User login
VIDEO: In 2018, the AGA Center for GI Innovation and Technology is going strong
BOSTON – The AGA Center for GI Innovation and Technology (CGIT) was founded 9 years ago to foster innovation in GI disease, according to Sri Komanduri, MD, AGAF, and V. Raman Muthusamy, MD, the current cochairs. The mandate is still the same, with the idea that CGIT will continue to provide support and resources to a wide variety of stakeholders throughout the daunting process of getting a new technology or product through funding and approval to reimbursement and adoption. Dr. Komanduri, the medical director of the GI laboratory and director of interventional endoscopy at Northwestern University in Chicago, emphasized the need to support the entire process from idea to adoption as a continuum that should not be handled by different silos – CGIT should be there every step of the way.
CGIT will concentrate on six main areas now, although Dr. Muthusamy, director of interventional endoscopy and general GI endoscopy at the University of California, Los Angeles, said in a video interview that they are flexible enough to work with any GI-applicable technology that will help practicing clinicians. These six areas are endoscopy for bariatric treatments, endoscopy for resection in place of surgery, endoscope reprocessing, interventional endoscopy, endoscopic reflux technology, and endoscopic diagnostic colorectal advances.
BOSTON – The AGA Center for GI Innovation and Technology (CGIT) was founded 9 years ago to foster innovation in GI disease, according to Sri Komanduri, MD, AGAF, and V. Raman Muthusamy, MD, the current cochairs. The mandate is still the same, with the idea that CGIT will continue to provide support and resources to a wide variety of stakeholders throughout the daunting process of getting a new technology or product through funding and approval to reimbursement and adoption. Dr. Komanduri, the medical director of the GI laboratory and director of interventional endoscopy at Northwestern University in Chicago, emphasized the need to support the entire process from idea to adoption as a continuum that should not be handled by different silos – CGIT should be there every step of the way.
CGIT will concentrate on six main areas now, although Dr. Muthusamy, director of interventional endoscopy and general GI endoscopy at the University of California, Los Angeles, said in a video interview that they are flexible enough to work with any GI-applicable technology that will help practicing clinicians. These six areas are endoscopy for bariatric treatments, endoscopy for resection in place of surgery, endoscope reprocessing, interventional endoscopy, endoscopic reflux technology, and endoscopic diagnostic colorectal advances.
BOSTON – The AGA Center for GI Innovation and Technology (CGIT) was founded 9 years ago to foster innovation in GI disease, according to Sri Komanduri, MD, AGAF, and V. Raman Muthusamy, MD, the current cochairs. The mandate is still the same, with the idea that CGIT will continue to provide support and resources to a wide variety of stakeholders throughout the daunting process of getting a new technology or product through funding and approval to reimbursement and adoption. Dr. Komanduri, the medical director of the GI laboratory and director of interventional endoscopy at Northwestern University in Chicago, emphasized the need to support the entire process from idea to adoption as a continuum that should not be handled by different silos – CGIT should be there every step of the way.
CGIT will concentrate on six main areas now, although Dr. Muthusamy, director of interventional endoscopy and general GI endoscopy at the University of California, Los Angeles, said in a video interview that they are flexible enough to work with any GI-applicable technology that will help practicing clinicians. These six areas are endoscopy for bariatric treatments, endoscopy for resection in place of surgery, endoscope reprocessing, interventional endoscopy, endoscopic reflux technology, and endoscopic diagnostic colorectal advances.
FROM THE 2018 AGA TECH SUMMIT
VIDEO: It’s all about improving the patient experience
BOSTON – “When I assess a new technology,” said V. Raman Muthusamy, MD, chair of the AGA Center for GI Innovation and Technology (CGIT), “I look for three things” – it should allow us to do something we couldn’t do before, give better outcomes and/or do the procedure less invasively, or provide cost savings. Ideally, he said during an interview at the AGA Tech Summit, it should do all three. Dr. Muthusamy, director of interventional endoscopy and general GI endoscopy at the University of California, Los Angeles, said one of the goals of the CGIT is to keep physicians up to date on new technologies, but he recommends all physicians assess the data on new technologies and weigh the advantages before incorporating a new device into their practice. Better diagnostic tools and novel therapeutics should improve the patient experience.
BOSTON – “When I assess a new technology,” said V. Raman Muthusamy, MD, chair of the AGA Center for GI Innovation and Technology (CGIT), “I look for three things” – it should allow us to do something we couldn’t do before, give better outcomes and/or do the procedure less invasively, or provide cost savings. Ideally, he said during an interview at the AGA Tech Summit, it should do all three. Dr. Muthusamy, director of interventional endoscopy and general GI endoscopy at the University of California, Los Angeles, said one of the goals of the CGIT is to keep physicians up to date on new technologies, but he recommends all physicians assess the data on new technologies and weigh the advantages before incorporating a new device into their practice. Better diagnostic tools and novel therapeutics should improve the patient experience.
BOSTON – “When I assess a new technology,” said V. Raman Muthusamy, MD, chair of the AGA Center for GI Innovation and Technology (CGIT), “I look for three things” – it should allow us to do something we couldn’t do before, give better outcomes and/or do the procedure less invasively, or provide cost savings. Ideally, he said during an interview at the AGA Tech Summit, it should do all three. Dr. Muthusamy, director of interventional endoscopy and general GI endoscopy at the University of California, Los Angeles, said one of the goals of the CGIT is to keep physicians up to date on new technologies, but he recommends all physicians assess the data on new technologies and weigh the advantages before incorporating a new device into their practice. Better diagnostic tools and novel therapeutics should improve the patient experience.
FROM THE 2018 AGA TECH SUMMIT
VIDEO: Women living with HIV have more myocardial steatosis, reduced diastolic function
CHICAGO – Median intramyocardial triglyceride content was nearly four times higher in a group of middle-age women living with HIV, compared with peers without the infection, according to a recent study that also found an association between high myocardial lipids and lower diastolic function.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
For women without HIV, the value was 0.13% (95% CI, 0.11-0.23; P = .004). Further, left atrial passive ejection fraction was significantly lower among women living with HIV, compared with those without HIV (28% vs. 38%, P = .02), said Mabel Toribio, MD, speaking at the annual meeting of the Endocrine Society.
“Probably the most important aspect is that we found an inverse relationship between the intramyocardial triglyceride content and the diastolic function; the higher the intracardiac lipid content of the women living with HIV, the worse their cardiac function,” Dr. Toribio said in an interview. She and her colleagues at Massachusetts General Hospital, Boston, where she is a clinical investigator, found a Spearman’s rank coefficient of –0.51 for the correlation (P = .03)
“The reason that this is important is that individuals with HIV do have an increased risk of heart failure,” said Dr. Toribio. People living with HIV have a hazard ratio for heart failure that ranges from about 1.2 to 1.7, she said.
For women living with HIV with heart failure, about 70% have heart failure with preserved ejection fraction (HFpEF), which is associated with diastolic dysfunction. “In women with HIV, this has been relatively understudied, and one of the mechanisms we were looking into is myocardial steatosis, where we have increased intramyocardial lipid content,” said Dr. Toribio.
“I think, certainly, our work has a lot of clinical implications,” said Dr. Toribio, noting that there are no therapies that improve survival after a diagnosis of HFpEF. In a population with increased rates of diastolic dysfunction, “It’s imperative that we understand the mechanism of this disease process in women living with HIV,” she said.
Intramyocardial lipid content was a reasonable line of inquiry, since it’s known that people living with HIV have increased deposition of fat in various organ systems, including the liver, skeletal muscle, and the heart, said Dr. Toribio. Both HIV and antiretroviral therapy can contribute to ectopic fat deposition, she said.
Women with (n = 18) and without (n = 6) HIV were matched according to age, body mass index (BMI), history of hypertension, and smoking status, said Dr. Toribio. For women with HIV, they had to be on stable antiretroviral therapy for at least 3 months and have no interruption in therapy greater than 2 weeks over the 3 months preceding enrollment.
The study excluded women who had known preexisting heart failure, diabetes, or atherosclerotic cardiovascular disease. Participants also could not be taking lipid-lowering agents or anti-inflammatory medications.
Participants were about 52 years old on average, and had a mean BMI of a little over 30 kg/m2. Lipid values did not differ significantly between groups, except that triglycerides were a mean 107 mg/dL in women living with HIV, compared with 69 mg/dL for women without HIV (P = .01).
Of the women living with HIV, 7/18 (38.5%) were white, the same number were black, and 2 were Hispanic. Three of six women without HIV were white, two were black, and one was Hispanic; racial and ethnic differences between the groups were not statistically significant overall.
Magnetic resonance spectroscopy was used to assess intramyocardial triglyceride levels, measured at the interventricular septum, a region where there’s little overlying pericardial fat.
“We found that the women living with HIV have an increased intramyocardial triglyceride content compared to women without HIV. And notably, we sought to see if there was any relationship between circulating triglyceride levels or body mass index, and there actually was no relationship between intramyocardial triglyceride content and these factors,” said Dr. Toribio in a video interview.
Next steps include two studies, said Dr. Toribio. The first is investigating whether statin therapy improves myocardial steatosis and heart function over time in women living with HIV. The second, involving the same population, is a pilot study to see if growth hormone releasing hormone – which is known to lessen visceral adiposity in people living with HIV – can reduce intramyocardial steatosis and boost cardiac function, she said.
