The Food and Drug Administration has approved a fully implantable glucose sensor that works with mobile technology to transmit continuous information about blood glucose levels for people with diabetes.

The sensor-mobile app combo, called the Eversense Continuous Glucose Monitoring (CGM) system, is designed to supplant the need for frequent blood sampling to monitor blood glucose levels.

[email protected]

The Food and Drug Administration has approved a fully implantable glucose sensor that works with mobile technology to transmit continuous information about blood glucose levels for people with diabetes.

The sensor-mobile app combo, called the Eversense Continuous Glucose Monitoring (CGM) system, is designed to supplant the need for frequent blood sampling to monitor blood glucose levels.

[email protected]

The Food and Drug Administration has approved a fully implantable glucose sensor that works with mobile technology to transmit continuous information about blood glucose levels for people with diabetes.

The sensor-mobile app combo, called the Eversense Continuous Glucose Monitoring (CGM) system, is designed to supplant the need for frequent blood sampling to monitor blood glucose levels.

[email protected]

The Trump policy of separating children and teenagers from their parents after crossing the U.S. border has been called un-American, immoral, cruel, and inhumane. The policy thankfully has been reversed or at least subject to delay. However, as I write today, 2,300 children and their parents are separated, not in contact, lost to each other, and with no clear plan on reunification. The ultimate outcome of immigration legislation and policy is unknown and mired in partisan politics. The policy hopefully has changed permanently, but what are the harms that will persist?

U.S. Customs and Border Control

1. Many if not all of the 2,300 children taken from their parents to institutional settings will have suffered acute anxiety and despair. Following data gathered by René Spitz and John Bowlby 80 years ago, children forced to separate from their parents for long hospitalizations with limited visitation went through phases of protest, despair, and if repeated or lengthy separations, “detachment” that impaired their ability to form relationships.¹

2. Many of these children have suffered traumas in their country of origin and through the journey to the U.S. border. Some of this traumatic experience was mitigated by being in the presence of their parent(s). Very likely some children have psychiatric and physical disorders that will add to the level of risk. The current trauma, forcible separation by armed guards into restrictive facilities, will compound or intensify the previous traumas without the benefit of parental support.

3. Will the harms persist? Likely this level of trauma has such a strong neurologic and psychological impact that many of the children will suffer from nightmares, depression, and persistent anxiety about trusting the safety of their setting. These harms will impact their health, their ability to learn, their relationships, and may increase the risk of self-medication through use of substances.²

4. The parents who are jailed, have had their children removed, and do not know where they are and aren’t able to talk to them have suffered a massive trauma. We all have lost sight of a child for a minute or two in a store or on the beach. Our anxiety is immediate, and if the separation is longer, we may remember those frightening minutes for the rest of our lives. How many immigrant parents will develop depression and posttraumatic stress disorder?

5. Guards were ordered to be the front-line implementers of the policy and must have been torn between their sworn duty and their inner knowledge that what they are doing is wrong. Hearing the children crying and calling for their parents must have elicited painful feelings of what it would have been like to have their own children taken away with no way to reach them or knowing where they were taken. Implementing this policy dehumanized them, and I believe made them feel guilty or unworthy.

6. Millions of immigrants – whether lawful, dreamers, or undocumented – must have felt fearful, powerless, and angry about this policy. Millions of their children must have been worried and lost a little bit of faith in their parents and in the United States.

7. Did U.S. citizens, many from immigrant roots, wonder if this could happen to them? How many children felt a little less secure? Was the anxiety higher for descendants of the U.S. citizens remembering the trauma of the World War II Japanese internment camps? Other descendants (like me) will remember quite vividly their mother’s story of being on the St. Louis steam ship and being turned away from the United States to face a high likelihood of death in Nazi Germany. A bit of fear will replace trust in and loyalty to the United States.

Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email him at [email protected].
 

References:

1. Dev Psychol. 1992;28:759-75.

2. www.cdc.gov/violenceprevention/acestudy/index.html

The Trump policy of separating children and teenagers from their parents after crossing the U.S. border has been called un-American, immoral, cruel, and inhumane. The policy thankfully has been reversed or at least subject to delay. However, as I write today, 2,300 children and their parents are separated, not in contact, lost to each other, and with no clear plan on reunification. The ultimate outcome of immigration legislation and policy is unknown and mired in partisan politics. The policy hopefully has changed permanently, but what are the harms that will persist?

U.S. Customs and Border Control

1. Many if not all of the 2,300 children taken from their parents to institutional settings will have suffered acute anxiety and despair. Following data gathered by René Spitz and John Bowlby 80 years ago, children forced to separate from their parents for long hospitalizations with limited visitation went through phases of protest, despair, and if repeated or lengthy separations, “detachment” that impaired their ability to form relationships.¹

2. Many of these children have suffered traumas in their country of origin and through the journey to the U.S. border. Some of this traumatic experience was mitigated by being in the presence of their parent(s). Very likely some children have psychiatric and physical disorders that will add to the level of risk. The current trauma, forcible separation by armed guards into restrictive facilities, will compound or intensify the previous traumas without the benefit of parental support.

3. Will the harms persist? Likely this level of trauma has such a strong neurologic and psychological impact that many of the children will suffer from nightmares, depression, and persistent anxiety about trusting the safety of their setting. These harms will impact their health, their ability to learn, their relationships, and may increase the risk of self-medication through use of substances.²

4. The parents who are jailed, have had their children removed, and do not know where they are and aren’t able to talk to them have suffered a massive trauma. We all have lost sight of a child for a minute or two in a store or on the beach. Our anxiety is immediate, and if the separation is longer, we may remember those frightening minutes for the rest of our lives. How many immigrant parents will develop depression and posttraumatic stress disorder?

5. Guards were ordered to be the front-line implementers of the policy and must have been torn between their sworn duty and their inner knowledge that what they are doing is wrong. Hearing the children crying and calling for their parents must have elicited painful feelings of what it would have been like to have their own children taken away with no way to reach them or knowing where they were taken. Implementing this policy dehumanized them, and I believe made them feel guilty or unworthy.

6. Millions of immigrants – whether lawful, dreamers, or undocumented – must have felt fearful, powerless, and angry about this policy. Millions of their children must have been worried and lost a little bit of faith in their parents and in the United States.

7. Did U.S. citizens, many from immigrant roots, wonder if this could happen to them? How many children felt a little less secure? Was the anxiety higher for descendants of the U.S. citizens remembering the trauma of the World War II Japanese internment camps? Other descendants (like me) will remember quite vividly their mother’s story of being on the St. Louis steam ship and being turned away from the United States to face a high likelihood of death in Nazi Germany. A bit of fear will replace trust in and loyalty to the United States.

Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email him at [email protected].
 

References:

1. Dev Psychol. 1992;28:759-75.

2. www.cdc.gov/violenceprevention/acestudy/index.html

The Trump policy of separating children and teenagers from their parents after crossing the U.S. border has been called un-American, immoral, cruel, and inhumane. The policy thankfully has been reversed or at least subject to delay. However, as I write today, 2,300 children and their parents are separated, not in contact, lost to each other, and with no clear plan on reunification. The ultimate outcome of immigration legislation and policy is unknown and mired in partisan politics. The policy hopefully has changed permanently, but what are the harms that will persist?

U.S. Customs and Border Control

1. Many if not all of the 2,300 children taken from their parents to institutional settings will have suffered acute anxiety and despair. Following data gathered by René Spitz and John Bowlby 80 years ago, children forced to separate from their parents for long hospitalizations with limited visitation went through phases of protest, despair, and if repeated or lengthy separations, “detachment” that impaired their ability to form relationships.¹

2. Many of these children have suffered traumas in their country of origin and through the journey to the U.S. border. Some of this traumatic experience was mitigated by being in the presence of their parent(s). Very likely some children have psychiatric and physical disorders that will add to the level of risk. The current trauma, forcible separation by armed guards into restrictive facilities, will compound or intensify the previous traumas without the benefit of parental support.

3. Will the harms persist? Likely this level of trauma has such a strong neurologic and psychological impact that many of the children will suffer from nightmares, depression, and persistent anxiety about trusting the safety of their setting. These harms will impact their health, their ability to learn, their relationships, and may increase the risk of self-medication through use of substances.²

4. The parents who are jailed, have had their children removed, and do not know where they are and aren’t able to talk to them have suffered a massive trauma. We all have lost sight of a child for a minute or two in a store or on the beach. Our anxiety is immediate, and if the separation is longer, we may remember those frightening minutes for the rest of our lives. How many immigrant parents will develop depression and posttraumatic stress disorder?

5. Guards were ordered to be the front-line implementers of the policy and must have been torn between their sworn duty and their inner knowledge that what they are doing is wrong. Hearing the children crying and calling for their parents must have elicited painful feelings of what it would have been like to have their own children taken away with no way to reach them or knowing where they were taken. Implementing this policy dehumanized them, and I believe made them feel guilty or unworthy.

6. Millions of immigrants – whether lawful, dreamers, or undocumented – must have felt fearful, powerless, and angry about this policy. Millions of their children must have been worried and lost a little bit of faith in their parents and in the United States.

7. Did U.S. citizens, many from immigrant roots, wonder if this could happen to them? How many children felt a little less secure? Was the anxiety higher for descendants of the U.S. citizens remembering the trauma of the World War II Japanese internment camps? Other descendants (like me) will remember quite vividly their mother’s story of being on the St. Louis steam ship and being turned away from the United States to face a high likelihood of death in Nazi Germany. A bit of fear will replace trust in and loyalty to the United States.

Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email him at [email protected].
 

References:

1. Dev Psychol. 1992;28:759-75.

2. www.cdc.gov/violenceprevention/acestudy/index.html

Quality, not quantity, is what Department of Health & Human Services Secretary Alex M. Azar II is looking for when it comes to physicians being paid through a value-based payment arrangement.

