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Algorithm for identifying IPF has low PPV
ICD-9 codes were poor at picking out idiopathic pulmonary fibrosis patients from administrative databases for epidemiologic studies, but a new tool could improve diagnostic accuracy, according to Kaiser Permanente and University of California, San Francisco (UCSF), investigators.
“In the age of large administrative databases and electronic medical records, there is rich opportunity to conduct population-based studies” of disease behavior, outcomes, health care use, and other matters, but researchers first need to be able to accurately identify patients with idiopathic pulmonary fibrosis (IPF) in large data sets, said investigators led by Brett Ley, MD, an assistant professor of medicine at UCSF.
The research community has traditionally relied on claims for specific IPF diagnostic codes – ICD-9 code 516.3 or ICD-9-CM code 516.31 – to identify patients, but the approach had never been validated. To see how well it works, the investigators applied it to the nearly 5.4 million adults in the Kaiser Permanente Northern California system during 2000-2014. After patients with interstitial lung disease-associated codes entered on or after the day of the last IPF code were excluded, the algorithm identified 2,608 patients as having IPF (Ann Am Thorac Soc. 2017 Jun;14[6]:880-7).
Next, the investigators randomly selected 150 of those patients and examined their medical records, procedure codes, CTs, and other patient-level data to see how many of them really had IPF. The results weren’t good. The positive predictive value of the IPF code-based algorithm was only 42.2%, with a sensitivity 55.6%.
The widely used code-based IPF algorithm does “not generate accurate estimates of IPF incidence and prevalence. ... Over half of the patients identified as having IPF ... did not have IPF on case review. Alarmingly, whereas half of the misclassified cases had an alternative [interstitial lung disease] diagnosis, the other half had no clinical or radiologic evidence of ILD [interstitial lung disease] at all.” The algorithm also “likely misses a substantial proportion of patients who do have IPF,” Dr. Ley and his colleagues said.
“We can only speculate about the reasons. ... It seems likely to be due to a combination of misdiagnosis at the clinical level and miscoding at the administrative level,” they said.
To try to improve the situation, the team tweaked the algorithm to include only patients 50 years or older who had at least two 516.3 or 516.31 claims 1 month or more apart and a chest CT procedure code beforehand. They again excluded ILD-associated claims on or after the day of the last IPF code.
Although the sensitivity of the modified algorithm was lower than the original, it had a more robust positive predictive value of 70.4% in the derivation cohort and 61.8% in the validation cohort, both derived from the 150 patients used to validate the original algorithm.
“By making a few simple, empirically derived changes to the IPF algorithm,” it’s possible to “more reliably identif[y] patients” with IPF. “We believe the modified IPF algorithm will be useful for population-based studies of IPF ... that require high diagnostic certainty,” the investigators concluded.
The traditional algorithm found an incidence of 6.8 cases per 100,000 person-years, which was on the low end of previous reports, perhaps because of the relative health and youth of the 5.4 million patient pool. As in past studies, IPF incidence increased with older age and was highest in white patients and men.
“Whether the more specific codes provided by the ICD-10 system will allow for improved case classification of IPF requires further study,” the investigators noted.
The work was funded by the National Institutes of Health. Dr. Ley reported speaker’s fees from Genentech, and one of the authors was an employee of the company. The senior author Harold Collard, MD, an associate professor in UCSF’s Division of Pulmonary and Critical Care Medicine, reported personal fees from Takeda, ImmuneWorks, Parexel, Pharma Capital Partners, and others.
This study glaringly displays potential problems with using ICD codes for research purposes and calls into question results from a handful of studies that yielded epidemiological estimates for idiopathic pulmonary fibrosis. We are reminded that practitioner-generated diagnostic codes of IPF recorded in the medical record are subject to inaccuracies, which can be illuminated by the “gold standard” – multidisciplinary adjudication.
Moving forward, particularly as longitudinal, nationwide IPF registries come online, patient-level case validation should be employed. As we move into the era of ICD-10, the study should serve as a call to improve IPF case ascertainment accuracy for any investigators choosing to use large data analytic strategies. Doing so will mute the background noise and allow us to better hear the signals of this complex disease.
Evans R. Fernandez Perez, MD, is a pulmonologist at National Jewish Health, Denver. He made his comments in an editorial, and reported speaker’s fees from Boehringer Ingelheim and Genentech (Ann Am Thorac Soc. 2017 Jun;14[6]:829-30).
This study glaringly displays potential problems with using ICD codes for research purposes and calls into question results from a handful of studies that yielded epidemiological estimates for idiopathic pulmonary fibrosis. We are reminded that practitioner-generated diagnostic codes of IPF recorded in the medical record are subject to inaccuracies, which can be illuminated by the “gold standard” – multidisciplinary adjudication.
Moving forward, particularly as longitudinal, nationwide IPF registries come online, patient-level case validation should be employed. As we move into the era of ICD-10, the study should serve as a call to improve IPF case ascertainment accuracy for any investigators choosing to use large data analytic strategies. Doing so will mute the background noise and allow us to better hear the signals of this complex disease.
Evans R. Fernandez Perez, MD, is a pulmonologist at National Jewish Health, Denver. He made his comments in an editorial, and reported speaker’s fees from Boehringer Ingelheim and Genentech (Ann Am Thorac Soc. 2017 Jun;14[6]:829-30).
This study glaringly displays potential problems with using ICD codes for research purposes and calls into question results from a handful of studies that yielded epidemiological estimates for idiopathic pulmonary fibrosis. We are reminded that practitioner-generated diagnostic codes of IPF recorded in the medical record are subject to inaccuracies, which can be illuminated by the “gold standard” – multidisciplinary adjudication.
