14, 2017, to coincide with their presentation at the meeting, also showed that the percentage change in LDL-C over time is “well sustained” and that 70% and 76% of patients with T1DM and T2DM, respectively, can achieve an LDL-C target of less than 70 mg/dL (1.8 mmol/L) and 79% and 71% can hit a non-HDL-C target of less than 100 mg/dL (2.6 mmol/L).
Other lipid parameters – including apolipoprotein (Apo) B, total cholesterol, Lp(a), and triglycerides – were also reduced to a greater extent in patients treated with alirocumab versus those given placebo. Dr. Colhoun drew attention to the reduction in Lp(a), which dropped by 23% in patients with T1DM and by 19% in patients with T2DM, as it is an important risk factor for peripheral vascular disease, and it is not affected by statin therapy.
“What this trial has told us is that coadministering alirocumab with insulin does not adversely affect its efficacy,” said Dr. Colhoun. “There’s absolutely no evidence of alirocumab altering HbA1c or fasting plasma glucose,” she added. There was also no affect on how patients were treated, either with insulin therapy or antihyperglycemic drugs.
Overall safety findings were “reassuring” and anti-drug antibodies were rare (2.1%) and did not affect the lipid-lowering effects of alirocumab.
Alirocumab beats fenofibrate as add-on lipid-lowering therapy
Presenting the ODYSSEY DM-DYSLIPIDEMIA data, which involved patients with T2DM, Dr. Del Prato observed that alirocumab was “generally well tolerated” and did not affect HbA1c or fasting plasma glucose levels.
He presented new data from a prespecified analysis that looked at the subgroup of 72 patients who were randomized into an alirocumab (n = 48) or fenofibrate (n = 24) as usual care arm. Dr. Del Prato reminded the audience that the choice of usual treatment was decided by the study investigators prior to randomizing patients, and that other usual care treatments included in the study were ezetimibe, omega-3 fatty acids, nicotinic acid, or no lipid-lowering therapy.
As in the insulin study, the majority (63.6%) of patients treated with alirocumab remained on the starting dose of 75 mg every 2 weeks and did not need up-titration.
Changes in the percentage of non-HDL-C from baseline over time were greater in the alirocumab group than in the usual care group, both in the overall population and in the fenofibrate subanalysis.
Higher percentages of patients treated with alirocumab achieved non-HDL-C compared with those given usual care (66.9% vs. 17.7% in overall population, 65.2% vs. 10.1% in fenofibrate sub-analysis) and LDL-C (70.8% vs. 16.3% and 71.9% vs. 17.5%, respectively) goals at week 24.
Alirocumab also significantly reduced levels of Apo B, total cholesterol, and Lp(a) versus the overall usual care group and also versus the fenofibrate usual care group, Dr. Del Prato said.
Taking the two studies together, he concluded: “These data support alirocumab as a treatment option in people with diabetes mellitus and hypercholesterolemia despite maximally tolerated statins,” Dr. Del Prato said.
Will the lipid-benefits translate into improved cardiovascular outcomes?
The question now is whether the lipid-lowering effects of alirocumab in patients with diabetes will translate into improved cardiovascular outcomes in patients with diabetes.
The results of the ODYSSEY OUTCOMES trial, which is evaluating cardiovascular outcomes during treatment with alirocumab after an acute coronary syndrome, are expected next year. While the trial is not being conducted specifically in patients with diabetes, it is expected that there will be subpopulations of T1DM and T2DM patients included.
Cardiovascular outcomes data on the PCSK9 inhibitor, evolocumab (Repatha, Amgen) in the FOURIER trial were published in March (N Engl J Med 2017;376:1713-22) and provide some evidence that a reduction in major cardiovascular events may be possible with these agents.
Providing independent comment on the study, Angelo Avogaro, MD, of the University of Padova, Italy, said that the additional LDL-C lowering effect of alirocumab on top of statins could theoretically halve the projected 10-year risk of cardiovascular disease using data from the two ODYSSEY studies and the UKPDS Risk Engine. Using a baseline 10-year cardiovascular risk of around 26%-28%, this could be reduced to 11%-13%, he suggested.
Of note, Dr. Avogaro said, was that, at baseline, not all patients were on high intensity statins, the majority received moderate doses, with a good number of patients taking none or who were intolerant to statins included. “This, I like,” he observed.
A reassuring point was that there was no signal of having a detrimental effect on neurocognitive dysfunction, Dr. Avogaro observed, which concurs with recent data published on evolocumab (N Engl J Med 2017; 377:633-43).
Nevertheless, longer-follow-up is needed to examine adverse effects, “especially in those insulin-treated patients experiencing severe hypoglycemic reactions.”
The ODYSSEY DM studies were funded by Sanofi and Regeneron Pharmaceuticals.
Dr. Colhoun has received research grants from AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Pfizer, Regeneron Pharmaceuticals, Roche Pharmaceuticals, and Sanofi. She has also been a consultant for Eli Lilly, Regeneron Pharmaceuticals, and Sanofi.