Dr. Toribio reported no financial disclosures. The study was supported by funding from the National Institutes of Health.
SOURCE: Toribio M et al. ENDO 2018, Abstract OR11-2.
CHICAGO – Median intramyocardial triglyceride content was nearly four times higher in a group of middle-age women living with HIV, compared with peers without the infection, according to a recent study that also found an association between high myocardial lipids and lower diastolic function.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
For women without HIV, the value was 0.13% (95% CI, 0.11-0.23; P = .004). Further, left atrial passive ejection fraction was significantly lower among women living with HIV, compared with those without HIV (28% vs. 38%, P = .02), said Mabel Toribio, MD, speaking at the annual meeting of the Endocrine Society.
“Probably the most important aspect is that we found an inverse relationship between the intramyocardial triglyceride content and the diastolic function; the higher the intracardiac lipid content of the women living with HIV, the worse their cardiac function,” Dr. Toribio said in an interview. She and her colleagues at Massachusetts General Hospital, Boston, where she is a clinical investigator, found a Spearman’s rank coefficient of –0.51 for the correlation (P = .03)
“The reason that this is important is that individuals with HIV do have an increased risk of heart failure,” said Dr. Toribio. People living with HIV have a hazard ratio for heart failure that ranges from about 1.2 to 1.7, she said.
For women living with HIV with heart failure, about 70% have heart failure with preserved ejection fraction (HFpEF), which is associated with diastolic dysfunction. “In women with HIV, this has been relatively understudied, and one of the mechanisms we were looking into is myocardial steatosis, where we have increased intramyocardial lipid content,” said Dr. Toribio.
“I think, certainly, our work has a lot of clinical implications,” said Dr. Toribio, noting that there are no therapies that improve survival after a diagnosis of HFpEF. In a population with increased rates of diastolic dysfunction, “It’s imperative that we understand the mechanism of this disease process in women living with HIV,” she said.
Intramyocardial lipid content was a reasonable line of inquiry, since it’s known that people living with HIV have increased deposition of fat in various organ systems, including the liver, skeletal muscle, and the heart, said Dr. Toribio. Both HIV and antiretroviral therapy can contribute to ectopic fat deposition, she said.
Women with (n = 18) and without (n = 6) HIV were matched according to age, body mass index (BMI), history of hypertension, and smoking status, said Dr. Toribio. For women with HIV, they had to be on stable antiretroviral therapy for at least 3 months and have no interruption in therapy greater than 2 weeks over the 3 months preceding enrollment.
The study excluded women who had known preexisting heart failure, diabetes, or atherosclerotic cardiovascular disease. Participants also could not be taking lipid-lowering agents or anti-inflammatory medications.
Participants were about 52 years old on average, and had a mean BMI of a little over 30 kg/m2. Lipid values did not differ significantly between groups, except that triglycerides were a mean 107 mg/dL in women living with HIV, compared with 69 mg/dL for women without HIV (P = .01).
Of the women living with HIV, 7/18 (38.5%) were white, the same number were black, and 2 were Hispanic. Three of six women without HIV were white, two were black, and one was Hispanic; racial and ethnic differences between the groups were not statistically significant overall.
Magnetic resonance spectroscopy was used to assess intramyocardial triglyceride levels, measured at the interventricular septum, a region where there’s little overlying pericardial fat.
“We found that the women living with HIV have an increased intramyocardial triglyceride content compared to women without HIV. And notably, we sought to see if there was any relationship between circulating triglyceride levels or body mass index, and there actually was no relationship between intramyocardial triglyceride content and these factors,” said Dr. Toribio in a video interview.
Next steps include two studies, said Dr. Toribio. The first is investigating whether statin therapy improves myocardial steatosis and heart function over time in women living with HIV. The second, involving the same population, is a pilot study to see if growth hormone releasing hormone – which is known to lessen visceral adiposity in people living with HIV – can reduce intramyocardial steatosis and boost cardiac function, she said.
Dr. Toribio reported no financial disclosures. The study was supported by funding from the National Institutes of Health.
SOURCE: Toribio M et al. ENDO 2018, Abstract OR11-2.
CHICAGO – Median intramyocardial triglyceride content was nearly four times higher in a group of middle-age women living with HIV, compared with peers without the infection, according to a recent study that also found an association between high myocardial lipids and lower diastolic function.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
For women without HIV, the value was 0.13% (95% CI, 0.11-0.23; P = .004). Further, left atrial passive ejection fraction was significantly lower among women living with HIV, compared with those without HIV (28% vs. 38%, P = .02), said Mabel Toribio, MD, speaking at the annual meeting of the Endocrine Society.
“Probably the most important aspect is that we found an inverse relationship between the intramyocardial triglyceride content and the diastolic function; the higher the intracardiac lipid content of the women living with HIV, the worse their cardiac function,” Dr. Toribio said in an interview. She and her colleagues at Massachusetts General Hospital, Boston, where she is a clinical investigator, found a Spearman’s rank coefficient of –0.51 for the correlation (P = .03)
“The reason that this is important is that individuals with HIV do have an increased risk of heart failure,” said Dr. Toribio. People living with HIV have a hazard ratio for heart failure that ranges from about 1.2 to 1.7, she said.
For women living with HIV with heart failure, about 70% have heart failure with preserved ejection fraction (HFpEF), which is associated with diastolic dysfunction. “In women with HIV, this has been relatively understudied, and one of the mechanisms we were looking into is myocardial steatosis, where we have increased intramyocardial lipid content,” said Dr. Toribio.
“I think, certainly, our work has a lot of clinical implications,” said Dr. Toribio, noting that there are no therapies that improve survival after a diagnosis of HFpEF. In a population with increased rates of diastolic dysfunction, “It’s imperative that we understand the mechanism of this disease process in women living with HIV,” she said.
Intramyocardial lipid content was a reasonable line of inquiry, since it’s known that people living with HIV have increased deposition of fat in various organ systems, including the liver, skeletal muscle, and the heart, said Dr. Toribio. Both HIV and antiretroviral therapy can contribute to ectopic fat deposition, she said.
Women with (n = 18) and without (n = 6) HIV were matched according to age, body mass index (BMI), history of hypertension, and smoking status, said Dr. Toribio. For women with HIV, they had to be on stable antiretroviral therapy for at least 3 months and have no interruption in therapy greater than 2 weeks over the 3 months preceding enrollment.
The study excluded women who had known preexisting heart failure, diabetes, or atherosclerotic cardiovascular disease. Participants also could not be taking lipid-lowering agents or anti-inflammatory medications.
Participants were about 52 years old on average, and had a mean BMI of a little over 30 kg/m2. Lipid values did not differ significantly between groups, except that triglycerides were a mean 107 mg/dL in women living with HIV, compared with 69 mg/dL for women without HIV (P = .01).
Of the women living with HIV, 7/18 (38.5%) were white, the same number were black, and 2 were Hispanic. Three of six women without HIV were white, two were black, and one was Hispanic; racial and ethnic differences between the groups were not statistically significant overall.
Magnetic resonance spectroscopy was used to assess intramyocardial triglyceride levels, measured at the interventricular septum, a region where there’s little overlying pericardial fat.
“We found that the women living with HIV have an increased intramyocardial triglyceride content compared to women without HIV. And notably, we sought to see if there was any relationship between circulating triglyceride levels or body mass index, and there actually was no relationship between intramyocardial triglyceride content and these factors,” said Dr. Toribio in a video interview.
Next steps include two studies, said Dr. Toribio. The first is investigating whether statin therapy improves myocardial steatosis and heart function over time in women living with HIV. The second, involving the same population, is a pilot study to see if growth hormone releasing hormone – which is known to lessen visceral adiposity in people living with HIV – can reduce intramyocardial steatosis and boost cardiac function, she said.
Dr. Toribio reported no financial disclosures. The study was supported by funding from the National Institutes of Health.
SOURCE: Toribio M et al. ENDO 2018, Abstract OR11-2.
REPORTING FROM ENDO 2018
VIDEO: Pelvic radiation surpasses brachytherapy/chemo for early endometrial cancer
NEW ORLEANS – Pelvic radiation was as effective for producing recurrence-free survival as vaginal cuff brachytherapy plus chemotherapy but with less acute toxicity and fewer local recurrences in women with high-risk stage I or stage II endometrial cancer in a multicenter, randomized trial with 601 patients.
These findings should result in wider use of pelvic radiation as the preferred treatment for these patients, Marcus E. Randall, MD, said at the annual meeting of the Society of Gynecologic Oncology. “It will change practice,” he predicted.
Dr. Randall and his colleagues from the Gynecologic Oncology Group (which recently became part of NRG Oncology) designed the trial, GOG-0249, to address recent interest in using vaginal cuff brachytherapy plus chemotherapy with carboplatin and paclitaxel as an alternative to the more standard approach of pelvic radiation for treating women with either high-risk stage I or stage II endometrial cancers. Clinicians had considered the brachytherapy plus chemotherapy approach a reasonable option by “extrapolating from studies with advanced” endometrial cancer, but with no direct evidence to support this alternative, Dr. Randall explained in a video interview.
To generate evidence, the researchers enrolled 601 patients at several participating U.S. centers and followed them for a median of 53 months (4.4 years), with 259 patients treated and followed in the pelvic radiation arm and 268 patients treated and followed in the brachytherapy plus chemotherapy arm. Clinicians administered the complete planned treatment regimen to 91% of patients assigned to pelvic radiation and to 87% of those assigned to brachytherapy plus chemotherapy. Three quarters of enrolled patients had high-risk stage I disease, and the entire study group averaged about 62 years old.