Moving forward, particularly as longitudinal, nationwide IPF registries come online, patient-level case validation should be employed. As we move into the era of ICD-10, the study should serve as a call to improve IPF case ascertainment accuracy for any investigators choosing to use large data analytic strategies. Doing so will mute the background noise and allow us to better hear the signals of this complex disease.
Evans R. Fernandez Perez, MD, is a pulmonologist at National Jewish Health, Denver. He made his comments in an editorial, and reported speaker’s fees from Boehringer Ingelheim and Genentech (Ann Am Thorac Soc. 2017 Jun;14[6]:829-30).
ICD-9 codes were poor at picking out idiopathic pulmonary fibrosis patients from administrative databases for epidemiologic studies, but a new tool could improve diagnostic accuracy, according to Kaiser Permanente and University of California, San Francisco (UCSF), investigators.
“In the age of large administrative databases and electronic medical records, there is rich opportunity to conduct population-based studies” of disease behavior, outcomes, health care use, and other matters, but researchers first need to be able to accurately identify patients with idiopathic pulmonary fibrosis (IPF) in large data sets, said investigators led by Brett Ley, MD, an assistant professor of medicine at UCSF.
The research community has traditionally relied on claims for specific IPF diagnostic codes – ICD-9 code 516.3 or ICD-9-CM code 516.31 – to identify patients, but the approach had never been validated. To see how well it works, the investigators applied it to the nearly 5.4 million adults in the Kaiser Permanente Northern California system during 2000-2014. After patients with interstitial lung disease-associated codes entered on or after the day of the last IPF code were excluded, the algorithm identified 2,608 patients as having IPF (Ann Am Thorac Soc. 2017 Jun;14[6]:880-7).
Next, the investigators randomly selected 150 of those patients and examined their medical records, procedure codes, CTs, and other patient-level data to see how many of them really had IPF. The results weren’t good. The positive predictive value of the IPF code-based algorithm was only 42.2%, with a sensitivity 55.6%.
The widely used code-based IPF algorithm does “not generate accurate estimates of IPF incidence and prevalence. ... Over half of the patients identified as having IPF ... did not have IPF on case review. Alarmingly, whereas half of the misclassified cases had an alternative [interstitial lung disease] diagnosis, the other half had no clinical or radiologic evidence of ILD [interstitial lung disease] at all.” The algorithm also “likely misses a substantial proportion of patients who do have IPF,” Dr. Ley and his colleagues said.
“We can only speculate about the reasons. ... It seems likely to be due to a combination of misdiagnosis at the clinical level and miscoding at the administrative level,” they said.
To try to improve the situation, the team tweaked the algorithm to include only patients 50 years or older who had at least two 516.3 or 516.31 claims 1 month or more apart and a chest CT procedure code beforehand. They again excluded ILD-associated claims on or after the day of the last IPF code.
Although the sensitivity of the modified algorithm was lower than the original, it had a more robust positive predictive value of 70.4% in the derivation cohort and 61.8% in the validation cohort, both derived from the 150 patients used to validate the original algorithm.
“By making a few simple, empirically derived changes to the IPF algorithm,” it’s possible to “more reliably identif[y] patients” with IPF. “We believe the modified IPF algorithm will be useful for population-based studies of IPF ... that require high diagnostic certainty,” the investigators concluded.
The traditional algorithm found an incidence of 6.8 cases per 100,000 person-years, which was on the low end of previous reports, perhaps because of the relative health and youth of the 5.4 million patient pool. As in past studies, IPF incidence increased with older age and was highest in white patients and men.
“Whether the more specific codes provided by the ICD-10 system will allow for improved case classification of IPF requires further study,” the investigators noted.
The work was funded by the National Institutes of Health. Dr. Ley reported speaker’s fees from Genentech, and one of the authors was an employee of the company. The senior author Harold Collard, MD, an associate professor in UCSF’s Division of Pulmonary and Critical Care Medicine, reported personal fees from Takeda, ImmuneWorks, Parexel, Pharma Capital Partners, and others.
ICD-9 codes were poor at picking out idiopathic pulmonary fibrosis patients from administrative databases for epidemiologic studies, but a new tool could improve diagnostic accuracy, according to Kaiser Permanente and University of California, San Francisco (UCSF), investigators.
“In the age of large administrative databases and electronic medical records, there is rich opportunity to conduct population-based studies” of disease behavior, outcomes, health care use, and other matters, but researchers first need to be able to accurately identify patients with idiopathic pulmonary fibrosis (IPF) in large data sets, said investigators led by Brett Ley, MD, an assistant professor of medicine at UCSF.
The research community has traditionally relied on claims for specific IPF diagnostic codes – ICD-9 code 516.3 or ICD-9-CM code 516.31 – to identify patients, but the approach had never been validated. To see how well it works, the investigators applied it to the nearly 5.4 million adults in the Kaiser Permanente Northern California system during 2000-2014. After patients with interstitial lung disease-associated codes entered on or after the day of the last IPF code were excluded, the algorithm identified 2,608 patients as having IPF (Ann Am Thorac Soc. 2017 Jun;14[6]:880-7).
Next, the investigators randomly selected 150 of those patients and examined their medical records, procedure codes, CTs, and other patient-level data to see how many of them really had IPF. The results weren’t good. The positive predictive value of the IPF code-based algorithm was only 42.2%, with a sensitivity 55.6%.
The widely used code-based IPF algorithm does “not generate accurate estimates of IPF incidence and prevalence. ... Over half of the patients identified as having IPF ... did not have IPF on case review. Alarmingly, whereas half of the misclassified cases had an alternative [interstitial lung disease] diagnosis, the other half had no clinical or radiologic evidence of ILD [interstitial lung disease] at all.” The algorithm also “likely misses a substantial proportion of patients who do have IPF,” Dr. Ley and his colleagues said.
