CHICAGO – Liquid biopsy, the testing of the blood for circulating tumor DNA (ctDNA), identified cancer mutations useful as biomarkers in 85% of all advanced cancer cases in the largest-ever genomic analysis performed using such technology.

In nearly half of those (49%), the biomarkers were associated with an approved targeted drug, Philip C. Mack, Ph.D., reported at the annual meeting of the American Society of Clinical Oncology.

The patterns of genetic changes detected in the 17,628 blood specimens analyzed for the study using a highly sensitive next-generation sequencing technique closely mirrored those identified using traditional tumor biopsies, suggesting that liquid biopsy provides a non-invasive alternative to tissue biopsy in certain cases, Dr. Mack, professor and director of molecular pharmacology at the University of California, Davis Comprehensive Cancer Center, said during a press briefing at the meeting.

Overall, taking into account FDA-approved drugs and eligibility for clinical trials, the ctDNA testing revealed a possible treatment option for 63.6% of the 15,191 patients who provided samples.

Further, the commercially available liquid biopsy assay used in the study (Guardant360) identified the presence of resistance alterations that could guide new therapy in patients with tumors that acquire resistance to an effective treatment, he said, noting that these resistance mutations are not typically present at the time of initial tissue-biopsy.

Of the patients included in the study, 37% had lung cancer, 14% had breast cancer, 10% had colorectal cancer, and 39% had other cancers. A comparison of genomic changes in ctDNA in 398 patients with available tumor tissue genetic test results showed that when ctDNA was positive for key abnormalities associated with tumor growth, the same mutations were reported in tissue 94% to 100% of the time.

©Zffoto/Thinkstock

Most of the ctDNA alterations were found at very low levels – with half occurring at a frequency below 0.4% of the total DNA in circulation; even at such low levels, the accuracy of the liquid biopsy assay remained high, Dr. Mack noted.

The ctDNA findings also compared well with those from publicly available population-scale sequencing projects, most notably the Cancer Genome Atlas, he said.

Alterations observed at ctDNA fractions as low as 0.06% responded to treatment, which highlights the importance of assay sensitivity.

Interest in comprehensive tumor genetic profiling to guide patients toward appropriate targeted therapies based on the molecular makeup of their tumors has been increasing, and the current findings underscore its potential value. Advantages of plasma testing include ease of use in any clinic setting, avoidance of biopsy-related complications, ability to monitor changes in disease over time, potential identification of mutations in metastatic lesions not observed in the original tumor biopsy (as genetic changes driving tumor growth often differ in different parts of the tumor), and the opportunity to identify treatment-induced resistance mechanisms, Dr. Mack said.

Additionally, liquid biopsy could be particularly helpful in cases involving tumors for which a traditional biopsy is difficult to obtain.

In fact, the clinical utility of liquid biopsy was evident among 362 lung cancer cases in the study. Tissue was insufficient for traditional biopsy in 63% of the cases, and ctDNA testing identified key genetic mutations at frequencies consistent with their prevalence in the published literature. Thus, ctDNA provided these patients with their only source of an actionable target, Dr. Mack noted.

As for whether liquid biopsy could or should replace tissue biopsy, he explained that it should be viewed more as an additional tool.

“I think there is always going to be a role for tissue-based biopsy,” he said, explaining that a tissue biopsy allows the pathologist to assess the morphological features of the cancer to diagnose it and determine what the tumor type is and where it originated. “That will always be required.”

Leftover tissue should be used for mutational testing, and this is the gold standard. It is in cases when the tissue is of insufficient quality or quantity to allow a broader array of testing that liquid biopsy can provide a complementary source of information, he said.

Further, while it would be ideal to have biopsies of any progressing lesion in a patient who initially had a great response to treatment, that is not feasible, he said.

“So probably, the biggest role for plasma analysis will be occurring down the road as patients are progressing on therapies, as their tumors are evolving, as a way to monitor progression of those cancers,” he said.

Dr. Sumanta Kumar Pal, an ASCO spokesperson and a panel member at the press briefing, noted that “the data that Dr. Mack reported provides key insights into the feasibility of the so-called liquid biopsy.”

“We’re increasingly using genomic data from day-to-day in our clinics to guide therapies,” he said, reiterating that tests such as this provide a useful alternative to tissue-based testing, particularly for the many patients in clinics who have tumors that are challenging to access, such as tumors on bone or near the brain.

“The authors have demonstrated not only the feasibility of the test in detecting alterations, but that the results are often potentially actionable as well ... As oncologists obtain this assay, it’s important to keep in mind trials such as the ASCO-led TAPUR study. TAPUR can potentially link patients with selected genomic alterations to relevant therapies that would otherwise be challenging to access,” he said.

Dr. Pal also noted that there are several other blood-based genomic tests emerging, and it will be important to “rigorously define which of these platforms deliver optimal results.”

Going forward, Dr. Mack and his colleagues will be working to increase the sensitivity of the Gaurdant360 assay to detect mutations at extremely low ctDNA level, as some tumors – glioblastomas, for example – diminish the ability to detect ctDNA. Improved sensitivity could also enable the use of the assay in earlier-stage cancers, he said.

This study was supported by funding from Guardant Health.

[email protected]

CHICAGO – Liquid biopsy, the testing of the blood for circulating tumor DNA (ctDNA), identified cancer mutations useful as biomarkers in 85% of all advanced cancer cases in the largest-ever genomic analysis performed using such technology.

In nearly half of those (49%), the biomarkers were associated with an approved targeted drug, Philip C. Mack, Ph.D., reported at the annual meeting of the American Society of Clinical Oncology.

The patterns of genetic changes detected in the 17,628 blood specimens analyzed for the study using a highly sensitive next-generation sequencing technique closely mirrored those identified using traditional tumor biopsies, suggesting that liquid biopsy provides a non-invasive alternative to tissue biopsy in certain cases, Dr. Mack, professor and director of molecular pharmacology at the University of California, Davis Comprehensive Cancer Center, said during a press briefing at the meeting.

Overall, taking into account FDA-approved drugs and eligibility for clinical trials, the ctDNA testing revealed a possible treatment option for 63.6% of the 15,191 patients who provided samples.

Further, the commercially available liquid biopsy assay used in the study (Guardant360) identified the presence of resistance alterations that could guide new therapy in patients with tumors that acquire resistance to an effective treatment, he said, noting that these resistance mutations are not typically present at the time of initial tissue-biopsy.

Of the patients included in the study, 37% had lung cancer, 14% had breast cancer, 10% had colorectal cancer, and 39% had other cancers. A comparison of genomic changes in ctDNA in 398 patients with available tumor tissue genetic test results showed that when ctDNA was positive for key abnormalities associated with tumor growth, the same mutations were reported in tissue 94% to 100% of the time.

©Zffoto/Thinkstock

Most of the ctDNA alterations were found at very low levels – with half occurring at a frequency below 0.4% of the total DNA in circulation; even at such low levels, the accuracy of the liquid biopsy assay remained high, Dr. Mack noted.

The ctDNA findings also compared well with those from publicly available population-scale sequencing projects, most notably the Cancer Genome Atlas, he said.

Alterations observed at ctDNA fractions as low as 0.06% responded to treatment, which highlights the importance of assay sensitivity.

Interest in comprehensive tumor genetic profiling to guide patients toward appropriate targeted therapies based on the molecular makeup of their tumors has been increasing, and the current findings underscore its potential value. Advantages of plasma testing include ease of use in any clinic setting, avoidance of biopsy-related complications, ability to monitor changes in disease over time, potential identification of mutations in metastatic lesions not observed in the original tumor biopsy (as genetic changes driving tumor growth often differ in different parts of the tumor), and the opportunity to identify treatment-induced resistance mechanisms, Dr. Mack said.

Additionally, liquid biopsy could be particularly helpful in cases involving tumors for which a traditional biopsy is difficult to obtain.

In fact, the clinical utility of liquid biopsy was evident among 362 lung cancer cases in the study. Tissue was insufficient for traditional biopsy in 63% of the cases, and ctDNA testing identified key genetic mutations at frequencies consistent with their prevalence in the published literature. Thus, ctDNA provided these patients with their only source of an actionable target, Dr. Mack noted.

As for whether liquid biopsy could or should replace tissue biopsy, he explained that it should be viewed more as an additional tool.

“I think there is always going to be a role for tissue-based biopsy,” he said, explaining that a tissue biopsy allows the pathologist to assess the morphological features of the cancer to diagnose it and determine what the tumor type is and where it originated. “That will always be required.”

Leftover tissue should be used for mutational testing, and this is the gold standard. It is in cases when the tissue is of insufficient quality or quantity to allow a broader array of testing that liquid biopsy can provide a complementary source of information, he said.

Further, while it would be ideal to have biopsies of any progressing lesion in a patient who initially had a great response to treatment, that is not feasible, he said.

“So probably, the biggest role for plasma analysis will be occurring down the road as patients are progressing on therapies, as their tumors are evolving, as a way to monitor progression of those cancers,” he said.

Dr. Sumanta Kumar Pal, an ASCO spokesperson and a panel member at the press briefing, noted that “the data that Dr. Mack reported provides key insights into the feasibility of the so-called liquid biopsy.”

“We’re increasingly using genomic data from day-to-day in our clinics to guide therapies,” he said, reiterating that tests such as this provide a useful alternative to tissue-based testing, particularly for the many patients in clinics who have tumors that are challenging to access, such as tumors on bone or near the brain.

“The authors have demonstrated not only the feasibility of the test in detecting alterations, but that the results are often potentially actionable as well ... As oncologists obtain this assay, it’s important to keep in mind trials such as the ASCO-led TAPUR study. TAPUR can potentially link patients with selected genomic alterations to relevant therapies that would otherwise be challenging to access,” he said.

Dr. Pal also noted that there are several other blood-based genomic tests emerging, and it will be important to “rigorously define which of these platforms deliver optimal results.”

Going forward, Dr. Mack and his colleagues will be working to increase the sensitivity of the Gaurdant360 assay to detect mutations at extremely low ctDNA level, as some tumors – glioblastomas, for example – diminish the ability to detect ctDNA. Improved sensitivity could also enable the use of the assay in earlier-stage cancers, he said.

This study was supported by funding from Guardant Health.

[email protected]

CHICAGO – Liquid biopsy, the testing of the blood for circulating tumor DNA (ctDNA), identified cancer mutations useful as biomarkers in 85% of all advanced cancer cases in the largest-ever genomic analysis performed using such technology.

In nearly half of those (49%), the biomarkers were associated with an approved targeted drug, Philip C. Mack, Ph.D., reported at the annual meeting of the American Society of Clinical Oncology.

The patterns of genetic changes detected in the 17,628 blood specimens analyzed for the study using a highly sensitive next-generation sequencing technique closely mirrored those identified using traditional tumor biopsies, suggesting that liquid biopsy provides a non-invasive alternative to tissue biopsy in certain cases, Dr. Mack, professor and director of molecular pharmacology at the University of California, Davis Comprehensive Cancer Center, said during a press briefing at the meeting.