Dr. Del Prato has received research funding from AstraZeneca, Boehringer Ingelheim, Novartis, Merck Sharpe & Dohme, and Novo Nordisk. He is a consultant for or has received honoraria from the preceding companies, as well as from Eli Lilly, GlaxoSmithKline, Janssen Pharmaceuticals, Laboratoires Servier, Sanofi-Aventis, and Takeda Pharmaceuticals.
AT EASD 2017
Key clinical point: Alicrocumab significantly reduced lipids in patients with type 1 and type 2 diabetes who remain at high cardiovascular risk despite statin therapy.
Major findings: From baseline to week 24, greater mean differences in low-density lipoprotein cholesterol were seen with alirocumab versus placebo in both T1DM (47.8%) and T2DM (49%) insulin-treated patients. In a separate trial, a 33% mean difference was seen between alirocumab and fenofibrate in the reduction of non–high density lipoprotein cholesterol.
Data source: Two randomized, controlled trials of alirocumab: ODYSSEY DM-INSULIN involving 441 T2DM and 76 T1DM insulin-treated patients and ODYSSEY DM-DYSLIPIDEMIA in 413 T2DM patients with mixed dyslipidemia.
Disclosures: Sanofi and Regeneron Pharmaceuticals funded the studies. All speakers except for the independent commentator disclosed receiving advisory fees, research grants, or both, from Sanofi/Regeneron Pharmaceuticals in addition to other companies involved in the manufacture and sale of drugs to treat diabetes.
Acquiring a REDcap data entry skill set
Editor’s Note: The Society of Hospital Medicine’s (SHM’s) Physician in Training Committee launched a scholarship program in 2015 for medical students to help transform health care and revolutionize patient care. The program has been expanded for the 2017-2018 year, offering two options for students to receive funding and engage in scholarly work during their first, second, and third years of medical school. As a part of the program, recipients are required to write about their experience on a biweekly basis.
To give a status update on my project, I am almost finished collecting data for the Emergency ICU Transfer cases in Cincinnati Children’s Hospital. The project timeline is going as planned, and I should be finishing my data collection within the next week or so. I have begun to match control subjects by age strata, time of transfer and hospital unit to the Emergency ICU Transfer cases, and hope to finish that within the next week as well.
To streamline data collection and make it available for analysis in the near future, I set up a REDcap data entry form for my project. This was initially a challenge because even though I have entered data using this online tool before, I had no experience creating my own forms. With a lot of help from Google, people who worked around me, and our campus REDcap administrators, I was able to set this up pretty quickly and independently. I have noticed that this tool is widely used for clinical research, and am glad that being able create project instruments within REDcap is now part of my skill set. This was a unique learning experience for me that I wasn’t expecting to gain. It helped me understand what needs to be done specifically in order to execute a clinical research project, such as the one I’m working on alongside my mentor.
I have also learned a little medical knowledge from reading patient charts as I’m collecting data. For example, for procedures such as intubation, I have been seeing what specific medications are being administered for the pediatric patient. It has been interesting to learn some medical details behind lifesaving procedures, before even having clinical exposure in my medical training.
Farah Hussain is a 2nd-year medical student at University of Cincinnati College of Medicine and student researcher at Cincinnati Children’s Hospital Medical Center. Her research interests involve bettering patient care to vulnerable populations.
Editor’s Note: The Society of Hospital Medicine’s (SHM’s) Physician in Training Committee launched a scholarship program in 2015 for medical students to help transform health care and revolutionize patient care. The program has been expanded for the 2017-2018 year, offering two options for students to receive funding and engage in scholarly work during their first, second, and third years of medical school. As a part of the program, recipients are required to write about their experience on a biweekly basis.
To give a status update on my project, I am almost finished collecting data for the Emergency ICU Transfer cases in Cincinnati Children’s Hospital. The project timeline is going as planned, and I should be finishing my data collection within the next week or so. I have begun to match control subjects by age strata, time of transfer and hospital unit to the Emergency ICU Transfer cases, and hope to finish that within the next week as well.
To streamline data collection and make it available for analysis in the near future, I set up a REDcap data entry form for my project. This was initially a challenge because even though I have entered data using this online tool before, I had no experience creating my own forms. With a lot of help from Google, people who worked around me, and our campus REDcap administrators, I was able to set this up pretty quickly and independently. I have noticed that this tool is widely used for clinical research, and am glad that being able create project instruments within REDcap is now part of my skill set. This was a unique learning experience for me that I wasn’t expecting to gain. It helped me understand what needs to be done specifically in order to execute a clinical research project, such as the one I’m working on alongside my mentor.
I have also learned a little medical knowledge from reading patient charts as I’m collecting data. For example, for procedures such as intubation, I have been seeing what specific medications are being administered for the pediatric patient. It has been interesting to learn some medical details behind lifesaving procedures, before even having clinical exposure in my medical training.
Farah Hussain is a 2nd-year medical student at University of Cincinnati College of Medicine and student researcher at Cincinnati Children’s Hospital Medical Center. Her research interests involve bettering patient care to vulnerable populations.