“We can only speculate about the reasons. ... It seems likely to be due to a combination of misdiagnosis at the clinical level and miscoding at the administrative level,” they said.
To try to improve the situation, the team tweaked the algorithm to include only patients 50 years or older who had at least two 516.3 or 516.31 claims 1 month or more apart and a chest CT procedure code beforehand. They again excluded ILD-associated claims on or after the day of the last IPF code.
Although the sensitivity of the modified algorithm was lower than the original, it had a more robust positive predictive value of 70.4% in the derivation cohort and 61.8% in the validation cohort, both derived from the 150 patients used to validate the original algorithm.
“By making a few simple, empirically derived changes to the IPF algorithm,” it’s possible to “more reliably identif[y] patients” with IPF. “We believe the modified IPF algorithm will be useful for population-based studies of IPF ... that require high diagnostic certainty,” the investigators concluded.
The traditional algorithm found an incidence of 6.8 cases per 100,000 person-years, which was on the low end of previous reports, perhaps because of the relative health and youth of the 5.4 million patient pool. As in past studies, IPF incidence increased with older age and was highest in white patients and men.
“Whether the more specific codes provided by the ICD-10 system will allow for improved case classification of IPF requires further study,” the investigators noted.
The work was funded by the National Institutes of Health. Dr. Ley reported speaker’s fees from Genentech, and one of the authors was an employee of the company. The senior author Harold Collard, MD, an associate professor in UCSF’s Division of Pulmonary and Critical Care Medicine, reported personal fees from Takeda, ImmuneWorks, Parexel, Pharma Capital Partners, and others.
FROM THE ANNALS OF THE AMERICAN THORACIC SOCIETY
Key clinical point:
Major finding: The positive predictive value of the traditional IPF code-based algorithm was only 42.2%, with a sensitivity of 55.6%.
Data source: A study including almost 5.4 million patients at Kaiser Permanente Northern California.
Disclosures: The work was funded by the National Institutes of Health. One of the investigators was a Genentech employee. Others reported speaker’s and personal fees from Genentech and other companies.
Do sleep interventions prevent atrial fibrillation?
WASHINGTON – If patients have sleep disordered breathing with obstructive sleep apnea, will its treatment have cardiovascular disease benefits, especially in terms of the incidence or severity of atrial fibrillation?
Observational evidence suggests that apnea interventions may help these patients, but no clear case yet exists to prove that a breathing intervention works, experts say, and, as a result, U.S. practice is mixed when it comes to using treatment for obstructive sleep apnea (OSA), specifically continuous positive airway pressure (CPAP), to prevent or treat atrial fibrillation.
“Only a very small number of patients with atrial fibrillation undergo a sleep study,” he said in an interview. “Before I’d send my mother for atrial fibrillation ablation, I would first look for sleep disordered breathing [SDB],” but this generally isn’t happening routinely. Patients with other types of cardiovascular disease who could potentially benefit from sleep disordered breathing diagnosis and treatment are those with hypertension, especially patients who don’t fully respond to three or more antihypertensive drugs and patients with heart failure with preserved ejection fraction, he added.
Dr. Oldenburg also echoed Dr. Mehra in saying that the evidence supporting this approach for managing atrial fibrillation is less than conclusive.
“We need more precise phenotyping of patients” to better focus on patients with cardiovascular disease and sleep disordered breathing who clearly benefit from CPAP intervention, he said.
Results from the Sleep Apnea Cardiovascular Endpoints (SAVE) trial, reported in September 2016, especially tarnished the notion that treating sleep disordered breathing in patients with various cardiovascular diseases can help avoid future cardiovascular events. The multicenter trial enrolled 2,717 adults with moderate to severe obstructive sleep apnea and cardiovascular disease to receive either CPAP plus optimal routine care or optimal routine care only. After an average follow-up of close to 4 years, the patients treated with CPAP showed no benefit in terms of reduced cardiovascular events (N Engl J Med. 2016 Sept 8;375[10]:919-31).
An editorial that ran with this report suggested that the neutral outcome may have occurred because the average nightly duration of CPAP that patients in the trial self administered was just over 3 hours, arguably an inadequate dose. Other possible reasons for the lack of benefit include the time during their sleep cycle when patients administered CPAP (at the start of sleep rather than later) and that CPAP may have a reduced ability to avert new cardiovascular events in patients with established cardiovascular disease (N Engl J Med. 2016 Sept 8;375[8]:994-6).
Regardless of the reasons, the SAVE results, coupled with the neutral results and suggestion of harm from using adaptive servo-ventilation in patients with heart failure with reduced ejection fraction and central sleep apnea in the SERVE-HF trial (N Engl J Med. 2015 Sept 17;373[12]:1095-105), have thrust the management of SDB in patients with cardiovascular disease back to the point where SDB interventions have no well-proven indications for cardiovascular disease patients.
“With the SERVE-HF and SAVE trials not showing benefit, we now have equipoise” for using or not using SDB interventions in these patients, Dr. Mehra said. “It’s not clear that treating OSA improves outcomes. That allows us to randomize patients to a control placebo arm” in future trials.
An important issue in the failure to clearly establish a role for treating OSA in patients with atrial fibrillation or other cardiovascular diseases may have been over reliance on the apnea-hypopnea index (AHI) as the arbiter of OSA severity, Dr. Oldenburg said. “Maybe there are parameters to look at aside from AHI, perhaps hypoxemia burden or desaturation time. AHI is not the whole truth; we need to look at other parameters. AHI may not be the correct metric to look at in patients with various cardiovascular diseases.”