“I am not sure that simply being in an alternative payment model, which was the metric the Obama administration used, is the one that I would find to be substantive and real in terms of transformation of our health care system,” Mr. Azar said June 20 at a forum hosted by the Washington Post.

Wikimedia Commons/WWsgConnect/CC-SA 4.0

The previous administration set a goal of having at least 50% of physician Medicare payments tied to quality by the end of this year. It’s first milestone of 30% by the end of 2016 was reached in March of that year.

The current administration may have had a tough time meeting the 50% goal because of changes it made to the Quality Payment Program exempted two-thirds of eligible clinicians from the Merit-Based Incentive Payment System track in 2018.

Mr. Azar said that he is working with the team at the Centers for Medicare & Medicaid Services to come up with a better way to determine whether paying for quality is effective.

“What I don’t want to do is have an approach where it’s a tag the base, hit a scorecard number,” he said. “We genuinely want to revolutionize how health care is paid for in this country in an outcome-based, health-based, non-procedure-, non-sickness-based way. We are working on that. We want to get to real concrete metrics.”

Mr. Azar also noted that the agency is working on “the concrete strategy for the Center for Medicare & Medicaid Innovation. That will also have dimensions for what we are doing within the fee-for-service program and Medicare Advantage around moving toward value-based payment arrangements.”

He praised the efforts of the Bush Administration and the Obama Administration as providing a good foundation for the transition to paying for quality and “we will build on that.”

[email protected]

Quality, not quantity, is what Department of Health & Human Services Secretary Alex M. Azar II is looking for when it comes to physicians being paid through a value-based payment arrangement.

“I am not sure that simply being in an alternative payment model, which was the metric the Obama administration used, is the one that I would find to be substantive and real in terms of transformation of our health care system,” Mr. Azar said June 20 at a forum hosted by the Washington Post.

Wikimedia Commons/WWsgConnect/CC-SA 4.0

The previous administration set a goal of having at least 50% of physician Medicare payments tied to quality by the end of this year. It’s first milestone of 30% by the end of 2016 was reached in March of that year.

The current administration may have had a tough time meeting the 50% goal because of changes it made to the Quality Payment Program exempted two-thirds of eligible clinicians from the Merit-Based Incentive Payment System track in 2018.

Mr. Azar said that he is working with the team at the Centers for Medicare & Medicaid Services to come up with a better way to determine whether paying for quality is effective.

“What I don’t want to do is have an approach where it’s a tag the base, hit a scorecard number,” he said. “We genuinely want to revolutionize how health care is paid for in this country in an outcome-based, health-based, non-procedure-, non-sickness-based way. We are working on that. We want to get to real concrete metrics.”

Mr. Azar also noted that the agency is working on “the concrete strategy for the Center for Medicare & Medicaid Innovation. That will also have dimensions for what we are doing within the fee-for-service program and Medicare Advantage around moving toward value-based payment arrangements.”

He praised the efforts of the Bush Administration and the Obama Administration as providing a good foundation for the transition to paying for quality and “we will build on that.”

[email protected]

Quality, not quantity, is what Department of Health & Human Services Secretary Alex M. Azar II is looking for when it comes to physicians being paid through a value-based payment arrangement.

“I am not sure that simply being in an alternative payment model, which was the metric the Obama administration used, is the one that I would find to be substantive and real in terms of transformation of our health care system,” Mr. Azar said June 20 at a forum hosted by the Washington Post.

Wikimedia Commons/WWsgConnect/CC-SA 4.0

The previous administration set a goal of having at least 50% of physician Medicare payments tied to quality by the end of this year. It’s first milestone of 30% by the end of 2016 was reached in March of that year.

The current administration may have had a tough time meeting the 50% goal because of changes it made to the Quality Payment Program exempted two-thirds of eligible clinicians from the Merit-Based Incentive Payment System track in 2018.

Mr. Azar said that he is working with the team at the Centers for Medicare & Medicaid Services to come up with a better way to determine whether paying for quality is effective.

“What I don’t want to do is have an approach where it’s a tag the base, hit a scorecard number,” he said. “We genuinely want to revolutionize how health care is paid for in this country in an outcome-based, health-based, non-procedure-, non-sickness-based way. We are working on that. We want to get to real concrete metrics.”

Mr. Azar also noted that the agency is working on “the concrete strategy for the Center for Medicare & Medicaid Innovation. That will also have dimensions for what we are doing within the fee-for-service program and Medicare Advantage around moving toward value-based payment arrangements.”

He praised the efforts of the Bush Administration and the Obama Administration as providing a good foundation for the transition to paying for quality and “we will build on that.”

[email protected]

CHICAGO – Are today’s myeloma drugs affordable? Two Mayo Clinic researchers agreed that costs are high but not whether the price is offset by the value.

“I don’t think there is any debate here. It’s like debating whether the Earth is flat or not,” S. Vincent Rajkumar, MD, of Mayo Clinic, Rochester, Minn., said during a debate at the annual meeting of the American Society of Clinical Oncology. “These drugs are expensive.”

“I would trust Dr. Rajkumar with my life if I were diagnosed with myeloma,” countered Rafael Fonseca, MD, of Mayo Clinic in Phoenix, Ariz., “But I think he’s wrong on drug economics.”

Dr. Rajkumar said the total lifetime costs to treat all patients diagnosed with multiple myeloma in 2017 were $22.4 billion, a “conservative estimate” that excluded hospital, infusion, laboratory, imaging, physician, nursing, and ancillary costs.

“Every single drug is expensive,” he said, referring to newer approved myeloma therapies that cost up to $192,000/year individually, and up to $590,000/year in triplet or quadruplet combination regimens, according to estimates he included in a related article he wrote for the 2018 ASCO Educational Book.

Of $50 billion spent in 2017 on cancer drugs, 80% of that spending was based on just 35 drugs, of which 6 were myeloma drugs – and myeloma is just 1% of all cancers. “Maybe it’s because of all the progress we’ve made in myeloma, but unless you think none of the other cancers should have the type of progress we have, this is not going to be affordable,” Dr. Rajkumar said.

Drugs approved by the Food and Drug Administration (FDA) in 2017 cost $100,000/year or more, with an average of $150,000/year, according to Dr. Rajkumar. He compared that with the average U.S. annual gross household income of $52,000, saying that the high price of drugs has contributed to compliance problems and medical bankruptcy.

While Dr. Fonseca agreed that drug prices are “skyrocketing,” he challenged the notion that the increases were not affordable in his presentation and an associated ASCO Educational Book article.

In his talk, Dr. Fonseca said the availability of new myeloma drugs has led to “astounding” improvements in overall survival, but today’s best drugs are still not good enough. “We cannot afford to stop innovation and the move forward as we are ever so close to curing a large fraction of myeloma patients,” he said.

The increasing cost of drugs has been offset by societal and health effects, Dr. Fonseca argued.

The war on cancer from 1988 to 2000 added 23 million additional life-years, which has equated to $1.9 trillion in social value for Americans, according to one analysis he cited. In one myeloma-specific study, investigators found myeloma drug costs increased from $36,607 in 2004 to $109,544 in 2009, but those increases were balanced out by $67,900 in health benefits.

Although the financial impact of myeloma on the individual patient can be significant, it’s not bankruptcies, but out-of-pocket costs such as copayments, that have the most direct effect on patients, Dr. Fonseca said. Research shows medical bankruptcies are not associated with drug copayments, he added, but rather other medical expenses, such as hospital and physician bills, along with loss of income and limited savings.

Dr. Rajkumar – unconvinced that myeloma drugs are currently affordable – urged action on several fronts, including value-based pricing or tying the price of a drug to how much value it produces.

The Medicare program has to be able to negotiate prices, he added, and patients should be allowed to reimport cancer drugs from other countries for personal use. He also pushed for more to be done to facilitate the entry of generics and biosimilars into the marketplace.

He also called for a relaxation of FDA regulations to lower drug development costs. “We have so many regulations so that every T is crossed and every I is dotted, to the point that it costs $30,000, $40,000 per patient to do a trial,” he said.

But Dr. Fonseca opposed market interference, saying that price controls would kill innovation.

“The patented drugs of today are the generics of the future, and absent innovation, we won’t have future generics,” he said in his presentation. “Price fixing kills innovation. ... So if we engage in that, today’s best is simply the best there is going to be.”

Dr. Rajkumar reported having no conflicts of interest. Dr. Fonseca reported consulting work with Amgen, Bristol-Myers Squibb, Celgene, Takeda Pharmaceutical, Bayer, Janssen, AbbVie, Pharmacyclics, Sanofi, Kite Pharma, and Juno Therapeutics, and scientific advisory board work with Adaptive Biotechnologies.

CHICAGO – Are today’s myeloma drugs affordable? Two Mayo Clinic researchers agreed that costs are high but not whether the price is offset by the value.

“I don’t think there is any debate here. It’s like debating whether the Earth is flat or not,” S. Vincent Rajkumar, MD, of Mayo Clinic, Rochester, Minn., said during a debate at the annual meeting of the American Society of Clinical Oncology. “These drugs are expensive.”

“I would trust Dr. Rajkumar with my life if I were diagnosed with myeloma,” countered Rafael Fonseca, MD, of Mayo Clinic in Phoenix, Ariz., “But I think he’s wrong on drug economics.”

Dr. Rajkumar said the total lifetime costs to treat all patients diagnosed with multiple myeloma in 2017 were $22.4 billion, a “conservative estimate” that excluded hospital, infusion, laboratory, imaging, physician, nursing, and ancillary costs.

“Every single drug is expensive,” he said, referring to newer approved myeloma therapies that cost up to $192,000/year individually, and up to $590,000/year in triplet or quadruplet combination regimens, according to estimates he included in a related article he wrote for the 2018 ASCO Educational Book.