The trial’s primary endpoint was recurrence-free survival, which occurred in 78% of the pelvic radiation patients and 79% of brachytherapy plus chemotherapy patients after 5 years when analyzed on an intention-to-treat basis. The two subgroups also showed similar rates of overall survival during follow-up.
Although the two treatments produced essentially identical outcomes for the primary result, they showed two important differences on secondary outcomes, reported Dr. Randall, professor and chair of radiation medicine at the University of Kentucky in Lexington.
Acute adverse effects rated as grade 3 severity or higher occurred in 11% of the pelvic radiation patients and in 64% of the brachytherapy plus chemotherapy patients, although late toxicities occurred at similar rates (13% and 12%, respectively) in the two subgroups.
Local pelvic and para-aortic nodal recurrences occurred in 4% of the pelvic radiation patients and in 9% of the brachytherapy plus chemotherapy patients, a 53% relative risk reduction with pelvic radiation. The difference in the nodal recurrences was apparent within the first year of follow-up, and the difference in rates continued to steadily widen over time after that. However the rates of both vaginal and distant recurrences were very similar in the two treatment arms. Distant recurrences were the most common type of treatment failure, occurring in about 18% of patients in both subgroups during complete follow-up.
“Pelvic radiation therapy remains an appropriate and preferable treatment for high-risk, early stage endometrial carcinoma,” Dr. Randall concluded.
SOURCE: Randall ME et al. SGO 2018.
NEW ORLEANS – Pelvic radiation was as effective for producing recurrence-free survival as vaginal cuff brachytherapy plus chemotherapy but with less acute toxicity and fewer local recurrences in women with high-risk stage I or stage II endometrial cancer in a multicenter, randomized trial with 601 patients.
These findings should result in wider use of pelvic radiation as the preferred treatment for these patients, Marcus E. Randall, MD, said at the annual meeting of the Society of Gynecologic Oncology. “It will change practice,” he predicted.
Dr. Randall and his colleagues from the Gynecologic Oncology Group (which recently became part of NRG Oncology) designed the trial, GOG-0249, to address recent interest in using vaginal cuff brachytherapy plus chemotherapy with carboplatin and paclitaxel as an alternative to the more standard approach of pelvic radiation for treating women with either high-risk stage I or stage II endometrial cancers. Clinicians had considered the brachytherapy plus chemotherapy approach a reasonable option by “extrapolating from studies with advanced” endometrial cancer, but with no direct evidence to support this alternative, Dr. Randall explained in a video interview.
To generate evidence, the researchers enrolled 601 patients at several participating U.S. centers and followed them for a median of 53 months (4.4 years), with 259 patients treated and followed in the pelvic radiation arm and 268 patients treated and followed in the brachytherapy plus chemotherapy arm. Clinicians administered the complete planned treatment regimen to 91% of patients assigned to pelvic radiation and to 87% of those assigned to brachytherapy plus chemotherapy. Three quarters of enrolled patients had high-risk stage I disease, and the entire study group averaged about 62 years old.
The trial’s primary endpoint was recurrence-free survival, which occurred in 78% of the pelvic radiation patients and 79% of brachytherapy plus chemotherapy patients after 5 years when analyzed on an intention-to-treat basis. The two subgroups also showed similar rates of overall survival during follow-up.
Although the two treatments produced essentially identical outcomes for the primary result, they showed two important differences on secondary outcomes, reported Dr. Randall, professor and chair of radiation medicine at the University of Kentucky in Lexington.
Acute adverse effects rated as grade 3 severity or higher occurred in 11% of the pelvic radiation patients and in 64% of the brachytherapy plus chemotherapy patients, although late toxicities occurred at similar rates (13% and 12%, respectively) in the two subgroups.
Local pelvic and para-aortic nodal recurrences occurred in 4% of the pelvic radiation patients and in 9% of the brachytherapy plus chemotherapy patients, a 53% relative risk reduction with pelvic radiation. The difference in the nodal recurrences was apparent within the first year of follow-up, and the difference in rates continued to steadily widen over time after that. However the rates of both vaginal and distant recurrences were very similar in the two treatment arms. Distant recurrences were the most common type of treatment failure, occurring in about 18% of patients in both subgroups during complete follow-up.
“Pelvic radiation therapy remains an appropriate and preferable treatment for high-risk, early stage endometrial carcinoma,” Dr. Randall concluded.
SOURCE: Randall ME et al. SGO 2018.
NEW ORLEANS – Pelvic radiation was as effective for producing recurrence-free survival as vaginal cuff brachytherapy plus chemotherapy but with less acute toxicity and fewer local recurrences in women with high-risk stage I or stage II endometrial cancer in a multicenter, randomized trial with 601 patients.
These findings should result in wider use of pelvic radiation as the preferred treatment for these patients, Marcus E. Randall, MD, said at the annual meeting of the Society of Gynecologic Oncology. “It will change practice,” he predicted.
Dr. Randall and his colleagues from the Gynecologic Oncology Group (which recently became part of NRG Oncology) designed the trial, GOG-0249, to address recent interest in using vaginal cuff brachytherapy plus chemotherapy with carboplatin and paclitaxel as an alternative to the more standard approach of pelvic radiation for treating women with either high-risk stage I or stage II endometrial cancers. Clinicians had considered the brachytherapy plus chemotherapy approach a reasonable option by “extrapolating from studies with advanced” endometrial cancer, but with no direct evidence to support this alternative, Dr. Randall explained in a video interview.
To generate evidence, the researchers enrolled 601 patients at several participating U.S. centers and followed them for a median of 53 months (4.4 years), with 259 patients treated and followed in the pelvic radiation arm and 268 patients treated and followed in the brachytherapy plus chemotherapy arm. Clinicians administered the complete planned treatment regimen to 91% of patients assigned to pelvic radiation and to 87% of those assigned to brachytherapy plus chemotherapy. Three quarters of enrolled patients had high-risk stage I disease, and the entire study group averaged about 62 years old.
The trial’s primary endpoint was recurrence-free survival, which occurred in 78% of the pelvic radiation patients and 79% of brachytherapy plus chemotherapy patients after 5 years when analyzed on an intention-to-treat basis. The two subgroups also showed similar rates of overall survival during follow-up.
Although the two treatments produced essentially identical outcomes for the primary result, they showed two important differences on secondary outcomes, reported Dr. Randall, professor and chair of radiation medicine at the University of Kentucky in Lexington.
Acute adverse effects rated as grade 3 severity or higher occurred in 11% of the pelvic radiation patients and in 64% of the brachytherapy plus chemotherapy patients, although late toxicities occurred at similar rates (13% and 12%, respectively) in the two subgroups.
Local pelvic and para-aortic nodal recurrences occurred in 4% of the pelvic radiation patients and in 9% of the brachytherapy plus chemotherapy patients, a 53% relative risk reduction with pelvic radiation. The difference in the nodal recurrences was apparent within the first year of follow-up, and the difference in rates continued to steadily widen over time after that. However the rates of both vaginal and distant recurrences were very similar in the two treatment arms. Distant recurrences were the most common type of treatment failure, occurring in about 18% of patients in both subgroups during complete follow-up.
“Pelvic radiation therapy remains an appropriate and preferable treatment for high-risk, early stage endometrial carcinoma,” Dr. Randall concluded.
SOURCE: Randall ME et al. SGO 2018.
REPORTING FROM SGO 2018
Key clinical point:
Major finding: Acute, higher-grade toxicities occurred in 11% of pelvic radiation patients and 64% of brachytherapy/chemotherapy patients.
Study details: GOG-0249, a multicenter, randomized phase III trial with 601 patients.
Disclosures: GOG-0249 had no commercial funding. Dr. Randall had no disclosures.
Source: Randall ME et al. SGO 2018.
VIDEO: How to prepare PTCL patients for transplant
LA JOLLA, CALIF. – according to Steven M. Horwitz, MD, of Memorial Sloan Kettering Cancer Center, New York.
“If you’re really trying to go to transplant, you want a complete remission or close to it. So that’s often been combination chemotherapy. But I think what we’re learning is, when some of the newer agents are combined, we’re seeing higher complete response rates. And we’re doing a better job at picking subtype specific approaches,” Dr. Horwitz said in a video interview at the annual T-cell Lymphoma Forum.
Dr. Horwitz also explored the role for reduced-intensity regimens in older patients, the use of radiation conditioning, and which new agents look most promising in peripheral T-cell lymphoma.
Dr. Horwitz had previously disclosed financial relationships with Celgene, Forty Seven, Huya Bioscience International, Infinity, Kyowa Hakko Kirin, Millennium, Seattle Genetics, and Takeda. The T-Cell Lymphoma Forum is held by Jonathan Wood & Associates, which is owned by the same company as this news organization.
mschneider@frontlinemedcom.com
SOURCE: Horwitz SM. TCLF 2018.
LA JOLLA, CALIF. – according to Steven M. Horwitz, MD, of Memorial Sloan Kettering Cancer Center, New York.