Her analysis also showed that patients with at least 10 minutes of sleep time with an oxygen saturation rate of 90% or less had a 64% increased rate of later atrial fibrillation hospitalizations, compared with those with fewer than 10 minutes spent in this state. Nearly a quarter of the patients studied fell into this category.
“Nocturnal oxygen desaturation may be stronger than AHI for predicting atrial fibrillation development,” Dr. Kendzerska concluded. “The severity of OSA-related intermittent hypoxia may be more important than sleep fragmentation in the development of atrial fibrillation. These findings support a relationship between OSA, chronic nocturnal hypoxemia, and new onset atrial fibrillation.”
However, using oxygen desaturation instead of AHI to gauge the severity of OSA won’t solve all the challenges that sleep researchers currently face in trying to determine the efficacy of breathing interventions to prevent or treat cardiovascular disease. In the neutral SAVE trial, researchers used nocturnal oxygen saturation levels to select patients with clinically meaningful OSA.
Dr. Mehra and Dr. Kendzerska had no disclosures. Dr. Oldenburg has received consultant fees, honoraria, and/or research support from ResMed, Respicardia, and Weinmann.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
This article was updated on 7/10/17.
WASHINGTON – If patients have sleep disordered breathing with obstructive sleep apnea, will its treatment have cardiovascular disease benefits, especially in terms of the incidence or severity of atrial fibrillation?
Observational evidence suggests that apnea interventions may help these patients, but no clear case yet exists to prove that a breathing intervention works, experts say, and, as a result, U.S. practice is mixed when it comes to using treatment for obstructive sleep apnea (OSA), specifically continuous positive airway pressure (CPAP), to prevent or treat atrial fibrillation.
“Only a very small number of patients with atrial fibrillation undergo a sleep study,” he said in an interview. “Before I’d send my mother for atrial fibrillation ablation, I would first look for sleep disordered breathing [SDB],” but this generally isn’t happening routinely. Patients with other types of cardiovascular disease who could potentially benefit from sleep disordered breathing diagnosis and treatment are those with hypertension, especially patients who don’t fully respond to three or more antihypertensive drugs and patients with heart failure with preserved ejection fraction, he added.
Dr. Oldenburg also echoed Dr. Mehra in saying that the evidence supporting this approach for managing atrial fibrillation is less than conclusive.
“We need more precise phenotyping of patients” to better focus on patients with cardiovascular disease and sleep disordered breathing who clearly benefit from CPAP intervention, he said.
Results from the Sleep Apnea Cardiovascular Endpoints (SAVE) trial, reported in September 2016, especially tarnished the notion that treating sleep disordered breathing in patients with various cardiovascular diseases can help avoid future cardiovascular events. The multicenter trial enrolled 2,717 adults with moderate to severe obstructive sleep apnea and cardiovascular disease to receive either CPAP plus optimal routine care or optimal routine care only. After an average follow-up of close to 4 years, the patients treated with CPAP showed no benefit in terms of reduced cardiovascular events (N Engl J Med. 2016 Sept 8;375[10]:919-31).
An editorial that ran with this report suggested that the neutral outcome may have occurred because the average nightly duration of CPAP that patients in the trial self administered was just over 3 hours, arguably an inadequate dose. Other possible reasons for the lack of benefit include the time during their sleep cycle when patients administered CPAP (at the start of sleep rather than later) and that CPAP may have a reduced ability to avert new cardiovascular events in patients with established cardiovascular disease (N Engl J Med. 2016 Sept 8;375[8]:994-6).
Regardless of the reasons, the SAVE results, coupled with the neutral results and suggestion of harm from using adaptive servo-ventilation in patients with heart failure with reduced ejection fraction and central sleep apnea in the SERVE-HF trial (N Engl J Med. 2015 Sept 17;373[12]:1095-105), have thrust the management of SDB in patients with cardiovascular disease back to the point where SDB interventions have no well-proven indications for cardiovascular disease patients.
“With the SERVE-HF and SAVE trials not showing benefit, we now have equipoise” for using or not using SDB interventions in these patients, Dr. Mehra said. “It’s not clear that treating OSA improves outcomes. That allows us to randomize patients to a control placebo arm” in future trials.
An important issue in the failure to clearly establish a role for treating OSA in patients with atrial fibrillation or other cardiovascular diseases may have been over reliance on the apnea-hypopnea index (AHI) as the arbiter of OSA severity, Dr. Oldenburg said. “Maybe there are parameters to look at aside from AHI, perhaps hypoxemia burden or desaturation time. AHI is not the whole truth; we need to look at other parameters. AHI may not be the correct metric to look at in patients with various cardiovascular diseases.”
Her analysis also showed that patients with at least 10 minutes of sleep time with an oxygen saturation rate of 90% or less had a 64% increased rate of later atrial fibrillation hospitalizations, compared with those with fewer than 10 minutes spent in this state. Nearly a quarter of the patients studied fell into this category.
“Nocturnal oxygen desaturation may be stronger than AHI for predicting atrial fibrillation development,” Dr. Kendzerska concluded. “The severity of OSA-related intermittent hypoxia may be more important than sleep fragmentation in the development of atrial fibrillation. These findings support a relationship between OSA, chronic nocturnal hypoxemia, and new onset atrial fibrillation.”
However, using oxygen desaturation instead of AHI to gauge the severity of OSA won’t solve all the challenges that sleep researchers currently face in trying to determine the efficacy of breathing interventions to prevent or treat cardiovascular disease. In the neutral SAVE trial, researchers used nocturnal oxygen saturation levels to select patients with clinically meaningful OSA.
Dr. Mehra and Dr. Kendzerska had no disclosures. Dr. Oldenburg has received consultant fees, honoraria, and/or research support from ResMed, Respicardia, and Weinmann.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
This article was updated on 7/10/17.