Of $50 billion spent in 2017 on cancer drugs, 80% of that spending was based on just 35 drugs, of which 6 were myeloma drugs – and myeloma is just 1% of all cancers. “Maybe it’s because of all the progress we’ve made in myeloma, but unless you think none of the other cancers should have the type of progress we have, this is not going to be affordable,” Dr. Rajkumar said.

Drugs approved by the Food and Drug Administration (FDA) in 2017 cost $100,000/year or more, with an average of $150,000/year, according to Dr. Rajkumar. He compared that with the average U.S. annual gross household income of $52,000, saying that the high price of drugs has contributed to compliance problems and medical bankruptcy.

While Dr. Fonseca agreed that drug prices are “skyrocketing,” he challenged the notion that the increases were not affordable in his presentation and an associated ASCO Educational Book article.

In his talk, Dr. Fonseca said the availability of new myeloma drugs has led to “astounding” improvements in overall survival, but today’s best drugs are still not good enough. “We cannot afford to stop innovation and the move forward as we are ever so close to curing a large fraction of myeloma patients,” he said.

The increasing cost of drugs has been offset by societal and health effects, Dr. Fonseca argued.

The war on cancer from 1988 to 2000 added 23 million additional life-years, which has equated to $1.9 trillion in social value for Americans, according to one analysis he cited. In one myeloma-specific study, investigators found myeloma drug costs increased from $36,607 in 2004 to $109,544 in 2009, but those increases were balanced out by $67,900 in health benefits.

Although the financial impact of myeloma on the individual patient can be significant, it’s not bankruptcies, but out-of-pocket costs such as copayments, that have the most direct effect on patients, Dr. Fonseca said. Research shows medical bankruptcies are not associated with drug copayments, he added, but rather other medical expenses, such as hospital and physician bills, along with loss of income and limited savings.

Dr. Rajkumar – unconvinced that myeloma drugs are currently affordable – urged action on several fronts, including value-based pricing or tying the price of a drug to how much value it produces.

The Medicare program has to be able to negotiate prices, he added, and patients should be allowed to reimport cancer drugs from other countries for personal use. He also pushed for more to be done to facilitate the entry of generics and biosimilars into the marketplace.

He also called for a relaxation of FDA regulations to lower drug development costs. “We have so many regulations so that every T is crossed and every I is dotted, to the point that it costs $30,000, $40,000 per patient to do a trial,” he said.

But Dr. Fonseca opposed market interference, saying that price controls would kill innovation.

“The patented drugs of today are the generics of the future, and absent innovation, we won’t have future generics,” he said in his presentation. “Price fixing kills innovation. ... So if we engage in that, today’s best is simply the best there is going to be.”

Dr. Rajkumar reported having no conflicts of interest. Dr. Fonseca reported consulting work with Amgen, Bristol-Myers Squibb, Celgene, Takeda Pharmaceutical, Bayer, Janssen, AbbVie, Pharmacyclics, Sanofi, Kite Pharma, and Juno Therapeutics, and scientific advisory board work with Adaptive Biotechnologies.

CHICAGO – Are today’s myeloma drugs affordable? Two Mayo Clinic researchers agreed that costs are high but not whether the price is offset by the value.

“I don’t think there is any debate here. It’s like debating whether the Earth is flat or not,” S. Vincent Rajkumar, MD, of Mayo Clinic, Rochester, Minn., said during a debate at the annual meeting of the American Society of Clinical Oncology. “These drugs are expensive.”

“I would trust Dr. Rajkumar with my life if I were diagnosed with myeloma,” countered Rafael Fonseca, MD, of Mayo Clinic in Phoenix, Ariz., “But I think he’s wrong on drug economics.”

Dr. Rajkumar said the total lifetime costs to treat all patients diagnosed with multiple myeloma in 2017 were $22.4 billion, a “conservative estimate” that excluded hospital, infusion, laboratory, imaging, physician, nursing, and ancillary costs.

“Every single drug is expensive,” he said, referring to newer approved myeloma therapies that cost up to $192,000/year individually, and up to $590,000/year in triplet or quadruplet combination regimens, according to estimates he included in a related article he wrote for the 2018 ASCO Educational Book.

Of $50 billion spent in 2017 on cancer drugs, 80% of that spending was based on just 35 drugs, of which 6 were myeloma drugs – and myeloma is just 1% of all cancers. “Maybe it’s because of all the progress we’ve made in myeloma, but unless you think none of the other cancers should have the type of progress we have, this is not going to be affordable,” Dr. Rajkumar said.

Drugs approved by the Food and Drug Administration (FDA) in 2017 cost $100,000/year or more, with an average of $150,000/year, according to Dr. Rajkumar. He compared that with the average U.S. annual gross household income of $52,000, saying that the high price of drugs has contributed to compliance problems and medical bankruptcy.

While Dr. Fonseca agreed that drug prices are “skyrocketing,” he challenged the notion that the increases were not affordable in his presentation and an associated ASCO Educational Book article.

In his talk, Dr. Fonseca said the availability of new myeloma drugs has led to “astounding” improvements in overall survival, but today’s best drugs are still not good enough. “We cannot afford to stop innovation and the move forward as we are ever so close to curing a large fraction of myeloma patients,” he said.

The increasing cost of drugs has been offset by societal and health effects, Dr. Fonseca argued.

The war on cancer from 1988 to 2000 added 23 million additional life-years, which has equated to $1.9 trillion in social value for Americans, according to one analysis he cited. In one myeloma-specific study, investigators found myeloma drug costs increased from $36,607 in 2004 to $109,544 in 2009, but those increases were balanced out by $67,900 in health benefits.

Although the financial impact of myeloma on the individual patient can be significant, it’s not bankruptcies, but out-of-pocket costs such as copayments, that have the most direct effect on patients, Dr. Fonseca said. Research shows medical bankruptcies are not associated with drug copayments, he added, but rather other medical expenses, such as hospital and physician bills, along with loss of income and limited savings.

Dr. Rajkumar – unconvinced that myeloma drugs are currently affordable – urged action on several fronts, including value-based pricing or tying the price of a drug to how much value it produces.

The Medicare program has to be able to negotiate prices, he added, and patients should be allowed to reimport cancer drugs from other countries for personal use. He also pushed for more to be done to facilitate the entry of generics and biosimilars into the marketplace.

He also called for a relaxation of FDA regulations to lower drug development costs. “We have so many regulations so that every T is crossed and every I is dotted, to the point that it costs $30,000, $40,000 per patient to do a trial,” he said.

But Dr. Fonseca opposed market interference, saying that price controls would kill innovation.

“The patented drugs of today are the generics of the future, and absent innovation, we won’t have future generics,” he said in his presentation. “Price fixing kills innovation. ... So if we engage in that, today’s best is simply the best there is going to be.”

Dr. Rajkumar reported having no conflicts of interest. Dr. Fonseca reported consulting work with Amgen, Bristol-Myers Squibb, Celgene, Takeda Pharmaceutical, Bayer, Janssen, AbbVie, Pharmacyclics, Sanofi, Kite Pharma, and Juno Therapeutics, and scientific advisory board work with Adaptive Biotechnologies.

Offspring of obese mothers should be regarded as a high-risk population for endothelial cell dysfunction and, therefore, for cardiovascular events later in life, authors of a thematic literature review concluded.

Maternal obesity has been tied to the development of cardiovascular disease (CVD) and premature death in epidemiologic studies, the authors noted in the review.

anopdesignstock/Thinkstock

“Raised leptin levels, secreted by the adipose tissue, inhibit the in vitro proliferation of smooth muscle cells and could impede the angiogenesis process in vivo, but this assumption needs scientific validation in humans,” they said in their review.

However, human studies are lacking, aside from the epidemiologic reports that “cannot be used to confirm or contradict” the fetal programming hypothesis, they said.

Meanwhile, an increasing body of evidence has suggested that stressors in critical periods of fetal development may lead to epigenetic alterations that could play a role in either up-regulating atherogenic genes or down-regulating enzymatic activities that guard against oxidative stress.

For example, cohort studies have shown differences in DNA methylation among offspring born before and after bariatric surgery in the mother, which has lent credence to the hypothesis that maternal obesity in pregnancy alters methylation patterns for those offspring, Ms. Van De Maele and her colleagues wrote.

Lifestyle changes in obese pregnant women may have an effect on adverse metabolic or cardiovascular outcomes in offspring, although results to date are inconclusive, they added.

Diet, exercise, or both during pregnancy may lower the risk of macrosomia, respiratory distress syndrome, or other neonatal outcomes, particularly in high-risk women, according to the conclusions of a 2015 Cochrane review that Ms. Van De Maele and her coauthors cited.

However, follow-up studies on offspring are scarce and have shown no clear effects on long-term metabolic profiles in offspring, likely because of insufficient follow-up time, they said in their review.

Ms. Van De Maele and her coauthors said they had no conflict of interest disclosures related to their manuscript.

SOURCE: Van De Maele K et al. Atherosclerosis. 2018 Jun. doi: 10.1016/j.atherosclerosis.2018.06.016.

Offspring of obese mothers should be regarded as a high-risk population for endothelial cell dysfunction and, therefore, for cardiovascular events later in life, authors of a thematic literature review concluded.

Maternal obesity has been tied to the development of cardiovascular disease (CVD) and premature death in epidemiologic studies, the authors noted in the review.

anopdesignstock/Thinkstock

“Raised leptin levels, secreted by the adipose tissue, inhibit the in vitro proliferation of smooth muscle cells and could impede the angiogenesis process in vivo, but this assumption needs scientific validation in humans,” they said in their review.

However, human studies are lacking, aside from the epidemiologic reports that “cannot be used to confirm or contradict” the fetal programming hypothesis, they said.

Meanwhile, an increasing body of evidence has suggested that stressors in critical periods of fetal development may lead to epigenetic alterations that could play a role in either up-regulating atherogenic genes or down-regulating enzymatic activities that guard against oxidative stress.