“If you’re really trying to go to transplant, you want a complete remission or close to it. So that’s often been combination chemotherapy. But I think what we’re learning is, when some of the newer agents are combined, we’re seeing higher complete response rates. And we’re doing a better job at picking subtype specific approaches,” Dr. Horwitz said in a video interview at the annual T-cell Lymphoma Forum.
Dr. Horwitz also explored the role for reduced-intensity regimens in older patients, the use of radiation conditioning, and which new agents look most promising in peripheral T-cell lymphoma.
Dr. Horwitz had previously disclosed financial relationships with Celgene, Forty Seven, Huya Bioscience International, Infinity, Kyowa Hakko Kirin, Millennium, Seattle Genetics, and Takeda. The T-Cell Lymphoma Forum is held by Jonathan Wood & Associates, which is owned by the same company as this news organization.
mschneider@frontlinemedcom.com
SOURCE: Horwitz SM. TCLF 2018.
LA JOLLA, CALIF. – according to Steven M. Horwitz, MD, of Memorial Sloan Kettering Cancer Center, New York.
“If you’re really trying to go to transplant, you want a complete remission or close to it. So that’s often been combination chemotherapy. But I think what we’re learning is, when some of the newer agents are combined, we’re seeing higher complete response rates. And we’re doing a better job at picking subtype specific approaches,” Dr. Horwitz said in a video interview at the annual T-cell Lymphoma Forum.
Dr. Horwitz also explored the role for reduced-intensity regimens in older patients, the use of radiation conditioning, and which new agents look most promising in peripheral T-cell lymphoma.
Dr. Horwitz had previously disclosed financial relationships with Celgene, Forty Seven, Huya Bioscience International, Infinity, Kyowa Hakko Kirin, Millennium, Seattle Genetics, and Takeda. The T-Cell Lymphoma Forum is held by Jonathan Wood & Associates, which is owned by the same company as this news organization.
mschneider@frontlinemedcom.com
SOURCE: Horwitz SM. TCLF 2018.
REPORTING FROM TCLF 2018
VIDEO: Everolimus/letrozole promising for recurrent endometrial cancer
NEW ORLEANS – Combined treatment for 28 days with the mammalian target of rapamycin inhibitor everolimus plus the aromatase inhibitor letrozole in 37 women with recurrent endometrial cancer produced an overall objective response rate of 24% and an average progression-free survival rate of 6.3 months in a randomized phase 2 study with a total of 74 patients. The treatment was also relatively well tolerated, with more serious adverse vents of anemia and hyperglycemia.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
But the most attention-grabbing finding of this study was that, in the subset of 15 women who had received no prior chemotherapy, the objective response rate on this regimen was 53% and median progression-free survival was 21.6 months, Brian M. Slomovitz, MD, said at the annual meeting of the Society of Gynecologic Oncology.
This level of response in the chemotherapy-naive subgroup was “very high, and not what we expected,” Dr. Slomovitz, , professor of ob.gyn. and human genetics and director of gynecologic oncology at the University of Miami, said in a video interview. “This is something we need to further investigate to see if we can make this part of standard care.”
Although he conceded that the data from this study were too limited to warrant a regulatory indication, he suggested that it might be enough to gain the everolimus plus letrozole combination used in the study citation as a treatment option in clinical guidelines. The next step should be a phase 3 trial that compares the everolimus plus letrozole combination with the traditional chemotherapy regimen of carboplatin plus paclitaxel, Dr. Slomovitz added.
The Everolimus and Letrozole or Hormonal Therapy to Treat Endometrial Cancer phase 2 trial, initiated by the Gynecologic Oncology Group, ran at 26 U.S. centers, and randomized patients with stage III or IV recurrent, advanced, or persistent endometrial cancer who had either no or at most one prior course of chemotherapy. The study design also excluded patients who had previously been treated with an mammalian target of rapamycin inhibitor or hormonal therapy for their endometrial cancer. The control arm placed 37 patients on a standard hormonal therapy regimen of tamoxifen plus medroxyprogesterone, with 36 of patients in this subgroup evaluable.
The overall results in the two treatment arms were roughly similar, except for the striking benefit seen with everolimus(Afinitor) plus letrozole(Femara) in the chemotherapy-naive patents; 15 patients in each arm had not received any chemotherapy before entering the study. In this subgroup, among the patients who received conventional hormonal therapy, the objective response rate was 43% and progression-free survival was 6.6 months.
The two arms also differed by their pattern of grade 3 or 4 adverse events. Among the patients on everolimus plus letrozole, the most common were anemia (24%) and hyperglycemia (14%), both expected consequences of the regimen. The hormonal therapy arm led to an 8% incidence of thromboembolic events, which did not occur in the everolimus plus letrozole arm.
Another attraction of the everolimus and letrozole regimen is that it is oral and avoids the need for drug infusions, Dr. Slomovitz noted.
The investigator-initiated study received funding from Novartis, the company that markets everolimus and letrozole. Dr. Slomovitz has been an advisor to Advaxis, AstraZeneca, Clovis, Genmab, Jannsen, and Tesaro, and he has received research funding from Novartis.
SOURCE: Slomovitz BM et al. SGO 2018, abstract 1.
The results from this study are exciting, with fairly compelling response rates. The rate of progression-free survival with everolimus and letrozole treatment is very impressive, compared with traditional chemotherapy using carboplatin and paclitaxel. The median progression-free survival rate of 21.6 months seen among the chemotherapy naive patients who received everolimus and letrozole showed a 7-month edge over the 14-month median progression-free survival previously reported with chemotherapy. This difference is very provocative and could be practice changing, but it of course needs further evaluation.
Paola A. Gehrig, MD , is professor of ob.gyn. and director of gynecologic oncology at the University of North Carolina in Chapel Hill. She made these comments as designated discussant for the study. She had no disclosures.
The results from this study are exciting, with fairly compelling response rates. The rate of progression-free survival with everolimus and letrozole treatment is very impressive, compared with traditional chemotherapy using carboplatin and paclitaxel. The median progression-free survival rate of 21.6 months seen among the chemotherapy naive patients who received everolimus and letrozole showed a 7-month edge over the 14-month median progression-free survival previously reported with chemotherapy. This difference is very provocative and could be practice changing, but it of course needs further evaluation.
Paola A. Gehrig, MD , is professor of ob.gyn. and director of gynecologic oncology at the University of North Carolina in Chapel Hill. She made these comments as designated discussant for the study. She had no disclosures.
The results from this study are exciting, with fairly compelling response rates. The rate of progression-free survival with everolimus and letrozole treatment is very impressive, compared with traditional chemotherapy using carboplatin and paclitaxel. The median progression-free survival rate of 21.6 months seen among the chemotherapy naive patients who received everolimus and letrozole showed a 7-month edge over the 14-month median progression-free survival previously reported with chemotherapy. This difference is very provocative and could be practice changing, but it of course needs further evaluation.
Paola A. Gehrig, MD , is professor of ob.gyn. and director of gynecologic oncology at the University of North Carolina in Chapel Hill. She made these comments as designated discussant for the study. She had no disclosures.
NEW ORLEANS – Combined treatment for 28 days with the mammalian target of rapamycin inhibitor everolimus plus the aromatase inhibitor letrozole in 37 women with recurrent endometrial cancer produced an overall objective response rate of 24% and an average progression-free survival rate of 6.3 months in a randomized phase 2 study with a total of 74 patients. The treatment was also relatively well tolerated, with more serious adverse vents of anemia and hyperglycemia.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
But the most attention-grabbing finding of this study was that, in the subset of 15 women who had received no prior chemotherapy, the objective response rate on this regimen was 53% and median progression-free survival was 21.6 months, Brian M. Slomovitz, MD, said at the annual meeting of the Society of Gynecologic Oncology.
This level of response in the chemotherapy-naive subgroup was “very high, and not what we expected,” Dr. Slomovitz, , professor of ob.gyn. and human genetics and director of gynecologic oncology at the University of Miami, said in a video interview. “This is something we need to further investigate to see if we can make this part of standard care.”
Although he conceded that the data from this study were too limited to warrant a regulatory indication, he suggested that it might be enough to gain the everolimus plus letrozole combination used in the study citation as a treatment option in clinical guidelines. The next step should be a phase 3 trial that compares the everolimus plus letrozole combination with the traditional chemotherapy regimen of carboplatin plus paclitaxel, Dr. Slomovitz added.
The Everolimus and Letrozole or Hormonal Therapy to Treat Endometrial Cancer phase 2 trial, initiated by the Gynecologic Oncology Group, ran at 26 U.S. centers, and randomized patients with stage III or IV recurrent, advanced, or persistent endometrial cancer who had either no or at most one prior course of chemotherapy. The study design also excluded patients who had previously been treated with an mammalian target of rapamycin inhibitor or hormonal therapy for their endometrial cancer. The control arm placed 37 patients on a standard hormonal therapy regimen of tamoxifen plus medroxyprogesterone, with 36 of patients in this subgroup evaluable.
The overall results in the two treatment arms were roughly similar, except for the striking benefit seen with everolimus(Afinitor) plus letrozole(Femara) in the chemotherapy-naive patents; 15 patients in each arm had not received any chemotherapy before entering the study. In this subgroup, among the patients who received conventional hormonal therapy, the objective response rate was 43% and progression-free survival was 6.6 months.
The two arms also differed by their pattern of grade 3 or 4 adverse events. Among the patients on everolimus plus letrozole, the most common were anemia (24%) and hyperglycemia (14%), both expected consequences of the regimen. The hormonal therapy arm led to an 8% incidence of thromboembolic events, which did not occur in the everolimus plus letrozole arm.