Overall, taking into account FDA-approved drugs and eligibility for clinical trials, the ctDNA testing revealed a possible treatment option for 63.6% of the 15,191 patients who provided samples.

Further, the commercially available liquid biopsy assay used in the study (Guardant360) identified the presence of resistance alterations that could guide new therapy in patients with tumors that acquire resistance to an effective treatment, he said, noting that these resistance mutations are not typically present at the time of initial tissue-biopsy.

Of the patients included in the study, 37% had lung cancer, 14% had breast cancer, 10% had colorectal cancer, and 39% had other cancers. A comparison of genomic changes in ctDNA in 398 patients with available tumor tissue genetic test results showed that when ctDNA was positive for key abnormalities associated with tumor growth, the same mutations were reported in tissue 94% to 100% of the time.

©Zffoto/Thinkstock

Most of the ctDNA alterations were found at very low levels – with half occurring at a frequency below 0.4% of the total DNA in circulation; even at such low levels, the accuracy of the liquid biopsy assay remained high, Dr. Mack noted.

The ctDNA findings also compared well with those from publicly available population-scale sequencing projects, most notably the Cancer Genome Atlas, he said.

Alterations observed at ctDNA fractions as low as 0.06% responded to treatment, which highlights the importance of assay sensitivity.

Interest in comprehensive tumor genetic profiling to guide patients toward appropriate targeted therapies based on the molecular makeup of their tumors has been increasing, and the current findings underscore its potential value. Advantages of plasma testing include ease of use in any clinic setting, avoidance of biopsy-related complications, ability to monitor changes in disease over time, potential identification of mutations in metastatic lesions not observed in the original tumor biopsy (as genetic changes driving tumor growth often differ in different parts of the tumor), and the opportunity to identify treatment-induced resistance mechanisms, Dr. Mack said.

Additionally, liquid biopsy could be particularly helpful in cases involving tumors for which a traditional biopsy is difficult to obtain.

In fact, the clinical utility of liquid biopsy was evident among 362 lung cancer cases in the study. Tissue was insufficient for traditional biopsy in 63% of the cases, and ctDNA testing identified key genetic mutations at frequencies consistent with their prevalence in the published literature. Thus, ctDNA provided these patients with their only source of an actionable target, Dr. Mack noted.

As for whether liquid biopsy could or should replace tissue biopsy, he explained that it should be viewed more as an additional tool.

“I think there is always going to be a role for tissue-based biopsy,” he said, explaining that a tissue biopsy allows the pathologist to assess the morphological features of the cancer to diagnose it and determine what the tumor type is and where it originated. “That will always be required.”

Leftover tissue should be used for mutational testing, and this is the gold standard. It is in cases when the tissue is of insufficient quality or quantity to allow a broader array of testing that liquid biopsy can provide a complementary source of information, he said.

Further, while it would be ideal to have biopsies of any progressing lesion in a patient who initially had a great response to treatment, that is not feasible, he said.

“So probably, the biggest role for plasma analysis will be occurring down the road as patients are progressing on therapies, as their tumors are evolving, as a way to monitor progression of those cancers,” he said.

Dr. Sumanta Kumar Pal, an ASCO spokesperson and a panel member at the press briefing, noted that “the data that Dr. Mack reported provides key insights into the feasibility of the so-called liquid biopsy.”

“We’re increasingly using genomic data from day-to-day in our clinics to guide therapies,” he said, reiterating that tests such as this provide a useful alternative to tissue-based testing, particularly for the many patients in clinics who have tumors that are challenging to access, such as tumors on bone or near the brain.

“The authors have demonstrated not only the feasibility of the test in detecting alterations, but that the results are often potentially actionable as well ... As oncologists obtain this assay, it’s important to keep in mind trials such as the ASCO-led TAPUR study. TAPUR can potentially link patients with selected genomic alterations to relevant therapies that would otherwise be challenging to access,” he said.

Dr. Pal also noted that there are several other blood-based genomic tests emerging, and it will be important to “rigorously define which of these platforms deliver optimal results.”

Going forward, Dr. Mack and his colleagues will be working to increase the sensitivity of the Gaurdant360 assay to detect mutations at extremely low ctDNA level, as some tumors – glioblastomas, for example – diminish the ability to detect ctDNA. Improved sensitivity could also enable the use of the assay in earlier-stage cancers, he said.

This study was supported by funding from Guardant Health.

[email protected]

NATIONAL HARBOR, MD—The Multiple Sclerosis @Point of Care clinician app, powered by IBM Watson, and the Multiple Sclerosis Association of America (MSAA) patient app My MS Manager facilitate the interface of clinicians and patients with multiple sclerosis (MS) and can lead to changes in MS management and improved patient outcomes, according to a presentation at the 2016 CMSC Annual Meeting. “A growing number of patients are using the My MS Manager app to enter their data, track their MS management, and share this data with their clinicians,” said lead author Elaine Rudell, PhD, CHCP, from @Point of Care in Livingston, New Jersey, and colleagues.

Multiple Sclerosis @Point of Care, powered by IBM Watson, and the patient app, the Multiple Sclerosis Association of America’s My MS Manager, use a HIPAA-compliant mobile platform to provide practice-based tools designed to enable shared decision-making. “These tools provide clinicians with access to evidence-based answers at the point of care while incorporating patient-reported outcomes,” said Dr. Rudell. The clinician platform contains up-to-date information about the etiology, epidemiology, pathophysiology, diagnosis, treatment, and management of MS. A cognitive learning tool answers specific questions clinicians pose to improve patient outcomes. The patient app provides patients with the ability to collect and track data (eg, activities of daily living, fatigue scale records, and medications) as well as utilize their personalized data for follow-up discussion with their health care provider.

In the present study, Dr. Rudell and colleagues sought to assess how clinicians utilize and value Multiple Sclerosis @Point of Care and the companion patient app. Data were collected and analyzed from clinicians caring for patients with MS and their participating patients. Data included demographic information, clinicians’ questions posed to the Ask Watson cognitive learning tool, clinicians’ self-reported impact of content on their patients’ health outcomes, number of registered patient app users, average active users/month, patient access frequency, patient record entries, and proprietary patient survey findings that further assess how patients use and value the app.

Currently, 10,627 clinicians use the platform. These providers spend an average of eight minutes per visit on the Multiple Sclerosis @Point of Care platform. Of these users, 77% are repeat users. Nearly 80% of learners posing questions on demand were neurologists, internists, general practitioners, or family practitioners treating patients with MS.

The patient app had 6,880 registered users at the time of the study, with an average of 1,022 active users per month. Active use of the app by patients with MS in this study resulted in 28,794 journal records for activities of daily living, 1,897 fatigue scale journal records, and 3,640 adherence journal records.

Patients accessed the patient app daily (31%), weekly (46%), and monthly (23%). Nearly 80% of patients reported that the app helps them better track how they are doing. Nearly 80% also agreed that regular use of the patient app improved their ability to discuss and manage their MS. Almost 90% of patient users agreed that the app motivated them to talk with clinicians about MS management. Nearly 75% of patient users shared their records with their clinicians. More than 70% of patients agreed that sharing records with their clinician has improved their MS management and sense of well-being.

Regarding the fatigue scale results, patients also agreed that clinicians are more aware of fatigue’s impact on their daily lives (80% of patient respondents), improved fatigue management (75%), and improved management of fatigue-related cognitive function (65%).

After reviewing patient records, clinicians changed medications (14%), changed other aspects of treatment plans (10%), suggested lifestyle changes (6%), requested more tests (1%), or concurred that treatment was on track (no changes, 69%).

This study was funded by @Point of Care.

—Glenn S. Williams

NATIONAL HARBOR, MD—The Multiple Sclerosis @Point of Care clinician app, powered by IBM Watson, and the Multiple Sclerosis Association of America (MSAA) patient app My MS Manager facilitate the interface of clinicians and patients with multiple sclerosis (MS) and can lead to changes in MS management and improved patient outcomes, according to a presentation at the 2016 CMSC Annual Meeting. “A growing number of patients are using the My MS Manager app to enter their data, track their MS management, and share this data with their clinicians,” said lead author Elaine Rudell, PhD, CHCP, from @Point of Care in Livingston, New Jersey, and colleagues.

Multiple Sclerosis @Point of Care, powered by IBM Watson, and the patient app, the Multiple Sclerosis Association of America’s My MS Manager, use a HIPAA-compliant mobile platform to provide practice-based tools designed to enable shared decision-making. “These tools provide clinicians with access to evidence-based answers at the point of care while incorporating patient-reported outcomes,” said Dr. Rudell. The clinician platform contains up-to-date information about the etiology, epidemiology, pathophysiology, diagnosis, treatment, and management of MS. A cognitive learning tool answers specific questions clinicians pose to improve patient outcomes. The patient app provides patients with the ability to collect and track data (eg, activities of daily living, fatigue scale records, and medications) as well as utilize their personalized data for follow-up discussion with their health care provider.

In the present study, Dr. Rudell and colleagues sought to assess how clinicians utilize and value Multiple Sclerosis @Point of Care and the companion patient app. Data were collected and analyzed from clinicians caring for patients with MS and their participating patients. Data included demographic information, clinicians’ questions posed to the Ask Watson cognitive learning tool, clinicians’ self-reported impact of content on their patients’ health outcomes, number of registered patient app users, average active users/month, patient access frequency, patient record entries, and proprietary patient survey findings that further assess how patients use and value the app.

Currently, 10,627 clinicians use the platform. These providers spend an average of eight minutes per visit on the Multiple Sclerosis @Point of Care platform. Of these users, 77% are repeat users. Nearly 80% of learners posing questions on demand were neurologists, internists, general practitioners, or family practitioners treating patients with MS.

The patient app had 6,880 registered users at the time of the study, with an average of 1,022 active users per month. Active use of the app by patients with MS in this study resulted in 28,794 journal records for activities of daily living, 1,897 fatigue scale journal records, and 3,640 adherence journal records.

Patients accessed the patient app daily (31%), weekly (46%), and monthly (23%). Nearly 80% of patients reported that the app helps them better track how they are doing. Nearly 80% also agreed that regular use of the patient app improved their ability to discuss and manage their MS. Almost 90% of patient users agreed that the app motivated them to talk with clinicians about MS management. Nearly 75% of patient users shared their records with their clinicians. More than 70% of patients agreed that sharing records with their clinician has improved their MS management and sense of well-being.

Regarding the fatigue scale results, patients also agreed that clinicians are more aware of fatigue’s impact on their daily lives (80% of patient respondents), improved fatigue management (75%), and improved management of fatigue-related cognitive function (65%).

After reviewing patient records, clinicians changed medications (14%), changed other aspects of treatment plans (10%), suggested lifestyle changes (6%), requested more tests (1%), or concurred that treatment was on track (no changes, 69%).

This study was funded by @Point of Care.

—Glenn S. Williams

NATIONAL HARBOR, MD—The Multiple Sclerosis @Point of Care clinician app, powered by IBM Watson, and the Multiple Sclerosis Association of America (MSAA) patient app My MS Manager facilitate the interface of clinicians and patients with multiple sclerosis (MS) and can lead to changes in MS management and improved patient outcomes, according to a presentation at the 2016 CMSC Annual Meeting. “A growing number of patients are using the My MS Manager app to enter their data, track their MS management, and share this data with their clinicians,” said lead author Elaine Rudell, PhD, CHCP, from @Point of Care in Livingston, New Jersey, and colleagues.