For example, cohort studies have shown differences in DNA methylation among offspring born before and after bariatric surgery in the mother, which has lent credence to the hypothesis that maternal obesity in pregnancy alters methylation patterns for those offspring, Ms. Van De Maele and her colleagues wrote.

Lifestyle changes in obese pregnant women may have an effect on adverse metabolic or cardiovascular outcomes in offspring, although results to date are inconclusive, they added.

Diet, exercise, or both during pregnancy may lower the risk of macrosomia, respiratory distress syndrome, or other neonatal outcomes, particularly in high-risk women, according to the conclusions of a 2015 Cochrane review that Ms. Van De Maele and her coauthors cited.

However, follow-up studies on offspring are scarce and have shown no clear effects on long-term metabolic profiles in offspring, likely because of insufficient follow-up time, they said in their review.

Ms. Van De Maele and her coauthors said they had no conflict of interest disclosures related to their manuscript.

SOURCE: Van De Maele K et al. Atherosclerosis. 2018 Jun. doi: 10.1016/j.atherosclerosis.2018.06.016.

Offspring of obese mothers should be regarded as a high-risk population for endothelial cell dysfunction and, therefore, for cardiovascular events later in life, authors of a thematic literature review concluded.

Maternal obesity has been tied to the development of cardiovascular disease (CVD) and premature death in epidemiologic studies, the authors noted in the review.

anopdesignstock/Thinkstock

“Raised leptin levels, secreted by the adipose tissue, inhibit the in vitro proliferation of smooth muscle cells and could impede the angiogenesis process in vivo, but this assumption needs scientific validation in humans,” they said in their review.

However, human studies are lacking, aside from the epidemiologic reports that “cannot be used to confirm or contradict” the fetal programming hypothesis, they said.

Meanwhile, an increasing body of evidence has suggested that stressors in critical periods of fetal development may lead to epigenetic alterations that could play a role in either up-regulating atherogenic genes or down-regulating enzymatic activities that guard against oxidative stress.

For example, cohort studies have shown differences in DNA methylation among offspring born before and after bariatric surgery in the mother, which has lent credence to the hypothesis that maternal obesity in pregnancy alters methylation patterns for those offspring, Ms. Van De Maele and her colleagues wrote.

Lifestyle changes in obese pregnant women may have an effect on adverse metabolic or cardiovascular outcomes in offspring, although results to date are inconclusive, they added.

Diet, exercise, or both during pregnancy may lower the risk of macrosomia, respiratory distress syndrome, or other neonatal outcomes, particularly in high-risk women, according to the conclusions of a 2015 Cochrane review that Ms. Van De Maele and her coauthors cited.

However, follow-up studies on offspring are scarce and have shown no clear effects on long-term metabolic profiles in offspring, likely because of insufficient follow-up time, they said in their review.

Ms. Van De Maele and her coauthors said they had no conflict of interest disclosures related to their manuscript.

SOURCE: Van De Maele K et al. Atherosclerosis. 2018 Jun. doi: 10.1016/j.atherosclerosis.2018.06.016.

There are recent advances in preexposure prophylaxis, or PrEP, as a promising prevention option for HIV, according to a recent study.¹

grandeduc/Thinkstock

Reference

1. Desai M, Field N, Grant R, McCormack S. “Recent advances in pre-exposure prophylaxis for HIV.” BMJ. 2017;359:j5011.

There are recent advances in preexposure prophylaxis, or PrEP, as a promising prevention option for HIV, according to a recent study.¹

grandeduc/Thinkstock

Reference

1. Desai M, Field N, Grant R, McCormack S. “Recent advances in pre-exposure prophylaxis for HIV.” BMJ. 2017;359:j5011.

There are recent advances in preexposure prophylaxis, or PrEP, as a promising prevention option for HIV, according to a recent study.¹

grandeduc/Thinkstock

Reference

1. Desai M, Field N, Grant R, McCormack S. “Recent advances in pre-exposure prophylaxis for HIV.” BMJ. 2017;359:j5011.

A controversial study on abdominal aortic aneurysm screening; the importance of healthy lifestyle in diabetes; how NIH scientists corrupted a big alcohol study; and how cardiologists fare in starting salaries.

Listen to MDedge Cardiocast for all the details on the week’s top news.


 

A controversial study on abdominal aortic aneurysm screening; the importance of healthy lifestyle in diabetes; how NIH scientists corrupted a big alcohol study; and how cardiologists fare in starting salaries.

Listen to MDedge Cardiocast for all the details on the week’s top news.


 

A controversial study on abdominal aortic aneurysm screening; the importance of healthy lifestyle in diabetes; how NIH scientists corrupted a big alcohol study; and how cardiologists fare in starting salaries.

Listen to MDedge Cardiocast for all the details on the week’s top news.


 

ABSTRACT

The articular surface replacement (ASR) monoblock metal-on-metal acetabular component was recalled due to a higher than expected early failure rate. We evaluated the survivorship of the device and variables that may be predictive of failure at a minimum of 5-year follow-up. A single-center, single-surgeon retrospective review was conducted in patients who received the DePuy Synthes ASR™ XL Acetabular hip system from December 2005 to November 2009. Mean values and percentages were calculated and compared using the Fisher’s exact test, simple logistic regression, and Student’s t-test. The significance level was P ≤ .05. This study included 29 patients (24 males, 5 females) with 32 ASR™ XL acetabular hip systems. Mean age and body mass index (BMI) reached 55.2 years and 28.9 kg/m², respectively. Mean postoperative follow-up was 6.2 years. A total of 2 patients (6.9%) died of an unrelated cause and 1 patient was lost to follow-up (3.4%), leaving 26 patients with 28 hip replacements, all of whom were available for follow-up. The 5-year revision rate was 34.4% (10 patients with 11 hip replacements). Mean time to revision was 3.1 years. Age (P = .76), gender (P = .49), BMI (P = .29), acetabular component abduction angle (P = .12), and acetabulum size (P = .59) were not associated with the increased rate for hip failure. Blood cobalt (7.6 vs 6.8 µg/L, P = .58) and chromium (5.0 vs 2.2 µg/L, P = .31) levels were not significantly higher in the revised group when compared with those of the unrevised group. In the revised group, a 91% decrease in cobalt and 78% decrease in chromium levels were observed at a mean of 6 months following the revision. This study demonstrates a high rate of failure of ASR acetabular components used in total hip arthroplasty at a minimum of 5 years of follow-up. No variable that was predictive of failure could be identified in this series. Close clinical surveillance of these patients is required.

Continue to: Metal-on-metal...

Metal-on-metal (MoM) articulations have been widely explored as an alternative to polyethylene bearings in total hip arthroplasty (THA), with proposed benefits including improved range of motion, lower dislocation rates, and enhanced durability.¹ Comprising cobalt and chromium, these MoM bearings gained widespread popularity in the United States, particularly in younger and more active patients looking for longer lasting devices.

The articular surface replacement (ASR) acetabular system (DePuy Synthes) was approved for sale by the US Food and Drug Administration in 2003 and implanted in an estimated 93,000 cases.² Since then, however, the early failure rate of the prosthesis has been well documented,^3-5 leading to a formal global product recall in August 2010. The Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) was amongst the first to report a 6.4% rate of failure of the device at 3 years when inserted with a Corail stem.⁶ An acceptable upper rate of hip prosthesis failure is considered to reach 1% per year, with the majority of implants reporting well below this value. A 10.9% failure rate at 5 years was documented when the prosthesis was inserted for resurfacing. The National Joint Registry of England and Wales confirmed these findings and observed a 13% and 12% rate of failure at 5 years for the acetabular and resurfacing systems, respectively.² With the notable failure of the ASR system, this study reports our single-center 5-year survivorship experience and evaluates any variable that might be predictive of an early failure to aid in patient counseling.

METHODS

A single-center, single-surgeon, retrospective review of a consecutive series of patients was performed from December 2005 to November 2009. This study included all patients who underwent a primary THA with a DePuy Synthes ASR™ XL Acetabular hip system. No patients were excluded. Institutional Review Board approval was obtained. Patient demographics comprising of age, gender, and body mass index (BMI) were recorded. The primary endpoint of this study was 5-year survivorship rates. Secondary endpoints included duration to revision surgery, blood cobalt and chromium levels, time interval of blood ion tests, acetabulum size, acetabular component abduction angle, and duration to follow-up.

Candidates for the ASR™ XL Acetabular hip system included young patients and/or those considered to be physically active. In a select few, ASR devices were implanted upon patient request.

All patients underwent primary total hip replacement with a DePuy Synthes ASR™ XL uncemented acetabular component and an uncemented femoral stem (DePuy Synthes, Summit, or Tri-Lock) inserted via a standard posterior approach (Figure 1). Acetabulum sizes ranged from 52 mm to 68 mm in diameter.

All patients were followed-up yearly in the outpatient setting. Routine (yearly) metal-ion level sampling (whole blood) was started in 2010 for all patients. Laboratory tests were conducted at a single laboratory (Lab Corp.). Abduction cup inclination angles were measured by the providing surgeon using digital radiology software (GE Centricity systems).

The Student’s t-test was used to compare mean values (such as age, BMI, and metal ion levels) between the failure and no-failure groups. The 2-sided Fisher’s exact test analyzed differences in gender. Simple logistic regression analyzed variables associated with the failure group. Significance was P ≤ .05.

Continue to: Results...

RESULTS

A total of 29 patients (24 males, 5 females) with 32 ASR hip replacements were included in this study. Indications for surgery comprised osteoarthritis (28 hips, 87.5%) and avascular necrosis of the hip (4 hips, 12.5%). Mean age and BMI were 55.2 years and 28.9 kg/m², respectively. A total of 2 patients (6.9%) died of an unrelated cause (1 myocardial infarct, 1 suicide), and 1 patient was lost to follow-up (3.4%), leaving 26 patients with 28 hip replacements, all of whom finished a 5-year minimum follow-up.