Another attraction of the everolimus and letrozole regimen is that it is oral and avoids the need for drug infusions, Dr. Slomovitz noted.
The investigator-initiated study received funding from Novartis, the company that markets everolimus and letrozole. Dr. Slomovitz has been an advisor to Advaxis, AstraZeneca, Clovis, Genmab, Jannsen, and Tesaro, and he has received research funding from Novartis.
SOURCE: Slomovitz BM et al. SGO 2018, abstract 1.
NEW ORLEANS – Combined treatment for 28 days with the mammalian target of rapamycin inhibitor everolimus plus the aromatase inhibitor letrozole in 37 women with recurrent endometrial cancer produced an overall objective response rate of 24% and an average progression-free survival rate of 6.3 months in a randomized phase 2 study with a total of 74 patients. The treatment was also relatively well tolerated, with more serious adverse vents of anemia and hyperglycemia.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
But the most attention-grabbing finding of this study was that, in the subset of 15 women who had received no prior chemotherapy, the objective response rate on this regimen was 53% and median progression-free survival was 21.6 months, Brian M. Slomovitz, MD, said at the annual meeting of the Society of Gynecologic Oncology.
This level of response in the chemotherapy-naive subgroup was “very high, and not what we expected,” Dr. Slomovitz, , professor of ob.gyn. and human genetics and director of gynecologic oncology at the University of Miami, said in a video interview. “This is something we need to further investigate to see if we can make this part of standard care.”
Although he conceded that the data from this study were too limited to warrant a regulatory indication, he suggested that it might be enough to gain the everolimus plus letrozole combination used in the study citation as a treatment option in clinical guidelines. The next step should be a phase 3 trial that compares the everolimus plus letrozole combination with the traditional chemotherapy regimen of carboplatin plus paclitaxel, Dr. Slomovitz added.
The Everolimus and Letrozole or Hormonal Therapy to Treat Endometrial Cancer phase 2 trial, initiated by the Gynecologic Oncology Group, ran at 26 U.S. centers, and randomized patients with stage III or IV recurrent, advanced, or persistent endometrial cancer who had either no or at most one prior course of chemotherapy. The study design also excluded patients who had previously been treated with an mammalian target of rapamycin inhibitor or hormonal therapy for their endometrial cancer. The control arm placed 37 patients on a standard hormonal therapy regimen of tamoxifen plus medroxyprogesterone, with 36 of patients in this subgroup evaluable.
The overall results in the two treatment arms were roughly similar, except for the striking benefit seen with everolimus(Afinitor) plus letrozole(Femara) in the chemotherapy-naive patents; 15 patients in each arm had not received any chemotherapy before entering the study. In this subgroup, among the patients who received conventional hormonal therapy, the objective response rate was 43% and progression-free survival was 6.6 months.
The two arms also differed by their pattern of grade 3 or 4 adverse events. Among the patients on everolimus plus letrozole, the most common were anemia (24%) and hyperglycemia (14%), both expected consequences of the regimen. The hormonal therapy arm led to an 8% incidence of thromboembolic events, which did not occur in the everolimus plus letrozole arm.
Another attraction of the everolimus and letrozole regimen is that it is oral and avoids the need for drug infusions, Dr. Slomovitz noted.
The investigator-initiated study received funding from Novartis, the company that markets everolimus and letrozole. Dr. Slomovitz has been an advisor to Advaxis, AstraZeneca, Clovis, Genmab, Jannsen, and Tesaro, and he has received research funding from Novartis.
SOURCE: Slomovitz BM et al. SGO 2018, abstract 1.
REPORTING FROM SGO 2018
Key clinical point: Treatment of recurrent endometrial cancer with everolimus and letrozole shows promise.
Major finding: Among 15 chemotherapy-naive patients, objective responses occurred in 53% and median progression-free survival was 21.6 months.
Study details: A multicenter, phase 2 randomized study in 74 patients.
Disclosures: The investigator-initiated study received funding from Novartis, the company that markets everolimus(Afinitor) and letrozole(Femara). Dr. Slomovitz has been an advisor to Advaxis, AstraZeneca, Clovis, Genmab, Jannsen, and Tesaro, and he has received research funding from Novartis.
Source: Slomovitz BM et al. SGO 2018, abstract 1.
VIDEO: It is an exciting time in obesity treatment
BOSTON – For those in obesity treatment, things are looking up, said Reem Z. Sharaiha, MD, MSc, in a video interview at the AGA Tech Summit, sponsored by the AGA Center for GI Innovation and Technology. There are several new therapies to choose from, said Dr. Sharaiha, assistant professor of medicine at Cornell University, New York – and a variety of therapies coming down the pipeline. The key is to choose the right treatment, or right combination of treatments – surgical, endoscopic, or medical – for the right patient at the right time and to follow up. Obesity is a chronic disease that needs long-term, team treatment. With obesity treatments there is sometimes a trade-off between risk and results, but the innovations coming along may balance that risk-results equation for some patients, she said.
BOSTON – For those in obesity treatment, things are looking up, said Reem Z. Sharaiha, MD, MSc, in a video interview at the AGA Tech Summit, sponsored by the AGA Center for GI Innovation and Technology. There are several new therapies to choose from, said Dr. Sharaiha, assistant professor of medicine at Cornell University, New York – and a variety of therapies coming down the pipeline. The key is to choose the right treatment, or right combination of treatments – surgical, endoscopic, or medical – for the right patient at the right time and to follow up. Obesity is a chronic disease that needs long-term, team treatment. With obesity treatments there is sometimes a trade-off between risk and results, but the innovations coming along may balance that risk-results equation for some patients, she said.
BOSTON – For those in obesity treatment, things are looking up, said Reem Z. Sharaiha, MD, MSc, in a video interview at the AGA Tech Summit, sponsored by the AGA Center for GI Innovation and Technology. There are several new therapies to choose from, said Dr. Sharaiha, assistant professor of medicine at Cornell University, New York – and a variety of therapies coming down the pipeline. The key is to choose the right treatment, or right combination of treatments – surgical, endoscopic, or medical – for the right patient at the right time and to follow up. Obesity is a chronic disease that needs long-term, team treatment. With obesity treatments there is sometimes a trade-off between risk and results, but the innovations coming along may balance that risk-results equation for some patients, she said.
REPORTING FROM 2018 AGA TECH SUMMIT
VIDEO: PFO closure device 100% effective against future strokes
ORLANDO – Closing a patent foramen ovale reduced the incidence of stroke and other adverse events in patients at increased risk the DEFENSE-PRO trial.
“The potential association between patent foramen ovale [PFO] and cryptogenic stroke has been a controversial issue for decades,” Jae Kwan Song, MD, of Asan Medical Center in Seoul, South Korea, said in an interview at the annual meeting of the American College of Cardiology.
In this study, 60 patients with high-risk PFOs (at least 2 mm) were randomized to receive anticoagulant or antiplatelet medications alone, and 60 were randomized to medication plus implantation of the Amplatzer PFO closure device.
The device implantation was successful for all patients in the device group. The primary endpoint was a combination of stroke, vascular death, and major bleeding within 2 years of follow-up after the procedure.
After an average follow-up of 2.8 years, none of the patients in the device group and six (10%) of patients in the medication-only group experienced a primary endpoint event. The events in the medication-only group included five cases of ischemic stroke, two cases of TIMI-defined major bleeding, one cerebral hemorrhage, and one transient ischemic attack.
Nonfatal procedural complications included two cases of atrial fibrillation, one case of pericardial effusion, and one pseudoaneurysm.
The average age of the patients was 54 years in the medication-only group and 49 years in the device group, and roughly one-third of the patients in each group were male. The baseline clinical characteristics, including the presence of hypertension, diabetes, smoking, and high cholesterol, were similar between the groups.
“We should consider two things before clinical decision of device closure,” Dr. Song said. First, exclude other causes of cryptogenic stroke; and second, conduct a comprehensive evaluation of the PFO to determine which patients are at highest risk and would be most likely to benefit from the procedure, he said.
To better determine which patients would benefit from the device implantation, Dr. Song and his colleagues used imaging to review data on the size and features of the PFO; patients with evidence of an atrial septal aneurysm or hypermobility (defined as a septal excursion 10 mm or larger) were deemed at especially high risk.
Dr. Song said that the next steps for research on management of PFOs include determining which medications are most effective in patients treated with medication alone, as well as clarifying the process of patient selection for device use based on PFO morphology.
The study was terminated early because of several factors, including low patient recruitment and the decision not to deny patients the closure treatment because of its demonstrated effectiveness, Dr. Song noted.
The study was supported by the Cardiovascular Research Foundation in Seoul, South Korea. Dr. Song had no financial conflicts to disclose. The findings were published simultaneously in the Journal of the American College of Cardiology (doi: 10.1016/j.jacc.2018.02.046).
SOURCE: Song J. ACC 2018.
ORLANDO – Closing a patent foramen ovale reduced the incidence of stroke and other adverse events in patients at increased risk the DEFENSE-PRO trial.
“The potential association between patent foramen ovale [PFO] and cryptogenic stroke has been a controversial issue for decades,” Jae Kwan Song, MD, of Asan Medical Center in Seoul, South Korea, said in an interview at the annual meeting of the American College of Cardiology.
