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Mitchel is a reporter for MDedge based in the Philadelphia area. He started with the company in 1992, when it was International Medical News Group (IMNG), and has since covered a range of medical specialties. Mitchel trained as a virologist at Roswell Park Memorial Institute in Buffalo, and then worked briefly as a researcher at Boston Children's Hospital before pivoting to journalism as a AAAS Mass Media Fellow in 1980. His first reporting job was with Science Digest magazine, and from the mid-1980s to early-1990s he was a reporter with Medical World News. @mitchelzoler
A Fib ablation surpasses drugs for improving quality of life
BARCELONA – Catheter ablation of symptomatic atrial fibrillation produced significantly better quality of life after 12 months than did continued treatment with antiarrhythmic drugs in a randomized, multicenter trial with 155 patients who had a history of failed drug treatment.
The trial was notable as the first prospective comparison of atrial fibrillation (AF) management by ablation with drug treatment to use quality of life as the primary efficacy endpoint. Such a quality of life–oriented assessment has been lacking “even though the main indication for ablation is symptom relief,” Carina Blomström-Lundqvist, MD, said at the annual congress of the European Society of Cardiology.
Clinicians have traditionally measured residual or recurrent AF after treatment with a periodic ECG to see whether patients experience AF episodes that last at least 30 seconds, but this is “hardly a measure of successful treatment,” said Dr. Blomström-Lundqvist, an electrophysiologist at the University Hospital in Uppsala, Sweden.
She and her associates placed an implanted cardiac monitor into each patient for continuous measurement of residual AF episodes. Twelve months after entry into the study, patients who underwent ablation had their AF burden decreased by an average of 20 percentage points compared with baseline, while the AF burden dropped by an average of 12 percentage points among patients maintained on antiarrhythmic drugs, a between-group difference that was not statistically significant.
Based on that finding, Dr. Blomström-Lundqvist inferred that the significantly better improvement in quality of life seen with ablation compared with drug treatment occurred because the ablated patients all came off antiarrhythmic drug treatment. The study protocol required patients randomized to the ablation regimen to be completely off antiarrhythmic drugs by 6 months after their ablation procedure.
Continued treatment with an antiarrhythmic drug in the drug-arm patients compared with no drug treatment in the ablated patients “is absolutely the explanation” for the observed difference in quality of life, she said. Patients randomized to the antiarrhythmic drug arm of the study received treatment with one of six eligible drugs: amiodarone, disopyramide, dronedarone, flecainide, propafenone, or sotalol. Patients could also be on a beta-blocker.
The Catheter Ablation Compared With Pharmacological Therapy for Atrial Fibrillation (CAPTAF) trial enrolled symptomatic patients with paroxysmal or persistent AF at four Swedish centers and at one center in Finland. All enrolled patients had to have a history of being refractory to or intolerant of a beta-blocker or an antiarrhythmic drug. Patients with paroxysmal AF had to have experienced an AF episode within the prior 2 months, while those with persistent AF had to have had at least two AF episodes within the prior year. The average age of the enrolled patients was 56 years. Nearly three-quarters had paroxysmal AF. Their average AF burden was about a quarter of the time, on average they had been diagnosed with AF for about 5 years, and 70%-80% of the patients had severe or disabling symptoms. At entry, about 90% of patients were on beta-blocker treatment and a bit more than a third were taking an antiarrhythmic drug.
The researchers measured quality of life using the 36-item Short Form Survey Instrument (SF-36). At baseline, the average SF-36 score (measured on a 0-100 scale) was 63 in the 79 patients randomized to ablation and 62 in 76 patients randomized for drug therapy. Patients randomized to an ablation procedure underwent pulmonary vein isolation by whatever technique their attending cardiologists preferred.
The average SF-36 score 12 months after study entry was 73 for the ablation patients, an average gain from baseline of 11 points, and 65 in the drug-treated patients, an average gain of 3 points. The 8-point difference in SF-36 gain between the two groups was statistically significant.
Contributing to the overall superiority of ablation for improving quality of life were statistically significant advantages for ablation over drug treatment in the individual SF-36 domains of general health, physical function, mental health, role-emotional, role-physical, and vitality. The two treatment arms of the study showed no significant differences in the two remaining SF-36 domains of bodily pain and social functioning.
Nine of the 79 patients (11%) who underwent ablation had a procedure-related serious adverse event, including four patients with an infection or septicemia, two patients with tamponade or pericardial effusion, one patient with a transient ischemic attack, and two with a different vascular complication. Serious cardiovascular adverse events during the 12 month follow-up occurred in 14 of the ablated patients (18%) and in 18 of the drug-treated patients (24%), a between-group difference that did not undergo statistical analysis. Dr. Blomström-Lundqvist called the rates “comparable,” but cautioned that the study was not powered to compare serious adverse event rates in the two treatment arms.
Héctor Bueno, MD, a cardiologist at the Spanish National Center for Cardiovascular Research in Madrid and a cochair of the session that included the CAPTAF report, voiced concern about the procedure-related serious adverse events among patients who underwent ablation.
“An 11% serious complication rate is not negligible,” he said. “Some of them were really serious complications.”
[email protected]
On Twitter @mitchelzoler
The CAPTAF trial is the first time that atrial fibrillation ablation has been compared with drug treatment in a prospective study that used quality of life as its primary endpoint. All of the prior prospective comparisons used atrial fibrillation recurrence as their endpoint. Prior reports that looked at the impact of treatment on quality of life were retrospective analyses.
The CAPTAF trial introduces a new way to prospectively assess the efficacy of atrial fibrillation (AF) treatment, and it is a game changer for how we follow patients. All future AF trials should now include quality-of-life assessment. To fully assess the success of AF treatment a clinician needs to do more than get an ECG at follow-up clinic visits because these only give a “snapshot” of a patient’s AF burden.
The CAPTAF results also confirm that pulmonary vein isolation is a reproducible ablation technique for both paroxysmal and persistent AF. The study also shows that implanted cardiac monitors are a very useful and practical tool for more comprehensively measuring rhythm outcomes following AF treatment.
Nassir F. Marrouche, MD, is an electrophysiologist and professor of medicine at the University of Utah in Salt Lake City. He has been a consultant to Abbott, Biosense Webster, Biotronik, Boston Scientific, Cardiac Design, Marrek, Medtronic, Preventice, Vytronus, and Wavelet Health, and he has received research funding from Abbott, Biosense Webster, Biotronik, Boston Scientific, GE Healthcare, Siemens, and Vytronus. He made these comments as designated discussant for the report.
The CAPTAF trial is the first time that atrial fibrillation ablation has been compared with drug treatment in a prospective study that used quality of life as its primary endpoint. All of the prior prospective comparisons used atrial fibrillation recurrence as their endpoint. Prior reports that looked at the impact of treatment on quality of life were retrospective analyses.
The CAPTAF trial introduces a new way to prospectively assess the efficacy of atrial fibrillation (AF) treatment, and it is a game changer for how we follow patients. All future AF trials should now include quality-of-life assessment. To fully assess the success of AF treatment a clinician needs to do more than get an ECG at follow-up clinic visits because these only give a “snapshot” of a patient’s AF burden.
The CAPTAF results also confirm that pulmonary vein isolation is a reproducible ablation technique for both paroxysmal and persistent AF. The study also shows that implanted cardiac monitors are a very useful and practical tool for more comprehensively measuring rhythm outcomes following AF treatment.
Nassir F. Marrouche, MD, is an electrophysiologist and professor of medicine at the University of Utah in Salt Lake City. He has been a consultant to Abbott, Biosense Webster, Biotronik, Boston Scientific, Cardiac Design, Marrek, Medtronic, Preventice, Vytronus, and Wavelet Health, and he has received research funding from Abbott, Biosense Webster, Biotronik, Boston Scientific, GE Healthcare, Siemens, and Vytronus. He made these comments as designated discussant for the report.
The CAPTAF trial is the first time that atrial fibrillation ablation has been compared with drug treatment in a prospective study that used quality of life as its primary endpoint. All of the prior prospective comparisons used atrial fibrillation recurrence as their endpoint. Prior reports that looked at the impact of treatment on quality of life were retrospective analyses.
The CAPTAF trial introduces a new way to prospectively assess the efficacy of atrial fibrillation (AF) treatment, and it is a game changer for how we follow patients. All future AF trials should now include quality-of-life assessment. To fully assess the success of AF treatment a clinician needs to do more than get an ECG at follow-up clinic visits because these only give a “snapshot” of a patient’s AF burden.
The CAPTAF results also confirm that pulmonary vein isolation is a reproducible ablation technique for both paroxysmal and persistent AF. The study also shows that implanted cardiac monitors are a very useful and practical tool for more comprehensively measuring rhythm outcomes following AF treatment.
Nassir F. Marrouche, MD, is an electrophysiologist and professor of medicine at the University of Utah in Salt Lake City. He has been a consultant to Abbott, Biosense Webster, Biotronik, Boston Scientific, Cardiac Design, Marrek, Medtronic, Preventice, Vytronus, and Wavelet Health, and he has received research funding from Abbott, Biosense Webster, Biotronik, Boston Scientific, GE Healthcare, Siemens, and Vytronus. He made these comments as designated discussant for the report.
BARCELONA – Catheter ablation of symptomatic atrial fibrillation produced significantly better quality of life after 12 months than did continued treatment with antiarrhythmic drugs in a randomized, multicenter trial with 155 patients who had a history of failed drug treatment.
The trial was notable as the first prospective comparison of atrial fibrillation (AF) management by ablation with drug treatment to use quality of life as the primary efficacy endpoint. Such a quality of life–oriented assessment has been lacking “even though the main indication for ablation is symptom relief,” Carina Blomström-Lundqvist, MD, said at the annual congress of the European Society of Cardiology.
Clinicians have traditionally measured residual or recurrent AF after treatment with a periodic ECG to see whether patients experience AF episodes that last at least 30 seconds, but this is “hardly a measure of successful treatment,” said Dr. Blomström-Lundqvist, an electrophysiologist at the University Hospital in Uppsala, Sweden.
She and her associates placed an implanted cardiac monitor into each patient for continuous measurement of residual AF episodes. Twelve months after entry into the study, patients who underwent ablation had their AF burden decreased by an average of 20 percentage points compared with baseline, while the AF burden dropped by an average of 12 percentage points among patients maintained on antiarrhythmic drugs, a between-group difference that was not statistically significant.
Based on that finding, Dr. Blomström-Lundqvist inferred that the significantly better improvement in quality of life seen with ablation compared with drug treatment occurred because the ablated patients all came off antiarrhythmic drug treatment. The study protocol required patients randomized to the ablation regimen to be completely off antiarrhythmic drugs by 6 months after their ablation procedure.
Continued treatment with an antiarrhythmic drug in the drug-arm patients compared with no drug treatment in the ablated patients “is absolutely the explanation” for the observed difference in quality of life, she said. Patients randomized to the antiarrhythmic drug arm of the study received treatment with one of six eligible drugs: amiodarone, disopyramide, dronedarone, flecainide, propafenone, or sotalol. Patients could also be on a beta-blocker.
The Catheter Ablation Compared With Pharmacological Therapy for Atrial Fibrillation (CAPTAF) trial enrolled symptomatic patients with paroxysmal or persistent AF at four Swedish centers and at one center in Finland. All enrolled patients had to have a history of being refractory to or intolerant of a beta-blocker or an antiarrhythmic drug. Patients with paroxysmal AF had to have experienced an AF episode within the prior 2 months, while those with persistent AF had to have had at least two AF episodes within the prior year. The average age of the enrolled patients was 56 years. Nearly three-quarters had paroxysmal AF. Their average AF burden was about a quarter of the time, on average they had been diagnosed with AF for about 5 years, and 70%-80% of the patients had severe or disabling symptoms. At entry, about 90% of patients were on beta-blocker treatment and a bit more than a third were taking an antiarrhythmic drug.
The researchers measured quality of life using the 36-item Short Form Survey Instrument (SF-36). At baseline, the average SF-36 score (measured on a 0-100 scale) was 63 in the 79 patients randomized to ablation and 62 in 76 patients randomized for drug therapy. Patients randomized to an ablation procedure underwent pulmonary vein isolation by whatever technique their attending cardiologists preferred.
The average SF-36 score 12 months after study entry was 73 for the ablation patients, an average gain from baseline of 11 points, and 65 in the drug-treated patients, an average gain of 3 points. The 8-point difference in SF-36 gain between the two groups was statistically significant.
Contributing to the overall superiority of ablation for improving quality of life were statistically significant advantages for ablation over drug treatment in the individual SF-36 domains of general health, physical function, mental health, role-emotional, role-physical, and vitality. The two treatment arms of the study showed no significant differences in the two remaining SF-36 domains of bodily pain and social functioning.
Nine of the 79 patients (11%) who underwent ablation had a procedure-related serious adverse event, including four patients with an infection or septicemia, two patients with tamponade or pericardial effusion, one patient with a transient ischemic attack, and two with a different vascular complication. Serious cardiovascular adverse events during the 12 month follow-up occurred in 14 of the ablated patients (18%) and in 18 of the drug-treated patients (24%), a between-group difference that did not undergo statistical analysis. Dr. Blomström-Lundqvist called the rates “comparable,” but cautioned that the study was not powered to compare serious adverse event rates in the two treatment arms.
Héctor Bueno, MD, a cardiologist at the Spanish National Center for Cardiovascular Research in Madrid and a cochair of the session that included the CAPTAF report, voiced concern about the procedure-related serious adverse events among patients who underwent ablation.
“An 11% serious complication rate is not negligible,” he said. “Some of them were really serious complications.”
[email protected]
On Twitter @mitchelzoler
BARCELONA – Catheter ablation of symptomatic atrial fibrillation produced significantly better quality of life after 12 months than did continued treatment with antiarrhythmic drugs in a randomized, multicenter trial with 155 patients who had a history of failed drug treatment.
The trial was notable as the first prospective comparison of atrial fibrillation (AF) management by ablation with drug treatment to use quality of life as the primary efficacy endpoint. Such a quality of life–oriented assessment has been lacking “even though the main indication for ablation is symptom relief,” Carina Blomström-Lundqvist, MD, said at the annual congress of the European Society of Cardiology.
Clinicians have traditionally measured residual or recurrent AF after treatment with a periodic ECG to see whether patients experience AF episodes that last at least 30 seconds, but this is “hardly a measure of successful treatment,” said Dr. Blomström-Lundqvist, an electrophysiologist at the University Hospital in Uppsala, Sweden.
She and her associates placed an implanted cardiac monitor into each patient for continuous measurement of residual AF episodes. Twelve months after entry into the study, patients who underwent ablation had their AF burden decreased by an average of 20 percentage points compared with baseline, while the AF burden dropped by an average of 12 percentage points among patients maintained on antiarrhythmic drugs, a between-group difference that was not statistically significant.
Based on that finding, Dr. Blomström-Lundqvist inferred that the significantly better improvement in quality of life seen with ablation compared with drug treatment occurred because the ablated patients all came off antiarrhythmic drug treatment. The study protocol required patients randomized to the ablation regimen to be completely off antiarrhythmic drugs by 6 months after their ablation procedure.
Continued treatment with an antiarrhythmic drug in the drug-arm patients compared with no drug treatment in the ablated patients “is absolutely the explanation” for the observed difference in quality of life, she said. Patients randomized to the antiarrhythmic drug arm of the study received treatment with one of six eligible drugs: amiodarone, disopyramide, dronedarone, flecainide, propafenone, or sotalol. Patients could also be on a beta-blocker.
The Catheter Ablation Compared With Pharmacological Therapy for Atrial Fibrillation (CAPTAF) trial enrolled symptomatic patients with paroxysmal or persistent AF at four Swedish centers and at one center in Finland. All enrolled patients had to have a history of being refractory to or intolerant of a beta-blocker or an antiarrhythmic drug. Patients with paroxysmal AF had to have experienced an AF episode within the prior 2 months, while those with persistent AF had to have had at least two AF episodes within the prior year. The average age of the enrolled patients was 56 years. Nearly three-quarters had paroxysmal AF. Their average AF burden was about a quarter of the time, on average they had been diagnosed with AF for about 5 years, and 70%-80% of the patients had severe or disabling symptoms. At entry, about 90% of patients were on beta-blocker treatment and a bit more than a third were taking an antiarrhythmic drug.