Multiple Sclerosis @Point of Care, powered by IBM Watson, and the patient app, the Multiple Sclerosis Association of America’s My MS Manager, use a HIPAA-compliant mobile platform to provide practice-based tools designed to enable shared decision-making. “These tools provide clinicians with access to evidence-based answers at the point of care while incorporating patient-reported outcomes,” said Dr. Rudell. The clinician platform contains up-to-date information about the etiology, epidemiology, pathophysiology, diagnosis, treatment, and management of MS. A cognitive learning tool answers specific questions clinicians pose to improve patient outcomes. The patient app provides patients with the ability to collect and track data (eg, activities of daily living, fatigue scale records, and medications) as well as utilize their personalized data for follow-up discussion with their health care provider.

In the present study, Dr. Rudell and colleagues sought to assess how clinicians utilize and value Multiple Sclerosis @Point of Care and the companion patient app. Data were collected and analyzed from clinicians caring for patients with MS and their participating patients. Data included demographic information, clinicians’ questions posed to the Ask Watson cognitive learning tool, clinicians’ self-reported impact of content on their patients’ health outcomes, number of registered patient app users, average active users/month, patient access frequency, patient record entries, and proprietary patient survey findings that further assess how patients use and value the app.

Currently, 10,627 clinicians use the platform. These providers spend an average of eight minutes per visit on the Multiple Sclerosis @Point of Care platform. Of these users, 77% are repeat users. Nearly 80% of learners posing questions on demand were neurologists, internists, general practitioners, or family practitioners treating patients with MS.

The patient app had 6,880 registered users at the time of the study, with an average of 1,022 active users per month. Active use of the app by patients with MS in this study resulted in 28,794 journal records for activities of daily living, 1,897 fatigue scale journal records, and 3,640 adherence journal records.

Patients accessed the patient app daily (31%), weekly (46%), and monthly (23%). Nearly 80% of patients reported that the app helps them better track how they are doing. Nearly 80% also agreed that regular use of the patient app improved their ability to discuss and manage their MS. Almost 90% of patient users agreed that the app motivated them to talk with clinicians about MS management. Nearly 75% of patient users shared their records with their clinicians. More than 70% of patients agreed that sharing records with their clinician has improved their MS management and sense of well-being.

Regarding the fatigue scale results, patients also agreed that clinicians are more aware of fatigue’s impact on their daily lives (80% of patient respondents), improved fatigue management (75%), and improved management of fatigue-related cognitive function (65%).

After reviewing patient records, clinicians changed medications (14%), changed other aspects of treatment plans (10%), suggested lifestyle changes (6%), requested more tests (1%), or concurred that treatment was on track (no changes, 69%).

This study was funded by @Point of Care.

—Glenn S. Williams

A history of trials where a well-reasoned heart failure intervention did not have the expected results is now coloring the way some clinicians view potential new treatments.

A couple of examples of this cautious, skeptical mindset cropped up during the annual meeting of the Heart Failure Association of the European Society of Cardiology in Florence, Italy, in May.

I previously reported on one of the major talks at the sessions, results from a pivotal trial of a phrenic nerve stimulation device in 151 patients with some type of cardiovascular disease (more than half had heart failure) and central sleep apnea. These patients generally had significant improvement in their apnea-hypopnea index while on active treatment with the phrenic nerve stimulator, designed to produce rhythmic contractions of the diaphragm to create negative chest pressure and enhance breathing in a way that mimics natural respiration and avoids the apparent danger from a positive-pressure intervention in patients with central sleep apnea and heart failure with reduced ejection fraction (HFrEF).

The positive-pressure danger in such patients occurred unexpectedly and dramatically in the form of significantly increased mortality among HFrEF patients with central sleep apnea enrolled in the SERVE-HF trial. Based on that chilling experience, “our understanding of central sleep apnea is imperfect,” said Dr. Martin R. Cowie, lead investigator of SERVE-HF, who rehashed his experience with that study during the recent meeting. “A really important message was that just because patients say they feel better [with the adaptive servo-ventilation tested in SERVE-HF], that doesn’t necessarily translate into benefit,” Dr. Cowie noted.

Mitchel L. Zoler/Frontline Medical News

Dr. Mariell L. Jessup, a leading U.S. heart failure expert, had a similar reaction when I spoke with her during the meeting.

“A lot of things made a lot of sense, including treating central sleep apnea in a patient with HFrEF with positive air pressure that made them feel better,” she said, also invoking the specter of SERVE-HF. “We have to now demand that sleep trials show benefit in clinical outcomes,” such as reduced mortality or a cut in heart failure hospitalizations, and certainly no increase in mortality. Until that’s shown for phrenic nerve stimulation she’ll stay a skeptic, she told me.

Another intervention recently available for U.S. heart failure patients that seems on track to confront this “show-me-the-outcomes” attitude involves new drugs that cut serum potassium levels by binding to potassium in the gastrointestinal tract. This class includes patiromer (Veltassa), approved by the Food and Drug Administration in October 2015. Another potassium binder, sodium zirconium cyclosilicate (ZS-9), seems on track to soon receive FDA approval.

Several speakers at the meeting spoke of the potential to use these drugs to control the hyperkalemia that often complicates treatment of heart failure patients with an ACE inhibitor, angiotensin receptor blocker, or a mineralocorticoid receptor antagonist, especially heart failure patients with concomitant renal disease. Study results showed treatment with patiromer or ZS-9 reversed hyperkalemia, thereby allowing patients to remain on these drugs that are known to significantly cut rates of mortality and heart failure hospitalizations in heart failure patients.

Mitchel L. Zoler/Frontline Medical News

“Right now, a lot of patients don’t get these lifesaving drugs” because of hyperkalemia, noted Dr. Bertram Pitt, a University of Michigan cardiologist who has been involved in several patiromer trials (and is a consultant to Relypsa, the company that markets patiromer).

The problem is that no studies of patiromer or ZS-9 treatment have so far shown that these drugs lead to reduced mortality or heart failure hospitalizations in heart failure patients. All that’s been shown is that patiromer and ZS-9 are effective at lowering potassium levels in patients with hyperkalemia out of the danger zone, levels above 5 mEq/L.

“I want to see outcome trials,” said Dr. Jessup.

Dr. Pitt agreed that outcomes data would be ideal, but also noted that currently no studies aimed at collecting these data are underway.

Without these data, clinicians need to decide whether they believe proven potassium lowering alone is a good enough reason to prescribe patiromer or ZS-9, or whether they need to see proof that these drugs give patients clinically meaningful benefits.

If they demand outcomes evidence they may need to wait quite a while.

[email protected]

On Twitter @mitchelzoler

A history of trials where a well-reasoned heart failure intervention did not have the expected results is now coloring the way some clinicians view potential new treatments.

A couple of examples of this cautious, skeptical mindset cropped up during the annual meeting of the Heart Failure Association of the European Society of Cardiology in Florence, Italy, in May.

I previously reported on one of the major talks at the sessions, results from a pivotal trial of a phrenic nerve stimulation device in 151 patients with some type of cardiovascular disease (more than half had heart failure) and central sleep apnea. These patients generally had significant improvement in their apnea-hypopnea index while on active treatment with the phrenic nerve stimulator, designed to produce rhythmic contractions of the diaphragm to create negative chest pressure and enhance breathing in a way that mimics natural respiration and avoids the apparent danger from a positive-pressure intervention in patients with central sleep apnea and heart failure with reduced ejection fraction (HFrEF).

The positive-pressure danger in such patients occurred unexpectedly and dramatically in the form of significantly increased mortality among HFrEF patients with central sleep apnea enrolled in the SERVE-HF trial. Based on that chilling experience, “our understanding of central sleep apnea is imperfect,” said Dr. Martin R. Cowie, lead investigator of SERVE-HF, who rehashed his experience with that study during the recent meeting. “A really important message was that just because patients say they feel better [with the adaptive servo-ventilation tested in SERVE-HF], that doesn’t necessarily translate into benefit,” Dr. Cowie noted.

Mitchel L. Zoler/Frontline Medical News

Dr. Mariell L. Jessup, a leading U.S. heart failure expert, had a similar reaction when I spoke with her during the meeting.

“A lot of things made a lot of sense, including treating central sleep apnea in a patient with HFrEF with positive air pressure that made them feel better,” she said, also invoking the specter of SERVE-HF. “We have to now demand that sleep trials show benefit in clinical outcomes,” such as reduced mortality or a cut in heart failure hospitalizations, and certainly no increase in mortality. Until that’s shown for phrenic nerve stimulation she’ll stay a skeptic, she told me.

Another intervention recently available for U.S. heart failure patients that seems on track to confront this “show-me-the-outcomes” attitude involves new drugs that cut serum potassium levels by binding to potassium in the gastrointestinal tract. This class includes patiromer (Veltassa), approved by the Food and Drug Administration in October 2015. Another potassium binder, sodium zirconium cyclosilicate (ZS-9), seems on track to soon receive FDA approval.

Several speakers at the meeting spoke of the potential to use these drugs to control the hyperkalemia that often complicates treatment of heart failure patients with an ACE inhibitor, angiotensin receptor blocker, or a mineralocorticoid receptor antagonist, especially heart failure patients with concomitant renal disease. Study results showed treatment with patiromer or ZS-9 reversed hyperkalemia, thereby allowing patients to remain on these drugs that are known to significantly cut rates of mortality and heart failure hospitalizations in heart failure patients.

Mitchel L. Zoler/Frontline Medical News

“Right now, a lot of patients don’t get these lifesaving drugs” because of hyperkalemia, noted Dr. Bertram Pitt, a University of Michigan cardiologist who has been involved in several patiromer trials (and is a consultant to Relypsa, the company that markets patiromer).

The problem is that no studies of patiromer or ZS-9 treatment have so far shown that these drugs lead to reduced mortality or heart failure hospitalizations in heart failure patients. All that’s been shown is that patiromer and ZS-9 are effective at lowering potassium levels in patients with hyperkalemia out of the danger zone, levels above 5 mEq/L.

“I want to see outcome trials,” said Dr. Jessup.

Dr. Pitt agreed that outcomes data would be ideal, but also noted that currently no studies aimed at collecting these data are underway.

Without these data, clinicians need to decide whether they believe proven potassium lowering alone is a good enough reason to prescribe patiromer or ZS-9, or whether they need to see proof that these drugs give patients clinically meaningful benefits.

If they demand outcomes evidence they may need to wait quite a while.

[email protected]

On Twitter @mitchelzoler

A history of trials where a well-reasoned heart failure intervention did not have the expected results is now coloring the way some clinicians view potential new treatments.

A couple of examples of this cautious, skeptical mindset cropped up during the annual meeting of the Heart Failure Association of the European Society of Cardiology in Florence, Italy, in May.