In this study, 60 patients with high-risk PFOs (at least 2 mm) were randomized to receive anticoagulant or antiplatelet medications alone, and 60 were randomized to medication plus implantation of the Amplatzer PFO closure device.
The device implantation was successful for all patients in the device group. The primary endpoint was a combination of stroke, vascular death, and major bleeding within 2 years of follow-up after the procedure.
After an average follow-up of 2.8 years, none of the patients in the device group and six (10%) of patients in the medication-only group experienced a primary endpoint event. The events in the medication-only group included five cases of ischemic stroke, two cases of TIMI-defined major bleeding, one cerebral hemorrhage, and one transient ischemic attack.
Nonfatal procedural complications included two cases of atrial fibrillation, one case of pericardial effusion, and one pseudoaneurysm.
The average age of the patients was 54 years in the medication-only group and 49 years in the device group, and roughly one-third of the patients in each group were male. The baseline clinical characteristics, including the presence of hypertension, diabetes, smoking, and high cholesterol, were similar between the groups.
“We should consider two things before clinical decision of device closure,” Dr. Song said. First, exclude other causes of cryptogenic stroke; and second, conduct a comprehensive evaluation of the PFO to determine which patients are at highest risk and would be most likely to benefit from the procedure, he said.
To better determine which patients would benefit from the device implantation, Dr. Song and his colleagues used imaging to review data on the size and features of the PFO; patients with evidence of an atrial septal aneurysm or hypermobility (defined as a septal excursion 10 mm or larger) were deemed at especially high risk.
Dr. Song said that the next steps for research on management of PFOs include determining which medications are most effective in patients treated with medication alone, as well as clarifying the process of patient selection for device use based on PFO morphology.
The study was terminated early because of several factors, including low patient recruitment and the decision not to deny patients the closure treatment because of its demonstrated effectiveness, Dr. Song noted.
The study was supported by the Cardiovascular Research Foundation in Seoul, South Korea. Dr. Song had no financial conflicts to disclose. The findings were published simultaneously in the Journal of the American College of Cardiology (doi: 10.1016/j.jacc.2018.02.046).
SOURCE: Song J. ACC 2018.
ORLANDO – Closing a patent foramen ovale reduced the incidence of stroke and other adverse events in patients at increased risk the DEFENSE-PRO trial.
“The potential association between patent foramen ovale [PFO] and cryptogenic stroke has been a controversial issue for decades,” Jae Kwan Song, MD, of Asan Medical Center in Seoul, South Korea, said in an interview at the annual meeting of the American College of Cardiology.
In this study, 60 patients with high-risk PFOs (at least 2 mm) were randomized to receive anticoagulant or antiplatelet medications alone, and 60 were randomized to medication plus implantation of the Amplatzer PFO closure device.
The device implantation was successful for all patients in the device group. The primary endpoint was a combination of stroke, vascular death, and major bleeding within 2 years of follow-up after the procedure.
After an average follow-up of 2.8 years, none of the patients in the device group and six (10%) of patients in the medication-only group experienced a primary endpoint event. The events in the medication-only group included five cases of ischemic stroke, two cases of TIMI-defined major bleeding, one cerebral hemorrhage, and one transient ischemic attack.
Nonfatal procedural complications included two cases of atrial fibrillation, one case of pericardial effusion, and one pseudoaneurysm.
The average age of the patients was 54 years in the medication-only group and 49 years in the device group, and roughly one-third of the patients in each group were male. The baseline clinical characteristics, including the presence of hypertension, diabetes, smoking, and high cholesterol, were similar between the groups.
“We should consider two things before clinical decision of device closure,” Dr. Song said. First, exclude other causes of cryptogenic stroke; and second, conduct a comprehensive evaluation of the PFO to determine which patients are at highest risk and would be most likely to benefit from the procedure, he said.
To better determine which patients would benefit from the device implantation, Dr. Song and his colleagues used imaging to review data on the size and features of the PFO; patients with evidence of an atrial septal aneurysm or hypermobility (defined as a septal excursion 10 mm or larger) were deemed at especially high risk.
Dr. Song said that the next steps for research on management of PFOs include determining which medications are most effective in patients treated with medication alone, as well as clarifying the process of patient selection for device use based on PFO morphology.
The study was terminated early because of several factors, including low patient recruitment and the decision not to deny patients the closure treatment because of its demonstrated effectiveness, Dr. Song noted.
The study was supported by the Cardiovascular Research Foundation in Seoul, South Korea. Dr. Song had no financial conflicts to disclose. The findings were published simultaneously in the Journal of the American College of Cardiology (doi: 10.1016/j.jacc.2018.02.046).
SOURCE: Song J. ACC 2018.
REPORTING FROM ACC 18
Key clinical point: Closure of patent foramen ovale resulted in no adverse events or recurrent strokes during 2 years’ follow-up.
Major finding: No adverse event or strokes occurred in the device-plus-medication group, compared with six events in the medication-only group.
Study details: The data come from DEFENSE-PFO, a randomized trial of 120 adults with a history of cryptogenic stroke and high-risk PFO.
Disclosures: DEFENSE-PFO was supported by the Cardiovascular Research Foundation in Seoul, South Korea. Dr. Song had no financial conflicts to disclose.
Source: Song J. ACC 2018.
VIDEO: Andexanet alfa effectively reverses factor Xa anticoagulant
ORLANDO – Andexanet alfa, a new agent that reverses the anticoagulant effect of direct factor Xa inhibitors, showed an acceptable level of efficacy and safety in 227 patients who received the drug in the agent’s pivotal trial.
These results, which placed andexanet in the same ballpark for efficacy and safety as idarucizumab (Praxbind), approved in 2015 for reversing the anticoagulant dabigatran (Pradaxa), suggest that andexanet is likely on track for its own Food and Drug Administration marketing approval, Stuart Connolly, MD, said at the annual meeting of the American College of Cardiology.
Portola Pharmaceuticals, the company developing andexanet alfa (AndexXa) previously announced that it expected Food and Drug Administration action on its marketing application by May 2018.
Andexanet reversal “has similar efficacy and safety as seen with other reversal agents” for other types of anticoagulants, said Dr. Connolly, a professor of medicine and an electrophysiologist at McMaster University in Hamilton, Ont. In the trial results he reported, andexanet treatment of patients who were bleeding while on treatment with a direct factor Xa inhibitor had an 83% rate of hemostatic efficacy and an 11% rate of thrombotic events. By comparison, idarucizumab, the FDA-approved reversal agent for the anticoagulant dabigatran, produced a 68% hemostatic efficacy and a 6% rate of thrombotic events in the idarucizumab pivotal trial, RE-VERSE AD (N Engl J Med. 2015 Aug 6;373[6]:511-20).
The Prospective, Open-Label Study of Andexanet Alfa in Patients Receiving a Factor Xa Inhibitor Who Have Acute Major Bleeding (ANNEXA-4) enrolled 227 patients at any of 60 centers, with efficacy data available from 132 of the patients. About 60% of the patients had an intracranial bleed, and about 30% had a gastrointestinal bleed, and their average age was 77 years. Roughly three-quarters of patients were on an anticoagulant for atrial fibrillation, with the rest treated for venous thromboembolism, with 4% having both conditions. The most commonly used direct factor Xa inhbitors in these patients were apixaban (Eliquis) in 105 and rivaroxaban (Xarelto) in 75. The ANNEXA-4 study has not enrolled patients treated with a direct factor Xa inhibitor anticoagulant and undergoing surgery, a setting that will be the subject of a future study, Dr. Connolly said.
Clinicians administered andexanet alfa as a bolus followed by a 2-hour continuous infusion, with hemostatic efficacy assessed 12 hours after the start of treatment. The results showed that factor Xa inhibition fell by about 75%-90% within minutes of starting the bolus and remained depressed at that level during the infusion but then began recovering by 2 hours after the stop of infusion. Andexanet is a factor Xa “decoy” molecule that acts by latching onto the inhibitor molecules and thereby preventing them from interacting with actual factor Xa, but andexanet also has a short half life and hence the effect quickly reduces once treatment stops.
“There is no doubt that andexanet rapidly decreases anti–factor Xa activity,” he said.
Adjudicated efficacy results were available for 132 patients and showed good or excellent hemostasis achieved on andexanet in 109 patients (83%), Dr. Connolly reported. The effect on hemostasis was consistent regardless of patient age, sex, bleeding site, type of anticoagulant, and dosage tested.
Thrombotic events during the 30 days following treatment occurred in 24 of 227 patients (11%) who received andexanet and were evaluable for safety. Notably, no clustering of thrombotic events occurred early, even among the 129 patients who restarted on an anticoagulant during the 30 days after treatment. Among the 129 patients who restarted on an anticoagulant, 9 (7%) had a thrombotic event during the 30-day follow-up, compared with 15 events among 98 patients (15%) who did not restart on an anticoagulant.
Dr. Connolly acknowledged that a limitation of the ANNEXA-4 study is the absence of a control group, but he added that he and his associates believed randomizing patients with a serious bleed to placebo control would not have been “practical, feasible, or ethical.”
ANNEXA-4 is sponsored by Portola Pharmaceuticals, the company developing andexanet alfa (AndexXa). Dr. Connolly has been a consultant to Portola, and also to Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, and Sanofi-Aventis. Dr. Kirtane has received research support from several device manufacturers.