The researchers measured quality of life using the 36-item Short Form Survey Instrument (SF-36). At baseline, the average SF-36 score (measured on a 0-100 scale) was 63 in the 79 patients randomized to ablation and 62 in 76 patients randomized for drug therapy. Patients randomized to an ablation procedure underwent pulmonary vein isolation by whatever technique their attending cardiologists preferred.
The average SF-36 score 12 months after study entry was 73 for the ablation patients, an average gain from baseline of 11 points, and 65 in the drug-treated patients, an average gain of 3 points. The 8-point difference in SF-36 gain between the two groups was statistically significant.
Contributing to the overall superiority of ablation for improving quality of life were statistically significant advantages for ablation over drug treatment in the individual SF-36 domains of general health, physical function, mental health, role-emotional, role-physical, and vitality. The two treatment arms of the study showed no significant differences in the two remaining SF-36 domains of bodily pain and social functioning.
Nine of the 79 patients (11%) who underwent ablation had a procedure-related serious adverse event, including four patients with an infection or septicemia, two patients with tamponade or pericardial effusion, one patient with a transient ischemic attack, and two with a different vascular complication. Serious cardiovascular adverse events during the 12 month follow-up occurred in 14 of the ablated patients (18%) and in 18 of the drug-treated patients (24%), a between-group difference that did not undergo statistical analysis. Dr. Blomström-Lundqvist called the rates “comparable,” but cautioned that the study was not powered to compare serious adverse event rates in the two treatment arms.
Héctor Bueno, MD, a cardiologist at the Spanish National Center for Cardiovascular Research in Madrid and a cochair of the session that included the CAPTAF report, voiced concern about the procedure-related serious adverse events among patients who underwent ablation.
“An 11% serious complication rate is not negligible,” he said. “Some of them were really serious complications.”
[email protected]
On Twitter @mitchelzoler
AT THE ESC CONGRESS 2017
Key clinical point:
Major finding: After 12 months, average SF-36 scores improved by 11 points with ablation and 3 points with drug therapy.
Data source: CAPTAF, a multicenter, randomized trial with 155 patients.
Disclosures: CAPTAF received partial funding from Medtronic. Dr. Blomström-Lundqvist has received research funding from Medtronic and Cardiome, and she has received honoraria for speaking from Medtronic and also from Bayer, Biotronik, Bristol-Myers Squibb, Merck, Pfizer, and Sanofi. Dr. Bueno has been a consultant to Abbott, Bayer, Bristol-Myers Squibb, Ferrer, Novartis, Pfizer, and Servier, and has received research funding from AstraZeneca, Bristol-Myers Squibb, Janssen, and Novartis.
VIDEO: Anacetrapib doubles HDL, but patients gain from its modest LDL cut
BARCELONA – After years of neutral study results in pivotal trials, a drug that raises patients’ high-density lipoprotein cholesterol finally showed a statistically significant and clinically meaningful benefit in a major trial with more than 30,000 patients run for 4 years.
The only catch? It didn’t seem to work by raising HDL.
Instead, it was the off-target effect of also lowering low density lipoprotein (LDL) cholesterol that seems to have driven a modest but clinically significant benefit from anacetrapib, a member of the class of drugs that inhibit the cholesterol ester transfer protein that includes the trial flame-out agents torcetrapib, dalcetrapib, and evacetrapib.
Daily treatment with 100 mg of anacetrapib on top of intensive therapy with atorvastatin led to a 9% relative risk reduction in major coronary events that didn’t become apparent compared with placebo until patients took the drug for more than 2 years, and was “well tolerated,” with a notably benign safety profile, Martin Landray, MD, said at the annual congress of the European Society of Cardiology.
“This is a drug that would have a role clinically, along the lines of ezetimibe,” said Louise Bowman, MD, a clinical epidemiologist and clinical trialist at Oxford who served with Dr. Landray as coprincipal investigator on the study.
Even at a time when proprotein convertase subtilisin–kexin type 9 (PCSK9) inhibitors are now routinely available to produce profound reductions in LDL cholesterol, a drug like anacetrapib that produces a more modest reduction can have a clinically useful role, she said. Having anacetrapib available as another option for safely lowering LDL cholesterol “could be complementary” to the lipid-lowering drug classes already in use, Dr. Bowman stressed in a video interview.
“This was a very well treated population on an intensive statin dosage, but when we added the new drug on top of that we saw a clear additional benefit.”
Despite this now proven potential to make a clinical impact, executives at Merck, the company developing anacetrapib, and a cosponsor of this trial, have not yet decided how to follow up on the results. A statement released by the company just before Dr. Landray’s report said: “Merck continues to review the results of the trial with external experts, and will consider whether to file new drug applications with the [Food and Drug Administration] and other regulatory agencies.”
The results also provided a striking lesson that proving a new drug’s value can require running a very large trial for several years.
“Why was this trial positive” when the earlier trials with torcetrapib, dalcetrapib, and evacetrapib were not? “One reason is that our trial had twice as many patients and twice as many events with much longer follow-up,” Dr. Landray said.
Concurrently with his report, the results appeared in an article published online (N Engl J Med. 2017 Aug 29. doi: 10.1056/NEJMoa1706444).
The Randomized Evaluation of the Effects of Anacetrapib Through Lipid-Modification (REVEAL) trial enrolled 30,449 patients at 431 centers in North America, Europe, and China. The average age of the patients was 67 years. Patients had to have established arterial disease: 88% had coronary artery disease, 22% had cerebrovascular disease, and 8% had peripheral artery disease (numbers total more than 100% because some patients had documented disease in more than one arterial bed). The average level of LDL cholesterol was 61 mg/dL, HDL cholesterol was 40 mg/dL, and non-HDL cholesterol averaged 92 mg/dL. During anacetrapib treatment HDL levels roughly doubled, while levels of non-HDL cholesterol fell by an average of 18%.
After a median treatment time of 4.1 years, the study’s primary endpoint – the combined rate of coronary death, nonfatal MI, or need for coronary revascularization – occurred in 10.8% of the patient on anacetrapib and in 11.8% of those in the placebo-control group, a 9% relative risk reduction that was consistent across all prespecified subgroups of patients in the study.
This level of benefit compared with the degree of non-HDL cholesterol lowering observed was strikingly consistent with the relationships between achieved lipid reductions and the clinical results seen in all the published studies with statins and with ezetimibe.
“Anacetrapib lowers LDL and raises HDL, so we knew it would be difficult to disentangle” which effects led to the clinical benefits seen, said Dr. Bowman. But the magnitude of the non-HDL lowering effect relative to the observed benefit “lined up very nicely” with the effects in the statin and ezetimibe trials. On the other hand, “if you double HDL cholesterol you’d expect to see a substantial contribution from that, and we did not, so if the HDL-lowering has an effect it’s probably small,” she said, cautioning that right now this is just an unproven inference. “Our findings are consistent with an LDL effect.”
REVEAL’s other major finding was anacetrapib’s good safety and tolerance profile, with 85% of patients randomized to receive anacetrapib continuing to take the drug through the end of the study. Treatment with the drug linked with a small but statistically significant 0.6% drop in the incidence of diabetes compared with placebo patients, and a small but statistically significant 0.84% increase in new onset stage 3 chronic kidney disease but with no increase in serious adverse events associated with kidney failure. The drug’s use showed no suggestion of a link with cancer, liver disease, muscle effects, cognitive effects, infections, or other serious or nonserious adverse effects. Patients on anacetrapib had on average a systolic blood pressure that was 0.7 mm Hg higher than that of patients on placebo and a diastolic blood pressure that averaged 0.3 mm Hg higher compared with the placebo group. The rate of hypertension-associated serious adverse events was low and virtually identical in the two study groups.
REVEAL received partial funding from Merck, the company developing anacetrapib. Dr. Landray and Dr. Bowman had no disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @mitchelzoler
The REVEAL results show for the first time that targeting the cholesterol ester transfer protein mechanism can result in a decrease in coronary events, even in patients with low baseline levels of cholesterol. The findings hold promise for the strategy of targeting this mechanism. But it’s very difficult to dissect out whether the benefits seen were largely due to increasing HDL cholesterol or reducing LDL cholesterol.
About half the enrolled patients had a baseline HDL cholesterol level of less than 40 mg/dL, the type of patient most likely to benefit from raising HDL levels. Another uncertainty when raising HDL cholesterol is whether the induced HDL has the physical and functional properties of the HDL cholesterol that exists in healthy people with normal HDL levels. We can’t exclude the possibility that the HDL cholesterol induced by anacetrapib doesn’t translate into improved physiologic function and clinical benefit. On the other hand, we cannot exclude a possible contribution from HDL.
It is also worth noting that the potential exists to pair anacetrapib treatment with another lipid-lowering treatment with a complimentary mechanism of action, specifically ezetimibe.
M. John Chapman, PhD , is a professor at the Pierre and Marie Curie University in Paris. He has received honoraria from Merck and also from Amgen, Kowa, Pfizer, Regeneron, Sanofi, Servier, and Unilever. He made these comments as designated discussant for the REVEAL report.
The REVEAL results show for the first time that targeting the cholesterol ester transfer protein mechanism can result in a decrease in coronary events, even in patients with low baseline levels of cholesterol. The findings hold promise for the strategy of targeting this mechanism. But it’s very difficult to dissect out whether the benefits seen were largely due to increasing HDL cholesterol or reducing LDL cholesterol.
About half the enrolled patients had a baseline HDL cholesterol level of less than 40 mg/dL, the type of patient most likely to benefit from raising HDL levels. Another uncertainty when raising HDL cholesterol is whether the induced HDL has the physical and functional properties of the HDL cholesterol that exists in healthy people with normal HDL levels. We can’t exclude the possibility that the HDL cholesterol induced by anacetrapib doesn’t translate into improved physiologic function and clinical benefit. On the other hand, we cannot exclude a possible contribution from HDL.
It is also worth noting that the potential exists to pair anacetrapib treatment with another lipid-lowering treatment with a complimentary mechanism of action, specifically ezetimibe.
M. John Chapman, PhD , is a professor at the Pierre and Marie Curie University in Paris. He has received honoraria from Merck and also from Amgen, Kowa, Pfizer, Regeneron, Sanofi, Servier, and Unilever. He made these comments as designated discussant for the REVEAL report.
The REVEAL results show for the first time that targeting the cholesterol ester transfer protein mechanism can result in a decrease in coronary events, even in patients with low baseline levels of cholesterol. The findings hold promise for the strategy of targeting this mechanism. But it’s very difficult to dissect out whether the benefits seen were largely due to increasing HDL cholesterol or reducing LDL cholesterol.
About half the enrolled patients had a baseline HDL cholesterol level of less than 40 mg/dL, the type of patient most likely to benefit from raising HDL levels. Another uncertainty when raising HDL cholesterol is whether the induced HDL has the physical and functional properties of the HDL cholesterol that exists in healthy people with normal HDL levels. We can’t exclude the possibility that the HDL cholesterol induced by anacetrapib doesn’t translate into improved physiologic function and clinical benefit. On the other hand, we cannot exclude a possible contribution from HDL.
It is also worth noting that the potential exists to pair anacetrapib treatment with another lipid-lowering treatment with a complimentary mechanism of action, specifically ezetimibe.
M. John Chapman, PhD , is a professor at the Pierre and Marie Curie University in Paris. He has received honoraria from Merck and also from Amgen, Kowa, Pfizer, Regeneron, Sanofi, Servier, and Unilever. He made these comments as designated discussant for the REVEAL report.
BARCELONA – After years of neutral study results in pivotal trials, a drug that raises patients’ high-density lipoprotein cholesterol finally showed a statistically significant and clinically meaningful benefit in a major trial with more than 30,000 patients run for 4 years.
The only catch? It didn’t seem to work by raising HDL.
Instead, it was the off-target effect of also lowering low density lipoprotein (LDL) cholesterol that seems to have driven a modest but clinically significant benefit from anacetrapib, a member of the class of drugs that inhibit the cholesterol ester transfer protein that includes the trial flame-out agents torcetrapib, dalcetrapib, and evacetrapib.
Daily treatment with 100 mg of anacetrapib on top of intensive therapy with atorvastatin led to a 9% relative risk reduction in major coronary events that didn’t become apparent compared with placebo until patients took the drug for more than 2 years, and was “well tolerated,” with a notably benign safety profile, Martin Landray, MD, said at the annual congress of the European Society of Cardiology.
“This is a drug that would have a role clinically, along the lines of ezetimibe,” said Louise Bowman, MD, a clinical epidemiologist and clinical trialist at Oxford who served with Dr. Landray as coprincipal investigator on the study.
Even at a time when proprotein convertase subtilisin–kexin type 9 (PCSK9) inhibitors are now routinely available to produce profound reductions in LDL cholesterol, a drug like anacetrapib that produces a more modest reduction can have a clinically useful role, she said. Having anacetrapib available as another option for safely lowering LDL cholesterol “could be complementary” to the lipid-lowering drug classes already in use, Dr. Bowman stressed in a video interview.
“This was a very well treated population on an intensive statin dosage, but when we added the new drug on top of that we saw a clear additional benefit.”
Despite this now proven potential to make a clinical impact, executives at Merck, the company developing anacetrapib, and a cosponsor of this trial, have not yet decided how to follow up on the results. A statement released by the company just before Dr. Landray’s report said: “Merck continues to review the results of the trial with external experts, and will consider whether to file new drug applications with the [Food and Drug Administration] and other regulatory agencies.”
The results also provided a striking lesson that proving a new drug’s value can require running a very large trial for several years.
“Why was this trial positive” when the earlier trials with torcetrapib, dalcetrapib, and evacetrapib were not? “One reason is that our trial had twice as many patients and twice as many events with much longer follow-up,” Dr. Landray said.
Concurrently with his report, the results appeared in an article published online (N Engl J Med. 2017 Aug 29. doi: 10.1056/NEJMoa1706444).
The Randomized Evaluation of the Effects of Anacetrapib Through Lipid-Modification (REVEAL) trial enrolled 30,449 patients at 431 centers in North America, Europe, and China. The average age of the patients was 67 years. Patients had to have established arterial disease: 88% had coronary artery disease, 22% had cerebrovascular disease, and 8% had peripheral artery disease (numbers total more than 100% because some patients had documented disease in more than one arterial bed). The average level of LDL cholesterol was 61 mg/dL, HDL cholesterol was 40 mg/dL, and non-HDL cholesterol averaged 92 mg/dL. During anacetrapib treatment HDL levels roughly doubled, while levels of non-HDL cholesterol fell by an average of 18%.
After a median treatment time of 4.1 years, the study’s primary endpoint – the combined rate of coronary death, nonfatal MI, or need for coronary revascularization – occurred in 10.8% of the patient on anacetrapib and in 11.8% of those in the placebo-control group, a 9% relative risk reduction that was consistent across all prespecified subgroups of patients in the study.
This level of benefit compared with the degree of non-HDL cholesterol lowering observed was strikingly consistent with the relationships between achieved lipid reductions and the clinical results seen in all the published studies with statins and with ezetimibe.
“Anacetrapib lowers LDL and raises HDL, so we knew it would be difficult to disentangle” which effects led to the clinical benefits seen, said Dr. Bowman. But the magnitude of the non-HDL lowering effect relative to the observed benefit “lined up very nicely” with the effects in the statin and ezetimibe trials. On the other hand, “if you double HDL cholesterol you’d expect to see a substantial contribution from that, and we did not, so if the HDL-lowering has an effect it’s probably small,” she said, cautioning that right now this is just an unproven inference. “Our findings are consistent with an LDL effect.”
REVEAL’s other major finding was anacetrapib’s good safety and tolerance profile, with 85% of patients randomized to receive anacetrapib continuing to take the drug through the end of the study. Treatment with the drug linked with a small but statistically significant 0.6% drop in the incidence of diabetes compared with placebo patients, and a small but statistically significant 0.84% increase in new onset stage 3 chronic kidney disease but with no increase in serious adverse events associated with kidney failure. The drug’s use showed no suggestion of a link with cancer, liver disease, muscle effects, cognitive effects, infections, or other serious or nonserious adverse effects. Patients on anacetrapib had on average a systolic blood pressure that was 0.7 mm Hg higher than that of patients on placebo and a diastolic blood pressure that averaged 0.3 mm Hg higher compared with the placebo group. The rate of hypertension-associated serious adverse events was low and virtually identical in the two study groups.