I previously reported on one of the major talks at the sessions, results from a pivotal trial of a phrenic nerve stimulation device in 151 patients with some type of cardiovascular disease (more than half had heart failure) and central sleep apnea. These patients generally had significant improvement in their apnea-hypopnea index while on active treatment with the phrenic nerve stimulator, designed to produce rhythmic contractions of the diaphragm to create negative chest pressure and enhance breathing in a way that mimics natural respiration and avoids the apparent danger from a positive-pressure intervention in patients with central sleep apnea and heart failure with reduced ejection fraction (HFrEF).

The positive-pressure danger in such patients occurred unexpectedly and dramatically in the form of significantly increased mortality among HFrEF patients with central sleep apnea enrolled in the SERVE-HF trial. Based on that chilling experience, “our understanding of central sleep apnea is imperfect,” said Dr. Martin R. Cowie, lead investigator of SERVE-HF, who rehashed his experience with that study during the recent meeting. “A really important message was that just because patients say they feel better [with the adaptive servo-ventilation tested in SERVE-HF], that doesn’t necessarily translate into benefit,” Dr. Cowie noted.

Mitchel L. Zoler/Frontline Medical News

Dr. Mariell L. Jessup, a leading U.S. heart failure expert, had a similar reaction when I spoke with her during the meeting.

“A lot of things made a lot of sense, including treating central sleep apnea in a patient with HFrEF with positive air pressure that made them feel better,” she said, also invoking the specter of SERVE-HF. “We have to now demand that sleep trials show benefit in clinical outcomes,” such as reduced mortality or a cut in heart failure hospitalizations, and certainly no increase in mortality. Until that’s shown for phrenic nerve stimulation she’ll stay a skeptic, she told me.

Another intervention recently available for U.S. heart failure patients that seems on track to confront this “show-me-the-outcomes” attitude involves new drugs that cut serum potassium levels by binding to potassium in the gastrointestinal tract. This class includes patiromer (Veltassa), approved by the Food and Drug Administration in October 2015. Another potassium binder, sodium zirconium cyclosilicate (ZS-9), seems on track to soon receive FDA approval.

Several speakers at the meeting spoke of the potential to use these drugs to control the hyperkalemia that often complicates treatment of heart failure patients with an ACE inhibitor, angiotensin receptor blocker, or a mineralocorticoid receptor antagonist, especially heart failure patients with concomitant renal disease. Study results showed treatment with patiromer or ZS-9 reversed hyperkalemia, thereby allowing patients to remain on these drugs that are known to significantly cut rates of mortality and heart failure hospitalizations in heart failure patients.

Mitchel L. Zoler/Frontline Medical News

“Right now, a lot of patients don’t get these lifesaving drugs” because of hyperkalemia, noted Dr. Bertram Pitt, a University of Michigan cardiologist who has been involved in several patiromer trials (and is a consultant to Relypsa, the company that markets patiromer).

The problem is that no studies of patiromer or ZS-9 treatment have so far shown that these drugs lead to reduced mortality or heart failure hospitalizations in heart failure patients. All that’s been shown is that patiromer and ZS-9 are effective at lowering potassium levels in patients with hyperkalemia out of the danger zone, levels above 5 mEq/L.

“I want to see outcome trials,” said Dr. Jessup.

Dr. Pitt agreed that outcomes data would be ideal, but also noted that currently no studies aimed at collecting these data are underway.

Without these data, clinicians need to decide whether they believe proven potassium lowering alone is a good enough reason to prescribe patiromer or ZS-9, or whether they need to see proof that these drugs give patients clinically meaningful benefits.

If they demand outcomes evidence they may need to wait quite a while.

[email protected]

On Twitter @mitchelzoler

Four in 10 women in the United States are obese, 1 in 10 women has a body mass index above 40 kg/m², and significantly more women are obese than a decade ago, according to a large study published June 7 in JAMA.

In contrast, obesity rates among men in the United States have remained stable since 2005, said Dr. Katherine Flegal of the National Center for Health Statistics. “Other studies are needed to determine the reasons for these trends,” she and her associates wrote.

©kikkerdirk/Thinkstockphotos.com

Between 1980 and 2000, obesity rates in the United States rose significantly among both men and women. Between 2000 and 2004, rates rose significantly for men, but not women. Rates then leveled off for both sexes through 2012. To further explore these trends, Dr. Flegal and her associates calculated the prevalence of obesity (BMI greater than 30 kg/m²) and class 3 obesity (BMI greater than 40 kg/m²) for 2,638 men and 2,817 women aged 20 and up during 2013-2014, the most recently available 2-year data period from the National Health and Nutrition Examination Survey (NHANES). The researchers also examined trends in obesity since 2005, based on NHANES data from 21,013 adults (JAMA. 2016 Jun 7. doi: 10.1001/jama.2016.6458).

About 38% of adults in the United States were obese during 2013-2014 (95% confidence interval, 36%-40%), including about 40% of women and 35% of men, the researchers found. A total of 7.7% of adults had a BMI of at least 40, including 5.5 % of men and 9.9% of women.

During the decade from 2005 through 2014, the prevalence of obesity among women rose significantly from 35.6% to 41.1% (P = .004), even after the investigators adjusted for age, race and Hispanic origin, smoking status, and education. Among men, the adjusted prevalence of obesity remained about 35% during this time period. Likewise, the adjusted prevalence of class 3 obesity (BMI of at least 40) rose significantly for women (P = .01), but not for men.

Black women also were significantly more likely to be obese or severely obese, compared with non-Hispanic white women in the study, the investigators found. Among men, current smokers were less likely to be obese than never smokers, and women with education beyond high school were less likely to be obese than women who had not finished high school.

The investigators reported no funding sources and had no disclosures.

Four in 10 women in the United States are obese, 1 in 10 women has a body mass index above 40 kg/m², and significantly more women are obese than a decade ago, according to a large study published June 7 in JAMA.

In contrast, obesity rates among men in the United States have remained stable since 2005, said Dr. Katherine Flegal of the National Center for Health Statistics. “Other studies are needed to determine the reasons for these trends,” she and her associates wrote.

©kikkerdirk/Thinkstockphotos.com

Between 1980 and 2000, obesity rates in the United States rose significantly among both men and women. Between 2000 and 2004, rates rose significantly for men, but not women. Rates then leveled off for both sexes through 2012. To further explore these trends, Dr. Flegal and her associates calculated the prevalence of obesity (BMI greater than 30 kg/m²) and class 3 obesity (BMI greater than 40 kg/m²) for 2,638 men and 2,817 women aged 20 and up during 2013-2014, the most recently available 2-year data period from the National Health and Nutrition Examination Survey (NHANES). The researchers also examined trends in obesity since 2005, based on NHANES data from 21,013 adults (JAMA. 2016 Jun 7. doi: 10.1001/jama.2016.6458).

About 38% of adults in the United States were obese during 2013-2014 (95% confidence interval, 36%-40%), including about 40% of women and 35% of men, the researchers found. A total of 7.7% of adults had a BMI of at least 40, including 5.5 % of men and 9.9% of women.

During the decade from 2005 through 2014, the prevalence of obesity among women rose significantly from 35.6% to 41.1% (P = .004), even after the investigators adjusted for age, race and Hispanic origin, smoking status, and education. Among men, the adjusted prevalence of obesity remained about 35% during this time period. Likewise, the adjusted prevalence of class 3 obesity (BMI of at least 40) rose significantly for women (P = .01), but not for men.

Black women also were significantly more likely to be obese or severely obese, compared with non-Hispanic white women in the study, the investigators found. Among men, current smokers were less likely to be obese than never smokers, and women with education beyond high school were less likely to be obese than women who had not finished high school.

The investigators reported no funding sources and had no disclosures.

Four in 10 women in the United States are obese, 1 in 10 women has a body mass index above 40 kg/m², and significantly more women are obese than a decade ago, according to a large study published June 7 in JAMA.

In contrast, obesity rates among men in the United States have remained stable since 2005, said Dr. Katherine Flegal of the National Center for Health Statistics. “Other studies are needed to determine the reasons for these trends,” she and her associates wrote.

©kikkerdirk/Thinkstockphotos.com

Between 1980 and 2000, obesity rates in the United States rose significantly among both men and women. Between 2000 and 2004, rates rose significantly for men, but not women. Rates then leveled off for both sexes through 2012. To further explore these trends, Dr. Flegal and her associates calculated the prevalence of obesity (BMI greater than 30 kg/m²) and class 3 obesity (BMI greater than 40 kg/m²) for 2,638 men and 2,817 women aged 20 and up during 2013-2014, the most recently available 2-year data period from the National Health and Nutrition Examination Survey (NHANES). The researchers also examined trends in obesity since 2005, based on NHANES data from 21,013 adults (JAMA. 2016 Jun 7. doi: 10.1001/jama.2016.6458).

About 38% of adults in the United States were obese during 2013-2014 (95% confidence interval, 36%-40%), including about 40% of women and 35% of men, the researchers found. A total of 7.7% of adults had a BMI of at least 40, including 5.5 % of men and 9.9% of women.

During the decade from 2005 through 2014, the prevalence of obesity among women rose significantly from 35.6% to 41.1% (P = .004), even after the investigators adjusted for age, race and Hispanic origin, smoking status, and education. Among men, the adjusted prevalence of obesity remained about 35% during this time period. Likewise, the adjusted prevalence of class 3 obesity (BMI of at least 40) rose significantly for women (P = .01), but not for men.

Black women also were significantly more likely to be obese or severely obese, compared with non-Hispanic white women in the study, the investigators found. Among men, current smokers were less likely to be obese than never smokers, and women with education beyond high school were less likely to be obese than women who had not finished high school.

The investigators reported no funding sources and had no disclosures.

The United Kingdom’s National Health Service (NHS) in England has invited around 1.3 million 65-year-old men for abdominal aortic aneurysm (AAA) screening since 2009. Dr. Jonothan Earnshaw and his colleagues performed a study to examine the results of this screening and the safety of the men in surveillance.

The NHS AAA Screening Programme (NAAASP) conducted ultrasound scans to look for AAAs, according to Dr. Earnshaw.

A total of 1,019,480 of those invited were scanned (79.5%). The prevalence of an AAA greater than 2.9 cm diameter was 1.3% (falling from 1.7% in 2009 and 2010 to 1.1% in 2015).

A total of 11,972 men had small (3-4.5 cm) or medium (4.5-5.4 cm) AAAs and were monitored via surveillance, with 13 deaths from AAA rupture.

Some 1,025 men with initial aortic diameter greater than 5.4 cm, and a further 898 men whose AAA grew during surveillance were referred for consideration of elective AAA repair. Mortality in those men who were electively treated was 0.91%.

“Although the prevalence of AAA in 65-year-old men is lower than expected and may be falling, the NAAASP remains cost-effective and is finding large numbers of AAA,” according to Dr. Earnshaw.

“It remains on course to prevent up to half of deaths from ruptured AAA by the end of the decade,” he concluded.

International Forum
3:00 - 6:00 p.m. Thursday
Potomac Ballroom A/B

The United Kingdom’s National Health Service (NHS) in England has invited around 1.3 million 65-year-old men for abdominal aortic aneurysm (AAA) screening since 2009. Dr. Jonothan Earnshaw and his colleagues performed a study to examine the results of this screening and the safety of the men in surveillance.