SOURCE: Connolly S. ACC 2018.
Treatment with andexanet alfa produced good or excellent hemostasis in 83% of patients in the ANNEXA-4 study, which is what matters when patients are bleeding. Clinicians want to know that you can restore coagulation to a level where you can stop bleeding, and that’s what the results show.
The lack of a reversal agent until now for direct-acting factor Xa inhibitor drugs has probably been a modest but real obstacle to widespread adoption of these agents. We can look at the example of another new oral anticoagulant, dabigatran (Pradaxa), which works by a different mechanism, specifically by inhibiting thrombin. After a reversal agent for dabigatran, idarucizumab (Praxbind) received Food and Drug Administration approval and became available in late 2015, an uptick in dabigatran prescriptions occurred. That experience shows that patients and providers want the safety net of a reversal agent. They want to know that, if there is bleeding or need for urgent surgery, there is a way to facilitate restoration of hemostasis.
It’s the same with direct factor Xa inhibitors: Some patients are concerned about the lack of a reversal agent, and having such an agent may help increase access to these agents for such patients. I think that, once andexanet becomes available for routine U.S. practice, we’ll see an uptick in prescribing of direct factor Xa inhibitors. Also, some patients who have opted for treatment with warfarin will switch to a safer class of drugs, the direct factor X a inhibitors. A myth exists that reversal agents can easily negate the anticoagulant effect of warfarin. The reality is that, despite having treatments that reverse warfarin’s effect, this is often not an easy process in actual practice.
On the safety side, there was no indication in the ANNEXA-4 results of rebound thrombosis with andexanet alfa treatment. Patients receiving a direct factor Xa inhibitor are prothrombotic – that’s why they are on an anticoagulant – so their risk for a thrombotic event is always there, especially when they are not fully anticoagulated, such as when a reversal agent is administered. We need to look to restarting treatment with an anticoagulant because these patients have a high thrombotic risk.
Gregory Piazza, MD , is a cardiologist at Brigham and Women’s Hospital in Boston. He has been an advisor to Portola Pharmaceuticals, the company developing andexanet alfa, as well as to Bayer and Pfizer, and he has received research funding from Bristol-Myers Squibb, Janssen, and Daiichi Sankyo. He made these comments in an interview .
Treatment with andexanet alfa produced good or excellent hemostasis in 83% of patients in the ANNEXA-4 study, which is what matters when patients are bleeding. Clinicians want to know that you can restore coagulation to a level where you can stop bleeding, and that’s what the results show.
The lack of a reversal agent until now for direct-acting factor Xa inhibitor drugs has probably been a modest but real obstacle to widespread adoption of these agents. We can look at the example of another new oral anticoagulant, dabigatran (Pradaxa), which works by a different mechanism, specifically by inhibiting thrombin. After a reversal agent for dabigatran, idarucizumab (Praxbind) received Food and Drug Administration approval and became available in late 2015, an uptick in dabigatran prescriptions occurred. That experience shows that patients and providers want the safety net of a reversal agent. They want to know that, if there is bleeding or need for urgent surgery, there is a way to facilitate restoration of hemostasis.
It’s the same with direct factor Xa inhibitors: Some patients are concerned about the lack of a reversal agent, and having such an agent may help increase access to these agents for such patients. I think that, once andexanet becomes available for routine U.S. practice, we’ll see an uptick in prescribing of direct factor Xa inhibitors. Also, some patients who have opted for treatment with warfarin will switch to a safer class of drugs, the direct factor X a inhibitors. A myth exists that reversal agents can easily negate the anticoagulant effect of warfarin. The reality is that, despite having treatments that reverse warfarin’s effect, this is often not an easy process in actual practice.
On the safety side, there was no indication in the ANNEXA-4 results of rebound thrombosis with andexanet alfa treatment. Patients receiving a direct factor Xa inhibitor are prothrombotic – that’s why they are on an anticoagulant – so their risk for a thrombotic event is always there, especially when they are not fully anticoagulated, such as when a reversal agent is administered. We need to look to restarting treatment with an anticoagulant because these patients have a high thrombotic risk.
Gregory Piazza, MD , is a cardiologist at Brigham and Women’s Hospital in Boston. He has been an advisor to Portola Pharmaceuticals, the company developing andexanet alfa, as well as to Bayer and Pfizer, and he has received research funding from Bristol-Myers Squibb, Janssen, and Daiichi Sankyo. He made these comments in an interview .
Treatment with andexanet alfa produced good or excellent hemostasis in 83% of patients in the ANNEXA-4 study, which is what matters when patients are bleeding. Clinicians want to know that you can restore coagulation to a level where you can stop bleeding, and that’s what the results show.
The lack of a reversal agent until now for direct-acting factor Xa inhibitor drugs has probably been a modest but real obstacle to widespread adoption of these agents. We can look at the example of another new oral anticoagulant, dabigatran (Pradaxa), which works by a different mechanism, specifically by inhibiting thrombin. After a reversal agent for dabigatran, idarucizumab (Praxbind) received Food and Drug Administration approval and became available in late 2015, an uptick in dabigatran prescriptions occurred. That experience shows that patients and providers want the safety net of a reversal agent. They want to know that, if there is bleeding or need for urgent surgery, there is a way to facilitate restoration of hemostasis.
It’s the same with direct factor Xa inhibitors: Some patients are concerned about the lack of a reversal agent, and having such an agent may help increase access to these agents for such patients. I think that, once andexanet becomes available for routine U.S. practice, we’ll see an uptick in prescribing of direct factor Xa inhibitors. Also, some patients who have opted for treatment with warfarin will switch to a safer class of drugs, the direct factor X a inhibitors. A myth exists that reversal agents can easily negate the anticoagulant effect of warfarin. The reality is that, despite having treatments that reverse warfarin’s effect, this is often not an easy process in actual practice.
On the safety side, there was no indication in the ANNEXA-4 results of rebound thrombosis with andexanet alfa treatment. Patients receiving a direct factor Xa inhibitor are prothrombotic – that’s why they are on an anticoagulant – so their risk for a thrombotic event is always there, especially when they are not fully anticoagulated, such as when a reversal agent is administered. We need to look to restarting treatment with an anticoagulant because these patients have a high thrombotic risk.
Gregory Piazza, MD , is a cardiologist at Brigham and Women’s Hospital in Boston. He has been an advisor to Portola Pharmaceuticals, the company developing andexanet alfa, as well as to Bayer and Pfizer, and he has received research funding from Bristol-Myers Squibb, Janssen, and Daiichi Sankyo. He made these comments in an interview .
ORLANDO – Andexanet alfa, a new agent that reverses the anticoagulant effect of direct factor Xa inhibitors, showed an acceptable level of efficacy and safety in 227 patients who received the drug in the agent’s pivotal trial.
These results, which placed andexanet in the same ballpark for efficacy and safety as idarucizumab (Praxbind), approved in 2015 for reversing the anticoagulant dabigatran (Pradaxa), suggest that andexanet is likely on track for its own Food and Drug Administration marketing approval, Stuart Connolly, MD, said at the annual meeting of the American College of Cardiology.
Portola Pharmaceuticals, the company developing andexanet alfa (AndexXa) previously announced that it expected Food and Drug Administration action on its marketing application by May 2018.
Andexanet reversal “has similar efficacy and safety as seen with other reversal agents” for other types of anticoagulants, said Dr. Connolly, a professor of medicine and an electrophysiologist at McMaster University in Hamilton, Ont. In the trial results he reported, andexanet treatment of patients who were bleeding while on treatment with a direct factor Xa inhibitor had an 83% rate of hemostatic efficacy and an 11% rate of thrombotic events. By comparison, idarucizumab, the FDA-approved reversal agent for the anticoagulant dabigatran, produced a 68% hemostatic efficacy and a 6% rate of thrombotic events in the idarucizumab pivotal trial, RE-VERSE AD (N Engl J Med. 2015 Aug 6;373[6]:511-20).
The Prospective, Open-Label Study of Andexanet Alfa in Patients Receiving a Factor Xa Inhibitor Who Have Acute Major Bleeding (ANNEXA-4) enrolled 227 patients at any of 60 centers, with efficacy data available from 132 of the patients. About 60% of the patients had an intracranial bleed, and about 30% had a gastrointestinal bleed, and their average age was 77 years. Roughly three-quarters of patients were on an anticoagulant for atrial fibrillation, with the rest treated for venous thromboembolism, with 4% having both conditions. The most commonly used direct factor Xa inhbitors in these patients were apixaban (Eliquis) in 105 and rivaroxaban (Xarelto) in 75. The ANNEXA-4 study has not enrolled patients treated with a direct factor Xa inhibitor anticoagulant and undergoing surgery, a setting that will be the subject of a future study, Dr. Connolly said.
Clinicians administered andexanet alfa as a bolus followed by a 2-hour continuous infusion, with hemostatic efficacy assessed 12 hours after the start of treatment. The results showed that factor Xa inhibition fell by about 75%-90% within minutes of starting the bolus and remained depressed at that level during the infusion but then began recovering by 2 hours after the stop of infusion. Andexanet is a factor Xa “decoy” molecule that acts by latching onto the inhibitor molecules and thereby preventing them from interacting with actual factor Xa, but andexanet also has a short half life and hence the effect quickly reduces once treatment stops.
“There is no doubt that andexanet rapidly decreases anti–factor Xa activity,” he said.