REVEAL received partial funding from Merck, the company developing anacetrapib. Dr. Landray and Dr. Bowman had no disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @mitchelzoler
BARCELONA – After years of neutral study results in pivotal trials, a drug that raises patients’ high-density lipoprotein cholesterol finally showed a statistically significant and clinically meaningful benefit in a major trial with more than 30,000 patients run for 4 years.
The only catch? It didn’t seem to work by raising HDL.
Instead, it was the off-target effect of also lowering low density lipoprotein (LDL) cholesterol that seems to have driven a modest but clinically significant benefit from anacetrapib, a member of the class of drugs that inhibit the cholesterol ester transfer protein that includes the trial flame-out agents torcetrapib, dalcetrapib, and evacetrapib.
Daily treatment with 100 mg of anacetrapib on top of intensive therapy with atorvastatin led to a 9% relative risk reduction in major coronary events that didn’t become apparent compared with placebo until patients took the drug for more than 2 years, and was “well tolerated,” with a notably benign safety profile, Martin Landray, MD, said at the annual congress of the European Society of Cardiology.
“This is a drug that would have a role clinically, along the lines of ezetimibe,” said Louise Bowman, MD, a clinical epidemiologist and clinical trialist at Oxford who served with Dr. Landray as coprincipal investigator on the study.
Even at a time when proprotein convertase subtilisin–kexin type 9 (PCSK9) inhibitors are now routinely available to produce profound reductions in LDL cholesterol, a drug like anacetrapib that produces a more modest reduction can have a clinically useful role, she said. Having anacetrapib available as another option for safely lowering LDL cholesterol “could be complementary” to the lipid-lowering drug classes already in use, Dr. Bowman stressed in a video interview.
“This was a very well treated population on an intensive statin dosage, but when we added the new drug on top of that we saw a clear additional benefit.”
Despite this now proven potential to make a clinical impact, executives at Merck, the company developing anacetrapib, and a cosponsor of this trial, have not yet decided how to follow up on the results. A statement released by the company just before Dr. Landray’s report said: “Merck continues to review the results of the trial with external experts, and will consider whether to file new drug applications with the [Food and Drug Administration] and other regulatory agencies.”
The results also provided a striking lesson that proving a new drug’s value can require running a very large trial for several years.
“Why was this trial positive” when the earlier trials with torcetrapib, dalcetrapib, and evacetrapib were not? “One reason is that our trial had twice as many patients and twice as many events with much longer follow-up,” Dr. Landray said.
Concurrently with his report, the results appeared in an article published online (N Engl J Med. 2017 Aug 29. doi: 10.1056/NEJMoa1706444).
The Randomized Evaluation of the Effects of Anacetrapib Through Lipid-Modification (REVEAL) trial enrolled 30,449 patients at 431 centers in North America, Europe, and China. The average age of the patients was 67 years. Patients had to have established arterial disease: 88% had coronary artery disease, 22% had cerebrovascular disease, and 8% had peripheral artery disease (numbers total more than 100% because some patients had documented disease in more than one arterial bed). The average level of LDL cholesterol was 61 mg/dL, HDL cholesterol was 40 mg/dL, and non-HDL cholesterol averaged 92 mg/dL. During anacetrapib treatment HDL levels roughly doubled, while levels of non-HDL cholesterol fell by an average of 18%.
After a median treatment time of 4.1 years, the study’s primary endpoint – the combined rate of coronary death, nonfatal MI, or need for coronary revascularization – occurred in 10.8% of the patient on anacetrapib and in 11.8% of those in the placebo-control group, a 9% relative risk reduction that was consistent across all prespecified subgroups of patients in the study.
This level of benefit compared with the degree of non-HDL cholesterol lowering observed was strikingly consistent with the relationships between achieved lipid reductions and the clinical results seen in all the published studies with statins and with ezetimibe.
“Anacetrapib lowers LDL and raises HDL, so we knew it would be difficult to disentangle” which effects led to the clinical benefits seen, said Dr. Bowman. But the magnitude of the non-HDL lowering effect relative to the observed benefit “lined up very nicely” with the effects in the statin and ezetimibe trials. On the other hand, “if you double HDL cholesterol you’d expect to see a substantial contribution from that, and we did not, so if the HDL-lowering has an effect it’s probably small,” she said, cautioning that right now this is just an unproven inference. “Our findings are consistent with an LDL effect.”
REVEAL’s other major finding was anacetrapib’s good safety and tolerance profile, with 85% of patients randomized to receive anacetrapib continuing to take the drug through the end of the study. Treatment with the drug linked with a small but statistically significant 0.6% drop in the incidence of diabetes compared with placebo patients, and a small but statistically significant 0.84% increase in new onset stage 3 chronic kidney disease but with no increase in serious adverse events associated with kidney failure. The drug’s use showed no suggestion of a link with cancer, liver disease, muscle effects, cognitive effects, infections, or other serious or nonserious adverse effects. Patients on anacetrapib had on average a systolic blood pressure that was 0.7 mm Hg higher than that of patients on placebo and a diastolic blood pressure that averaged 0.3 mm Hg higher compared with the placebo group. The rate of hypertension-associated serious adverse events was low and virtually identical in the two study groups.
REVEAL received partial funding from Merck, the company developing anacetrapib. Dr. Landray and Dr. Bowman had no disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @mitchelzoler
AT THE ESC CONGRESS 2017
Key clinical point:
Major finding: Patients treated with anacetrapib had a statistically significant 9% decrease in major coronary events, compared with placebo-treated controls.
Data source: REVEAL, a multicenter, pivotal trial with 30,449 patients treated for about 4 years.
Disclosures: REVEAL received partial funding from Merck, the company developing anacetrapib. Dr. Landray and Dr. Bowman had no disclosures.
VIDEO: Rivaroxaban plus aspirin cut cardiovascular events in stable patients
BARCELONA – Combined treatment with a very low dosage of the anticoagulant rivaroxaban plus low-dose aspirin produced significant cuts in major adverse coronary, cerebral, and peripheral artery disease events with just a modest rise in major bleeding events in patients with stable disease in the COMPASS pivotal, randomized trial with more than 27,000 patients.
The benefits from the rivaroxaban plus aspirin regimen included a statistically significant 24% relative risk reduction in the study’s primary, combined endpoint, and a significant 18% relative risk reduction in all-cause death compared with a standard regimen of aspirin only, John W. Eikelboom, MD, said at the annual congress of the European Society of Cardiology. In addition, analysis of the net clinical benefit from treatment that took into account both the major adverse cardiovascular events prevented and major bleeding events induced, showed that the rivaroxaban-plus-aspirin regimen cut these by a statistically significant 20%, compared with aspirin alone.
Other notable benefits documented by the findings included a statistically significant 42% relative risk reduction for stroke and a statistically significant 46% relative risk reduction in the incidence of major adverse limb events among the roughly one-quarter of enrolled patients who entered the study with evidence of peripheral artery disease.
These risk reductions are similar in magnitude to the secondary-prevention benefits produced by controlling hypertension or dyslipidemia, noted Dr. Eikelboom, a researcher at McMaster University in Hamilton, Ont. “In the future, rivaroxaban will take its place among the other foundational treatments for long-term, secondary prevention,” he predicted in a video interview.
The COMPASS trial produced “unambiguous results that should change guidelines and the management of stable coronary artery disease,” commented Eugene Braunwald, MD, designated discussant for Dr. Eikelboom’s report. The results are “an important step for thrombocardiology,” said Dr. Braunwald, professor of medicine at Harvard Medical School in Boston.
Concurrently with Dr. Eikelboom’s report the results appeared in an article published online (N Engl J Med. 2017 Aug 27. doi: 10.1056/NEJMoa1709118). This publication also include an editorial by Dr. Braunwald (N Engl J Med. 2017 Aug 27. doi: 10.1056/NEJMe1710241).
The Rivaroxaban for the Prevention of Major Cardiovascular Events in Coronary or Peripheral Artery Disease (COMPASS) trial enrolled 27,395 patients with stable coronary, carotid, or peripheral artery disease, or a combination of two or more of these, at 602 centers in 33 countries. About 90% of enrolled patients had coronary artery disease and 27% had peripheral artery disease. The enrolled patients averaged 68 year old and were an average of 7 years removed from their index arterial event. Randomization assigned patients to receive 2.5 mg rivaroxaban (Xarelto) twice daily plus 100 mg aspirin daily, 5 mg rivaroxaban twice daily, or 100 mg aspirin once daily. The trial stopped early, after an average follow-up of 23 months, because of the overwhelming benefit seen for the rivaroxaban plus aspirin combination. The rivaroxaban-monotherapy arm failed to show any statistically significant benefits, compared with the aspirin-monotherapy control group.
The study’s primary endpoint – the combined rate of cardiovascular disease death, nonfatal stroke, and nonfatal MI – occurred in 4.1% of patients in the rivaroxaban-plus-aspirin group and in 5.4% of patients on aspirin alone. The rate of major bleeding events was 3.1% among patients on rivaroxaban plus aspirin and 1.9% in those who received aspirin only, a 51% relative increase among patients on the dual regimen, but the results showed no statistically significant increase in the rates of fatal bleeds, intracerebral bleeds, or bleeding in other critical organs.
Sonia Anand, MD, a colleague of Dr. Eikelboom’s at McMaster, presented a separate set of analyses that focused on the 7,470 enrolled patients who had been diagnosed at enrollment with peripheral artery disease. In this subgroup, the rivaroxaban-plus-aspirin regimen produced a statistically significant 28% relative risk reduction in the rate of the primary endpoint, compared with the aspirin control group. The dual regimen also produced a statistically significant 46% relative risk reduction in major adverse limb events and a significant 70% relative reduction in the incidence of major lower-extremity amputations, reported Dr. Anand, professor of medicine and director of the vascular medicine clinic at McMaster.
The COMPASS findings follow a 2012 published report from the ATLAS ACS 2-TIMI 51 trial showing that treatment with the same low-dose rivaroxaban regimen plus aspirin and a thienopyridine (clopidogrel or ticlopidine) reduced the same combined triple endpoint by a statistically significant 16%, compared with aspirin and a thienopyridine alone, in patients with a recent acute coronary syndrome event (N Engl J Med. 2012 Jan 5;366[1]:9-19). Despite this evidence, the Food and Drug Administration never approved the 2.5-mg formulation of rivaroxaban, nor did it approve marketing of rivaroxaban for this acute coronary syndrome population. This decision may have been driven in part by a problem with incomplete follow-up of several of the enrolled patients.
The COMPASS results were “very consistent” with the ATLAS ACS 2-TIMI 51 results. noted Dr. Eikelboom. “I think it’s time to look at these two trials in combination,” he suggested. Availability of the 2.5-mg rivaroxaban formulation used in both trials would allow “a treatment strategy that could start early after an acute coronary syndrome event and then extend long term,” he said.
COMPASS was sponsored by Bayer, which markets rivaroxaban (Xarelto). Dr. Eikelboom has received research support from Bayer and also from Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi, Janssen, Pfizer, Portola, and Sanofi. Dr. Anand has received speaking honoraria from several drug compnies. Dr. Braunwald had no disclosures.
[email protected]
On Twitter @mitchelzoler
The key message from COMPASS was that, although adding a very low dosage of rivaroxaban to aspirin in patients with stable coronary or peripheral artery disease resulted in a clear increase in major bleeding events, patients received an overall net beneficial effect from the combined regimen. The finding that clinches the net benefit from the rivaroxaban plus aspirin combination, compared with aspirin alone, was that the combined regimen produced a statistically significant relative risk reduction of 18% for all-cause mortality. This finding reinforces the idea that the primary outcome was beneficial despite an increase in major bleeding events.
The finding that rivaroxaban plus aspirin produced benefit with a modest increase in bleeding risk in patients with peripheral artery disease (PAD) is especially important because PAD is really difficult to treat. Very few interventions have previously been proven to have a beneficial effect for patients with PAD. It’s very important to find an intervention that can reduce critical limb ischemia events in addition to reducing coronary events, stroke, and overall mortality.
The very low dosage of rivaroxaban used in COMPASS, 2.5 mg twice daily, seems to be a very important part of the study’s design. This dosage appeared to hit the sweet spot of being large enough to reduce events but with a gentle enough anticoagulation effect to avoid a significant increase in fatal, intracerebral, or critical organ bleeds. However, the patients enrolled in COMPASS, like most patients who enter trials, were generally at a lower risk for bleeding complications than we usually see in routine practice in patients with stable coronary or peripheral artery disease. Presuming that the Food and Drug Administration will soon approve the 2.5-mg formulation of rivaroxaban used in COMPASS, clinicians will need to be careful using this regimen on patients at increased risk for bleeding, such as frail or elderly patients with a history of bleeding events or taking other treatments that could increase bleeding risk, such as nonsteroidal anti-inflammatory drugs. In general, clinicians are wary of using treatments that increase bleeding risk, and so they may hesitate to use this combination of rivaroxaban plus aspirin in patients with a high bleeding risk.
The success of the approach used in COMPASS became possible with the introduction of the new oral anticoagulant drugs. Now that this class of agents has been available for a few years, clinicians have grown increasingly comfortable with them, compared with warfarin. When the new oral anticoagulants first came out, many considered them similar to warfarin. Today, there is a better appreciation that these drugs are distinct from warfarin by really causing fewer bleeding complications.
Christopher B. Granger, MD , is a cardiologist and professor of medicine at Duke University in Durham, N.C. He has been a consultant to and has received research support from Bayer and from other drugs companies that market new oral anticoagulants. He made these comments in an interview.
The key message from COMPASS was that, although adding a very low dosage of rivaroxaban to aspirin in patients with stable coronary or peripheral artery disease resulted in a clear increase in major bleeding events, patients received an overall net beneficial effect from the combined regimen. The finding that clinches the net benefit from the rivaroxaban plus aspirin combination, compared with aspirin alone, was that the combined regimen produced a statistically significant relative risk reduction of 18% for all-cause mortality. This finding reinforces the idea that the primary outcome was beneficial despite an increase in major bleeding events.
The finding that rivaroxaban plus aspirin produced benefit with a modest increase in bleeding risk in patients with peripheral artery disease (PAD) is especially important because PAD is really difficult to treat. Very few interventions have previously been proven to have a beneficial effect for patients with PAD. It’s very important to find an intervention that can reduce critical limb ischemia events in addition to reducing coronary events, stroke, and overall mortality.
The very low dosage of rivaroxaban used in COMPASS, 2.5 mg twice daily, seems to be a very important part of the study’s design. This dosage appeared to hit the sweet spot of being large enough to reduce events but with a gentle enough anticoagulation effect to avoid a significant increase in fatal, intracerebral, or critical organ bleeds. However, the patients enrolled in COMPASS, like most patients who enter trials, were generally at a lower risk for bleeding complications than we usually see in routine practice in patients with stable coronary or peripheral artery disease. Presuming that the Food and Drug Administration will soon approve the 2.5-mg formulation of rivaroxaban used in COMPASS, clinicians will need to be careful using this regimen on patients at increased risk for bleeding, such as frail or elderly patients with a history of bleeding events or taking other treatments that could increase bleeding risk, such as nonsteroidal anti-inflammatory drugs. In general, clinicians are wary of using treatments that increase bleeding risk, and so they may hesitate to use this combination of rivaroxaban plus aspirin in patients with a high bleeding risk.
The success of the approach used in COMPASS became possible with the introduction of the new oral anticoagulant drugs. Now that this class of agents has been available for a few years, clinicians have grown increasingly comfortable with them, compared with warfarin. When the new oral anticoagulants first came out, many considered them similar to warfarin. Today, there is a better appreciation that these drugs are distinct from warfarin by really causing fewer bleeding complications.
Christopher B. Granger, MD , is a cardiologist and professor of medicine at Duke University in Durham, N.C. He has been a consultant to and has received research support from Bayer and from other drugs companies that market new oral anticoagulants. He made these comments in an interview.