WASHINGTON – If patients have sleep disordered breathing with obstructive sleep apnea, will its treatment have cardiovascular disease benefits, especially in terms of the incidence or severity of atrial fibrillation?
Observational evidence suggests that apnea interventions may help these patients, but no clear case yet exists to prove that a breathing intervention works, experts say, and, as a result, U.S. practice is mixed when it comes to using treatment for obstructive sleep apnea (OSA), specifically continuous positive airway pressure (CPAP), to prevent or treat atrial fibrillation.
“Only a very small number of patients with atrial fibrillation undergo a sleep study,” he said in an interview. “Before I’d send my mother for atrial fibrillation ablation, I would first look for sleep disordered breathing [SDB],” but this generally isn’t happening routinely. Patients with other types of cardiovascular disease who could potentially benefit from sleep disordered breathing diagnosis and treatment are those with hypertension, especially patients who don’t fully respond to three or more antihypertensive drugs and patients with heart failure with preserved ejection fraction, he added.
Dr. Oldenburg also echoed Dr. Mehra in saying that the evidence supporting this approach for managing atrial fibrillation is less than conclusive.
“We need more precise phenotyping of patients” to better focus on patients with cardiovascular disease and sleep disordered breathing who clearly benefit from CPAP intervention, he said.
Results from the Sleep Apnea Cardiovascular Endpoints (SAVE) trial, reported in September 2016, especially tarnished the notion that treating sleep disordered breathing in patients with various cardiovascular diseases can help avoid future cardiovascular events. The multicenter trial enrolled 2,717 adults with moderate to severe obstructive sleep apnea and cardiovascular disease to receive either CPAP plus optimal routine care or optimal routine care only. After an average follow-up of close to 4 years, the patients treated with CPAP showed no benefit in terms of reduced cardiovascular events (N Engl J Med. 2016 Sept 8;375[10]:919-31).
An editorial that ran with this report suggested that the neutral outcome may have occurred because the average nightly duration of CPAP that patients in the trial self administered was just over 3 hours, arguably an inadequate dose. Other possible reasons for the lack of benefit include the time during their sleep cycle when patients administered CPAP (at the start of sleep rather than later) and that CPAP may have a reduced ability to avert new cardiovascular events in patients with established cardiovascular disease (N Engl J Med. 2016 Sept 8;375[8]:994-6).
Regardless of the reasons, the SAVE results, coupled with the neutral results and suggestion of harm from using adaptive servo-ventilation in patients with heart failure with reduced ejection fraction and central sleep apnea in the SERVE-HF trial (N Engl J Med. 2015 Sept 17;373[12]:1095-105), have thrust the management of SDB in patients with cardiovascular disease back to the point where SDB interventions have no well-proven indications for cardiovascular disease patients.
“With the SERVE-HF and SAVE trials not showing benefit, we now have equipoise” for using or not using SDB interventions in these patients, Dr. Mehra said. “It’s not clear that treating OSA improves outcomes. That allows us to randomize patients to a control placebo arm” in future trials.
An important issue in the failure to clearly establish a role for treating OSA in patients with atrial fibrillation or other cardiovascular diseases may have been over reliance on the apnea-hypopnea index (AHI) as the arbiter of OSA severity, Dr. Oldenburg said. “Maybe there are parameters to look at aside from AHI, perhaps hypoxemia burden or desaturation time. AHI is not the whole truth; we need to look at other parameters. AHI may not be the correct metric to look at in patients with various cardiovascular diseases.”
Her analysis also showed that patients with at least 10 minutes of sleep time with an oxygen saturation rate of 90% or less had a 64% increased rate of later atrial fibrillation hospitalizations, compared with those with fewer than 10 minutes spent in this state. Nearly a quarter of the patients studied fell into this category.
“Nocturnal oxygen desaturation may be stronger than AHI for predicting atrial fibrillation development,” Dr. Kendzerska concluded. “The severity of OSA-related intermittent hypoxia may be more important than sleep fragmentation in the development of atrial fibrillation. These findings support a relationship between OSA, chronic nocturnal hypoxemia, and new onset atrial fibrillation.”
However, using oxygen desaturation instead of AHI to gauge the severity of OSA won’t solve all the challenges that sleep researchers currently face in trying to determine the efficacy of breathing interventions to prevent or treat cardiovascular disease. In the neutral SAVE trial, researchers used nocturnal oxygen saturation levels to select patients with clinically meaningful OSA.
Dr. Mehra and Dr. Kendzerska had no disclosures. Dr. Oldenburg has received consultant fees, honoraria, and/or research support from ResMed, Respicardia, and Weinmann.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
This article was updated on 7/10/17.
EXPERT ANALYSIS FROM ATS 2017
TB meningitis cases in U.S. are fewer but more complicated
BOSTON – The number of cases of meningitis caused by tuberculosis has fallen dramatically in the United States in recent decades as TB itself has become less common, according to findings from a study presented at the annual meeting of the American Academy of Neurology.
However, these findings from patient hospitalizations during 1993-2013 in the Nationwide Inpatient Sample database also indicate that neurologic complications from TB meningitis are on the rise.
The findings suggest that neurologists need to become involved whenever a patient with TB shows signs of neurologic problems, said study lead author Alexander E. Merkler, MD, of Cornell University, New York, in an interview. “They’re at high risk, and some complications can be life threatening.”
According to Dr. Merkler, TB meningitis occurs when a patient’s case of TB invades the meninges surrounding the brain. “It can lead to seizures, stroke, hydrocephalus, and death,” he said at the meeting.
TB meningitis can affect anyone with TB, he said, but those who are immunocompromised and those with diabetes are especially vulnerable.