The NHS AAA Screening Programme (NAAASP) conducted ultrasound scans to look for AAAs, according to Dr. Earnshaw.

A total of 1,019,480 of those invited were scanned (79.5%). The prevalence of an AAA greater than 2.9 cm diameter was 1.3% (falling from 1.7% in 2009 and 2010 to 1.1% in 2015).

A total of 11,972 men had small (3-4.5 cm) or medium (4.5-5.4 cm) AAAs and were monitored via surveillance, with 13 deaths from AAA rupture.

Some 1,025 men with initial aortic diameter greater than 5.4 cm, and a further 898 men whose AAA grew during surveillance were referred for consideration of elective AAA repair. Mortality in those men who were electively treated was 0.91%.

“Although the prevalence of AAA in 65-year-old men is lower than expected and may be falling, the NAAASP remains cost-effective and is finding large numbers of AAA,” according to Dr. Earnshaw.

“It remains on course to prevent up to half of deaths from ruptured AAA by the end of the decade,” he concluded.

International Forum
3:00 - 6:00 p.m. Thursday
Potomac Ballroom A/B

The United Kingdom’s National Health Service (NHS) in England has invited around 1.3 million 65-year-old men for abdominal aortic aneurysm (AAA) screening since 2009. Dr. Jonothan Earnshaw and his colleagues performed a study to examine the results of this screening and the safety of the men in surveillance.

The NHS AAA Screening Programme (NAAASP) conducted ultrasound scans to look for AAAs, according to Dr. Earnshaw.

A total of 1,019,480 of those invited were scanned (79.5%). The prevalence of an AAA greater than 2.9 cm diameter was 1.3% (falling from 1.7% in 2009 and 2010 to 1.1% in 2015).

A total of 11,972 men had small (3-4.5 cm) or medium (4.5-5.4 cm) AAAs and were monitored via surveillance, with 13 deaths from AAA rupture.

Some 1,025 men with initial aortic diameter greater than 5.4 cm, and a further 898 men whose AAA grew during surveillance were referred for consideration of elective AAA repair. Mortality in those men who were electively treated was 0.91%.

“Although the prevalence of AAA in 65-year-old men is lower than expected and may be falling, the NAAASP remains cost-effective and is finding large numbers of AAA,” according to Dr. Earnshaw.

“It remains on course to prevent up to half of deaths from ruptured AAA by the end of the decade,” he concluded.

International Forum
3:00 - 6:00 p.m. Thursday
Potomac Ballroom A/B

Dr. Jeffrey Siracuse will report on the study he and his colleagues performed to analyze practice patterns and outcomes from endovascular treatment of the common femoral (CFA) and deep femoral arteries (DFA). The Vascular Quality Initiative (2010-2015) was queried for all endovascular interventions on the CFA and DFA. They identified 3,960 endovascular CFA/DFA interventions; 1296 (nearly 33%) were isolated to the CFA/DFA. The average age of this isolated cohort was 68 years and 59% were men.

Indications for treatment were claudication (62%), rest pain (18%), and tissue loss (19%). Stents and atherectomy were used in about 28% and 18% of cases, respectively. The intervention was a technical success in nearly 92% of cases.

Perioperative complications included embolization, perforation, access hematoma, and dissection.

They found that thirty-day mortality was 1.6%, with survival of 93% and 87% at 1 and 3 years.

Dr. Siracuse, from the Boston University School of Medicine, will detail their results showing that the significant predictors of mortality were end-stage renal disease (hazard ratio [HR], 3.21, tissue loss, HR, 2.59), combined CFA/DFA intervention (HR, 1.88), chronic obstructive pulmonary disease (HR, 1.73), and nonambulatory status (HR, 1.61).

Freedom from loss of patency/death was 83% at 1 year, according to the researchers. Predictors of patency loss/death were tissue loss (HR, 2.67) and nonambulatory status (HR, 2.17). Freedom from reintervention/death was 83%. Signficant predictors of reintervention or death were tissue loss (HR, 3.52),and stenting (HR, 1.73); with P2Y12 antagonists (HR, 0.62) being signficantly protective.

Amputation-free survival at 1 year was 92%. Significant predictors of amputation/death were tissue loss (HR, 18.9), rest pain (HR, 5.47), previous major amputation (HR, 4.02), and stenting (HR, 2.83), with aspirin use (HR, 0.42) and P2Y12 antagonists (HR, 0.25) being protective.

“Endovascular interventions of the CFA/DFA have a low rate of perioperative morbidity and mortality. One-year patency is lower than historical controls of CFA endarterectomy. Stent use is associated with reinterventions and amputation and should be avoided if possible. Longer-term analysis is needed to better assess durability,” Dr. Siracuse concluded.

VON LIEBIG FORUM
8:30 – 10:00 a.m. Thursday
Potomac Ballroom A/B

Dr. Jeffrey Siracuse will report on the study he and his colleagues performed to analyze practice patterns and outcomes from endovascular treatment of the common femoral (CFA) and deep femoral arteries (DFA). The Vascular Quality Initiative (2010-2015) was queried for all endovascular interventions on the CFA and DFA. They identified 3,960 endovascular CFA/DFA interventions; 1296 (nearly 33%) were isolated to the CFA/DFA. The average age of this isolated cohort was 68 years and 59% were men.

Indications for treatment were claudication (62%), rest pain (18%), and tissue loss (19%). Stents and atherectomy were used in about 28% and 18% of cases, respectively. The intervention was a technical success in nearly 92% of cases.

Perioperative complications included embolization, perforation, access hematoma, and dissection.

They found that thirty-day mortality was 1.6%, with survival of 93% and 87% at 1 and 3 years.

Dr. Siracuse, from the Boston University School of Medicine, will detail their results showing that the significant predictors of mortality were end-stage renal disease (hazard ratio [HR], 3.21, tissue loss, HR, 2.59), combined CFA/DFA intervention (HR, 1.88), chronic obstructive pulmonary disease (HR, 1.73), and nonambulatory status (HR, 1.61).

Freedom from loss of patency/death was 83% at 1 year, according to the researchers. Predictors of patency loss/death were tissue loss (HR, 2.67) and nonambulatory status (HR, 2.17). Freedom from reintervention/death was 83%. Signficant predictors of reintervention or death were tissue loss (HR, 3.52),and stenting (HR, 1.73); with P2Y12 antagonists (HR, 0.62) being signficantly protective.

Amputation-free survival at 1 year was 92%. Significant predictors of amputation/death were tissue loss (HR, 18.9), rest pain (HR, 5.47), previous major amputation (HR, 4.02), and stenting (HR, 2.83), with aspirin use (HR, 0.42) and P2Y12 antagonists (HR, 0.25) being protective.

“Endovascular interventions of the CFA/DFA have a low rate of perioperative morbidity and mortality. One-year patency is lower than historical controls of CFA endarterectomy. Stent use is associated with reinterventions and amputation and should be avoided if possible. Longer-term analysis is needed to better assess durability,” Dr. Siracuse concluded.

VON LIEBIG FORUM
8:30 – 10:00 a.m. Thursday
Potomac Ballroom A/B

Dr. Jeffrey Siracuse will report on the study he and his colleagues performed to analyze practice patterns and outcomes from endovascular treatment of the common femoral (CFA) and deep femoral arteries (DFA). The Vascular Quality Initiative (2010-2015) was queried for all endovascular interventions on the CFA and DFA. They identified 3,960 endovascular CFA/DFA interventions; 1296 (nearly 33%) were isolated to the CFA/DFA. The average age of this isolated cohort was 68 years and 59% were men.

Indications for treatment were claudication (62%), rest pain (18%), and tissue loss (19%). Stents and atherectomy were used in about 28% and 18% of cases, respectively. The intervention was a technical success in nearly 92% of cases.

Perioperative complications included embolization, perforation, access hematoma, and dissection.

They found that thirty-day mortality was 1.6%, with survival of 93% and 87% at 1 and 3 years.

Dr. Siracuse, from the Boston University School of Medicine, will detail their results showing that the significant predictors of mortality were end-stage renal disease (hazard ratio [HR], 3.21, tissue loss, HR, 2.59), combined CFA/DFA intervention (HR, 1.88), chronic obstructive pulmonary disease (HR, 1.73), and nonambulatory status (HR, 1.61).

Freedom from loss of patency/death was 83% at 1 year, according to the researchers. Predictors of patency loss/death were tissue loss (HR, 2.67) and nonambulatory status (HR, 2.17). Freedom from reintervention/death was 83%. Signficant predictors of reintervention or death were tissue loss (HR, 3.52),and stenting (HR, 1.73); with P2Y12 antagonists (HR, 0.62) being signficantly protective.

Amputation-free survival at 1 year was 92%. Significant predictors of amputation/death were tissue loss (HR, 18.9), rest pain (HR, 5.47), previous major amputation (HR, 4.02), and stenting (HR, 2.83), with aspirin use (HR, 0.42) and P2Y12 antagonists (HR, 0.25) being protective.

“Endovascular interventions of the CFA/DFA have a low rate of perioperative morbidity and mortality. One-year patency is lower than historical controls of CFA endarterectomy. Stent use is associated with reinterventions and amputation and should be avoided if possible. Longer-term analysis is needed to better assess durability,” Dr. Siracuse concluded.

VON LIEBIG FORUM
8:30 – 10:00 a.m. Thursday
Potomac Ballroom A/B

NATIONAL HARBOR, MD—Total health care costs increase following initiation of a disease-modifying therapy for multiple sclerosis (MS), but a subsequent overall decrease in health care resource utilization may partially offset the increased costs, according to data presented at the 2016 CMSC Annual Meeting. Upon initiation of disease-modifying therapy, total health care costs increase by $38,561 for patients receiving dimethyl fumarate and by $53,626 for patients receiving fingolimod.

There are limited real-world data on comparative health care resource utilization and costs associated with disease-modifying therapy use in routine clinical practice. Researchers decided to further investigate the effect of the initiation of disease-modifying therapy (ie, dimethyl fumarate, interferon β, glatiramer acetate, teriflunomide, or fingolimod) on health care resource utilization. Jacqueline Nicholas, MD, MPH, a neuroimmunologist at OhioHealth in Columbus, and her colleagues conducted this study.

Researchers used data collected between January 2012 and December 2014 from the Truven MarketScan Commercial Claims Databases, which included administrative claims and eligibility records of 80 million commercially insured people from the United States. Demographic information included age at index date, sex, type of health plan, and region of residence. The mean patient age was 43.2 for patients who initiated glatiramer acetate and 48.6 for patients who initiated teriflunomide. Between 76.9% and 84.1% of patients were female.

Jacqueline Nicholas, MD, MPH

Patients with MS who initiated a disease-modifying therapy in 2013 were analyzed. The index date was defined as the first claim for the disease-modifying therapy. Only patients with no disease-modifying therapy exposure in the year before the index date were included in this study. Researchers evaluated baseline clinical characteristics based on claims dated within one year before the index date and included chronic disease burden (measured using Charlson Comorbidity Index and MS-related symptoms).