No implant failures were noted in the first year. The 5-year revision rate reached 34.4% (10 patients with 11 hip replacements). Mean time to revision for this subgroup was 3.1 years. Overall, an implant failure was observed in 37.5% of patients (11 patients with 12 hip replacements) at a mean postoperative follow-up of 6.2 years (Figure 2). Indications for implant revision were pain in 11 (92.7%) cases and infection in 1 (8.3%).

Of the 11 hips revised due to pain, 9 were performed by the original surgeon (8 were completed with primary acetabular components, 1 with a revision shell). Figure 3 shows a bilateral revision performed with primary acetabular components and retained DePuy Synthes Pinnacle femoral stems. In all these cases except 1, the ASR component was grossly loose. One case presented with pseudotumor and impingement between the femoral prosthetic neck and acetabular component after migration of a loose component. After revision, the patient returned with substantial anterior hip pain and heterotopic ossification, and failed conservative treatment, requiring another surgery with prosthesis retention, removal of heterotopic ossification, and iliopsoas lengthening. The surgery successfully relieved the symptoms. No other patients required additional surgery after their revision. In comparison to the original ASR component, the revision shell was 2 to 4 mm larger in diameter. No patient required component revision at a mean of 2.9 years after the revision surgery.

The patient with secondary revision developed a hematogenous streptococcal infection after a dental procedure performed without prophylactic antibiotics. The patient was initially lost to follow-up after the primary surgery and reported no antecedent pain prior to the revision. A substantial metal fluid collection was identified in the hip at the time of débridement and without component loosening. After débridement, the patient developed persistent metal stained wound drainage, necessitating ultimate successful treatment with a 2-stage exchange procedure.

Age (P = .76), gender (P = .49), BMI (P = .29), acetabular component abduction angle (P = .12), and acetabulum size (P = .59) were not associated with an increased rate for hip failure (Table). Blood cobalt (7.6 vs 6.8 µg/L, P = .58) and chromium (5.0 vs 2.2 µg/L, P = .31) levels were not significantly higher in the revised group when compared with those of the unrevised group. The upper limits of blood cobalt and chromium levels reached 18.9 and 15.9 µg/L for the revised group and 16.8 and 5.4 µg/L for the non-revised group, respectively. In the revised group, a 91% decrease in cobalt and 78% decrease in chromium levels were observed at a mean of 6 months after the revision (Figure 4).

Table. Variables Not Associated with Early ASR Failure

Continue to: Discussion...

DISCUSSION

According to the Center for Disease Control and Prevention, 310,800 total hip replacements were performed among inpatients aged 45 years and older in the US in 2010.⁷ Specifically, in the 55- to 64-year-old age group, the number of procedures performed tripled from 2000 through 2010. As younger and more active patients opt for hip replacements, a growing need for prosthesis with enhanced durability is observed.

Despite the early proposed advantages of large head MoM bearings, our retrospective study of the DePuy Synthes ASR™ XL Acetabular hip system yielded 15.6% and 34.4% failure rates at 3 and 5 years, respectively. These higher-than-expected rates of failure are consistent with published data. The British Hip Society reported a 21% to 35% revision rate at 4 years and 49% at 6 years for the ASR XL prosthesis.⁸ In comparison, other MoM prosthesis, on average, report a 12% to 15% rate of failure at 5 years.

Considerable controversy surrounds the causes of adverse wear failure in MoM bearings.^9,10 The non-modular design of the ASR prostheses is frequently implicated as a cause of early failure. The lack of a central hole in the 1-piece component compromises the tactile feel of insertion, thereby reducing the surgeon’s ability to assess complete seating.¹¹ This condition may potentially increase the abduction angle at the time of insertion. Screw fixation of the non-modular device is not possible. The ASR XL device (148^° to 160^°) is less than a hemisphere (180^°) in size and hence features a diminished functional articular surface, further compromising implant fixation.¹¹ The functional articular surface is defined as the optimal surface area (10 mm) needed for a MoM implant.¹² Griffin and colleagues¹³ reported a 48 mm ASR XL component, when implanted at 45^° of abduction, to function similar to an implant at 59^° of abduction, leading to diminished lubrication, metallosis, and edge loading. The version of the acetabular component may similarly and adversely affect implant wear characteristics. Furthermore, the variable thickness of the implant, which is thicker at the dome and thinner at the rim, may further promote edge loading by shifting the center of rotation of the femoral head out from the center of the acetabular prosthesis.¹¹ Studies have also shown that increased wear of the MoM articulation is associated with an acetabular component inclination angle in excess of 55^°10,14 and a failure of fixation at time of implantation.¹⁵ This study, however, found no correlation between the abduction angle and risk of early implant failure for the ASR acetabular component. No correlation was also detected between the acetabulum size and revision surgery.

The AOANJRR reported loosening (44%), infection (20%), metal sensitivity (12%), fracture (9%), and dislocation of prosthesis (7%) as the indications for revision surgery for the ASR prosthesis.⁶ Furthermore, a single-center retrospective review of 70 consecutive MoM THAs with ultra-large diameter femoral head and monoblock acetabular components showed that 17.1% required revision within 3 years for loosening, pain, and squeaking.¹ Overall, 28.6% of patients reported implant dysfunction. In this study, we observed a similar rate of failure at 3 years (15.6%) for pain (11) and infection (1). The revision surgery successfully relieved all of these symptoms. One patient presented with heterotopic ossification and anterior hip pain after the original revision and required additional surgery with prosthesis retention. No patient in this series required repeat component revisions at a mean of 2.9 years after surgery. In all but 1 case, primary acetabular components were used in the revision, and in all cases except that with infection, the femoral component was retained. Replacement shells were 2 to 4 mm larger in diameter than the original ASR component.

Recently, concerns have arisen regarding the long-term effects of serum cobalt and chromium metal ions levels. Studies have shown increased serum metal ion levels,¹⁵ groin pain,¹⁶ pseudotumor formation,¹⁷ and metallosis¹⁸ after the implantation of MoM bearings. In a case study by Mao and colleagues,¹⁹ 1 patient reported headaches, anorexia, continuous metallic taste in her mouth, and weight loss. A cerebrospinal fluid analysis revealed cobalt and chromium levels at 9 and 13 nmol/L, respectively, indicating that these metal ions can cross the blood-brain barrier. Another patient reported painful muscle fatigue, night cramps, fainting spells, cognitive decline, and an inability to climb stairs. His serum cobalt level reached 258 nmol/L (reference range, 0-20 nmol/L), and chromium level totaled 88 nmol/L (reference range, 0-100 nmol/L). At 8-week follow-up after revision surgery, the symptoms of the patient had resolved, with serum cobalt levels dropping to 42 nmol/L.¹⁹ None of the patients in this study presented with any signs or symptoms of metal toxicity. The upper limits of blood cobalt and chromium levels in our study population reached 18.9 and 15.9 µg/L for the revised group and 16.8 and 5.4 µg/L for the non-revised group, respectively. However, we noted a similar drop in post-revision blood cobalt (91% decrease) and chromium (78% decrease) levels.

In summary, our data showed a high revision rate of the DePuy Synthes ASR™ XL Acetabular hip system. Our findings are consistent with internationally published data. In the absence of reliable predictors of early failure, continued close clinical surveillance and laboratory monitoring of these patients are warranted.

CONCLUSION

This study demonstrates the high failure rate of the DePuy Synthes ASR™ XL Acetabular hip system used in THA at a minimum of 5 years of follow-up. No variable that was predictive of failure could be identified in this series. Close clinical surveillance of these patients is therefore required. Metal levels dropped quickly after revision, and the revision surgery can generally be performed with slightly larger primary components. Symptomatic patients with ASR hip replacements, regardless of blood metal-ion levels, were candidates for the revision surgery. Not all failed hips exhibited substantially elevated metal levels. Asymptomatic patients with high blood metal-ion levels should be closely followed-up and revision surgery should be strongly considered, consistent with recently published guidelines.²⁰

ABSTRACT

The articular surface replacement (ASR) monoblock metal-on-metal acetabular component was recalled due to a higher than expected early failure rate. We evaluated the survivorship of the device and variables that may be predictive of failure at a minimum of 5-year follow-up. A single-center, single-surgeon retrospective review was conducted in patients who received the DePuy Synthes ASR™ XL Acetabular hip system from December 2005 to November 2009. Mean values and percentages were calculated and compared using the Fisher’s exact test, simple logistic regression, and Student’s t-test. The significance level was P ≤ .05. This study included 29 patients (24 males, 5 females) with 32 ASR™ XL acetabular hip systems. Mean age and body mass index (BMI) reached 55.2 years and 28.9 kg/m², respectively. Mean postoperative follow-up was 6.2 years. A total of 2 patients (6.9%) died of an unrelated cause and 1 patient was lost to follow-up (3.4%), leaving 26 patients with 28 hip replacements, all of whom were available for follow-up. The 5-year revision rate was 34.4% (10 patients with 11 hip replacements). Mean time to revision was 3.1 years. Age (P = .76), gender (P = .49), BMI (P = .29), acetabular component abduction angle (P = .12), and acetabulum size (P = .59) were not associated with the increased rate for hip failure. Blood cobalt (7.6 vs 6.8 µg/L, P = .58) and chromium (5.0 vs 2.2 µg/L, P = .31) levels were not significantly higher in the revised group when compared with those of the unrevised group. In the revised group, a 91% decrease in cobalt and 78% decrease in chromium levels were observed at a mean of 6 months following the revision. This study demonstrates a high rate of failure of ASR acetabular components used in total hip arthroplasty at a minimum of 5 years of follow-up. No variable that was predictive of failure could be identified in this series. Close clinical surveillance of these patients is required.

Continue to: Metal-on-metal...

Metal-on-metal (MoM) articulations have been widely explored as an alternative to polyethylene bearings in total hip arthroplasty (THA), with proposed benefits including improved range of motion, lower dislocation rates, and enhanced durability.¹ Comprising cobalt and chromium, these MoM bearings gained widespread popularity in the United States, particularly in younger and more active patients looking for longer lasting devices.