The key message from COMPASS was that, although adding a very low dosage of rivaroxaban to aspirin in patients with stable coronary or peripheral artery disease resulted in a clear increase in major bleeding events, patients received an overall net beneficial effect from the combined regimen. The finding that clinches the net benefit from the rivaroxaban plus aspirin combination, compared with aspirin alone, was that the combined regimen produced a statistically significant relative risk reduction of 18% for all-cause mortality. This finding reinforces the idea that the primary outcome was beneficial despite an increase in major bleeding events.
The finding that rivaroxaban plus aspirin produced benefit with a modest increase in bleeding risk in patients with peripheral artery disease (PAD) is especially important because PAD is really difficult to treat. Very few interventions have previously been proven to have a beneficial effect for patients with PAD. It’s very important to find an intervention that can reduce critical limb ischemia events in addition to reducing coronary events, stroke, and overall mortality.
The very low dosage of rivaroxaban used in COMPASS, 2.5 mg twice daily, seems to be a very important part of the study’s design. This dosage appeared to hit the sweet spot of being large enough to reduce events but with a gentle enough anticoagulation effect to avoid a significant increase in fatal, intracerebral, or critical organ bleeds. However, the patients enrolled in COMPASS, like most patients who enter trials, were generally at a lower risk for bleeding complications than we usually see in routine practice in patients with stable coronary or peripheral artery disease. Presuming that the Food and Drug Administration will soon approve the 2.5-mg formulation of rivaroxaban used in COMPASS, clinicians will need to be careful using this regimen on patients at increased risk for bleeding, such as frail or elderly patients with a history of bleeding events or taking other treatments that could increase bleeding risk, such as nonsteroidal anti-inflammatory drugs. In general, clinicians are wary of using treatments that increase bleeding risk, and so they may hesitate to use this combination of rivaroxaban plus aspirin in patients with a high bleeding risk.
The success of the approach used in COMPASS became possible with the introduction of the new oral anticoagulant drugs. Now that this class of agents has been available for a few years, clinicians have grown increasingly comfortable with them, compared with warfarin. When the new oral anticoagulants first came out, many considered them similar to warfarin. Today, there is a better appreciation that these drugs are distinct from warfarin by really causing fewer bleeding complications.
Christopher B. Granger, MD , is a cardiologist and professor of medicine at Duke University in Durham, N.C. He has been a consultant to and has received research support from Bayer and from other drugs companies that market new oral anticoagulants. He made these comments in an interview.
BARCELONA – Combined treatment with a very low dosage of the anticoagulant rivaroxaban plus low-dose aspirin produced significant cuts in major adverse coronary, cerebral, and peripheral artery disease events with just a modest rise in major bleeding events in patients with stable disease in the COMPASS pivotal, randomized trial with more than 27,000 patients.
The benefits from the rivaroxaban plus aspirin regimen included a statistically significant 24% relative risk reduction in the study’s primary, combined endpoint, and a significant 18% relative risk reduction in all-cause death compared with a standard regimen of aspirin only, John W. Eikelboom, MD, said at the annual congress of the European Society of Cardiology. In addition, analysis of the net clinical benefit from treatment that took into account both the major adverse cardiovascular events prevented and major bleeding events induced, showed that the rivaroxaban-plus-aspirin regimen cut these by a statistically significant 20%, compared with aspirin alone.
Other notable benefits documented by the findings included a statistically significant 42% relative risk reduction for stroke and a statistically significant 46% relative risk reduction in the incidence of major adverse limb events among the roughly one-quarter of enrolled patients who entered the study with evidence of peripheral artery disease.
These risk reductions are similar in magnitude to the secondary-prevention benefits produced by controlling hypertension or dyslipidemia, noted Dr. Eikelboom, a researcher at McMaster University in Hamilton, Ont. “In the future, rivaroxaban will take its place among the other foundational treatments for long-term, secondary prevention,” he predicted in a video interview.
The COMPASS trial produced “unambiguous results that should change guidelines and the management of stable coronary artery disease,” commented Eugene Braunwald, MD, designated discussant for Dr. Eikelboom’s report. The results are “an important step for thrombocardiology,” said Dr. Braunwald, professor of medicine at Harvard Medical School in Boston.
Concurrently with Dr. Eikelboom’s report the results appeared in an article published online (N Engl J Med. 2017 Aug 27. doi: 10.1056/NEJMoa1709118). This publication also include an editorial by Dr. Braunwald (N Engl J Med. 2017 Aug 27. doi: 10.1056/NEJMe1710241).
The Rivaroxaban for the Prevention of Major Cardiovascular Events in Coronary or Peripheral Artery Disease (COMPASS) trial enrolled 27,395 patients with stable coronary, carotid, or peripheral artery disease, or a combination of two or more of these, at 602 centers in 33 countries. About 90% of enrolled patients had coronary artery disease and 27% had peripheral artery disease. The enrolled patients averaged 68 year old and were an average of 7 years removed from their index arterial event. Randomization assigned patients to receive 2.5 mg rivaroxaban (Xarelto) twice daily plus 100 mg aspirin daily, 5 mg rivaroxaban twice daily, or 100 mg aspirin once daily. The trial stopped early, after an average follow-up of 23 months, because of the overwhelming benefit seen for the rivaroxaban plus aspirin combination. The rivaroxaban-monotherapy arm failed to show any statistically significant benefits, compared with the aspirin-monotherapy control group.
The study’s primary endpoint – the combined rate of cardiovascular disease death, nonfatal stroke, and nonfatal MI – occurred in 4.1% of patients in the rivaroxaban-plus-aspirin group and in 5.4% of patients on aspirin alone. The rate of major bleeding events was 3.1% among patients on rivaroxaban plus aspirin and 1.9% in those who received aspirin only, a 51% relative increase among patients on the dual regimen, but the results showed no statistically significant increase in the rates of fatal bleeds, intracerebral bleeds, or bleeding in other critical organs.
Sonia Anand, MD, a colleague of Dr. Eikelboom’s at McMaster, presented a separate set of analyses that focused on the 7,470 enrolled patients who had been diagnosed at enrollment with peripheral artery disease. In this subgroup, the rivaroxaban-plus-aspirin regimen produced a statistically significant 28% relative risk reduction in the rate of the primary endpoint, compared with the aspirin control group. The dual regimen also produced a statistically significant 46% relative risk reduction in major adverse limb events and a significant 70% relative reduction in the incidence of major lower-extremity amputations, reported Dr. Anand, professor of medicine and director of the vascular medicine clinic at McMaster.
The COMPASS findings follow a 2012 published report from the ATLAS ACS 2-TIMI 51 trial showing that treatment with the same low-dose rivaroxaban regimen plus aspirin and a thienopyridine (clopidogrel or ticlopidine) reduced the same combined triple endpoint by a statistically significant 16%, compared with aspirin and a thienopyridine alone, in patients with a recent acute coronary syndrome event (N Engl J Med. 2012 Jan 5;366[1]:9-19). Despite this evidence, the Food and Drug Administration never approved the 2.5-mg formulation of rivaroxaban, nor did it approve marketing of rivaroxaban for this acute coronary syndrome population. This decision may have been driven in part by a problem with incomplete follow-up of several of the enrolled patients.
The COMPASS results were “very consistent” with the ATLAS ACS 2-TIMI 51 results. noted Dr. Eikelboom. “I think it’s time to look at these two trials in combination,” he suggested. Availability of the 2.5-mg rivaroxaban formulation used in both trials would allow “a treatment strategy that could start early after an acute coronary syndrome event and then extend long term,” he said.
COMPASS was sponsored by Bayer, which markets rivaroxaban (Xarelto). Dr. Eikelboom has received research support from Bayer and also from Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi, Janssen, Pfizer, Portola, and Sanofi. Dr. Anand has received speaking honoraria from several drug compnies. Dr. Braunwald had no disclosures.
[email protected]
On Twitter @mitchelzoler
BARCELONA – Combined treatment with a very low dosage of the anticoagulant rivaroxaban plus low-dose aspirin produced significant cuts in major adverse coronary, cerebral, and peripheral artery disease events with just a modest rise in major bleeding events in patients with stable disease in the COMPASS pivotal, randomized trial with more than 27,000 patients.
The benefits from the rivaroxaban plus aspirin regimen included a statistically significant 24% relative risk reduction in the study’s primary, combined endpoint, and a significant 18% relative risk reduction in all-cause death compared with a standard regimen of aspirin only, John W. Eikelboom, MD, said at the annual congress of the European Society of Cardiology. In addition, analysis of the net clinical benefit from treatment that took into account both the major adverse cardiovascular events prevented and major bleeding events induced, showed that the rivaroxaban-plus-aspirin regimen cut these by a statistically significant 20%, compared with aspirin alone.
Other notable benefits documented by the findings included a statistically significant 42% relative risk reduction for stroke and a statistically significant 46% relative risk reduction in the incidence of major adverse limb events among the roughly one-quarter of enrolled patients who entered the study with evidence of peripheral artery disease.
These risk reductions are similar in magnitude to the secondary-prevention benefits produced by controlling hypertension or dyslipidemia, noted Dr. Eikelboom, a researcher at McMaster University in Hamilton, Ont. “In the future, rivaroxaban will take its place among the other foundational treatments for long-term, secondary prevention,” he predicted in a video interview.
The COMPASS trial produced “unambiguous results that should change guidelines and the management of stable coronary artery disease,” commented Eugene Braunwald, MD, designated discussant for Dr. Eikelboom’s report. The results are “an important step for thrombocardiology,” said Dr. Braunwald, professor of medicine at Harvard Medical School in Boston.
Concurrently with Dr. Eikelboom’s report the results appeared in an article published online (N Engl J Med. 2017 Aug 27. doi: 10.1056/NEJMoa1709118). This publication also include an editorial by Dr. Braunwald (N Engl J Med. 2017 Aug 27. doi: 10.1056/NEJMe1710241).
The Rivaroxaban for the Prevention of Major Cardiovascular Events in Coronary or Peripheral Artery Disease (COMPASS) trial enrolled 27,395 patients with stable coronary, carotid, or peripheral artery disease, or a combination of two or more of these, at 602 centers in 33 countries. About 90% of enrolled patients had coronary artery disease and 27% had peripheral artery disease. The enrolled patients averaged 68 year old and were an average of 7 years removed from their index arterial event. Randomization assigned patients to receive 2.5 mg rivaroxaban (Xarelto) twice daily plus 100 mg aspirin daily, 5 mg rivaroxaban twice daily, or 100 mg aspirin once daily. The trial stopped early, after an average follow-up of 23 months, because of the overwhelming benefit seen for the rivaroxaban plus aspirin combination. The rivaroxaban-monotherapy arm failed to show any statistically significant benefits, compared with the aspirin-monotherapy control group.
The study’s primary endpoint – the combined rate of cardiovascular disease death, nonfatal stroke, and nonfatal MI – occurred in 4.1% of patients in the rivaroxaban-plus-aspirin group and in 5.4% of patients on aspirin alone. The rate of major bleeding events was 3.1% among patients on rivaroxaban plus aspirin and 1.9% in those who received aspirin only, a 51% relative increase among patients on the dual regimen, but the results showed no statistically significant increase in the rates of fatal bleeds, intracerebral bleeds, or bleeding in other critical organs.
Sonia Anand, MD, a colleague of Dr. Eikelboom’s at McMaster, presented a separate set of analyses that focused on the 7,470 enrolled patients who had been diagnosed at enrollment with peripheral artery disease. In this subgroup, the rivaroxaban-plus-aspirin regimen produced a statistically significant 28% relative risk reduction in the rate of the primary endpoint, compared with the aspirin control group. The dual regimen also produced a statistically significant 46% relative risk reduction in major adverse limb events and a significant 70% relative reduction in the incidence of major lower-extremity amputations, reported Dr. Anand, professor of medicine and director of the vascular medicine clinic at McMaster.
The COMPASS findings follow a 2012 published report from the ATLAS ACS 2-TIMI 51 trial showing that treatment with the same low-dose rivaroxaban regimen plus aspirin and a thienopyridine (clopidogrel or ticlopidine) reduced the same combined triple endpoint by a statistically significant 16%, compared with aspirin and a thienopyridine alone, in patients with a recent acute coronary syndrome event (N Engl J Med. 2012 Jan 5;366[1]:9-19). Despite this evidence, the Food and Drug Administration never approved the 2.5-mg formulation of rivaroxaban, nor did it approve marketing of rivaroxaban for this acute coronary syndrome population. This decision may have been driven in part by a problem with incomplete follow-up of several of the enrolled patients.
The COMPASS results were “very consistent” with the ATLAS ACS 2-TIMI 51 results. noted Dr. Eikelboom. “I think it’s time to look at these two trials in combination,” he suggested. Availability of the 2.5-mg rivaroxaban formulation used in both trials would allow “a treatment strategy that could start early after an acute coronary syndrome event and then extend long term,” he said.
COMPASS was sponsored by Bayer, which markets rivaroxaban (Xarelto). Dr. Eikelboom has received research support from Bayer and also from Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi, Janssen, Pfizer, Portola, and Sanofi. Dr. Anand has received speaking honoraria from several drug compnies. Dr. Braunwald had no disclosures.
[email protected]
On Twitter @mitchelzoler
AT THE ESC CONGRESS 2017
Key clinical point:
Major finding: The dual regimen reduced the combined rate of cardiovascular disease events by 24%, compared with aspirin alone.
Data source: COMPASS is a multicenter, randomized controlled trial with 27,395 patients.
Disclosures: COMPASS was sponsored by Bayer, which markets rivaroxaban (Xarelto). Dr. Eikelboom has received research support from Bayer and also from Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi, Janssen, Pfizer, Portola, and Sanofi. Dr. Anand has received speaking honoraria from several drug compnies. Dr. Braunwald had no disclosures.
Orsiro coronary DES outperforms Xience
BARCELONA – A new model of drug-eluting coronary stent outperformed the reigning benchmark Xience stent in a head-to-head, pivotal comparison with 1,334 patients.
The results “advance a new standard for drug eluting stents,” David E. Kandzari, MD, said at the annual congress of the European Society of Cardiology. The trial tested the Orsiro stent, which features very thin, 60-micron-thick cobalt chromium struts, a bioresorbable polymer, and sirolimus as the antiproliferative drug that’s released during the first 90 days of stent placement.
“To our knowledge, this is the only trial that has demonstrated superiority [of a new stent] to the Xience drug-eluting stent in a large, randomized trial. This is a landmark in interventional cardiology that raises the bar for future comparisons” of drug eluting coronary stents, Dr. Kandzari said in an interview.
The study’s primary endpoint of target lesion failure after 12 months of follow-up – a rate that combined the incidence of cardiovascular death, target-vessel related MI, and ischemia-driven target-lesion revascularization – stood at 6.2% for the 884 patients treated with the Orsiro stent and 9.6% of the 450 randomized to treatment with the Xience stent, which has struts that are 81 microns wide, and a durable polymer that releases everolimus as the antiproliferative drug.
The difference in the primary endpoint was driven primarily by a 3.6% absolute difference in the rate of target-vessel related MIs, a statistically significant difference, plus the Orsiro-treated patients showed numerically smaller rates of cardiac death and ischemia-driven target lesion revascularization, although the between-group differences for each of these two endpoints were not statistically significant. The Orsiro stent also showed a significantly reduced rate of late stent thrombosis, occurring during day 31 through 1 year, a 0.1% rate in the Orsiro-treated patients and a 0.9% rate in those who received Xience stents.
“These are remarkable results,” said Michael Haude, MD, an interventional cardiologist at Lukas Hospital in Neuss, Germany, and a cochair of the session in which Dr. Kandzari gave his report.
These results from the Safety and Effectiveness of the Orsiro Sirolimus Eluting Coronary Stent System in Subjects With Coronary Artery Lesions (BIOFLOW-V) trial will be the centerpiece of an application for U.S. marketing approval for the Orsiro stent, Dr. Kandzari said. The BIOFLOW-V trial enrolled patients at 90 centers in 13 countries including the United States.
Concurrently with his report, the results were published online (Lancet. 2017 Aug 26. doi: 10.1016/S0140-6736[17]32249-3).
The potential advantage of a thinner-strut drug eluting stent showed up during the initial treatment phase, with a procedural success rate of 94% using the Orsiro stent and 90% with the Xience stent. This difference in procedural success seemed largely the result of an increased rate of periprocedural MIs, a difference that might be explained by the difference in strut thickness, said Dr. Kandzari, of Piedmont Heart Institute, Atlanta. Based on this success, designers of future drug-eluting stents may focus on thinner-strut models, he suggested.