For their current study, Dr. Merkler and his associates used the Nationwide Inpatient Sample database to track patients hospitalized in the United States with TB meningitis from 1993 to 2013. They found 16,196 new cases over the 20-year period and uncovered a dramatic decrease in the rate of hospitalizations: The incidence fell from 6.2 to 1.9 hospitalizations per million people (rate difference, 4.3; 95% confidence interval, 2.1-6.5; P less than .001), and mortality during index hospitalization fell from 17.6% (95% CI, 12.0%-23.2%) to 7.6%, (95% CI, 2.2%-13.0%).
Dr. Merkler said that mortality appears to have declined as TB itself has become less common. According to the Centers for Disease Control and Prevention, the number of reported TB cases nationally was 9,557 in 2015, a rate of 3.0 cases per 100,000 persons. The total number of annual cases fell each year from 1993 to 2014, the CDC reported, although the rate leveled off at around 3.0/100,000 from 2013 to 2015.
“The fewer people have lung TB, the less they’ll have it going into meningitis and the brain,” Dr. Merkler said. “In terms of mortality, it is going down because we have better supportive care. We’re better at keeping these patients alive and giving them antibiotics sooner.”
However, the study found that the rates of the following complications in hospitalized TB meningitis patients rose over the 20-year period:
• Hydrocephalus, from 2.3% (95% confidence interval, 0.5%-4.2%) to 5.4% (95% CI, 2.3%-10.0%).
• Seizure, from 2.9% (95% CI, 0.3%-5.4%) to 14.1% (95% CI, 7.3%-21.0%).
• Stroke, from 2.9% (95% CI, 0.6%-5.3%) to 13.0% (95% CI, 6.3%-19.8%).
• Vision and hearing impairment, from 8.2% (95% CI, 4.8%-11.6%) to 10.9% (95% CI, 4.1%-17.6%), and from 1.1% (95% CI, 0.0%-2.3%) to 3.3% (95% CI, 0.0%-6.9%), respectively.
Dr. Merkler said it’s not clear why these rates are going up, but it may be because patients have more complications as a result of living longer. Another theory is that a form of drug-resistant TB is boosting the level of these complications, Dr. Merkler said, but he’s skeptical of that idea: “I don’t know why drug resistance would lead to more neurological complications.”
The study was funded by the National Institute of Neurological Disorders and Stroke and the Michael Goldberg Stroke Research Fund. Dr. Merkler reported no relevant financial disclosures.
BOSTON – The number of cases of meningitis caused by tuberculosis has fallen dramatically in the United States in recent decades as TB itself has become less common, according to findings from a study presented at the annual meeting of the American Academy of Neurology.
However, these findings from patient hospitalizations during 1993-2013 in the Nationwide Inpatient Sample database also indicate that neurologic complications from TB meningitis are on the rise.
The findings suggest that neurologists need to become involved whenever a patient with TB shows signs of neurologic problems, said study lead author Alexander E. Merkler, MD, of Cornell University, New York, in an interview. “They’re at high risk, and some complications can be life threatening.”
According to Dr. Merkler, TB meningitis occurs when a patient’s case of TB invades the meninges surrounding the brain. “It can lead to seizures, stroke, hydrocephalus, and death,” he said at the meeting.
TB meningitis can affect anyone with TB, he said, but those who are immunocompromised and those with diabetes are especially vulnerable.
For their current study, Dr. Merkler and his associates used the Nationwide Inpatient Sample database to track patients hospitalized in the United States with TB meningitis from 1993 to 2013. They found 16,196 new cases over the 20-year period and uncovered a dramatic decrease in the rate of hospitalizations: The incidence fell from 6.2 to 1.9 hospitalizations per million people (rate difference, 4.3; 95% confidence interval, 2.1-6.5; P less than .001), and mortality during index hospitalization fell from 17.6% (95% CI, 12.0%-23.2%) to 7.6%, (95% CI, 2.2%-13.0%).
Dr. Merkler said that mortality appears to have declined as TB itself has become less common. According to the Centers for Disease Control and Prevention, the number of reported TB cases nationally was 9,557 in 2015, a rate of 3.0 cases per 100,000 persons. The total number of annual cases fell each year from 1993 to 2014, the CDC reported, although the rate leveled off at around 3.0/100,000 from 2013 to 2015.
“The fewer people have lung TB, the less they’ll have it going into meningitis and the brain,” Dr. Merkler said. “In terms of mortality, it is going down because we have better supportive care. We’re better at keeping these patients alive and giving them antibiotics sooner.”
However, the study found that the rates of the following complications in hospitalized TB meningitis patients rose over the 20-year period:
• Hydrocephalus, from 2.3% (95% confidence interval, 0.5%-4.2%) to 5.4% (95% CI, 2.3%-10.0%).
• Seizure, from 2.9% (95% CI, 0.3%-5.4%) to 14.1% (95% CI, 7.3%-21.0%).
• Stroke, from 2.9% (95% CI, 0.6%-5.3%) to 13.0% (95% CI, 6.3%-19.8%).
• Vision and hearing impairment, from 8.2% (95% CI, 4.8%-11.6%) to 10.9% (95% CI, 4.1%-17.6%), and from 1.1% (95% CI, 0.0%-2.3%) to 3.3% (95% CI, 0.0%-6.9%), respectively.
Dr. Merkler said it’s not clear why these rates are going up, but it may be because patients have more complications as a result of living longer. Another theory is that a form of drug-resistant TB is boosting the level of these complications, Dr. Merkler said, but he’s skeptical of that idea: “I don’t know why drug resistance would lead to more neurological complications.”
The study was funded by the National Institute of Neurological Disorders and Stroke and the Michael Goldberg Stroke Research Fund. Dr. Merkler reported no relevant financial disclosures.