The articular surface replacement (ASR) acetabular system (DePuy Synthes) was approved for sale by the US Food and Drug Administration in 2003 and implanted in an estimated 93,000 cases.² Since then, however, the early failure rate of the prosthesis has been well documented,^3-5 leading to a formal global product recall in August 2010. The Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) was amongst the first to report a 6.4% rate of failure of the device at 3 years when inserted with a Corail stem.⁶ An acceptable upper rate of hip prosthesis failure is considered to reach 1% per year, with the majority of implants reporting well below this value. A 10.9% failure rate at 5 years was documented when the prosthesis was inserted for resurfacing. The National Joint Registry of England and Wales confirmed these findings and observed a 13% and 12% rate of failure at 5 years for the acetabular and resurfacing systems, respectively.² With the notable failure of the ASR system, this study reports our single-center 5-year survivorship experience and evaluates any variable that might be predictive of an early failure to aid in patient counseling.

METHODS

A single-center, single-surgeon, retrospective review of a consecutive series of patients was performed from December 2005 to November 2009. This study included all patients who underwent a primary THA with a DePuy Synthes ASR™ XL Acetabular hip system. No patients were excluded. Institutional Review Board approval was obtained. Patient demographics comprising of age, gender, and body mass index (BMI) were recorded. The primary endpoint of this study was 5-year survivorship rates. Secondary endpoints included duration to revision surgery, blood cobalt and chromium levels, time interval of blood ion tests, acetabulum size, acetabular component abduction angle, and duration to follow-up.

Candidates for the ASR™ XL Acetabular hip system included young patients and/or those considered to be physically active. In a select few, ASR devices were implanted upon patient request.

All patients underwent primary total hip replacement with a DePuy Synthes ASR™ XL uncemented acetabular component and an uncemented femoral stem (DePuy Synthes, Summit, or Tri-Lock) inserted via a standard posterior approach (Figure 1). Acetabulum sizes ranged from 52 mm to 68 mm in diameter.

All patients were followed-up yearly in the outpatient setting. Routine (yearly) metal-ion level sampling (whole blood) was started in 2010 for all patients. Laboratory tests were conducted at a single laboratory (Lab Corp.). Abduction cup inclination angles were measured by the providing surgeon using digital radiology software (GE Centricity systems).

The Student’s t-test was used to compare mean values (such as age, BMI, and metal ion levels) between the failure and no-failure groups. The 2-sided Fisher’s exact test analyzed differences in gender. Simple logistic regression analyzed variables associated with the failure group. Significance was P ≤ .05.

Continue to: Results...

RESULTS

A total of 29 patients (24 males, 5 females) with 32 ASR hip replacements were included in this study. Indications for surgery comprised osteoarthritis (28 hips, 87.5%) and avascular necrosis of the hip (4 hips, 12.5%). Mean age and BMI were 55.2 years and 28.9 kg/m², respectively. A total of 2 patients (6.9%) died of an unrelated cause (1 myocardial infarct, 1 suicide), and 1 patient was lost to follow-up (3.4%), leaving 26 patients with 28 hip replacements, all of whom finished a 5-year minimum follow-up.

No implant failures were noted in the first year. The 5-year revision rate reached 34.4% (10 patients with 11 hip replacements). Mean time to revision for this subgroup was 3.1 years. Overall, an implant failure was observed in 37.5% of patients (11 patients with 12 hip replacements) at a mean postoperative follow-up of 6.2 years (Figure 2). Indications for implant revision were pain in 11 (92.7%) cases and infection in 1 (8.3%).

Of the 11 hips revised due to pain, 9 were performed by the original surgeon (8 were completed with primary acetabular components, 1 with a revision shell). Figure 3 shows a bilateral revision performed with primary acetabular components and retained DePuy Synthes Pinnacle femoral stems. In all these cases except 1, the ASR component was grossly loose. One case presented with pseudotumor and impingement between the femoral prosthetic neck and acetabular component after migration of a loose component. After revision, the patient returned with substantial anterior hip pain and heterotopic ossification, and failed conservative treatment, requiring another surgery with prosthesis retention, removal of heterotopic ossification, and iliopsoas lengthening. The surgery successfully relieved the symptoms. No other patients required additional surgery after their revision. In comparison to the original ASR component, the revision shell was 2 to 4 mm larger in diameter. No patient required component revision at a mean of 2.9 years after the revision surgery.

The patient with secondary revision developed a hematogenous streptococcal infection after a dental procedure performed without prophylactic antibiotics. The patient was initially lost to follow-up after the primary surgery and reported no antecedent pain prior to the revision. A substantial metal fluid collection was identified in the hip at the time of débridement and without component loosening. After débridement, the patient developed persistent metal stained wound drainage, necessitating ultimate successful treatment with a 2-stage exchange procedure.

Age (P = .76), gender (P = .49), BMI (P = .29), acetabular component abduction angle (P = .12), and acetabulum size (P = .59) were not associated with an increased rate for hip failure (Table). Blood cobalt (7.6 vs 6.8 µg/L, P = .58) and chromium (5.0 vs 2.2 µg/L, P = .31) levels were not significantly higher in the revised group when compared with those of the unrevised group. The upper limits of blood cobalt and chromium levels reached 18.9 and 15.9 µg/L for the revised group and 16.8 and 5.4 µg/L for the non-revised group, respectively. In the revised group, a 91% decrease in cobalt and 78% decrease in chromium levels were observed at a mean of 6 months after the revision (Figure 4).

Table. Variables Not Associated with Early ASR Failure

Continue to: Discussion...

DISCUSSION

According to the Center for Disease Control and Prevention, 310,800 total hip replacements were performed among inpatients aged 45 years and older in the US in 2010.⁷ Specifically, in the 55- to 64-year-old age group, the number of procedures performed tripled from 2000 through 2010. As younger and more active patients opt for hip replacements, a growing need for prosthesis with enhanced durability is observed.

Despite the early proposed advantages of large head MoM bearings, our retrospective study of the DePuy Synthes ASR™ XL Acetabular hip system yielded 15.6% and 34.4% failure rates at 3 and 5 years, respectively. These higher-than-expected rates of failure are consistent with published data. The British Hip Society reported a 21% to 35% revision rate at 4 years and 49% at 6 years for the ASR XL prosthesis.⁸ In comparison, other MoM prosthesis, on average, report a 12% to 15% rate of failure at 5 years.

Considerable controversy surrounds the causes of adverse wear failure in MoM bearings.^9,10 The non-modular design of the ASR prostheses is frequently implicated as a cause of early failure. The lack of a central hole in the 1-piece component compromises the tactile feel of insertion, thereby reducing the surgeon’s ability to assess complete seating.¹¹ This condition may potentially increase the abduction angle at the time of insertion. Screw fixation of the non-modular device is not possible. The ASR XL device (148^° to 160^°) is less than a hemisphere (180^°) in size and hence features a diminished functional articular surface, further compromising implant fixation.¹¹ The functional articular surface is defined as the optimal surface area (10 mm) needed for a MoM implant.¹² Griffin and colleagues¹³ reported a 48 mm ASR XL component, when implanted at 45^° of abduction, to function similar to an implant at 59^° of abduction, leading to diminished lubrication, metallosis, and edge loading. The version of the acetabular component may similarly and adversely affect implant wear characteristics. Furthermore, the variable thickness of the implant, which is thicker at the dome and thinner at the rim, may further promote edge loading by shifting the center of rotation of the femoral head out from the center of the acetabular prosthesis.¹¹ Studies have also shown that increased wear of the MoM articulation is associated with an acetabular component inclination angle in excess of 55^°10,14 and a failure of fixation at time of implantation.¹⁵ This study, however, found no correlation between the abduction angle and risk of early implant failure for the ASR acetabular component. No correlation was also detected between the acetabulum size and revision surgery.

The AOANJRR reported loosening (44%), infection (20%), metal sensitivity (12%), fracture (9%), and dislocation of prosthesis (7%) as the indications for revision surgery for the ASR prosthesis.⁶ Furthermore, a single-center retrospective review of 70 consecutive MoM THAs with ultra-large diameter femoral head and monoblock acetabular components showed that 17.1% required revision within 3 years for loosening, pain, and squeaking.¹ Overall, 28.6% of patients reported implant dysfunction. In this study, we observed a similar rate of failure at 3 years (15.6%) for pain (11) and infection (1). The revision surgery successfully relieved all of these symptoms. One patient presented with heterotopic ossification and anterior hip pain after the original revision and required additional surgery with prosthesis retention. No patient in this series required repeat component revisions at a mean of 2.9 years after surgery. In all but 1 case, primary acetabular components were used in the revision, and in all cases except that with infection, the femoral component was retained. Replacement shells were 2 to 4 mm larger in diameter than the original ASR component.

Recently, concerns have arisen regarding the long-term effects of serum cobalt and chromium metal ions levels. Studies have shown increased serum metal ion levels,¹⁵ groin pain,¹⁶ pseudotumor formation,¹⁷ and metallosis¹⁸ after the implantation of MoM bearings. In a case study by Mao and colleagues,¹⁹ 1 patient reported headaches, anorexia, continuous metallic taste in her mouth, and weight loss. A cerebrospinal fluid analysis revealed cobalt and chromium levels at 9 and 13 nmol/L, respectively, indicating that these metal ions can cross the blood-brain barrier. Another patient reported painful muscle fatigue, night cramps, fainting spells, cognitive decline, and an inability to climb stairs. His serum cobalt level reached 258 nmol/L (reference range, 0-20 nmol/L), and chromium level totaled 88 nmol/L (reference range, 0-100 nmol/L). At 8-week follow-up after revision surgery, the symptoms of the patient had resolved, with serum cobalt levels dropping to 42 nmol/L.¹⁹ None of the patients in this study presented with any signs or symptoms of metal toxicity. The upper limits of blood cobalt and chromium levels in our study population reached 18.9 and 15.9 µg/L for the revised group and 16.8 and 5.4 µg/L for the non-revised group, respectively. However, we noted a similar drop in post-revision blood cobalt (91% decrease) and chromium (78% decrease) levels.