An additional analysis that Dr. Kandzari reported combined results from two prior randomized comparisons of the Orsiro and Xience stents, creating a pooled analysis with 2,208 patients. This Bayesian analysis calculated a 100% probability of noninferiority of the Orsiro stent compared with the Xience stent, and a 97% probability of superiority. This 97% probability of superiority fell just short of the 97.5% threshold for establishing superiority that Dr. Kandzari and his associates had prespecified for this analysis.
[email protected]
On Twitter @mitchelzoler
BARCELONA – A new model of drug-eluting coronary stent outperformed the reigning benchmark Xience stent in a head-to-head, pivotal comparison with 1,334 patients.
The results “advance a new standard for drug eluting stents,” David E. Kandzari, MD, said at the annual congress of the European Society of Cardiology. The trial tested the Orsiro stent, which features very thin, 60-micron-thick cobalt chromium struts, a bioresorbable polymer, and sirolimus as the antiproliferative drug that’s released during the first 90 days of stent placement.
“To our knowledge, this is the only trial that has demonstrated superiority [of a new stent] to the Xience drug-eluting stent in a large, randomized trial. This is a landmark in interventional cardiology that raises the bar for future comparisons” of drug eluting coronary stents, Dr. Kandzari said in an interview.
The study’s primary endpoint of target lesion failure after 12 months of follow-up – a rate that combined the incidence of cardiovascular death, target-vessel related MI, and ischemia-driven target-lesion revascularization – stood at 6.2% for the 884 patients treated with the Orsiro stent and 9.6% of the 450 randomized to treatment with the Xience stent, which has struts that are 81 microns wide, and a durable polymer that releases everolimus as the antiproliferative drug.
The difference in the primary endpoint was driven primarily by a 3.6% absolute difference in the rate of target-vessel related MIs, a statistically significant difference, plus the Orsiro-treated patients showed numerically smaller rates of cardiac death and ischemia-driven target lesion revascularization, although the between-group differences for each of these two endpoints were not statistically significant. The Orsiro stent also showed a significantly reduced rate of late stent thrombosis, occurring during day 31 through 1 year, a 0.1% rate in the Orsiro-treated patients and a 0.9% rate in those who received Xience stents.
“These are remarkable results,” said Michael Haude, MD, an interventional cardiologist at Lukas Hospital in Neuss, Germany, and a cochair of the session in which Dr. Kandzari gave his report.
These results from the Safety and Effectiveness of the Orsiro Sirolimus Eluting Coronary Stent System in Subjects With Coronary Artery Lesions (BIOFLOW-V) trial will be the centerpiece of an application for U.S. marketing approval for the Orsiro stent, Dr. Kandzari said. The BIOFLOW-V trial enrolled patients at 90 centers in 13 countries including the United States.
Concurrently with his report, the results were published online (Lancet. 2017 Aug 26. doi: 10.1016/S0140-6736[17]32249-3).
The potential advantage of a thinner-strut drug eluting stent showed up during the initial treatment phase, with a procedural success rate of 94% using the Orsiro stent and 90% with the Xience stent. This difference in procedural success seemed largely the result of an increased rate of periprocedural MIs, a difference that might be explained by the difference in strut thickness, said Dr. Kandzari, of Piedmont Heart Institute, Atlanta. Based on this success, designers of future drug-eluting stents may focus on thinner-strut models, he suggested.
An additional analysis that Dr. Kandzari reported combined results from two prior randomized comparisons of the Orsiro and Xience stents, creating a pooled analysis with 2,208 patients. This Bayesian analysis calculated a 100% probability of noninferiority of the Orsiro stent compared with the Xience stent, and a 97% probability of superiority. This 97% probability of superiority fell just short of the 97.5% threshold for establishing superiority that Dr. Kandzari and his associates had prespecified for this analysis.
[email protected]
On Twitter @mitchelzoler
BARCELONA – A new model of drug-eluting coronary stent outperformed the reigning benchmark Xience stent in a head-to-head, pivotal comparison with 1,334 patients.
The results “advance a new standard for drug eluting stents,” David E. Kandzari, MD, said at the annual congress of the European Society of Cardiology. The trial tested the Orsiro stent, which features very thin, 60-micron-thick cobalt chromium struts, a bioresorbable polymer, and sirolimus as the antiproliferative drug that’s released during the first 90 days of stent placement.
“To our knowledge, this is the only trial that has demonstrated superiority [of a new stent] to the Xience drug-eluting stent in a large, randomized trial. This is a landmark in interventional cardiology that raises the bar for future comparisons” of drug eluting coronary stents, Dr. Kandzari said in an interview.
The study’s primary endpoint of target lesion failure after 12 months of follow-up – a rate that combined the incidence of cardiovascular death, target-vessel related MI, and ischemia-driven target-lesion revascularization – stood at 6.2% for the 884 patients treated with the Orsiro stent and 9.6% of the 450 randomized to treatment with the Xience stent, which has struts that are 81 microns wide, and a durable polymer that releases everolimus as the antiproliferative drug.
The difference in the primary endpoint was driven primarily by a 3.6% absolute difference in the rate of target-vessel related MIs, a statistically significant difference, plus the Orsiro-treated patients showed numerically smaller rates of cardiac death and ischemia-driven target lesion revascularization, although the between-group differences for each of these two endpoints were not statistically significant. The Orsiro stent also showed a significantly reduced rate of late stent thrombosis, occurring during day 31 through 1 year, a 0.1% rate in the Orsiro-treated patients and a 0.9% rate in those who received Xience stents.
“These are remarkable results,” said Michael Haude, MD, an interventional cardiologist at Lukas Hospital in Neuss, Germany, and a cochair of the session in which Dr. Kandzari gave his report.
These results from the Safety and Effectiveness of the Orsiro Sirolimus Eluting Coronary Stent System in Subjects With Coronary Artery Lesions (BIOFLOW-V) trial will be the centerpiece of an application for U.S. marketing approval for the Orsiro stent, Dr. Kandzari said. The BIOFLOW-V trial enrolled patients at 90 centers in 13 countries including the United States.
Concurrently with his report, the results were published online (Lancet. 2017 Aug 26. doi: 10.1016/S0140-6736[17]32249-3).
The potential advantage of a thinner-strut drug eluting stent showed up during the initial treatment phase, with a procedural success rate of 94% using the Orsiro stent and 90% with the Xience stent. This difference in procedural success seemed largely the result of an increased rate of periprocedural MIs, a difference that might be explained by the difference in strut thickness, said Dr. Kandzari, of Piedmont Heart Institute, Atlanta. Based on this success, designers of future drug-eluting stents may focus on thinner-strut models, he suggested.
An additional analysis that Dr. Kandzari reported combined results from two prior randomized comparisons of the Orsiro and Xience stents, creating a pooled analysis with 2,208 patients. This Bayesian analysis calculated a 100% probability of noninferiority of the Orsiro stent compared with the Xience stent, and a 97% probability of superiority. This 97% probability of superiority fell just short of the 97.5% threshold for establishing superiority that Dr. Kandzari and his associates had prespecified for this analysis.
[email protected]
On Twitter @mitchelzoler
AT THE ESC CONGRESS 2017
Key clinical point:
Major finding: The target-lesion failure rate after 12 months was 6.2% with the Orsiro stent and 9.6% with the Xience stent.
Data source: BIOFLOW-V, a multicenter, randomized trial with 1,334 patients.
Disclosures: BIOFLOW-V was sponsored by Biotronik, the company that markets the Orsiro stent. Dr. Kandzari has been a consultant to and/or has received research funding from Biotronik, Boston Scientific, Medtronic, Micell Technologies, Abbott Vascular, St. Jude, Medinol, and OrbusNeich. Dr. Haude has been a consultant to and has received honoraria from Biotronik and from several other device and drug companies.
Big changes coming for thyroid cancer staging
BOSTON – When the American Joint Committee on Cancer’s Eighth Edition Cancer Staging Manual becomes effective for U.S. practice on Jan. 1, 2018, substantially more patients with thyroid cancer will meet the definition for stage I disease, but their survival prognosis will remain as good as it was for the smaller slice of patients defined with stage I thyroid cancer by the seventh edition, Bryan R. Haugen, MD, predicted during a talk at the World Congress on Thyroid Cancer.
Under current stage definitions in the seventh edition, roughly 60% of thyroid cancer patients have stage I disease, but this will kick up to about 80% under the eighth edition, said Dr. Haugen, professor of medicine and head of the division of endocrinology, metabolism, and diabetes at the University of Colorado in Aurora. Despite this influx of more patients, “survival rates in stage I patients haven’t changed,” with a disease-specific survival (DSS) of 98%-100% for stage I patients in the eighth edition compared with 97%-100% in the seventh edition, he noted.
Dr. Haugen credited this apparent paradox to the revised staging system’s superior discrimination among various grades of disease progression. “The eighth edition better separates patients based on their projected survival.” As more patients fit stage I classification with its highest level of projected survival, fewer patients will classify with more advanced disease and its worse projected survival.
For example, in the seventh edition patients with stage IV disease had a projected DSS rate of 50%-75%; in the eighth edition that rate is now less than 50%. The projected DSS rate for patients with stage II disease has down shifted from 97%-100% in the seventh edition to 85%-95% in the eighth. For patients with stage III thyroid cancer the DSS rate of 88%-95% in the seventh edition became 60%-70% in the eighth edition.
‘The new system will take some getting used to,” Dr. Haugen admitted, and it involves even more “big” changes, he warned. These include:
• Changing the cutpoint separating younger from older patients to 55 years of age in the eighth edition, a rise from the 45-year-old cutpoint in the seventh edition.
• Allowing tumors classified as stage I to be as large as 4 cm, up from the 2 cm or less defining stage I in the seventh edition.
• Reserving stage II designation for patients with tumors larger than 4 cm. In the seventh edition tumors had to be 2-4 cm in size.
• Expanding stage II disease to include not only patients with disease confined to their thyroid, but also patients with N1 lymph node spread or gross extrathyroidal extension. In the seventh edition tumor spread like this put patients into stage III.
• Specifying in the eighth edition that stage III disease must feature gross extrathyroidal extension into the larynx, trachea, esophagus, or recurrent laryngial nerve. To qualify for stage IV in the eighth edition, spread must extend into prevertebral fascia or encase major vessels, for stage IVA, or involve distant metastases for stage IVB.
• Paring down three stage IV subgroups, A, B, and C, in the seventh edition to just an A or B subgroup in the eighth edition.
Dr. Haugen coauthored a recent editorial that laid out an assessment of the eighth edition in greater detail (Thyroid. 2017 Jun;27[6]:751-6).
[email protected]
On Twitter @mitchelzoler
BOSTON – When the American Joint Committee on Cancer’s Eighth Edition Cancer Staging Manual becomes effective for U.S. practice on Jan. 1, 2018, substantially more patients with thyroid cancer will meet the definition for stage I disease, but their survival prognosis will remain as good as it was for the smaller slice of patients defined with stage I thyroid cancer by the seventh edition, Bryan R. Haugen, MD, predicted during a talk at the World Congress on Thyroid Cancer.
Under current stage definitions in the seventh edition, roughly 60% of thyroid cancer patients have stage I disease, but this will kick up to about 80% under the eighth edition, said Dr. Haugen, professor of medicine and head of the division of endocrinology, metabolism, and diabetes at the University of Colorado in Aurora. Despite this influx of more patients, “survival rates in stage I patients haven’t changed,” with a disease-specific survival (DSS) of 98%-100% for stage I patients in the eighth edition compared with 97%-100% in the seventh edition, he noted.
Dr. Haugen credited this apparent paradox to the revised staging system’s superior discrimination among various grades of disease progression. “The eighth edition better separates patients based on their projected survival.” As more patients fit stage I classification with its highest level of projected survival, fewer patients will classify with more advanced disease and its worse projected survival.
For example, in the seventh edition patients with stage IV disease had a projected DSS rate of 50%-75%; in the eighth edition that rate is now less than 50%. The projected DSS rate for patients with stage II disease has down shifted from 97%-100% in the seventh edition to 85%-95% in the eighth. For patients with stage III thyroid cancer the DSS rate of 88%-95% in the seventh edition became 60%-70% in the eighth edition.
‘The new system will take some getting used to,” Dr. Haugen admitted, and it involves even more “big” changes, he warned. These include:
• Changing the cutpoint separating younger from older patients to 55 years of age in the eighth edition, a rise from the 45-year-old cutpoint in the seventh edition.
• Allowing tumors classified as stage I to be as large as 4 cm, up from the 2 cm or less defining stage I in the seventh edition.
• Reserving stage II designation for patients with tumors larger than 4 cm. In the seventh edition tumors had to be 2-4 cm in size.
• Expanding stage II disease to include not only patients with disease confined to their thyroid, but also patients with N1 lymph node spread or gross extrathyroidal extension. In the seventh edition tumor spread like this put patients into stage III.
• Specifying in the eighth edition that stage III disease must feature gross extrathyroidal extension into the larynx, trachea, esophagus, or recurrent laryngial nerve. To qualify for stage IV in the eighth edition, spread must extend into prevertebral fascia or encase major vessels, for stage IVA, or involve distant metastases for stage IVB.
• Paring down three stage IV subgroups, A, B, and C, in the seventh edition to just an A or B subgroup in the eighth edition.
Dr. Haugen coauthored a recent editorial that laid out an assessment of the eighth edition in greater detail (Thyroid. 2017 Jun;27[6]:751-6).
[email protected]
On Twitter @mitchelzoler
BOSTON – When the American Joint Committee on Cancer’s Eighth Edition Cancer Staging Manual becomes effective for U.S. practice on Jan. 1, 2018, substantially more patients with thyroid cancer will meet the definition for stage I disease, but their survival prognosis will remain as good as it was for the smaller slice of patients defined with stage I thyroid cancer by the seventh edition, Bryan R. Haugen, MD, predicted during a talk at the World Congress on Thyroid Cancer.
Under current stage definitions in the seventh edition, roughly 60% of thyroid cancer patients have stage I disease, but this will kick up to about 80% under the eighth edition, said Dr. Haugen, professor of medicine and head of the division of endocrinology, metabolism, and diabetes at the University of Colorado in Aurora. Despite this influx of more patients, “survival rates in stage I patients haven’t changed,” with a disease-specific survival (DSS) of 98%-100% for stage I patients in the eighth edition compared with 97%-100% in the seventh edition, he noted.
Dr. Haugen credited this apparent paradox to the revised staging system’s superior discrimination among various grades of disease progression. “The eighth edition better separates patients based on their projected survival.” As more patients fit stage I classification with its highest level of projected survival, fewer patients will classify with more advanced disease and its worse projected survival.
For example, in the seventh edition patients with stage IV disease had a projected DSS rate of 50%-75%; in the eighth edition that rate is now less than 50%. The projected DSS rate for patients with stage II disease has down shifted from 97%-100% in the seventh edition to 85%-95% in the eighth. For patients with stage III thyroid cancer the DSS rate of 88%-95% in the seventh edition became 60%-70% in the eighth edition.
‘The new system will take some getting used to,” Dr. Haugen admitted, and it involves even more “big” changes, he warned. These include:
• Changing the cutpoint separating younger from older patients to 55 years of age in the eighth edition, a rise from the 45-year-old cutpoint in the seventh edition.
• Allowing tumors classified as stage I to be as large as 4 cm, up from the 2 cm or less defining stage I in the seventh edition.
• Reserving stage II designation for patients with tumors larger than 4 cm. In the seventh edition tumors had to be 2-4 cm in size.
• Expanding stage II disease to include not only patients with disease confined to their thyroid, but also patients with N1 lymph node spread or gross extrathyroidal extension. In the seventh edition tumor spread like this put patients into stage III.
• Specifying in the eighth edition that stage III disease must feature gross extrathyroidal extension into the larynx, trachea, esophagus, or recurrent laryngial nerve. To qualify for stage IV in the eighth edition, spread must extend into prevertebral fascia or encase major vessels, for stage IVA, or involve distant metastases for stage IVB.
• Paring down three stage IV subgroups, A, B, and C, in the seventh edition to just an A or B subgroup in the eighth edition.
Dr. Haugen coauthored a recent editorial that laid out an assessment of the eighth edition in greater detail (Thyroid. 2017 Jun;27[6]:751-6).