Editor’s Note: The Society of Hospital Medicine’s (SHM’s) Physician in Training Committee launched a scholarship program in 2015 for medical students to help transform health care and revolutionize patient care. The program has been expanded for the 2017-2018 year, offering two options for students to receive funding and engage in scholarly work during their first, second, and third years of medical school. As a part of the program, recipients are required to write about their experience on a biweekly basis.
To give a status update on my project, I am almost finished collecting data for the Emergency ICU Transfer cases in Cincinnati Children’s Hospital. The project timeline is going as planned, and I should be finishing my data collection within the next week or so. I have begun to match control subjects by age strata, time of transfer and hospital unit to the Emergency ICU Transfer cases, and hope to finish that within the next week as well.
To streamline data collection and make it available for analysis in the near future, I set up a REDcap data entry form for my project. This was initially a challenge because even though I have entered data using this online tool before, I had no experience creating my own forms. With a lot of help from Google, people who worked around me, and our campus REDcap administrators, I was able to set this up pretty quickly and independently. I have noticed that this tool is widely used for clinical research, and am glad that being able create project instruments within REDcap is now part of my skill set. This was a unique learning experience for me that I wasn’t expecting to gain. It helped me understand what needs to be done specifically in order to execute a clinical research project, such as the one I’m working on alongside my mentor.
I have also learned a little medical knowledge from reading patient charts as I’m collecting data. For example, for procedures such as intubation, I have been seeing what specific medications are being administered for the pediatric patient. It has been interesting to learn some medical details behind lifesaving procedures, before even having clinical exposure in my medical training.
Farah Hussain is a 2nd-year medical student at University of Cincinnati College of Medicine and student researcher at Cincinnati Children’s Hospital Medical Center. Her research interests involve bettering patient care to vulnerable populations.
HPV vaccine pioneers win 2017 Lasker-DeBakey Clinical Medical Research Award
Douglas R. Lowy, MD, and John T. Schiller, PhD, received the 2017 Lasker-DeBakey Clinical Medical Research Award for their development of the virus-like particle technology used to create the human papillomavirus (HPV) vaccine. Their team discovered that proteins making up the outer shell of HPV could form virus-like particles that closely resemble the original virus but are not infectious, and these particles could trigger the immune system to produce protective antibodies that could neutralize HPV in a later infection. These particles eventually became the basis of the HPV vaccines Gardasil, Gardasil 9, and Cervarix.
HPV causes cervical cancer and other cancers such as cancer of the vulva, vagina, penis, or anus, as well as oropharyngeal cancer. Two of the high-risk types of HPV – HPV-16 and HPV-18 – cause about 70% of cervical cancers worldwide; it ranks 14th in frequency in the United States, according to the National Cancer Institute. The HPV vaccines are very effective in preventing persistent infections with HPV-16 and HPV-18. The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices continues to recommend routine HPV vaccination for girls and boys at age 11 or 12 years, with a second vaccine given 6-12 months later.
Douglas R. Lowy, MD, and John T. Schiller, PhD, received the 2017 Lasker-DeBakey Clinical Medical Research Award for their development of the virus-like particle technology used to create the human papillomavirus (HPV) vaccine. Their team discovered that proteins making up the outer shell of HPV could form virus-like particles that closely resemble the original virus but are not infectious, and these particles could trigger the immune system to produce protective antibodies that could neutralize HPV in a later infection. These particles eventually became the basis of the HPV vaccines Gardasil, Gardasil 9, and Cervarix.
HPV causes cervical cancer and other cancers such as cancer of the vulva, vagina, penis, or anus, as well as oropharyngeal cancer. Two of the high-risk types of HPV – HPV-16 and HPV-18 – cause about 70% of cervical cancers worldwide; it ranks 14th in frequency in the United States, according to the National Cancer Institute. The HPV vaccines are very effective in preventing persistent infections with HPV-16 and HPV-18. The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices continues to recommend routine HPV vaccination for girls and boys at age 11 or 12 years, with a second vaccine given 6-12 months later.
Douglas R. Lowy, MD, and John T. Schiller, PhD, received the 2017 Lasker-DeBakey Clinical Medical Research Award for their development of the virus-like particle technology used to create the human papillomavirus (HPV) vaccine. Their team discovered that proteins making up the outer shell of HPV could form virus-like particles that closely resemble the original virus but are not infectious, and these particles could trigger the immune system to produce protective antibodies that could neutralize HPV in a later infection. These particles eventually became the basis of the HPV vaccines Gardasil, Gardasil 9, and Cervarix.
HPV causes cervical cancer and other cancers such as cancer of the vulva, vagina, penis, or anus, as well as oropharyngeal cancer. Two of the high-risk types of HPV – HPV-16 and HPV-18 – cause about 70% of cervical cancers worldwide; it ranks 14th in frequency in the United States, according to the National Cancer Institute. The HPV vaccines are very effective in preventing persistent infections with HPV-16 and HPV-18. The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices continues to recommend routine HPV vaccination for girls and boys at age 11 or 12 years, with a second vaccine given 6-12 months later.