In summary, our data showed a high revision rate of the DePuy Synthes ASR™ XL Acetabular hip system. Our findings are consistent with internationally published data. In the absence of reliable predictors of early failure, continued close clinical surveillance and laboratory monitoring of these patients are warranted.

CONCLUSION

This study demonstrates the high failure rate of the DePuy Synthes ASR™ XL Acetabular hip system used in THA at a minimum of 5 years of follow-up. No variable that was predictive of failure could be identified in this series. Close clinical surveillance of these patients is therefore required. Metal levels dropped quickly after revision, and the revision surgery can generally be performed with slightly larger primary components. Symptomatic patients with ASR hip replacements, regardless of blood metal-ion levels, were candidates for the revision surgery. Not all failed hips exhibited substantially elevated metal levels. Asymptomatic patients with high blood metal-ion levels should be closely followed-up and revision surgery should be strongly considered, consistent with recently published guidelines.²⁰

ABSTRACT

The articular surface replacement (ASR) monoblock metal-on-metal acetabular component was recalled due to a higher than expected early failure rate. We evaluated the survivorship of the device and variables that may be predictive of failure at a minimum of 5-year follow-up. A single-center, single-surgeon retrospective review was conducted in patients who received the DePuy Synthes ASR™ XL Acetabular hip system from December 2005 to November 2009. Mean values and percentages were calculated and compared using the Fisher’s exact test, simple logistic regression, and Student’s t-test. The significance level was P ≤ .05. This study included 29 patients (24 males, 5 females) with 32 ASR™ XL acetabular hip systems. Mean age and body mass index (BMI) reached 55.2 years and 28.9 kg/m², respectively. Mean postoperative follow-up was 6.2 years. A total of 2 patients (6.9%) died of an unrelated cause and 1 patient was lost to follow-up (3.4%), leaving 26 patients with 28 hip replacements, all of whom were available for follow-up. The 5-year revision rate was 34.4% (10 patients with 11 hip replacements). Mean time to revision was 3.1 years. Age (P = .76), gender (P = .49), BMI (P = .29), acetabular component abduction angle (P = .12), and acetabulum size (P = .59) were not associated with the increased rate for hip failure. Blood cobalt (7.6 vs 6.8 µg/L, P = .58) and chromium (5.0 vs 2.2 µg/L, P = .31) levels were not significantly higher in the revised group when compared with those of the unrevised group. In the revised group, a 91% decrease in cobalt and 78% decrease in chromium levels were observed at a mean of 6 months following the revision. This study demonstrates a high rate of failure of ASR acetabular components used in total hip arthroplasty at a minimum of 5 years of follow-up. No variable that was predictive of failure could be identified in this series. Close clinical surveillance of these patients is required.

Continue to: Metal-on-metal...

Metal-on-metal (MoM) articulations have been widely explored as an alternative to polyethylene bearings in total hip arthroplasty (THA), with proposed benefits including improved range of motion, lower dislocation rates, and enhanced durability.¹ Comprising cobalt and chromium, these MoM bearings gained widespread popularity in the United States, particularly in younger and more active patients looking for longer lasting devices.

The articular surface replacement (ASR) acetabular system (DePuy Synthes) was approved for sale by the US Food and Drug Administration in 2003 and implanted in an estimated 93,000 cases.² Since then, however, the early failure rate of the prosthesis has been well documented,^3-5 leading to a formal global product recall in August 2010. The Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) was amongst the first to report a 6.4% rate of failure of the device at 3 years when inserted with a Corail stem.⁶ An acceptable upper rate of hip prosthesis failure is considered to reach 1% per year, with the majority of implants reporting well below this value. A 10.9% failure rate at 5 years was documented when the prosthesis was inserted for resurfacing. The National Joint Registry of England and Wales confirmed these findings and observed a 13% and 12% rate of failure at 5 years for the acetabular and resurfacing systems, respectively.² With the notable failure of the ASR system, this study reports our single-center 5-year survivorship experience and evaluates any variable that might be predictive of an early failure to aid in patient counseling.

METHODS

A single-center, single-surgeon, retrospective review of a consecutive series of patients was performed from December 2005 to November 2009. This study included all patients who underwent a primary THA with a DePuy Synthes ASR™ XL Acetabular hip system. No patients were excluded. Institutional Review Board approval was obtained. Patient demographics comprising of age, gender, and body mass index (BMI) were recorded. The primary endpoint of this study was 5-year survivorship rates. Secondary endpoints included duration to revision surgery, blood cobalt and chromium levels, time interval of blood ion tests, acetabulum size, acetabular component abduction angle, and duration to follow-up.

Candidates for the ASR™ XL Acetabular hip system included young patients and/or those considered to be physically active. In a select few, ASR devices were implanted upon patient request.

All patients underwent primary total hip replacement with a DePuy Synthes ASR™ XL uncemented acetabular component and an uncemented femoral stem (DePuy Synthes, Summit, or Tri-Lock) inserted via a standard posterior approach (Figure 1). Acetabulum sizes ranged from 52 mm to 68 mm in diameter.

All patients were followed-up yearly in the outpatient setting. Routine (yearly) metal-ion level sampling (whole blood) was started in 2010 for all patients. Laboratory tests were conducted at a single laboratory (Lab Corp.). Abduction cup inclination angles were measured by the providing surgeon using digital radiology software (GE Centricity systems).

The Student’s t-test was used to compare mean values (such as age, BMI, and metal ion levels) between the failure and no-failure groups. The 2-sided Fisher’s exact test analyzed differences in gender. Simple logistic regression analyzed variables associated with the failure group. Significance was P ≤ .05.

Continue to: Results...

RESULTS

A total of 29 patients (24 males, 5 females) with 32 ASR hip replacements were included in this study. Indications for surgery comprised osteoarthritis (28 hips, 87.5%) and avascular necrosis of the hip (4 hips, 12.5%). Mean age and BMI were 55.2 years and 28.9 kg/m², respectively. A total of 2 patients (6.9%) died of an unrelated cause (1 myocardial infarct, 1 suicide), and 1 patient was lost to follow-up (3.4%), leaving 26 patients with 28 hip replacements, all of whom finished a 5-year minimum follow-up.

No implant failures were noted in the first year. The 5-year revision rate reached 34.4% (10 patients with 11 hip replacements). Mean time to revision for this subgroup was 3.1 years. Overall, an implant failure was observed in 37.5% of patients (11 patients with 12 hip replacements) at a mean postoperative follow-up of 6.2 years (Figure 2). Indications for implant revision were pain in 11 (92.7%) cases and infection in 1 (8.3%).

Of the 11 hips revised due to pain, 9 were performed by the original surgeon (8 were completed with primary acetabular components, 1 with a revision shell). Figure 3 shows a bilateral revision performed with primary acetabular components and retained DePuy Synthes Pinnacle femoral stems. In all these cases except 1, the ASR component was grossly loose. One case presented with pseudotumor and impingement between the femoral prosthetic neck and acetabular component after migration of a loose component. After revision, the patient returned with substantial anterior hip pain and heterotopic ossification, and failed conservative treatment, requiring another surgery with prosthesis retention, removal of heterotopic ossification, and iliopsoas lengthening. The surgery successfully relieved the symptoms. No other patients required additional surgery after their revision. In comparison to the original ASR component, the revision shell was 2 to 4 mm larger in diameter. No patient required component revision at a mean of 2.9 years after the revision surgery.

The patient with secondary revision developed a hematogenous streptococcal infection after a dental procedure performed without prophylactic antibiotics. The patient was initially lost to follow-up after the primary surgery and reported no antecedent pain prior to the revision. A substantial metal fluid collection was identified in the hip at the time of débridement and without component loosening. After débridement, the patient developed persistent metal stained wound drainage, necessitating ultimate successful treatment with a 2-stage exchange procedure.

Age (P = .76), gender (P = .49), BMI (P = .29), acetabular component abduction angle (P = .12), and acetabulum size (P = .59) were not associated with an increased rate for hip failure (Table). Blood cobalt (7.6 vs 6.8 µg/L, P = .58) and chromium (5.0 vs 2.2 µg/L, P = .31) levels were not significantly higher in the revised group when compared with those of the unrevised group. The upper limits of blood cobalt and chromium levels reached 18.9 and 15.9 µg/L for the revised group and 16.8 and 5.4 µg/L for the non-revised group, respectively. In the revised group, a 91% decrease in cobalt and 78% decrease in chromium levels were observed at a mean of 6 months after the revision (Figure 4).

Table. Variables Not Associated with Early ASR Failure

Continue to: Discussion...

DISCUSSION

According to the Center for Disease Control and Prevention, 310,800 total hip replacements were performed among inpatients aged 45 years and older in the US in 2010.⁷ Specifically, in the 55- to 64-year-old age group, the number of procedures performed tripled from 2000 through 2010. As younger and more active patients opt for hip replacements, a growing need for prosthesis with enhanced durability is observed.

Despite the early proposed advantages of large head MoM bearings, our retrospective study of the DePuy Synthes ASR™ XL Acetabular hip system yielded 15.6% and 34.4% failure rates at 3 and 5 years, respectively. These higher-than-expected rates of failure are consistent with published data. The British Hip Society reported a 21% to 35% revision rate at 4 years and 49% at 6 years for the ASR XL prosthesis.⁸ In comparison, other MoM prosthesis, on average, report a 12% to 15% rate of failure at 5 years.