Health care resource utilization was defined as the proportion of patients who were hospitalized or who had visited the emergency room during one year before and one year after the index date. Total health care costs were estimated for one year before and one year after the index date. Costs of prescriptions were not included, and costs were adjusted to the 2014 values based on the Consumer Price Index Medical Component.

There was a significant increase in health care costs in the post-index period for all disease-modifying therapies. Patients receiving dimethyl fumarate had a lower increase in their health care costs, compared with patients receiving interferon β, glatiramer acetate, or fingolimod. Following the initiation of disease-modifying therapy, medical costs decreased significantly among patients receiving dimethyl fumarate or interferon β.

Medical cost reductions (excluding prescription medicine costs) were highly dependent on a decreased use of outpatient services and hospital stays, which suggests that the increased costs of disease-modifying therapies are partially offset by reduced health resource utilization and costs.

One limitation of this study was that it focused on health resource utilization and costs only one year before and one year after initiation of disease-modifying therapy. Researchers recommend that future studies assess outcomes over a longer period of time. In addition, the claims data were not collected specifically for clinical research and did not provide the clinical information needed to assess disease severity.

This study was supported by Biogen.

—Erica Robinson

NATIONAL HARBOR, MD—Total health care costs increase following initiation of a disease-modifying therapy for multiple sclerosis (MS), but a subsequent overall decrease in health care resource utilization may partially offset the increased costs, according to data presented at the 2016 CMSC Annual Meeting. Upon initiation of disease-modifying therapy, total health care costs increase by $38,561 for patients receiving dimethyl fumarate and by $53,626 for patients receiving fingolimod.

There are limited real-world data on comparative health care resource utilization and costs associated with disease-modifying therapy use in routine clinical practice. Researchers decided to further investigate the effect of the initiation of disease-modifying therapy (ie, dimethyl fumarate, interferon β, glatiramer acetate, teriflunomide, or fingolimod) on health care resource utilization. Jacqueline Nicholas, MD, MPH, a neuroimmunologist at OhioHealth in Columbus, and her colleagues conducted this study.

Researchers used data collected between January 2012 and December 2014 from the Truven MarketScan Commercial Claims Databases, which included administrative claims and eligibility records of 80 million commercially insured people from the United States. Demographic information included age at index date, sex, type of health plan, and region of residence. The mean patient age was 43.2 for patients who initiated glatiramer acetate and 48.6 for patients who initiated teriflunomide. Between 76.9% and 84.1% of patients were female.

Jacqueline Nicholas, MD, MPH

Patients with MS who initiated a disease-modifying therapy in 2013 were analyzed. The index date was defined as the first claim for the disease-modifying therapy. Only patients with no disease-modifying therapy exposure in the year before the index date were included in this study. Researchers evaluated baseline clinical characteristics based on claims dated within one year before the index date and included chronic disease burden (measured using Charlson Comorbidity Index and MS-related symptoms).

Health care resource utilization was defined as the proportion of patients who were hospitalized or who had visited the emergency room during one year before and one year after the index date. Total health care costs were estimated for one year before and one year after the index date. Costs of prescriptions were not included, and costs were adjusted to the 2014 values based on the Consumer Price Index Medical Component.

There was a significant increase in health care costs in the post-index period for all disease-modifying therapies. Patients receiving dimethyl fumarate had a lower increase in their health care costs, compared with patients receiving interferon β, glatiramer acetate, or fingolimod. Following the initiation of disease-modifying therapy, medical costs decreased significantly among patients receiving dimethyl fumarate or interferon β.

Medical cost reductions (excluding prescription medicine costs) were highly dependent on a decreased use of outpatient services and hospital stays, which suggests that the increased costs of disease-modifying therapies are partially offset by reduced health resource utilization and costs.

One limitation of this study was that it focused on health resource utilization and costs only one year before and one year after initiation of disease-modifying therapy. Researchers recommend that future studies assess outcomes over a longer period of time. In addition, the claims data were not collected specifically for clinical research and did not provide the clinical information needed to assess disease severity.

This study was supported by Biogen.

—Erica Robinson

NATIONAL HARBOR, MD—Total health care costs increase following initiation of a disease-modifying therapy for multiple sclerosis (MS), but a subsequent overall decrease in health care resource utilization may partially offset the increased costs, according to data presented at the 2016 CMSC Annual Meeting. Upon initiation of disease-modifying therapy, total health care costs increase by $38,561 for patients receiving dimethyl fumarate and by $53,626 for patients receiving fingolimod.

There are limited real-world data on comparative health care resource utilization and costs associated with disease-modifying therapy use in routine clinical practice. Researchers decided to further investigate the effect of the initiation of disease-modifying therapy (ie, dimethyl fumarate, interferon β, glatiramer acetate, teriflunomide, or fingolimod) on health care resource utilization. Jacqueline Nicholas, MD, MPH, a neuroimmunologist at OhioHealth in Columbus, and her colleagues conducted this study.

Researchers used data collected between January 2012 and December 2014 from the Truven MarketScan Commercial Claims Databases, which included administrative claims and eligibility records of 80 million commercially insured people from the United States. Demographic information included age at index date, sex, type of health plan, and region of residence. The mean patient age was 43.2 for patients who initiated glatiramer acetate and 48.6 for patients who initiated teriflunomide. Between 76.9% and 84.1% of patients were female.

Jacqueline Nicholas, MD, MPH

Patients with MS who initiated a disease-modifying therapy in 2013 were analyzed. The index date was defined as the first claim for the disease-modifying therapy. Only patients with no disease-modifying therapy exposure in the year before the index date were included in this study. Researchers evaluated baseline clinical characteristics based on claims dated within one year before the index date and included chronic disease burden (measured using Charlson Comorbidity Index and MS-related symptoms).

Health care resource utilization was defined as the proportion of patients who were hospitalized or who had visited the emergency room during one year before and one year after the index date. Total health care costs were estimated for one year before and one year after the index date. Costs of prescriptions were not included, and costs were adjusted to the 2014 values based on the Consumer Price Index Medical Component.

There was a significant increase in health care costs in the post-index period for all disease-modifying therapies. Patients receiving dimethyl fumarate had a lower increase in their health care costs, compared with patients receiving interferon β, glatiramer acetate, or fingolimod. Following the initiation of disease-modifying therapy, medical costs decreased significantly among patients receiving dimethyl fumarate or interferon β.

Medical cost reductions (excluding prescription medicine costs) were highly dependent on a decreased use of outpatient services and hospital stays, which suggests that the increased costs of disease-modifying therapies are partially offset by reduced health resource utilization and costs.

One limitation of this study was that it focused on health resource utilization and costs only one year before and one year after initiation of disease-modifying therapy. Researchers recommend that future studies assess outcomes over a longer period of time. In addition, the claims data were not collected specifically for clinical research and did not provide the clinical information needed to assess disease severity.

This study was supported by Biogen.

—Erica Robinson

Higher hospital and surgeon volumes have been found to be correlated with improved outcomes after open repair of abdominal aortic aneurysm (AAA). However, the effect of both surgeon and hospital volumes on open and endovascular repair (EVAR) in the current era remains unclear, according to Dr. Sara L. Zettervall.

Dr. Zettervall of the Beth Israel Deaconess Medical Center will present a study that she and her colleagues performed on all Medicare beneficiaries who underwent elective AAA repair from 2001 to 2008.

They measured volume by repair type for the 1-year period before repair and assessed all AAA repairs (including elective, ruptured, contiguous, etc.). They used continuous volume and also divided volume into quintiles, which were constructed based on annual volumes across the entire study period for surgeons and hospitals, according to Dr. Zettervall.

A total of 122,495 patients underwent repair of an aortic aneurysm (open: 45,451 patients, EVAR: 77,044).

When examining surgeon and hospital volume together, EVAR perioperative mortality was not signficantly associated with surgeon volume, but was with hospital volume (OR, 1.5), according to Dr. Zettervall.

“Surgeon volume independently predicts mortality following open AAA repair,” said Dr. Zettervall. “In contrast, surgeon volume was not associated with mortality following EVAR, but hospital volume remained associated with patient survival,” she concluded.

Vess Paper
SESSION 1
8:00 – 11:30 a.m. Thursday
Maryland Ballroom A

Higher hospital and surgeon volumes have been found to be correlated with improved outcomes after open repair of abdominal aortic aneurysm (AAA). However, the effect of both surgeon and hospital volumes on open and endovascular repair (EVAR) in the current era remains unclear, according to Dr. Sara L. Zettervall.

Dr. Zettervall of the Beth Israel Deaconess Medical Center will present a study that she and her colleagues performed on all Medicare beneficiaries who underwent elective AAA repair from 2001 to 2008.

They measured volume by repair type for the 1-year period before repair and assessed all AAA repairs (including elective, ruptured, contiguous, etc.). They used continuous volume and also divided volume into quintiles, which were constructed based on annual volumes across the entire study period for surgeons and hospitals, according to Dr. Zettervall.

A total of 122,495 patients underwent repair of an aortic aneurysm (open: 45,451 patients, EVAR: 77,044).

When examining surgeon and hospital volume together, EVAR perioperative mortality was not signficantly associated with surgeon volume, but was with hospital volume (OR, 1.5), according to Dr. Zettervall.

“Surgeon volume independently predicts mortality following open AAA repair,” said Dr. Zettervall. “In contrast, surgeon volume was not associated with mortality following EVAR, but hospital volume remained associated with patient survival,” she concluded.

Vess Paper
SESSION 1
8:00 – 11:30 a.m. Thursday
Maryland Ballroom A

Higher hospital and surgeon volumes have been found to be correlated with improved outcomes after open repair of abdominal aortic aneurysm (AAA). However, the effect of both surgeon and hospital volumes on open and endovascular repair (EVAR) in the current era remains unclear, according to Dr. Sara L. Zettervall.

Dr. Zettervall of the Beth Israel Deaconess Medical Center will present a study that she and her colleagues performed on all Medicare beneficiaries who underwent elective AAA repair from 2001 to 2008.

They measured volume by repair type for the 1-year period before repair and assessed all AAA repairs (including elective, ruptured, contiguous, etc.). They used continuous volume and also divided volume into quintiles, which were constructed based on annual volumes across the entire study period for surgeons and hospitals, according to Dr. Zettervall.

A total of 122,495 patients underwent repair of an aortic aneurysm (open: 45,451 patients, EVAR: 77,044).

When examining surgeon and hospital volume together, EVAR perioperative mortality was not signficantly associated with surgeon volume, but was with hospital volume (OR, 1.5), according to Dr. Zettervall.

“Surgeon volume independently predicts mortality following open AAA repair,” said Dr. Zettervall. “In contrast, surgeon volume was not associated with mortality following EVAR, but hospital volume remained associated with patient survival,” she concluded.

Vess Paper
SESSION 1
8:00 – 11:30 a.m. Thursday
Maryland Ballroom A

NATIONAL HARBOR, MD—After eight years of fingolimod treatment, disability improves or remains stable for a majority of patients with relapsing-remitting multiple sclerosis (MS), according to data presented at the 2016 CMSC Annual Meeting.