[email protected]
On Twitter @mitchelzoler
EXPERT ANALYSIS FROM WCTC 2017
Contralateral nodal thyroid metastases show slow progression
BOSTON – More than a third of 63 patients with unilateral papillary thyroid carcinoma and ipsilateral lymph node metastases also had occult, contralateral, lateral-neck lymph nodes with metastases, but the low reported rate of contralateral neck recurrence has raised the question of whether routine resection of these contralateral lymph nodes benefits patients.
“Prophylactic contralateral lateral-neck dissection may not be relevant for patients with unilateral N1b tumors,” Dana Hartl, MD, PhD, said at the World Congress on Thyroid Cancer.
She envisioned a more targeted approach to using surgical resection of contralateral, lateral-neck lymph nodes. “We would still do this surgery for patients with lots of big, bulky nodules; it just takes an additional 10-20 minutes. It’s not that long or morbid. For patients with lots of [affected] nodes, you’ve got to clear it out. But for a patient with a small, level III node on one side I will no longer do [prophylactic, contralateral, lateral-neck lymph node removal].”
Dr. Hartl and her associates reviewed records for 63 patients with unilateral, unifocal papillary thyroid carcinoma who underwent prophylactic, contralateral, lymph node removal during 1997-2016. They ranged from 11-84 years old, and 60% had extrathyroidal extension of their primary tumor. The patients averaged having four lymph nodes with metastatic cells in the ipsilateral lateral neck, an average of five affected lymph nodes in the ipsilateral central neck, and an average of two affected lymph nodes in the contralateral central neck.
Among the 63 patients, 23 (37%) had metastases-containing lymph nodes at levels III and IV in the contralateral lateral neck, with a range of 1-17 metastases per node. All nodes were less than 1 cm in diameter. Extracapsular spread had occurred in 11 of the 23 cases.
The relatively frequent presence of metastases in the contralateral, lateral-neck lymph nodes contrasted with the reported low 5%-15% rate of recurrence in these lymph nodes in patients with N1b disease, Dr. Hartl said.
The analysis identified two factors that significantly linked with having contralateral, lateral-neck metastases: having a bilateral tumor with contralateral microcancer, or having at least four lymph nodes positive for metastases in the ipsilateral central compartment, she reported. When patients had fewer than five positive lymph nodes in the ipsilateral central neck, their risk for occult metastases in contralateral lymph nodes was 26%.
“It’s not very strong data; we were a little disappointed” with the results, Dr. Hartl said.
[email protected]
On Twitter @mitchelzoler
The finding reported by Dr. Hartl is consistent with recent experience with other tumor types, like prostate cancer, that often show low aggressiveness. The need to routinely resect what may be indolent microscopic metastases remains a big open question.
The dilemma for thyroid cancer was nicely summarized by Gilbert Welch, MD, and his associates who highlighted the risk of overdiagnosing thyroid cancer with aggressive screening. In South Korea, this resulted in a 15-fold increase in thyroid cancer diagnoses between 1993 and 2011, which led to substantial increases in the rates of thyroidectomy including patients with tumors too small to warrant surgery (N Engl J Med. 2014 Nov 6;371[19]:1765-7).
Pamela Hartzband, MD , is an endocrinologist at Beth Israel Deaconess Medical Center in Boston. She had no disclosures. She made these comments in an interview.
The finding reported by Dr. Hartl is consistent with recent experience with other tumor types, like prostate cancer, that often show low aggressiveness. The need to routinely resect what may be indolent microscopic metastases remains a big open question.
The dilemma for thyroid cancer was nicely summarized by Gilbert Welch, MD, and his associates who highlighted the risk of overdiagnosing thyroid cancer with aggressive screening. In South Korea, this resulted in a 15-fold increase in thyroid cancer diagnoses between 1993 and 2011, which led to substantial increases in the rates of thyroidectomy including patients with tumors too small to warrant surgery (N Engl J Med. 2014 Nov 6;371[19]:1765-7).
Pamela Hartzband, MD , is an endocrinologist at Beth Israel Deaconess Medical Center in Boston. She had no disclosures. She made these comments in an interview.
The finding reported by Dr. Hartl is consistent with recent experience with other tumor types, like prostate cancer, that often show low aggressiveness. The need to routinely resect what may be indolent microscopic metastases remains a big open question.
The dilemma for thyroid cancer was nicely summarized by Gilbert Welch, MD, and his associates who highlighted the risk of overdiagnosing thyroid cancer with aggressive screening. In South Korea, this resulted in a 15-fold increase in thyroid cancer diagnoses between 1993 and 2011, which led to substantial increases in the rates of thyroidectomy including patients with tumors too small to warrant surgery (N Engl J Med. 2014 Nov 6;371[19]:1765-7).
Pamela Hartzband, MD , is an endocrinologist at Beth Israel Deaconess Medical Center in Boston. She had no disclosures. She made these comments in an interview.
BOSTON – More than a third of 63 patients with unilateral papillary thyroid carcinoma and ipsilateral lymph node metastases also had occult, contralateral, lateral-neck lymph nodes with metastases, but the low reported rate of contralateral neck recurrence has raised the question of whether routine resection of these contralateral lymph nodes benefits patients.
“Prophylactic contralateral lateral-neck dissection may not be relevant for patients with unilateral N1b tumors,” Dana Hartl, MD, PhD, said at the World Congress on Thyroid Cancer.
She envisioned a more targeted approach to using surgical resection of contralateral, lateral-neck lymph nodes. “We would still do this surgery for patients with lots of big, bulky nodules; it just takes an additional 10-20 minutes. It’s not that long or morbid. For patients with lots of [affected] nodes, you’ve got to clear it out. But for a patient with a small, level III node on one side I will no longer do [prophylactic, contralateral, lateral-neck lymph node removal].”
Dr. Hartl and her associates reviewed records for 63 patients with unilateral, unifocal papillary thyroid carcinoma who underwent prophylactic, contralateral, lymph node removal during 1997-2016. They ranged from 11-84 years old, and 60% had extrathyroidal extension of their primary tumor. The patients averaged having four lymph nodes with metastatic cells in the ipsilateral lateral neck, an average of five affected lymph nodes in the ipsilateral central neck, and an average of two affected lymph nodes in the contralateral central neck.
Among the 63 patients, 23 (37%) had metastases-containing lymph nodes at levels III and IV in the contralateral lateral neck, with a range of 1-17 metastases per node. All nodes were less than 1 cm in diameter. Extracapsular spread had occurred in 11 of the 23 cases.
The relatively frequent presence of metastases in the contralateral, lateral-neck lymph nodes contrasted with the reported low 5%-15% rate of recurrence in these lymph nodes in patients with N1b disease, Dr. Hartl said.
The analysis identified two factors that significantly linked with having contralateral, lateral-neck metastases: having a bilateral tumor with contralateral microcancer, or having at least four lymph nodes positive for metastases in the ipsilateral central compartment, she reported. When patients had fewer than five positive lymph nodes in the ipsilateral central neck, their risk for occult metastases in contralateral lymph nodes was 26%.
“It’s not very strong data; we were a little disappointed” with the results, Dr. Hartl said.
[email protected]
On Twitter @mitchelzoler
BOSTON – More than a third of 63 patients with unilateral papillary thyroid carcinoma and ipsilateral lymph node metastases also had occult, contralateral, lateral-neck lymph nodes with metastases, but the low reported rate of contralateral neck recurrence has raised the question of whether routine resection of these contralateral lymph nodes benefits patients.
“Prophylactic contralateral lateral-neck dissection may not be relevant for patients with unilateral N1b tumors,” Dana Hartl, MD, PhD, said at the World Congress on Thyroid Cancer.
She envisioned a more targeted approach to using surgical resection of contralateral, lateral-neck lymph nodes. “We would still do this surgery for patients with lots of big, bulky nodules; it just takes an additional 10-20 minutes. It’s not that long or morbid. For patients with lots of [affected] nodes, you’ve got to clear it out. But for a patient with a small, level III node on one side I will no longer do [prophylactic, contralateral, lateral-neck lymph node removal].”
Dr. Hartl and her associates reviewed records for 63 patients with unilateral, unifocal papillary thyroid carcinoma who underwent prophylactic, contralateral, lymph node removal during 1997-2016. They ranged from 11-84 years old, and 60% had extrathyroidal extension of their primary tumor. The patients averaged having four lymph nodes with metastatic cells in the ipsilateral lateral neck, an average of five affected lymph nodes in the ipsilateral central neck, and an average of two affected lymph nodes in the contralateral central neck.
Among the 63 patients, 23 (37%) had metastases-containing lymph nodes at levels III and IV in the contralateral lateral neck, with a range of 1-17 metastases per node. All nodes were less than 1 cm in diameter. Extracapsular spread had occurred in 11 of the 23 cases.
The relatively frequent presence of metastases in the contralateral, lateral-neck lymph nodes contrasted with the reported low 5%-15% rate of recurrence in these lymph nodes in patients with N1b disease, Dr. Hartl said.
The analysis identified two factors that significantly linked with having contralateral, lateral-neck metastases: having a bilateral tumor with contralateral microcancer, or having at least four lymph nodes positive for metastases in the ipsilateral central compartment, she reported. When patients had fewer than five positive lymph nodes in the ipsilateral central neck, their risk for occult metastases in contralateral lymph nodes was 26%.
“It’s not very strong data; we were a little disappointed” with the results, Dr. Hartl said.
[email protected]
On Twitter @mitchelzoler
AT WCTC 2017
Key clinical point:
Major finding: Thirty-seven percent of patients with unilateral N1b thyroid tumors also had metastases in their contralateral lateral-neck lymph nodes.
Data source: Review of 63 patients treated at a single French center during a 20-year period.
Disclosures: Dr. Hartl had no disclosures.
Revised thyroid Bethesda System resets malignant risks
BOSTON – Under the newly revised Bethesda System for Reporting Thyroid Cytology, slated for official release in October 2017, the six cytology-based diagnostic categories for thyroid lesions stay exactly the same as in the 10-year-old first edition, but some associated malignancy risks have changed.
Important changes include molecular testing to further assess malignancy risk in thyroid nodules and the introduction of lobectomy as a treatment option, “which really wasn’t an option 10 years ago,” in the first iteration of the Bethesda System (New York: Springer US, 2010), its coauthor Edmund S. Cibas, MD, said at the World Congress on Thyroid Cancer.
An Endocrine Pathology Society working group created the NIFTP designation in 2016 to describe an encapsulated follicular variant of papillary thyroid carcinoma that is characterized by lack of invasion, a follicular growth pattern, and nuclear features of papillary thyroid carcinoma with a very low risk of an adverse outcome (JAMA Oncology. 2016 Aug;2[8]:1023-9) (Cancer Cytopathol. 2016 Sep;124[9]:616-20).
NIFTP is not an overt malignancy. The revised Bethesda System “limits malignancy to cases with features of classic malignant papillary thyroid carcinoma,” explained Dr. Cibas, professor of pathology at Harvard Medical School and director of cytopathology at Brigham and Women’s Hospital, both in Boston.
Because the Bethesda System categories link to specific management recommendations, the new edition orients patients toward more conservative management decisions, specifically lobectomies instead of total thyroidectomies, he said in an interview.
The International Cytology Congress held a symposium during its meeting in Yokohama, Japan, in 2016, which resulted in the second edition of the Bethesda System (ACTA Cytol. 2016 Sep-Oct; 60[5]:399-405).
The changes in risk of malignancy occurred primarily in two categories, either “atypia of undetermined significance” (AUS) or “follicular lesions of undetermined significance” (FLUS). The risk of malignancy jumped from 5%-15% in the Bethesda System first edition up to 10%-30% in the revision. A smaller bump-up hit the category of “follicular neoplasm” or “suspicious for follicular neoplasm,” in which the risk of malignancy increased from 20%-30% in the first edition to 25%-40% in the revision. And, in the suspicion of malignancy category, the risk of malignancy actually lowered modestly, easing from 60%-75% in the first edition to 50%-75% in the revision.
Dr. Cibas highlighted the AUS/FLUS category with further notable features. The limit on laboratories reporting this category increased to 10% of total reports, up from 7% in the first edition. Management changed from the single options of a repeat fine-needle aspiration specimen to either that or molecular testing. Also, “the first edition was not clear that AUS and FLUS are synonyms. That will be a lot clearer” in the second edition, Dr. Cibas promised. The revision “will encourage labs that currently use [the terms] AUS and FLUS to mean two different things to make a choice between them.”
Another quirk of the AUS and FLUS category is that the risk of malignancy estimates are based on what Dr. Cibas called “flawed” data from only the selected subset of AUS or FLUS patients who have their nodule resected. “The reality is that most of the nodules are not resected” from patients with AUS or FLUS, so conclusions about the risk of malignancy come from a subset with considerable selection bias.
The definition of “follicular neoplasm” or “suspicious for follicular neoplasm” category also added “mild nuclear changes,” which can include increased nuclear size, contour irregularity, or chromatin clearing. The “suspicious for malignancy” category made a modest tweak to the risk of malignancy. Plus, “some of these patients will now undergo lobectomy rather than total thyroidectomy, which has been usual management.
The “suspicious for malignant” and “malignant” categories had little change aside from wider use of lobectomy, now feasible for any patient except those with metastatic disease, Dr. Cibas said.
[email protected]
On Twitter @mitchelzoler
BOSTON – Under the newly revised Bethesda System for Reporting Thyroid Cytology, slated for official release in October 2017, the six cytology-based diagnostic categories for thyroid lesions stay exactly the same as in the 10-year-old first edition, but some associated malignancy risks have changed.
Important changes include molecular testing to further assess malignancy risk in thyroid nodules and the introduction of lobectomy as a treatment option, “which really wasn’t an option 10 years ago,” in the first iteration of the Bethesda System (New York: Springer US, 2010), its coauthor Edmund S. Cibas, MD, said at the World Congress on Thyroid Cancer.
An Endocrine Pathology Society working group created the NIFTP designation in 2016 to describe an encapsulated follicular variant of papillary thyroid carcinoma that is characterized by lack of invasion, a follicular growth pattern, and nuclear features of papillary thyroid carcinoma with a very low risk of an adverse outcome (JAMA Oncology. 2016 Aug;2[8]:1023-9) (Cancer Cytopathol. 2016 Sep;124[9]:616-20).
NIFTP is not an overt malignancy. The revised Bethesda System “limits malignancy to cases with features of classic malignant papillary thyroid carcinoma,” explained Dr. Cibas, professor of pathology at Harvard Medical School and director of cytopathology at Brigham and Women’s Hospital, both in Boston.
Because the Bethesda System categories link to specific management recommendations, the new edition orients patients toward more conservative management decisions, specifically lobectomies instead of total thyroidectomies, he said in an interview.
The International Cytology Congress held a symposium during its meeting in Yokohama, Japan, in 2016, which resulted in the second edition of the Bethesda System (ACTA Cytol. 2016 Sep-Oct; 60[5]:399-405).
The changes in risk of malignancy occurred primarily in two categories, either “atypia of undetermined significance” (AUS) or “follicular lesions of undetermined significance” (FLUS). The risk of malignancy jumped from 5%-15% in the Bethesda System first edition up to 10%-30% in the revision. A smaller bump-up hit the category of “follicular neoplasm” or “suspicious for follicular neoplasm,” in which the risk of malignancy increased from 20%-30% in the first edition to 25%-40% in the revision. And, in the suspicion of malignancy category, the risk of malignancy actually lowered modestly, easing from 60%-75% in the first edition to 50%-75% in the revision.
Dr. Cibas highlighted the AUS/FLUS category with further notable features. The limit on laboratories reporting this category increased to 10% of total reports, up from 7% in the first edition. Management changed from the single options of a repeat fine-needle aspiration specimen to either that or molecular testing. Also, “the first edition was not clear that AUS and FLUS are synonyms. That will be a lot clearer” in the second edition, Dr. Cibas promised. The revision “will encourage labs that currently use [the terms] AUS and FLUS to mean two different things to make a choice between them.”
Another quirk of the AUS and FLUS category is that the risk of malignancy estimates are based on what Dr. Cibas called “flawed” data from only the selected subset of AUS or FLUS patients who have their nodule resected. “The reality is that most of the nodules are not resected” from patients with AUS or FLUS, so conclusions about the risk of malignancy come from a subset with considerable selection bias.