Adjudicated efficacy results were available for 132 patients and showed good or excellent hemostasis achieved on andexanet in 109 patients (83%), Dr. Connolly reported. The effect on hemostasis was consistent regardless of patient age, sex, bleeding site, type of anticoagulant, and dosage tested.
Thrombotic events during the 30 days following treatment occurred in 24 of 227 patients (11%) who received andexanet and were evaluable for safety. Notably, no clustering of thrombotic events occurred early, even among the 129 patients who restarted on an anticoagulant during the 30 days after treatment. Among the 129 patients who restarted on an anticoagulant, 9 (7%) had a thrombotic event during the 30-day follow-up, compared with 15 events among 98 patients (15%) who did not restart on an anticoagulant.
Dr. Connolly acknowledged that a limitation of the ANNEXA-4 study is the absence of a control group, but he added that he and his associates believed randomizing patients with a serious bleed to placebo control would not have been “practical, feasible, or ethical.”
ANNEXA-4 is sponsored by Portola Pharmaceuticals, the company developing andexanet alfa (AndexXa). Dr. Connolly has been a consultant to Portola, and also to Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, and Sanofi-Aventis. Dr. Kirtane has received research support from several device manufacturers.
SOURCE: Connolly S. ACC 2018.
ORLANDO – Andexanet alfa, a new agent that reverses the anticoagulant effect of direct factor Xa inhibitors, showed an acceptable level of efficacy and safety in 227 patients who received the drug in the agent’s pivotal trial.
These results, which placed andexanet in the same ballpark for efficacy and safety as idarucizumab (Praxbind), approved in 2015 for reversing the anticoagulant dabigatran (Pradaxa), suggest that andexanet is likely on track for its own Food and Drug Administration marketing approval, Stuart Connolly, MD, said at the annual meeting of the American College of Cardiology.
Portola Pharmaceuticals, the company developing andexanet alfa (AndexXa) previously announced that it expected Food and Drug Administration action on its marketing application by May 2018.
Andexanet reversal “has similar efficacy and safety as seen with other reversal agents” for other types of anticoagulants, said Dr. Connolly, a professor of medicine and an electrophysiologist at McMaster University in Hamilton, Ont. In the trial results he reported, andexanet treatment of patients who were bleeding while on treatment with a direct factor Xa inhibitor had an 83% rate of hemostatic efficacy and an 11% rate of thrombotic events. By comparison, idarucizumab, the FDA-approved reversal agent for the anticoagulant dabigatran, produced a 68% hemostatic efficacy and a 6% rate of thrombotic events in the idarucizumab pivotal trial, RE-VERSE AD (N Engl J Med. 2015 Aug 6;373[6]:511-20).
The Prospective, Open-Label Study of Andexanet Alfa in Patients Receiving a Factor Xa Inhibitor Who Have Acute Major Bleeding (ANNEXA-4) enrolled 227 patients at any of 60 centers, with efficacy data available from 132 of the patients. About 60% of the patients had an intracranial bleed, and about 30% had a gastrointestinal bleed, and their average age was 77 years. Roughly three-quarters of patients were on an anticoagulant for atrial fibrillation, with the rest treated for venous thromboembolism, with 4% having both conditions. The most commonly used direct factor Xa inhbitors in these patients were apixaban (Eliquis) in 105 and rivaroxaban (Xarelto) in 75. The ANNEXA-4 study has not enrolled patients treated with a direct factor Xa inhibitor anticoagulant and undergoing surgery, a setting that will be the subject of a future study, Dr. Connolly said.
Clinicians administered andexanet alfa as a bolus followed by a 2-hour continuous infusion, with hemostatic efficacy assessed 12 hours after the start of treatment. The results showed that factor Xa inhibition fell by about 75%-90% within minutes of starting the bolus and remained depressed at that level during the infusion but then began recovering by 2 hours after the stop of infusion. Andexanet is a factor Xa “decoy” molecule that acts by latching onto the inhibitor molecules and thereby preventing them from interacting with actual factor Xa, but andexanet also has a short half life and hence the effect quickly reduces once treatment stops.
“There is no doubt that andexanet rapidly decreases anti–factor Xa activity,” he said.
Adjudicated efficacy results were available for 132 patients and showed good or excellent hemostasis achieved on andexanet in 109 patients (83%), Dr. Connolly reported. The effect on hemostasis was consistent regardless of patient age, sex, bleeding site, type of anticoagulant, and dosage tested.
Thrombotic events during the 30 days following treatment occurred in 24 of 227 patients (11%) who received andexanet and were evaluable for safety. Notably, no clustering of thrombotic events occurred early, even among the 129 patients who restarted on an anticoagulant during the 30 days after treatment. Among the 129 patients who restarted on an anticoagulant, 9 (7%) had a thrombotic event during the 30-day follow-up, compared with 15 events among 98 patients (15%) who did not restart on an anticoagulant.
Dr. Connolly acknowledged that a limitation of the ANNEXA-4 study is the absence of a control group, but he added that he and his associates believed randomizing patients with a serious bleed to placebo control would not have been “practical, feasible, or ethical.”
ANNEXA-4 is sponsored by Portola Pharmaceuticals, the company developing andexanet alfa (AndexXa). Dr. Connolly has been a consultant to Portola, and also to Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, and Sanofi-Aventis. Dr. Kirtane has received research support from several device manufacturers.
SOURCE: Connolly S. ACC 2018.
REPORTING FROM ACC 18
Key clinical point:
Major finding: Hemostatic efficacy of andexanet alfa was 83%, and thrombotic events occurred in 11%.
Study details: ANNEXA-4, a single arm cohort study with 227 patients.
Disclosures: ANNEXA-4 is sponsored by Portola Pharmaceuticals, the company developing andexanet alfa (AndexXa). Dr. Connolly has been a consultant to Portola and also to Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, and Sanofi-Aventis.
Source: Connolly S. ACC 2018.
VIDEO: Researchers closing in on the elusive ‘male pill’
CHICAGO –
It blocks gonadotropin signaling and testosterone production in the testes. When capsules ranging in dose from 100 mg to 400 mg were given once daily to 100 men in a randomized, placebo controlled trial, the drop in testosterone was more than sufficient to block sperm production. Testosterone levels jumped back up to normal after the end of the 28-day trial, all without inducing liver toxicity or other serious problems.
“We are very excited [about] the results. It’s a big step forward in the development of the male pill. Our last great advance in male contraception was over 300 years ago with the development of the condom,” said senior investigator Stephanie Page, MD, PhD, head of the division of metabolism, endocrinology, and nutrition at the University of Washington, Seattle.
Some men reported a drop in libido that resolved by the end of the study. There was also mild weight gain and small reductions in HDL cholesterol. A few tweaks to the formulation or dosing might fix those problems. “Overall, we were very encouraged about the safety profile,” Dr. Page said.
She explained the work, its promise, and the next steps in a video interview at the Endocrine Society’s annual meeting. The National Institutes of Health is funding development. Dr. Page didn’t have any relevant disclosures.
SOURCE: Page S et al. ENDO 2018, Abstract OR15-2.
CHICAGO –
It blocks gonadotropin signaling and testosterone production in the testes. When capsules ranging in dose from 100 mg to 400 mg were given once daily to 100 men in a randomized, placebo controlled trial, the drop in testosterone was more than sufficient to block sperm production. Testosterone levels jumped back up to normal after the end of the 28-day trial, all without inducing liver toxicity or other serious problems.
“We are very excited [about] the results. It’s a big step forward in the development of the male pill. Our last great advance in male contraception was over 300 years ago with the development of the condom,” said senior investigator Stephanie Page, MD, PhD, head of the division of metabolism, endocrinology, and nutrition at the University of Washington, Seattle.
Some men reported a drop in libido that resolved by the end of the study. There was also mild weight gain and small reductions in HDL cholesterol. A few tweaks to the formulation or dosing might fix those problems. “Overall, we were very encouraged about the safety profile,” Dr. Page said.
She explained the work, its promise, and the next steps in a video interview at the Endocrine Society’s annual meeting. The National Institutes of Health is funding development. Dr. Page didn’t have any relevant disclosures.
SOURCE: Page S et al. ENDO 2018, Abstract OR15-2.
CHICAGO –
It blocks gonadotropin signaling and testosterone production in the testes. When capsules ranging in dose from 100 mg to 400 mg were given once daily to 100 men in a randomized, placebo controlled trial, the drop in testosterone was more than sufficient to block sperm production. Testosterone levels jumped back up to normal after the end of the 28-day trial, all without inducing liver toxicity or other serious problems.
“We are very excited [about] the results. It’s a big step forward in the development of the male pill. Our last great advance in male contraception was over 300 years ago with the development of the condom,” said senior investigator Stephanie Page, MD, PhD, head of the division of metabolism, endocrinology, and nutrition at the University of Washington, Seattle.
Some men reported a drop in libido that resolved by the end of the study. There was also mild weight gain and small reductions in HDL cholesterol. A few tweaks to the formulation or dosing might fix those problems. “Overall, we were very encouraged about the safety profile,” Dr. Page said.
She explained the work, its promise, and the next steps in a video interview at the Endocrine Society’s annual meeting. The National Institutes of Health is funding development. Dr. Page didn’t have any relevant disclosures.
SOURCE: Page S et al. ENDO 2018, Abstract OR15-2.
REPORTING FROM ENDO 2018