The two-year phase III FREEDOMS and FREEDOMS II trial data revealed that fingolimod reduced confirmed disability progression in patients with MS, but evaluating disability over a longer time span may help to determine the full impact of treatment. Shannon Ritter, MD, an employee of Novartis Pharmaceuticals, and her colleagues examined trends in changes in Expanded Disability Status Scale (EDSS) scores over a maximum of eight years. Their objective was to investigate patients’ evolving disability patterns and the impact of fingolimod treatment on long-term disability.

The investigators conducted post hoc analyses that included data collected for as long as 96 months from baseline from patients randomized to fingolimod 0.5 mg or placebo in both two- year FREEDOMS trials. In addition, patients who switched or continued 0.5 mg fingolimod in the extension trials, and those who continuously received 0.5 mg fingolimod in the LONGTERMS trial, were also included in the analysis.

Disability progression was considered minimal if there was an increase or decrease of 0.5 points from a baseline EDSS score of 5.5 or lower, or if there was no change in a baseline score greater than 5.5. Disability was considered to have improved if the baseline EDSS score decreased by 1.0 or more points, either confirmed at six months only, or confirmed at six months and sustained until month 24, 48, or 96. Worsening was defined as an increase of 1.0 point or more from the baseline EDSS score, either confirmed at six months only or confirmed at six months and sustained until month 24, 48, and 96. Stable/improving was defined as the minimal and improving categories combined, and fluctuating was identified as changes in the EDSS score that were different from those defined in other categories.

Results showed that significant improvements were more likely to be noted after longer periods of continuous fingolimod treatment. Disability fluctuated or changed minimally at 24 months, and the proportion of patients in these categories decreased by almost 50% at 96 months. Researchers noted that 22.6% of patients in the continuous fingolimod group were improving, 22.6% were worsening, and 54.7% of patients had minimal change or were fluctuating at 96 months. However, 20% of patients in the switch group were improving, 28% were worsening, and 52% had changed minimally or were fluctuating at 96 months. Overall, the proportion of patients improving or worsening was larger at 96 months than at 24 months.

Researchers also investigated the impact of delaying fingolimod treatment on long-term disability and concluded that patients with worsening disability over 96 months benefited from early fingolimod treatment. Fewer patients in the continuous fingolimod group had worsening disability, compared with the switch group, at 24 months. By 96 months, the continuous fingolimod group maintained proportionally fewer patients with worsening disability, compared with the switch group. The data indicate that the majority of patients receiving continuous fingolimod treatment were either stable or improving at 96 months. Proportionally more patients had improving disability at 96 months, compared to 24 months. These results support the practice of longer follow-up periods to properly detect the impact of treatment.

This study was supported by Oxford PharmaGenesis in Oxford UK, and funded by Novartis Pharmaceuticals.

—Erica Robinson

NATIONAL HARBOR, MD—After eight years of fingolimod treatment, disability improves or remains stable for a majority of patients with relapsing-remitting multiple sclerosis (MS), according to data presented at the 2016 CMSC Annual Meeting.

The two-year phase III FREEDOMS and FREEDOMS II trial data revealed that fingolimod reduced confirmed disability progression in patients with MS, but evaluating disability over a longer time span may help to determine the full impact of treatment. Shannon Ritter, MD, an employee of Novartis Pharmaceuticals, and her colleagues examined trends in changes in Expanded Disability Status Scale (EDSS) scores over a maximum of eight years. Their objective was to investigate patients’ evolving disability patterns and the impact of fingolimod treatment on long-term disability.

The investigators conducted post hoc analyses that included data collected for as long as 96 months from baseline from patients randomized to fingolimod 0.5 mg or placebo in both two- year FREEDOMS trials. In addition, patients who switched or continued 0.5 mg fingolimod in the extension trials, and those who continuously received 0.5 mg fingolimod in the LONGTERMS trial, were also included in the analysis.

Disability progression was considered minimal if there was an increase or decrease of 0.5 points from a baseline EDSS score of 5.5 or lower, or if there was no change in a baseline score greater than 5.5. Disability was considered to have improved if the baseline EDSS score decreased by 1.0 or more points, either confirmed at six months only, or confirmed at six months and sustained until month 24, 48, or 96. Worsening was defined as an increase of 1.0 point or more from the baseline EDSS score, either confirmed at six months only or confirmed at six months and sustained until month 24, 48, and 96. Stable/improving was defined as the minimal and improving categories combined, and fluctuating was identified as changes in the EDSS score that were different from those defined in other categories.

Results showed that significant improvements were more likely to be noted after longer periods of continuous fingolimod treatment. Disability fluctuated or changed minimally at 24 months, and the proportion of patients in these categories decreased by almost 50% at 96 months. Researchers noted that 22.6% of patients in the continuous fingolimod group were improving, 22.6% were worsening, and 54.7% of patients had minimal change or were fluctuating at 96 months. However, 20% of patients in the switch group were improving, 28% were worsening, and 52% had changed minimally or were fluctuating at 96 months. Overall, the proportion of patients improving or worsening was larger at 96 months than at 24 months.

Researchers also investigated the impact of delaying fingolimod treatment on long-term disability and concluded that patients with worsening disability over 96 months benefited from early fingolimod treatment. Fewer patients in the continuous fingolimod group had worsening disability, compared with the switch group, at 24 months. By 96 months, the continuous fingolimod group maintained proportionally fewer patients with worsening disability, compared with the switch group. The data indicate that the majority of patients receiving continuous fingolimod treatment were either stable or improving at 96 months. Proportionally more patients had improving disability at 96 months, compared to 24 months. These results support the practice of longer follow-up periods to properly detect the impact of treatment.

This study was supported by Oxford PharmaGenesis in Oxford UK, and funded by Novartis Pharmaceuticals.

—Erica Robinson

NATIONAL HARBOR, MD—After eight years of fingolimod treatment, disability improves or remains stable for a majority of patients with relapsing-remitting multiple sclerosis (MS), according to data presented at the 2016 CMSC Annual Meeting.

The two-year phase III FREEDOMS and FREEDOMS II trial data revealed that fingolimod reduced confirmed disability progression in patients with MS, but evaluating disability over a longer time span may help to determine the full impact of treatment. Shannon Ritter, MD, an employee of Novartis Pharmaceuticals, and her colleagues examined trends in changes in Expanded Disability Status Scale (EDSS) scores over a maximum of eight years. Their objective was to investigate patients’ evolving disability patterns and the impact of fingolimod treatment on long-term disability.

The investigators conducted post hoc analyses that included data collected for as long as 96 months from baseline from patients randomized to fingolimod 0.5 mg or placebo in both two- year FREEDOMS trials. In addition, patients who switched or continued 0.5 mg fingolimod in the extension trials, and those who continuously received 0.5 mg fingolimod in the LONGTERMS trial, were also included in the analysis.

Disability progression was considered minimal if there was an increase or decrease of 0.5 points from a baseline EDSS score of 5.5 or lower, or if there was no change in a baseline score greater than 5.5. Disability was considered to have improved if the baseline EDSS score decreased by 1.0 or more points, either confirmed at six months only, or confirmed at six months and sustained until month 24, 48, or 96. Worsening was defined as an increase of 1.0 point or more from the baseline EDSS score, either confirmed at six months only or confirmed at six months and sustained until month 24, 48, and 96. Stable/improving was defined as the minimal and improving categories combined, and fluctuating was identified as changes in the EDSS score that were different from those defined in other categories.

Results showed that significant improvements were more likely to be noted after longer periods of continuous fingolimod treatment. Disability fluctuated or changed minimally at 24 months, and the proportion of patients in these categories decreased by almost 50% at 96 months. Researchers noted that 22.6% of patients in the continuous fingolimod group were improving, 22.6% were worsening, and 54.7% of patients had minimal change or were fluctuating at 96 months. However, 20% of patients in the switch group were improving, 28% were worsening, and 52% had changed minimally or were fluctuating at 96 months. Overall, the proportion of patients improving or worsening was larger at 96 months than at 24 months.

Researchers also investigated the impact of delaying fingolimod treatment on long-term disability and concluded that patients with worsening disability over 96 months benefited from early fingolimod treatment. Fewer patients in the continuous fingolimod group had worsening disability, compared with the switch group, at 24 months. By 96 months, the continuous fingolimod group maintained proportionally fewer patients with worsening disability, compared with the switch group. The data indicate that the majority of patients receiving continuous fingolimod treatment were either stable or improving at 96 months. Proportionally more patients had improving disability at 96 months, compared to 24 months. These results support the practice of longer follow-up periods to properly detect the impact of treatment.

This study was supported by Oxford PharmaGenesis in Oxford UK, and funded by Novartis Pharmaceuticals.

—Erica Robinson

CHICAGO – The novel antibody IMAB362 extended survival of patients with advanced gastric cancer when added to chemotherapy, according to a phase II trial presented at the annual meeting of the Society of Clinical Oncology.

IMAB362 is a first-in-class monoclonal antibody targeting claudin18.2, a protein component of cellular tight junctions abundant in gastric tumors, as well as tumors of the pancreas, lung, esophagus, and ovaries.

IMAB362 significantly extended median overall survival (OS) when added to standard chemotherapy (13.2 vs. 8.4 months, hazard ratio [HR] = 0.51, P = .0001). Patients with the highest levels of claudin18.2 had an even longer median overall survival (16.7 vs. 9.0 months, HR = 0.45, P less than .0005).

The FAST (Phase II First-Line Therapy in Patients With Advanced CLDN18.2+ Gastric and Gastroesophageal Junction Adenocarcinoma) trial included patients who had no prior chemotherapy for locally advanced or metastatic disease. Tumors had to have 2+/3+ CLDN18.2 expression in 40% or more of tumor cells, and patients had an Eastern Cooperative Oncology Group performance status of 0-1.

Patients with tumors that expressed higher levels of claudin18,2, the target antigen, did better than the overall cohort in terms of progression-free survival (PFS), the primary endpoint.

“The FAST trial clearly met its primary endpoint, and there is a significant improvement in PFS and OS in the entire cohort and also in the higher expressers,” lead author Dr. Salah-Eddin Al-Batran, medical director of the Institute of Clinical Cancer Research, Nordwest Hospital in Frankfurst am Main, Germany, said in a news conference at the meeting.

The IMAB362 monoclonal antibody is highly specific for CLDN18.2 and works through antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. In combination with chemotherapy, by binding to tumor debris, it is an immunomodulator of the tumor microenvironment.

About 50% of gastric tumors express CLDN18.2. After screening, the investigators randomized 246 patients to three treatment arms: epirubicin/oxaliplatin/capecitabine (EOX), n = 84; EOX + IMAB362 at a loading dose of 800 mg/m², then 600 mg/m² on day 1 every 3 weeks, n = 77; or a higher dose of IMAB362 with EOX, n = 85. Dr. Al-Batran reported results of the first two arms and will present results for the third arm at a later time.

Median progression-free survival was 4.8 months with EOX and 7.9 months with EOX plus IMAB362 (HR = .47; P = .0001).