The definition of “follicular neoplasm” or “suspicious for follicular neoplasm” category also added “mild nuclear changes,” which can include increased nuclear size, contour irregularity, or chromatin clearing. The “suspicious for malignancy” category made a modest tweak to the risk of malignancy. Plus, “some of these patients will now undergo lobectomy rather than total thyroidectomy, which has been usual management.
The “suspicious for malignant” and “malignant” categories had little change aside from wider use of lobectomy, now feasible for any patient except those with metastatic disease, Dr. Cibas said.
[email protected]
On Twitter @mitchelzoler
BOSTON – Under the newly revised Bethesda System for Reporting Thyroid Cytology, slated for official release in October 2017, the six cytology-based diagnostic categories for thyroid lesions stay exactly the same as in the 10-year-old first edition, but some associated malignancy risks have changed.
Important changes include molecular testing to further assess malignancy risk in thyroid nodules and the introduction of lobectomy as a treatment option, “which really wasn’t an option 10 years ago,” in the first iteration of the Bethesda System (New York: Springer US, 2010), its coauthor Edmund S. Cibas, MD, said at the World Congress on Thyroid Cancer.
An Endocrine Pathology Society working group created the NIFTP designation in 2016 to describe an encapsulated follicular variant of papillary thyroid carcinoma that is characterized by lack of invasion, a follicular growth pattern, and nuclear features of papillary thyroid carcinoma with a very low risk of an adverse outcome (JAMA Oncology. 2016 Aug;2[8]:1023-9) (Cancer Cytopathol. 2016 Sep;124[9]:616-20).
NIFTP is not an overt malignancy. The revised Bethesda System “limits malignancy to cases with features of classic malignant papillary thyroid carcinoma,” explained Dr. Cibas, professor of pathology at Harvard Medical School and director of cytopathology at Brigham and Women’s Hospital, both in Boston.
Because the Bethesda System categories link to specific management recommendations, the new edition orients patients toward more conservative management decisions, specifically lobectomies instead of total thyroidectomies, he said in an interview.
The International Cytology Congress held a symposium during its meeting in Yokohama, Japan, in 2016, which resulted in the second edition of the Bethesda System (ACTA Cytol. 2016 Sep-Oct; 60[5]:399-405).
The changes in risk of malignancy occurred primarily in two categories, either “atypia of undetermined significance” (AUS) or “follicular lesions of undetermined significance” (FLUS). The risk of malignancy jumped from 5%-15% in the Bethesda System first edition up to 10%-30% in the revision. A smaller bump-up hit the category of “follicular neoplasm” or “suspicious for follicular neoplasm,” in which the risk of malignancy increased from 20%-30% in the first edition to 25%-40% in the revision. And, in the suspicion of malignancy category, the risk of malignancy actually lowered modestly, easing from 60%-75% in the first edition to 50%-75% in the revision.
Dr. Cibas highlighted the AUS/FLUS category with further notable features. The limit on laboratories reporting this category increased to 10% of total reports, up from 7% in the first edition. Management changed from the single options of a repeat fine-needle aspiration specimen to either that or molecular testing. Also, “the first edition was not clear that AUS and FLUS are synonyms. That will be a lot clearer” in the second edition, Dr. Cibas promised. The revision “will encourage labs that currently use [the terms] AUS and FLUS to mean two different things to make a choice between them.”
Another quirk of the AUS and FLUS category is that the risk of malignancy estimates are based on what Dr. Cibas called “flawed” data from only the selected subset of AUS or FLUS patients who have their nodule resected. “The reality is that most of the nodules are not resected” from patients with AUS or FLUS, so conclusions about the risk of malignancy come from a subset with considerable selection bias.
The definition of “follicular neoplasm” or “suspicious for follicular neoplasm” category also added “mild nuclear changes,” which can include increased nuclear size, contour irregularity, or chromatin clearing. The “suspicious for malignancy” category made a modest tweak to the risk of malignancy. Plus, “some of these patients will now undergo lobectomy rather than total thyroidectomy, which has been usual management.
The “suspicious for malignant” and “malignant” categories had little change aside from wider use of lobectomy, now feasible for any patient except those with metastatic disease, Dr. Cibas said.
[email protected]
On Twitter @mitchelzoler
EXPERT ANALYSIS FROM WCTC 2017
VIDEO: Lenvatinib’s real-world thyroid cancer performance matches trial
BOSTON – Lenvatinib’s real-world performance treating advanced, radio-iodine refractory, differentiated thyroid cancer closely followed the efficacy and adverse effect profiles the drug showed in its pivotal trial.
Lenvatinib showed good efficacy in 75 French registry patients, while also producing adverse effects in virtually every patient, but with the possibility to resolve the adverse effects with dose reductions or short-term treatment discontinuations, Martin Schlumberger, MD, said at the World Congress on Thyroid Cancer.
“Lenvatinib is toxic, but the toxicity can be managed in almost all patients by drug withholding or by reducing the dosage, and with symptomatic treatments,” Dr. Schlumberger said in a video interview. But adverse events are a “major problem” for the drug, so patients receiving lenvatinib “should be seen very frequently, and as soon as toxicity appears it should be treated,” said Dr. Schlumberger, professor of medicine and chairman of nuclear medicine and endocrine oncology at Gustave Roussy in Paris.
But lenvatinib’s efficacy makes it a first-line option despite the frequent adverse effects it causes.
“Without doubt it is the most effective drug” for treating advanced, rapidly progressing, radio-iodine refractory thyroid cancer, he said. “When patients really need systemic therapy they should get lenvatinib. It’s a balance of risk and benefit, and the risk from not being treated is higher than the risk from adverse effects.”
A similar pattern of adverse effects and efficacy was seen for lenvatinib in the pivotal Study of Lenvatinib in Differentiated Cancer of the Thyroid (SELECT) trial, which reported a median 18-month progression-free survival rate among patients treated with the drug compared with a median 4-month progression-free survival rate in placebo-treated patients (N Engl J Med. 2015 Feb 12;372[7]:621-30).
Among the 75 patients enrolled in the French registry, the median time of progression-free survival was 10 months, with 8 patients on continued therapy without progression. The response rate in the registry was 31% compared with 65% in the SELECT trial (and 2% in placebo-treated patients in SELECT), but the registry included many patients with advanced disease, comorbidities, and pretreatment, Dr. Schlumberger reported. Just 17 of the registry patients (23%) would have met the enrollment criteria for SELECT. Among this subset the response rate to lenvatinib was 47%.
A multivariate analysis identified three factors that significantly linked with drug responses, Dr. Schlumberger said: pretreatment, more advanced disease, and comorbidities.
Treatment-related adverse effects occurred in 71 of the registry patients (95%), with half of these grade 3 or higher. Twelve patients (16%) discontinued treatment because of an adverse effect. Hypertension was the most common adverse effect, occurring in 50 patients (67%), with 26 having grade 3 or higher hypertension. Other common adverse effects were fatigue, weight loss, diarrhea, and anorexia.
The 75 patients began treatment with lenvatinib for advanced thyroid cancer at any of 24 French centers during April 2015–June 2016. This marked the first year when lenvatinib was available in France for routine use, which roughly coincided with its U.S. introduction after lenvatinib received Food and Drug Administration marketing approval for advanced thyroid cancer in February 2015. Fifty-four patients (72%) began treatment on the labeled dosage of 24 mg/day; the remaining patients started the drug at a lower dosage.
[email protected]
On Twitter @mitchelzoler
Because of its efficacy lenvatinib is absolutely the top thymidine kinase inhibitor to use today to treat patients with radio-iodine-resistant, progressive, differentiated thyroid cancer. Although comparing drugs across trials is unreliable, the activity of lenvatinib in the SELECT trial (N Engl J Med. 2015 Feb 12;372[7]:621-30) was better than the activity of sorafenib in the DECISION trial (Lancet. 2014 July 26;384[9940]:319-28). There was enough of a difference between lenvatinib and sorafenib in the SELECT and DECISION trials to convince me that lenvatinib is the better drug.
Many of the patients enrolled in the French registry would not have qualified to enter the SELECT trial, so I’m not surprised that there was a lower response rate in the registry. We know that lenvatinib works better when the tumor burden is low, and some of the registry patients had a high tumor burden. In addition, a fraction of the registry patients did not receive a dosage of 24 mg/day, and data from the SELECT trial suggests that dosage size matters. The full dosage of 24 mg/day should be used as the starting dosage for lenvatinib, but that isn’t always possible for elderly patients or those with comorbidities.
A rise in blood pressure with lenvatinib treatment is not a completely bad outcome, because our experience with lenvatinib shows that this adverse effect actually links with a survival benefit. A spike in a patient’s blood pressure in response to lenvatinib is a sign that the drug is working and the patient will have a good treatment response, an association that we’ve seen with other tumor types and with other thymidine kinase inhibitors.
Unfortunately, a good response to lenvatinib is usually not enough in the long run. Experience shows that even when advanced thyroid cancer responds to lenvatinib or to another thymidine kinase inhibitor, eventually the disease will progress despite this treatment.
Lori J. Wirth, MD , is medical director of the Center for Head and Neck Cancers at Massachusetts General Hospital in Boston. She has been a consultant to Eisai, Blueprint Medicines, Loxo, and Merck. She made these comments in an interview.
Because of its efficacy lenvatinib is absolutely the top thymidine kinase inhibitor to use today to treat patients with radio-iodine-resistant, progressive, differentiated thyroid cancer. Although comparing drugs across trials is unreliable, the activity of lenvatinib in the SELECT trial (N Engl J Med. 2015 Feb 12;372[7]:621-30) was better than the activity of sorafenib in the DECISION trial (Lancet. 2014 July 26;384[9940]:319-28). There was enough of a difference between lenvatinib and sorafenib in the SELECT and DECISION trials to convince me that lenvatinib is the better drug.
Many of the patients enrolled in the French registry would not have qualified to enter the SELECT trial, so I’m not surprised that there was a lower response rate in the registry. We know that lenvatinib works better when the tumor burden is low, and some of the registry patients had a high tumor burden. In addition, a fraction of the registry patients did not receive a dosage of 24 mg/day, and data from the SELECT trial suggests that dosage size matters. The full dosage of 24 mg/day should be used as the starting dosage for lenvatinib, but that isn’t always possible for elderly patients or those with comorbidities.
A rise in blood pressure with lenvatinib treatment is not a completely bad outcome, because our experience with lenvatinib shows that this adverse effect actually links with a survival benefit. A spike in a patient’s blood pressure in response to lenvatinib is a sign that the drug is working and the patient will have a good treatment response, an association that we’ve seen with other tumor types and with other thymidine kinase inhibitors.
Unfortunately, a good response to lenvatinib is usually not enough in the long run. Experience shows that even when advanced thyroid cancer responds to lenvatinib or to another thymidine kinase inhibitor, eventually the disease will progress despite this treatment.
Lori J. Wirth, MD , is medical director of the Center for Head and Neck Cancers at Massachusetts General Hospital in Boston. She has been a consultant to Eisai, Blueprint Medicines, Loxo, and Merck. She made these comments in an interview.
Because of its efficacy lenvatinib is absolutely the top thymidine kinase inhibitor to use today to treat patients with radio-iodine-resistant, progressive, differentiated thyroid cancer. Although comparing drugs across trials is unreliable, the activity of lenvatinib in the SELECT trial (N Engl J Med. 2015 Feb 12;372[7]:621-30) was better than the activity of sorafenib in the DECISION trial (Lancet. 2014 July 26;384[9940]:319-28). There was enough of a difference between lenvatinib and sorafenib in the SELECT and DECISION trials to convince me that lenvatinib is the better drug.
Many of the patients enrolled in the French registry would not have qualified to enter the SELECT trial, so I’m not surprised that there was a lower response rate in the registry. We know that lenvatinib works better when the tumor burden is low, and some of the registry patients had a high tumor burden. In addition, a fraction of the registry patients did not receive a dosage of 24 mg/day, and data from the SELECT trial suggests that dosage size matters. The full dosage of 24 mg/day should be used as the starting dosage for lenvatinib, but that isn’t always possible for elderly patients or those with comorbidities.
A rise in blood pressure with lenvatinib treatment is not a completely bad outcome, because our experience with lenvatinib shows that this adverse effect actually links with a survival benefit. A spike in a patient’s blood pressure in response to lenvatinib is a sign that the drug is working and the patient will have a good treatment response, an association that we’ve seen with other tumor types and with other thymidine kinase inhibitors.
Unfortunately, a good response to lenvatinib is usually not enough in the long run. Experience shows that even when advanced thyroid cancer responds to lenvatinib or to another thymidine kinase inhibitor, eventually the disease will progress despite this treatment.
Lori J. Wirth, MD , is medical director of the Center for Head and Neck Cancers at Massachusetts General Hospital in Boston. She has been a consultant to Eisai, Blueprint Medicines, Loxo, and Merck. She made these comments in an interview.
BOSTON – Lenvatinib’s real-world performance treating advanced, radio-iodine refractory, differentiated thyroid cancer closely followed the efficacy and adverse effect profiles the drug showed in its pivotal trial.
Lenvatinib showed good efficacy in 75 French registry patients, while also producing adverse effects in virtually every patient, but with the possibility to resolve the adverse effects with dose reductions or short-term treatment discontinuations, Martin Schlumberger, MD, said at the World Congress on Thyroid Cancer.
“Lenvatinib is toxic, but the toxicity can be managed in almost all patients by drug withholding or by reducing the dosage, and with symptomatic treatments,” Dr. Schlumberger said in a video interview. But adverse events are a “major problem” for the drug, so patients receiving lenvatinib “should be seen very frequently, and as soon as toxicity appears it should be treated,” said Dr. Schlumberger, professor of medicine and chairman of nuclear medicine and endocrine oncology at Gustave Roussy in Paris.
But lenvatinib’s efficacy makes it a first-line option despite the frequent adverse effects it causes.
“Without doubt it is the most effective drug” for treating advanced, rapidly progressing, radio-iodine refractory thyroid cancer, he said. “When patients really need systemic therapy they should get lenvatinib. It’s a balance of risk and benefit, and the risk from not being treated is higher than the risk from adverse effects.”
A similar pattern of adverse effects and efficacy was seen for lenvatinib in the pivotal Study of Lenvatinib in Differentiated Cancer of the Thyroid (SELECT) trial, which reported a median 18-month progression-free survival rate among patients treated with the drug compared with a median 4-month progression-free survival rate in placebo-treated patients (N Engl J Med. 2015 Feb 12;372[7]:621-30).
Among the 75 patients enrolled in the French registry, the median time of progression-free survival was 10 months, with 8 patients on continued therapy without progression. The response rate in the registry was 31% compared with 65% in the SELECT trial (and 2% in placebo-treated patients in SELECT), but the registry included many patients with advanced disease, comorbidities, and pretreatment, Dr. Schlumberger reported. Just 17 of the registry patients (23%) would have met the enrollment criteria for SELECT. Among this subset the response rate to lenvatinib was 47%.
A multivariate analysis identified three factors that significantly linked with drug responses, Dr. Schlumberger said: pretreatment, more advanced disease, and comorbidities.
Treatment-related adverse effects occurred in 71 of the registry patients (95%), with half of these grade 3 or higher. Twelve patients (16%) discontinued treatment because of an adverse effect. Hypertension was the most common adverse effect, occurring in 50 patients (67%), with 26 having grade 3 or higher hypertension. Other common adverse effects were fatigue, weight loss, diarrhea, and anorexia.
The 75 patients began treatment with lenvatinib for advanced thyroid cancer at any of 24 French centers during April 2015–June 2016. This marked the first year when lenvatinib was available in France for routine use, which roughly coincided with its U.S. introduction after lenvatinib received Food and Drug Administration marketing approval for advanced thyroid cancer in February 2015. Fifty-four patients (72%) began treatment on the labeled dosage of 24 mg/day; the remaining patients started the drug at a lower dosage.
[email protected]
On Twitter @mitchelzoler
BOSTON – Lenvatinib’s real-world performance treating advanced, radio-iodine refractory, differentiated thyroid cancer closely followed the efficacy and adverse effect profiles the drug showed in its pivotal trial.