BOSTON – The number of cases of meningitis caused by tuberculosis has fallen dramatically in the United States in recent decades as TB itself has become less common, according to findings from a study presented at the annual meeting of the American Academy of Neurology.
However, these findings from patient hospitalizations during 1993-2013 in the Nationwide Inpatient Sample database also indicate that neurologic complications from TB meningitis are on the rise.
The findings suggest that neurologists need to become involved whenever a patient with TB shows signs of neurologic problems, said study lead author Alexander E. Merkler, MD, of Cornell University, New York, in an interview. “They’re at high risk, and some complications can be life threatening.”
According to Dr. Merkler, TB meningitis occurs when a patient’s case of TB invades the meninges surrounding the brain. “It can lead to seizures, stroke, hydrocephalus, and death,” he said at the meeting.
TB meningitis can affect anyone with TB, he said, but those who are immunocompromised and those with diabetes are especially vulnerable.
For their current study, Dr. Merkler and his associates used the Nationwide Inpatient Sample database to track patients hospitalized in the United States with TB meningitis from 1993 to 2013. They found 16,196 new cases over the 20-year period and uncovered a dramatic decrease in the rate of hospitalizations: The incidence fell from 6.2 to 1.9 hospitalizations per million people (rate difference, 4.3; 95% confidence interval, 2.1-6.5; P less than .001), and mortality during index hospitalization fell from 17.6% (95% CI, 12.0%-23.2%) to 7.6%, (95% CI, 2.2%-13.0%).
Dr. Merkler said that mortality appears to have declined as TB itself has become less common. According to the Centers for Disease Control and Prevention, the number of reported TB cases nationally was 9,557 in 2015, a rate of 3.0 cases per 100,000 persons. The total number of annual cases fell each year from 1993 to 2014, the CDC reported, although the rate leveled off at around 3.0/100,000 from 2013 to 2015.
“The fewer people have lung TB, the less they’ll have it going into meningitis and the brain,” Dr. Merkler said. “In terms of mortality, it is going down because we have better supportive care. We’re better at keeping these patients alive and giving them antibiotics sooner.”
However, the study found that the rates of the following complications in hospitalized TB meningitis patients rose over the 20-year period:
• Hydrocephalus, from 2.3% (95% confidence interval, 0.5%-4.2%) to 5.4% (95% CI, 2.3%-10.0%).
• Seizure, from 2.9% (95% CI, 0.3%-5.4%) to 14.1% (95% CI, 7.3%-21.0%).
• Stroke, from 2.9% (95% CI, 0.6%-5.3%) to 13.0% (95% CI, 6.3%-19.8%).
• Vision and hearing impairment, from 8.2% (95% CI, 4.8%-11.6%) to 10.9% (95% CI, 4.1%-17.6%), and from 1.1% (95% CI, 0.0%-2.3%) to 3.3% (95% CI, 0.0%-6.9%), respectively.
Dr. Merkler said it’s not clear why these rates are going up, but it may be because patients have more complications as a result of living longer. Another theory is that a form of drug-resistant TB is boosting the level of these complications, Dr. Merkler said, but he’s skeptical of that idea: “I don’t know why drug resistance would lead to more neurological complications.”
The study was funded by the National Institute of Neurological Disorders and Stroke and the Michael Goldberg Stroke Research Fund. Dr. Merkler reported no relevant financial disclosures.
AT AAN 2017
Key clinical point:
Major finding: The rate of TB meningitis hospitalizations fell from 6.2 to 1.9 per million people (rate difference, 4.3; 95% CI, 2.1-6.5; P less than .001).
Data source: The Nationwide Inpatient Sample database, which revealed 16,196 new cases of TB meningitis from 1993 to 2013.
Disclosures: The study was funded by the National Institute of Neurological Disorders and Stroke and the Michael Goldberg Stroke Research Fund. Dr. Merkler reported no relevant financial disclosures.
Dacomitinib boosts PFS in advanced NSCLC
CHICAGO – The clear advantage goes to the second-generation tyrosine kinase inhibitor in a new trial comparing dacomitinib to gefitinib for advanced non–small cell lung cancer.
In a randomized, open-label phase III trial designed as a head-to-head comparison of the two drugs for the first-line treatment of advanced non–small cell lung cancer (NSCLC), “the blinded, independent review showed that we have a median progression-free survival (PFS) of 14.7 months versus 9.2 months,” said first author Tony Mok, MD, professor and chair of the department of clinical oncology at the Chinese University of Hong Kong. This PFS rate, he said, “is among the highest of randomized phase III trials in the first-line setting.”
Two years into the study, those taking dacomitinib had triple the PFS rate of those on gefitinib (30.6% versus 9.6%). The overall hazard ratio (HR) for PFS with dacomitinib compared to gefitinib was 0.59 (95% confidence interval [CI], 0.47-0.74, P less than .0001).
A previous single-arm phase II trial of the drug, ARCHER 2017, showed a response rate of 75.6% and a median PFS of 18.2 months for patients with NSCLC and an EGFR-activating mutation.
“Based on these data, we thought it was likely that we could have a hypothesis for dacomitinib to be superior to gefitinib, a first-generation TKI [tyrosine kinase inhibitor], in terms of progression-free survival,” Dr. Mok said in a press conference at the annual meeting of the American Society of Clinical Oncology. Dacomitinib is a second-generation TKI.
Patients in the new study, ARCHER 1050, had advanced NSCLC with EGFR-activating mutations and no prior systemic treatment for their advanced disease. In addition, patients had good performance status, could not have had prior TKI exposure, and could not have CNS metastases. This last exclusion, explained Dr. Mok, was because investigators were uncertain about dacomitinib’s CNS penetration at the time of study design, and because gefitinib may also not be the best therapeutic choice for CNS metastases.