If 70% or more of the tumor cells expressed CLDN18.2, IMAB362 improved the median PFS from 5.6 months for EOX alone to 7.2 months (HR = 0.36, P less than .0005), and OS improved from 9 months to 16.7 months (HR = 0.45, P less than .0005).

Response rates were also better with the addition of IMAB362. The objective response rate by RECIST criteria was 39.0% with EOX + IMAB362 vs. 25.0% with EOX alone. Most of the responses were partial (28.6% vs. 21.4%, respectively) or stable disease (44.2% vs. 51.2%, respectively). There were only 10.4% complete responses with IMAB362 and 3.6% with EOX alone. About 12% of the patients in each arm were not evaluable, or the data were missing.

Both treatments were well tolerated, with most adverse effects being grade 1/2. However, there was more grade 3/4 neutropenia with the combination (32.5% vs. 21.4% for EOX alone) as well as grade 3/4 vomiting (10.4% vs. 3.6%, respectively). Grade 1/2 vomiting was common in both arms, with about one-third of patients receiving EOX alone and just over half of patients on EOX + IMAB362 being affected.

Susan London

Dr. Al-Batran said that there may have been more vomiting with IMAB362 because tight junction proteins, including claudin, are present in the gastric mucosa. Diarrhea was largely grade 1/2, affected about one-third of patients receiving EOX alone, and was only about half as common among patients receiving the combination.

Dr. Al-Batran said this trial “provides a strong rationale for a confirmatory phase III trial.”

Press conference moderator Dr. Smitha Krishnamurthi said the study is important because it documents the activity of a first-in-class antibody in patients with advanced gastric and gastroesophageal junction cancers. Since CLDN18.2 is expressed in about 50% of these cancers, “this treatment could apply to many patients,” she said.

The study was initiated and sponsored by Ganymed Pharmaceuticals. Dr. Al-Batran has had a consulting or advisory role with Merck, Roche, Celgene, and Lilly; has been on the speakers bureau of Lilly, Roche, Celgene, and Nordic Bioscience; and has received research funding from Celgene, Roche Pharma, Lilly, Novartis, Vfor Pharma, Medac, and Hospira.

On Twitter @OncologyPractic

CHICAGO – The novel antibody IMAB362 extended survival of patients with advanced gastric cancer when added to chemotherapy, according to a phase II trial presented at the annual meeting of the Society of Clinical Oncology.

IMAB362 is a first-in-class monoclonal antibody targeting claudin18.2, a protein component of cellular tight junctions abundant in gastric tumors, as well as tumors of the pancreas, lung, esophagus, and ovaries.

IMAB362 significantly extended median overall survival (OS) when added to standard chemotherapy (13.2 vs. 8.4 months, hazard ratio [HR] = 0.51, P = .0001). Patients with the highest levels of claudin18.2 had an even longer median overall survival (16.7 vs. 9.0 months, HR = 0.45, P less than .0005).

The FAST (Phase II First-Line Therapy in Patients With Advanced CLDN18.2+ Gastric and Gastroesophageal Junction Adenocarcinoma) trial included patients who had no prior chemotherapy for locally advanced or metastatic disease. Tumors had to have 2+/3+ CLDN18.2 expression in 40% or more of tumor cells, and patients had an Eastern Cooperative Oncology Group performance status of 0-1.

Patients with tumors that expressed higher levels of claudin18,2, the target antigen, did better than the overall cohort in terms of progression-free survival (PFS), the primary endpoint.

“The FAST trial clearly met its primary endpoint, and there is a significant improvement in PFS and OS in the entire cohort and also in the higher expressers,” lead author Dr. Salah-Eddin Al-Batran, medical director of the Institute of Clinical Cancer Research, Nordwest Hospital in Frankfurst am Main, Germany, said in a news conference at the meeting.

The IMAB362 monoclonal antibody is highly specific for CLDN18.2 and works through antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. In combination with chemotherapy, by binding to tumor debris, it is an immunomodulator of the tumor microenvironment.

About 50% of gastric tumors express CLDN18.2. After screening, the investigators randomized 246 patients to three treatment arms: epirubicin/oxaliplatin/capecitabine (EOX), n = 84; EOX + IMAB362 at a loading dose of 800 mg/m², then 600 mg/m² on day 1 every 3 weeks, n = 77; or a higher dose of IMAB362 with EOX, n = 85. Dr. Al-Batran reported results of the first two arms and will present results for the third arm at a later time.

Median progression-free survival was 4.8 months with EOX and 7.9 months with EOX plus IMAB362 (HR = .47; P = .0001).

If 70% or more of the tumor cells expressed CLDN18.2, IMAB362 improved the median PFS from 5.6 months for EOX alone to 7.2 months (HR = 0.36, P less than .0005), and OS improved from 9 months to 16.7 months (HR = 0.45, P less than .0005).

Response rates were also better with the addition of IMAB362. The objective response rate by RECIST criteria was 39.0% with EOX + IMAB362 vs. 25.0% with EOX alone. Most of the responses were partial (28.6% vs. 21.4%, respectively) or stable disease (44.2% vs. 51.2%, respectively). There were only 10.4% complete responses with IMAB362 and 3.6% with EOX alone. About 12% of the patients in each arm were not evaluable, or the data were missing.

Both treatments were well tolerated, with most adverse effects being grade 1/2. However, there was more grade 3/4 neutropenia with the combination (32.5% vs. 21.4% for EOX alone) as well as grade 3/4 vomiting (10.4% vs. 3.6%, respectively). Grade 1/2 vomiting was common in both arms, with about one-third of patients receiving EOX alone and just over half of patients on EOX + IMAB362 being affected.

Susan London

Dr. Al-Batran said that there may have been more vomiting with IMAB362 because tight junction proteins, including claudin, are present in the gastric mucosa. Diarrhea was largely grade 1/2, affected about one-third of patients receiving EOX alone, and was only about half as common among patients receiving the combination.

Dr. Al-Batran said this trial “provides a strong rationale for a confirmatory phase III trial.”

Press conference moderator Dr. Smitha Krishnamurthi said the study is important because it documents the activity of a first-in-class antibody in patients with advanced gastric and gastroesophageal junction cancers. Since CLDN18.2 is expressed in about 50% of these cancers, “this treatment could apply to many patients,” she said.

The study was initiated and sponsored by Ganymed Pharmaceuticals. Dr. Al-Batran has had a consulting or advisory role with Merck, Roche, Celgene, and Lilly; has been on the speakers bureau of Lilly, Roche, Celgene, and Nordic Bioscience; and has received research funding from Celgene, Roche Pharma, Lilly, Novartis, Vfor Pharma, Medac, and Hospira.

On Twitter @OncologyPractic

CHICAGO – The novel antibody IMAB362 extended survival of patients with advanced gastric cancer when added to chemotherapy, according to a phase II trial presented at the annual meeting of the Society of Clinical Oncology.

IMAB362 is a first-in-class monoclonal antibody targeting claudin18.2, a protein component of cellular tight junctions abundant in gastric tumors, as well as tumors of the pancreas, lung, esophagus, and ovaries.

IMAB362 significantly extended median overall survival (OS) when added to standard chemotherapy (13.2 vs. 8.4 months, hazard ratio [HR] = 0.51, P = .0001). Patients with the highest levels of claudin18.2 had an even longer median overall survival (16.7 vs. 9.0 months, HR = 0.45, P less than .0005).

The FAST (Phase II First-Line Therapy in Patients With Advanced CLDN18.2+ Gastric and Gastroesophageal Junction Adenocarcinoma) trial included patients who had no prior chemotherapy for locally advanced or metastatic disease. Tumors had to have 2+/3+ CLDN18.2 expression in 40% or more of tumor cells, and patients had an Eastern Cooperative Oncology Group performance status of 0-1.

Patients with tumors that expressed higher levels of claudin18,2, the target antigen, did better than the overall cohort in terms of progression-free survival (PFS), the primary endpoint.

“The FAST trial clearly met its primary endpoint, and there is a significant improvement in PFS and OS in the entire cohort and also in the higher expressers,” lead author Dr. Salah-Eddin Al-Batran, medical director of the Institute of Clinical Cancer Research, Nordwest Hospital in Frankfurst am Main, Germany, said in a news conference at the meeting.

The IMAB362 monoclonal antibody is highly specific for CLDN18.2 and works through antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. In combination with chemotherapy, by binding to tumor debris, it is an immunomodulator of the tumor microenvironment.

About 50% of gastric tumors express CLDN18.2. After screening, the investigators randomized 246 patients to three treatment arms: epirubicin/oxaliplatin/capecitabine (EOX), n = 84; EOX + IMAB362 at a loading dose of 800 mg/m², then 600 mg/m² on day 1 every 3 weeks, n = 77; or a higher dose of IMAB362 with EOX, n = 85. Dr. Al-Batran reported results of the first two arms and will present results for the third arm at a later time.

Median progression-free survival was 4.8 months with EOX and 7.9 months with EOX plus IMAB362 (HR = .47; P = .0001).

If 70% or more of the tumor cells expressed CLDN18.2, IMAB362 improved the median PFS from 5.6 months for EOX alone to 7.2 months (HR = 0.36, P less than .0005), and OS improved from 9 months to 16.7 months (HR = 0.45, P less than .0005).

Response rates were also better with the addition of IMAB362. The objective response rate by RECIST criteria was 39.0% with EOX + IMAB362 vs. 25.0% with EOX alone. Most of the responses were partial (28.6% vs. 21.4%, respectively) or stable disease (44.2% vs. 51.2%, respectively). There were only 10.4% complete responses with IMAB362 and 3.6% with EOX alone. About 12% of the patients in each arm were not evaluable, or the data were missing.

Both treatments were well tolerated, with most adverse effects being grade 1/2. However, there was more grade 3/4 neutropenia with the combination (32.5% vs. 21.4% for EOX alone) as well as grade 3/4 vomiting (10.4% vs. 3.6%, respectively). Grade 1/2 vomiting was common in both arms, with about one-third of patients receiving EOX alone and just over half of patients on EOX + IMAB362 being affected.

Susan London

Dr. Al-Batran said that there may have been more vomiting with IMAB362 because tight junction proteins, including claudin, are present in the gastric mucosa. Diarrhea was largely grade 1/2, affected about one-third of patients receiving EOX alone, and was only about half as common among patients receiving the combination.

Dr. Al-Batran said this trial “provides a strong rationale for a confirmatory phase III trial.”

Press conference moderator Dr. Smitha Krishnamurthi said the study is important because it documents the activity of a first-in-class antibody in patients with advanced gastric and gastroesophageal junction cancers. Since CLDN18.2 is expressed in about 50% of these cancers, “this treatment could apply to many patients,” she said.

The study was initiated and sponsored by Ganymed Pharmaceuticals. Dr. Al-Batran has had a consulting or advisory role with Merck, Roche, Celgene, and Lilly; has been on the speakers bureau of Lilly, Roche, Celgene, and Nordic Bioscience; and has received research funding from Celgene, Roche Pharma, Lilly, Novartis, Vfor Pharma, Medac, and Hospira.

On Twitter @OncologyPractic