Considerable controversy surrounds the causes of adverse wear failure in MoM bearings.^9,10 The non-modular design of the ASR prostheses is frequently implicated as a cause of early failure. The lack of a central hole in the 1-piece component compromises the tactile feel of insertion, thereby reducing the surgeon’s ability to assess complete seating.¹¹ This condition may potentially increase the abduction angle at the time of insertion. Screw fixation of the non-modular device is not possible. The ASR XL device (148^° to 160^°) is less than a hemisphere (180^°) in size and hence features a diminished functional articular surface, further compromising implant fixation.¹¹ The functional articular surface is defined as the optimal surface area (10 mm) needed for a MoM implant.¹² Griffin and colleagues¹³ reported a 48 mm ASR XL component, when implanted at 45^° of abduction, to function similar to an implant at 59^° of abduction, leading to diminished lubrication, metallosis, and edge loading. The version of the acetabular component may similarly and adversely affect implant wear characteristics. Furthermore, the variable thickness of the implant, which is thicker at the dome and thinner at the rim, may further promote edge loading by shifting the center of rotation of the femoral head out from the center of the acetabular prosthesis.¹¹ Studies have also shown that increased wear of the MoM articulation is associated with an acetabular component inclination angle in excess of 55^°10,14 and a failure of fixation at time of implantation.¹⁵ This study, however, found no correlation between the abduction angle and risk of early implant failure for the ASR acetabular component. No correlation was also detected between the acetabulum size and revision surgery.

The AOANJRR reported loosening (44%), infection (20%), metal sensitivity (12%), fracture (9%), and dislocation of prosthesis (7%) as the indications for revision surgery for the ASR prosthesis.⁶ Furthermore, a single-center retrospective review of 70 consecutive MoM THAs with ultra-large diameter femoral head and monoblock acetabular components showed that 17.1% required revision within 3 years for loosening, pain, and squeaking.¹ Overall, 28.6% of patients reported implant dysfunction. In this study, we observed a similar rate of failure at 3 years (15.6%) for pain (11) and infection (1). The revision surgery successfully relieved all of these symptoms. One patient presented with heterotopic ossification and anterior hip pain after the original revision and required additional surgery with prosthesis retention. No patient in this series required repeat component revisions at a mean of 2.9 years after surgery. In all but 1 case, primary acetabular components were used in the revision, and in all cases except that with infection, the femoral component was retained. Replacement shells were 2 to 4 mm larger in diameter than the original ASR component.

Recently, concerns have arisen regarding the long-term effects of serum cobalt and chromium metal ions levels. Studies have shown increased serum metal ion levels,¹⁵ groin pain,¹⁶ pseudotumor formation,¹⁷ and metallosis¹⁸ after the implantation of MoM bearings. In a case study by Mao and colleagues,¹⁹ 1 patient reported headaches, anorexia, continuous metallic taste in her mouth, and weight loss. A cerebrospinal fluid analysis revealed cobalt and chromium levels at 9 and 13 nmol/L, respectively, indicating that these metal ions can cross the blood-brain barrier. Another patient reported painful muscle fatigue, night cramps, fainting spells, cognitive decline, and an inability to climb stairs. His serum cobalt level reached 258 nmol/L (reference range, 0-20 nmol/L), and chromium level totaled 88 nmol/L (reference range, 0-100 nmol/L). At 8-week follow-up after revision surgery, the symptoms of the patient had resolved, with serum cobalt levels dropping to 42 nmol/L.¹⁹ None of the patients in this study presented with any signs or symptoms of metal toxicity. The upper limits of blood cobalt and chromium levels in our study population reached 18.9 and 15.9 µg/L for the revised group and 16.8 and 5.4 µg/L for the non-revised group, respectively. However, we noted a similar drop in post-revision blood cobalt (91% decrease) and chromium (78% decrease) levels.

In summary, our data showed a high revision rate of the DePuy Synthes ASR™ XL Acetabular hip system. Our findings are consistent with internationally published data. In the absence of reliable predictors of early failure, continued close clinical surveillance and laboratory monitoring of these patients are warranted.

CONCLUSION

This study demonstrates the high failure rate of the DePuy Synthes ASR™ XL Acetabular hip system used in THA at a minimum of 5 years of follow-up. No variable that was predictive of failure could be identified in this series. Close clinical surveillance of these patients is therefore required. Metal levels dropped quickly after revision, and the revision surgery can generally be performed with slightly larger primary components. Symptomatic patients with ASR hip replacements, regardless of blood metal-ion levels, were candidates for the revision surgery. Not all failed hips exhibited substantially elevated metal levels. Asymptomatic patients with high blood metal-ion levels should be closely followed-up and revision surgery should be strongly considered, consistent with recently published guidelines.²⁰

BARCELONA – The immune checkpoint inhibitor pembrolizumab (Keytruda) did not significantly improve overall survival of advanced/metastatic gastric or gastroesophageal junction cancer compared with paclitaxel, the results of the KEYNOTE-061 study show.

Among 395 patients with gastric or gastroesophageal junction (GEJ) cancer who had expression of the programmed death ligand 1 (PD-L1) on 1% or more of their tumor cells, lymphocytes, and macrophages, median overall survival (OS) for patients treated with pembrolizumab was 9.1 months, compared with 8.3 months. This translated into a hazard ratio (HR) for death in the pembrolizumab arm of 0.82, but with the 95% confidence interval crossing 1.00, and a P value (.04205) that did not meet the prespecified threshold for significance (P equal to or less than .0135).

Neil Osterweil/MDedge News

Neil Osterweil/MDedge News

SOURCE: Shitara K. et al. ESMO World Congress on Gastrointestinal Cancer 2018. Abstract LBA-005.

BARCELONA – The immune checkpoint inhibitor pembrolizumab (Keytruda) did not significantly improve overall survival of advanced/metastatic gastric or gastroesophageal junction cancer compared with paclitaxel, the results of the KEYNOTE-061 study show.

Among 395 patients with gastric or gastroesophageal junction (GEJ) cancer who had expression of the programmed death ligand 1 (PD-L1) on 1% or more of their tumor cells, lymphocytes, and macrophages, median overall survival (OS) for patients treated with pembrolizumab was 9.1 months, compared with 8.3 months. This translated into a hazard ratio (HR) for death in the pembrolizumab arm of 0.82, but with the 95% confidence interval crossing 1.00, and a P value (.04205) that did not meet the prespecified threshold for significance (P equal to or less than .0135).

Neil Osterweil/MDedge News

Neil Osterweil/MDedge News

SOURCE: Shitara K. et al. ESMO World Congress on Gastrointestinal Cancer 2018. Abstract LBA-005.

BARCELONA – The immune checkpoint inhibitor pembrolizumab (Keytruda) did not significantly improve overall survival of advanced/metastatic gastric or gastroesophageal junction cancer compared with paclitaxel, the results of the KEYNOTE-061 study show.

Among 395 patients with gastric or gastroesophageal junction (GEJ) cancer who had expression of the programmed death ligand 1 (PD-L1) on 1% or more of their tumor cells, lymphocytes, and macrophages, median overall survival (OS) for patients treated with pembrolizumab was 9.1 months, compared with 8.3 months. This translated into a hazard ratio (HR) for death in the pembrolizumab arm of 0.82, but with the 95% confidence interval crossing 1.00, and a P value (.04205) that did not meet the prespecified threshold for significance (P equal to or less than .0135).

Neil Osterweil/MDedge News

Neil Osterweil/MDedge News

SOURCE: Shitara K. et al. ESMO World Congress on Gastrointestinal Cancer 2018. Abstract LBA-005.

BARCELONA – For patients with hepatocellular carcinoma (HCC) with elevated alpha-fetoprotein (AFP) levels who have disease progression following first-line sorafenib (Nexavar), the antiangiogenic agent ramucirumab was associated with a modest but significant improvement in overall survival, compared with placebo, a pooled analysis of clinical trial data showed.

Among 316 patients assigned to receive ramucirumab in the phase 3 REACH and REACH-2 trials, median overall survival was 8.1 months, compared with 5.0 months for placebo, an absolute difference of 3.1 months that translated into a hazard ratio favoring ramucirumab of 0.694 (P = .0002), reported Andrew X. Zhu, MD, PhD of the Massachusetts General Hospital Cancer Center in Boston.

Neil Osterweil/MDedge News

SOURCE: Zhu AX et al. ESMO GI 2018, Abstract LBA-001.

BARCELONA – For patients with hepatocellular carcinoma (HCC) with elevated alpha-fetoprotein (AFP) levels who have disease progression following first-line sorafenib (Nexavar), the antiangiogenic agent ramucirumab was associated with a modest but significant improvement in overall survival, compared with placebo, a pooled analysis of clinical trial data showed.

Among 316 patients assigned to receive ramucirumab in the phase 3 REACH and REACH-2 trials, median overall survival was 8.1 months, compared with 5.0 months for placebo, an absolute difference of 3.1 months that translated into a hazard ratio favoring ramucirumab of 0.694 (P = .0002), reported Andrew X. Zhu, MD, PhD of the Massachusetts General Hospital Cancer Center in Boston.

Neil Osterweil/MDedge News

SOURCE: Zhu AX et al. ESMO GI 2018, Abstract LBA-001.

BARCELONA – For patients with hepatocellular carcinoma (HCC) with elevated alpha-fetoprotein (AFP) levels who have disease progression following first-line sorafenib (Nexavar), the antiangiogenic agent ramucirumab was associated with a modest but significant improvement in overall survival, compared with placebo, a pooled analysis of clinical trial data showed.

Among 316 patients assigned to receive ramucirumab in the phase 3 REACH and REACH-2 trials, median overall survival was 8.1 months, compared with 5.0 months for placebo, an absolute difference of 3.1 months that translated into a hazard ratio favoring ramucirumab of 0.694 (P = .0002), reported Andrew X. Zhu, MD, PhD of the Massachusetts General Hospital Cancer Center in Boston.

Neil Osterweil/MDedge News

SOURCE: Zhu AX et al. ESMO GI 2018, Abstract LBA-001.