Lenvatinib showed good efficacy in 75 French registry patients, while also producing adverse effects in virtually every patient, but with the possibility to resolve the adverse effects with dose reductions or short-term treatment discontinuations, Martin Schlumberger, MD, said at the World Congress on Thyroid Cancer.
“Lenvatinib is toxic, but the toxicity can be managed in almost all patients by drug withholding or by reducing the dosage, and with symptomatic treatments,” Dr. Schlumberger said in a video interview. But adverse events are a “major problem” for the drug, so patients receiving lenvatinib “should be seen very frequently, and as soon as toxicity appears it should be treated,” said Dr. Schlumberger, professor of medicine and chairman of nuclear medicine and endocrine oncology at Gustave Roussy in Paris.
But lenvatinib’s efficacy makes it a first-line option despite the frequent adverse effects it causes.
“Without doubt it is the most effective drug” for treating advanced, rapidly progressing, radio-iodine refractory thyroid cancer, he said. “When patients really need systemic therapy they should get lenvatinib. It’s a balance of risk and benefit, and the risk from not being treated is higher than the risk from adverse effects.”
A similar pattern of adverse effects and efficacy was seen for lenvatinib in the pivotal Study of Lenvatinib in Differentiated Cancer of the Thyroid (SELECT) trial, which reported a median 18-month progression-free survival rate among patients treated with the drug compared with a median 4-month progression-free survival rate in placebo-treated patients (N Engl J Med. 2015 Feb 12;372[7]:621-30).
Among the 75 patients enrolled in the French registry, the median time of progression-free survival was 10 months, with 8 patients on continued therapy without progression. The response rate in the registry was 31% compared with 65% in the SELECT trial (and 2% in placebo-treated patients in SELECT), but the registry included many patients with advanced disease, comorbidities, and pretreatment, Dr. Schlumberger reported. Just 17 of the registry patients (23%) would have met the enrollment criteria for SELECT. Among this subset the response rate to lenvatinib was 47%.
A multivariate analysis identified three factors that significantly linked with drug responses, Dr. Schlumberger said: pretreatment, more advanced disease, and comorbidities.
Treatment-related adverse effects occurred in 71 of the registry patients (95%), with half of these grade 3 or higher. Twelve patients (16%) discontinued treatment because of an adverse effect. Hypertension was the most common adverse effect, occurring in 50 patients (67%), with 26 having grade 3 or higher hypertension. Other common adverse effects were fatigue, weight loss, diarrhea, and anorexia.
The 75 patients began treatment with lenvatinib for advanced thyroid cancer at any of 24 French centers during April 2015–June 2016. This marked the first year when lenvatinib was available in France for routine use, which roughly coincided with its U.S. introduction after lenvatinib received Food and Drug Administration marketing approval for advanced thyroid cancer in February 2015. Fifty-four patients (72%) began treatment on the labeled dosage of 24 mg/day; the remaining patients started the drug at a lower dosage.
[email protected]
On Twitter @mitchelzoler
AT WCTC 2017
Key clinical point:
Major finding: The median time of progression-free survival was 10 months in the registry and 18 months in the pivotal trial.
Data source: A retrospective review of the first 75 French patients with advanced differentiated thyroid cancer who received lenvatinib following its marketing approval.
Disclosures: Dr. Schlumberger has received research funding from Eisai, the company that markets lenvatinib (Lenvima). He has also received research support and honoraria from AstraZeneca, Bayer, and Excelixis.
Thyroid-nodule size boosts serum thyroglobulin’s diagnostic value
BOSTON – Normalizing the serum thyroglobulin level by thyroid nodule size in patients surgically treated for a thyroid nodule produced a strongly significant link between the level of this marker and nodule malignancy in a review of nearly 200 patients treated at any of three Montreal centers.
After normalization, the serum thyroglobulin of patients with a malignant nodule averaged 51 mcg/L*cm, more than double the average 23 mcg/L*cm among patients with benign nodules, Neil Verma, MD, said at the World Congress on Thyroid Cancer.
But the senior investigator on the study said that, even if the MTNS+ gets a little more accurate by using a nodule size-normalized serum thyroglobulin level, the clinical utility of the MTNS+ will soon be completely eclipsed by widespread reliance on molecular tests, whereas the MTNS+ combines many clinical and conventional laboratory measures. It‘s only a matter of cost, said Richard J. Payne, MD, a head and neck surgeon at McGill.
Routine reimbursement for molecular diagnostic tests for the malignancy of thyroid nodules was discussed at a recent meeting of Canadian head and neck surgeons, who decided to lobby provincial governments to try to get it covered, according to Dr. Payne. “I’d be very surprised if we don’t have government coverage within 4-5 years,” in part because the cost for molecular testing will likely fall significantly in that time frame, he predicted.
The analysis reported by Dr. Verma included 196 patients with thyroid nodules who underwent a partial or total thyroidectomy at any of three McGill teaching hospitals during 2010-2015. He determined the benign or malignant status of their nodules based on their histology. The analysis he presented also showed that malignancy had no clear relationship to nodule size. Nodules that were less than 2 cm in diameter were about as likely to be malignant as were those that were 3 cm or larger in diameter, Dr. Verma reported.
Size-normalized serum thyroglobulin will now be incorporated into the MTNS+, which will be the fourth change to the original MTNS scoring system since it was developed more than a decade ago, noted Dr. Payne. But, while the MTNS+ allows better prediction of malignant potential than does the Bethesda system for evaluating nodule cytopathology in a fine-needle aspirate, it still falls short of molecular testing in its predictive accuracy, Dr. Payne said.
Dr. Verma and Dr. Payne had no disclosures.
[email protected]
On Twitter @mitchelzoler
BOSTON – Normalizing the serum thyroglobulin level by thyroid nodule size in patients surgically treated for a thyroid nodule produced a strongly significant link between the level of this marker and nodule malignancy in a review of nearly 200 patients treated at any of three Montreal centers.
After normalization, the serum thyroglobulin of patients with a malignant nodule averaged 51 mcg/L*cm, more than double the average 23 mcg/L*cm among patients with benign nodules, Neil Verma, MD, said at the World Congress on Thyroid Cancer.
But the senior investigator on the study said that, even if the MTNS+ gets a little more accurate by using a nodule size-normalized serum thyroglobulin level, the clinical utility of the MTNS+ will soon be completely eclipsed by widespread reliance on molecular tests, whereas the MTNS+ combines many clinical and conventional laboratory measures. It‘s only a matter of cost, said Richard J. Payne, MD, a head and neck surgeon at McGill.
Routine reimbursement for molecular diagnostic tests for the malignancy of thyroid nodules was discussed at a recent meeting of Canadian head and neck surgeons, who decided to lobby provincial governments to try to get it covered, according to Dr. Payne. “I’d be very surprised if we don’t have government coverage within 4-5 years,” in part because the cost for molecular testing will likely fall significantly in that time frame, he predicted.
The analysis reported by Dr. Verma included 196 patients with thyroid nodules who underwent a partial or total thyroidectomy at any of three McGill teaching hospitals during 2010-2015. He determined the benign or malignant status of their nodules based on their histology. The analysis he presented also showed that malignancy had no clear relationship to nodule size. Nodules that were less than 2 cm in diameter were about as likely to be malignant as were those that were 3 cm or larger in diameter, Dr. Verma reported.
Size-normalized serum thyroglobulin will now be incorporated into the MTNS+, which will be the fourth change to the original MTNS scoring system since it was developed more than a decade ago, noted Dr. Payne. But, while the MTNS+ allows better prediction of malignant potential than does the Bethesda system for evaluating nodule cytopathology in a fine-needle aspirate, it still falls short of molecular testing in its predictive accuracy, Dr. Payne said.
Dr. Verma and Dr. Payne had no disclosures.
[email protected]
On Twitter @mitchelzoler
BOSTON – Normalizing the serum thyroglobulin level by thyroid nodule size in patients surgically treated for a thyroid nodule produced a strongly significant link between the level of this marker and nodule malignancy in a review of nearly 200 patients treated at any of three Montreal centers.
After normalization, the serum thyroglobulin of patients with a malignant nodule averaged 51 mcg/L*cm, more than double the average 23 mcg/L*cm among patients with benign nodules, Neil Verma, MD, said at the World Congress on Thyroid Cancer.
But the senior investigator on the study said that, even if the MTNS+ gets a little more accurate by using a nodule size-normalized serum thyroglobulin level, the clinical utility of the MTNS+ will soon be completely eclipsed by widespread reliance on molecular tests, whereas the MTNS+ combines many clinical and conventional laboratory measures. It‘s only a matter of cost, said Richard J. Payne, MD, a head and neck surgeon at McGill.
Routine reimbursement for molecular diagnostic tests for the malignancy of thyroid nodules was discussed at a recent meeting of Canadian head and neck surgeons, who decided to lobby provincial governments to try to get it covered, according to Dr. Payne. “I’d be very surprised if we don’t have government coverage within 4-5 years,” in part because the cost for molecular testing will likely fall significantly in that time frame, he predicted.
The analysis reported by Dr. Verma included 196 patients with thyroid nodules who underwent a partial or total thyroidectomy at any of three McGill teaching hospitals during 2010-2015. He determined the benign or malignant status of their nodules based on their histology. The analysis he presented also showed that malignancy had no clear relationship to nodule size. Nodules that were less than 2 cm in diameter were about as likely to be malignant as were those that were 3 cm or larger in diameter, Dr. Verma reported.
Size-normalized serum thyroglobulin will now be incorporated into the MTNS+, which will be the fourth change to the original MTNS scoring system since it was developed more than a decade ago, noted Dr. Payne. But, while the MTNS+ allows better prediction of malignant potential than does the Bethesda system for evaluating nodule cytopathology in a fine-needle aspirate, it still falls short of molecular testing in its predictive accuracy, Dr. Payne said.
Dr. Verma and Dr. Payne had no disclosures.
[email protected]
On Twitter @mitchelzoler
AT WCTC 2017
Key clinical point:
Major finding: The average size-normalized serum thyroglobulin level was 51 mcg/L*cm in patients with malignant nodules and 23 mcg/L*cm with benign nodules.
Data source: Review of 196 patients who underwent partial or complete thyroidectomy at any of three Montreal centers.
Disclosures: Dr. Verma and Dr. Payne had no disclosures.
VIDEO: Less follow-up proposed for low-risk thyroid cancer
BOSTON – , Bryan R. Haugen, MD, suggested in a keynote lecture during the World Congress on Thyroid Cancer.
Traditionally, thyroid cancer specialists have monitored these patients for persistent or recurrent disease as often as every 6 or 12 months. “But what we’ve realized with recent assessments of response to treatment is that some patients do well without a recurrence over many years; so, the concept of doing less monitoring and less imaging, especially in patients with an excellent response [to their initial treatment], is being studied,” Dr. Haugen said in a video interview following his talk.
He estimated that perhaps two-thirds or as many as three-quarters of patients with differentiated thyroid cancer fall into the category of having low- or intermediate-risk disease with an excellent or good response to treatment, and hence they are potential candidates for eventually transitioning to less frequent follow-up.
During his talk, Dr. Haugen suggested that after several years with no sign of disease recurrence, lower-risk patients with an excellent treatment response may be able to stop undergoing regular monitoring, and those with a good treatment response may be able to safely have their monitoring intervals extended.
According to the most recent (2015) guidelines for differentiated thyroid cancer management from the American Thyroid Association, lower-risk patients with an excellent treatment response should have their serum thyroglobulin measured every 12-24 months and undergo an ultrasound examination every 3-5 years, while patients with a good response are targeted for serum thyroglobulin measurement annually with an ultrasound every 1-3 years (Thyroid. 2016 Jan;26[1]:1-133). Dr. Haugen chaired the expert panel that wrote these guidelines.
In another provocative suggestion, Dr. Haugen proposed that once well-responsive, lower-risk patients have remained disease free for several years, their less frequent follow-up monitoring could be continued by a primary care physician or another less specialized clinician.
At some time in the future, “a patient’s primary care physician could follow a simple tumor marker, thyroglobulin, maybe once every 5 years,” said Dr. Haugen, professor of medicine and head of the division of endocrinology, metabolism, and diabetes at the University of Colorado in Aurora. “At the University of Colorado, we use advanced-practice providers to do long-term follow-up” for lower-risk, treatment-responsive patients, he said.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @mitchelzoler
BOSTON – , Bryan R. Haugen, MD, suggested in a keynote lecture during the World Congress on Thyroid Cancer.
Traditionally, thyroid cancer specialists have monitored these patients for persistent or recurrent disease as often as every 6 or 12 months. “But what we’ve realized with recent assessments of response to treatment is that some patients do well without a recurrence over many years; so, the concept of doing less monitoring and less imaging, especially in patients with an excellent response [to their initial treatment], is being studied,” Dr. Haugen said in a video interview following his talk.
He estimated that perhaps two-thirds or as many as three-quarters of patients with differentiated thyroid cancer fall into the category of having low- or intermediate-risk disease with an excellent or good response to treatment, and hence they are potential candidates for eventually transitioning to less frequent follow-up.
During his talk, Dr. Haugen suggested that after several years with no sign of disease recurrence, lower-risk patients with an excellent treatment response may be able to stop undergoing regular monitoring, and those with a good treatment response may be able to safely have their monitoring intervals extended.
According to the most recent (2015) guidelines for differentiated thyroid cancer management from the American Thyroid Association, lower-risk patients with an excellent treatment response should have their serum thyroglobulin measured every 12-24 months and undergo an ultrasound examination every 3-5 years, while patients with a good response are targeted for serum thyroglobulin measurement annually with an ultrasound every 1-3 years (Thyroid. 2016 Jan;26[1]:1-133). Dr. Haugen chaired the expert panel that wrote these guidelines.
In another provocative suggestion, Dr. Haugen proposed that once well-responsive, lower-risk patients have remained disease free for several years, their less frequent follow-up monitoring could be continued by a primary care physician or another less specialized clinician.
At some time in the future, “a patient’s primary care physician could follow a simple tumor marker, thyroglobulin, maybe once every 5 years,” said Dr. Haugen, professor of medicine and head of the division of endocrinology, metabolism, and diabetes at the University of Colorado in Aurora. “At the University of Colorado, we use advanced-practice providers to do long-term follow-up” for lower-risk, treatment-responsive patients, he said.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @mitchelzoler
BOSTON – , Bryan R. Haugen, MD, suggested in a keynote lecture during the World Congress on Thyroid Cancer.
Traditionally, thyroid cancer specialists have monitored these patients for persistent or recurrent disease as often as every 6 or 12 months. “But what we’ve realized with recent assessments of response to treatment is that some patients do well without a recurrence over many years; so, the concept of doing less monitoring and less imaging, especially in patients with an excellent response [to their initial treatment], is being studied,” Dr. Haugen said in a video interview following his talk.
He estimated that perhaps two-thirds or as many as three-quarters of patients with differentiated thyroid cancer fall into the category of having low- or intermediate-risk disease with an excellent or good response to treatment, and hence they are potential candidates for eventually transitioning to less frequent follow-up.
During his talk, Dr. Haugen suggested that after several years with no sign of disease recurrence, lower-risk patients with an excellent treatment response may be able to stop undergoing regular monitoring, and those with a good treatment response may be able to safely have their monitoring intervals extended.
According to the most recent (2015) guidelines for differentiated thyroid cancer management from the American Thyroid Association, lower-risk patients with an excellent treatment response should have their serum thyroglobulin measured every 12-24 months and undergo an ultrasound examination every 3-5 years, while patients with a good response are targeted for serum thyroglobulin measurement annually with an ultrasound every 1-3 years (Thyroid. 2016 Jan;26[1]:1-133). Dr. Haugen chaired the expert panel that wrote these guidelines.
In another provocative suggestion, Dr. Haugen proposed that once well-responsive, lower-risk patients have remained disease free for several years, their less frequent follow-up monitoring could be continued by a primary care physician or another less specialized clinician.
At some time in the future, “a patient’s primary care physician could follow a simple tumor marker, thyroglobulin, maybe once every 5 years,” said Dr. Haugen, professor of medicine and head of the division of endocrinology, metabolism, and diabetes at the University of Colorado in Aurora. “At the University of Colorado, we use advanced-practice providers to do long-term follow-up” for lower-risk, treatment-responsive patients, he said.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @mitchelzoler
AT WCTC 2017