Patients were randomized 1:1 to receive either dacomitinib 45 mg orally daily (n = 227), or gefitinib 250 mg orally daily (n = 225). Patients were stratified by whether or not they were ethnically Asian, and by whether they had EGFR mutation of exon 19 or exon 21. Patients were balanced in terms of age, gender, ethnicity, smoking, and performance status between arms. About 75% of the patients were Asian, and 65% were nonsmokers.
The international study enrolled patients from 71 centers in Asia and Europe. At the time of the data cutoff, investigators saw PFS events totaling 59.9% in the dacomitinib arm and 79.6% in the gefitinib arm. Patients were followed for PFS for a median of 22.1 months. “We have relatively mature data,” said Dr. Mok, except for overall survival, with only 36.9% of events occurring at the time of the data cutoff.
The primary endpoint in the open-label trial was PFS in the intention-to-treat population, as assessed by an independent, blinded reviewer. Dr. Mok said that the study was powered to see at least 256 PFS events, and to see an improvement in PFS for dacomitinib that equated to an HR of no more than 0.667. This would translate to median PFS for dacomitinib of 14.3 months versus 9.5 months for gefitinib, values Dr. Mok said were “reasonable.” And, he pointed out, the study results fell almost exactly in line with these predictions, though the actual HR was a bit lower than predicted.
An analysis of PFS by subgroup, also conducted by independent review, found that dacomitinib was favored for all subgroups except for non-Asian patients, for whom the HR was 0.89 but did not reach statistical significance. Since these patients made up about one-fourth of the study population, said Dr. Mok, small sample size was a potential issue. “But we have to ask ourselves the question, do they really perform worse than the Asians, if they have a response?”
To attempt to answer this question, the investigators performed an exploratory analysis of the 72 non-Asian patients who had responded to therapy. Among this group, they saw data similar to that of the overall group, with an HR of 0.547 (95% CI, 0.321-0.933, P less than .0123).
Secondary endpoints included investigator-assessed PFS, overall survival, objective response rate, duration of response, quality of life, and safety assessments.
Objective response rates were similar between arms, at 74.9% for dacomitinib and 71.6% for gefitinib (P = .3883). However, the median duration of response was significantly longer for those on dacomitinib (14.8 versus 8.3 months, P less than .0001).
“This may be best explained by looking into the depth of the response,” said Dr. Mok. Patient-level data showed that dacomitinib patients had a larger reduction in target lesion size; “this may reflect a more potent inhibition of EGFR,” he said.
With the more potent inhibition, however, came more frequent grade 3 adverse events involving diarrhea, dermatitis, stomatitis, and paronychia for those on dacomitinib; however, noted Dr. Mok, serious transaminase elevations were more common in the gefitinib group. “There is no new signal” for concerning toxicity, he said. Dose reductions were more common in dacomitinib than in gefitinib (66.1% versus 18%), but there are two tiers of dose reductions permissible with dacomitinib, giving some flexibility.
Dr. Mok reported financial relationships with multiple pharmaceutical companies, including Pfizer and SFJ Pharmaceuticals, which sponsored the study.
koakes@frontlinemedcom.com
On Twitter @karioakes
CHICAGO – The clear advantage goes to the second-generation tyrosine kinase inhibitor in a new trial comparing dacomitinib to gefitinib for advanced non–small cell lung cancer.
In a randomized, open-label phase III trial designed as a head-to-head comparison of the two drugs for the first-line treatment of advanced non–small cell lung cancer (NSCLC), “the blinded, independent review showed that we have a median progression-free survival (PFS) of 14.7 months versus 9.2 months,” said first author Tony Mok, MD, professor and chair of the department of clinical oncology at the Chinese University of Hong Kong. This PFS rate, he said, “is among the highest of randomized phase III trials in the first-line setting.”
Two years into the study, those taking dacomitinib had triple the PFS rate of those on gefitinib (30.6% versus 9.6%). The overall hazard ratio (HR) for PFS with dacomitinib compared to gefitinib was 0.59 (95% confidence interval [CI], 0.47-0.74, P less than .0001).
A previous single-arm phase II trial of the drug, ARCHER 2017, showed a response rate of 75.6% and a median PFS of 18.2 months for patients with NSCLC and an EGFR-activating mutation.
“Based on these data, we thought it was likely that we could have a hypothesis for dacomitinib to be superior to gefitinib, a first-generation TKI [tyrosine kinase inhibitor], in terms of progression-free survival,” Dr. Mok said in a press conference at the annual meeting of the American Society of Clinical Oncology. Dacomitinib is a second-generation TKI.
Patients in the new study, ARCHER 1050, had advanced NSCLC with EGFR-activating mutations and no prior systemic treatment for their advanced disease. In addition, patients had good performance status, could not have had prior TKI exposure, and could not have CNS metastases. This last exclusion, explained Dr. Mok, was because investigators were uncertain about dacomitinib’s CNS penetration at the time of study design, and because gefitinib may also not be the best therapeutic choice for CNS metastases.
Patients were randomized 1:1 to receive either dacomitinib 45 mg orally daily (n = 227), or gefitinib 250 mg orally daily (n = 225). Patients were stratified by whether or not they were ethnically Asian, and by whether they had EGFR mutation of exon 19 or exon 21. Patients were balanced in terms of age, gender, ethnicity, smoking, and performance status between arms. About 75% of the patients were Asian, and 65% were nonsmokers.
The international study enrolled patients from 71 centers in Asia and Europe. At the time of the data cutoff, investigators saw PFS events totaling 59.9% in the dacomitinib arm and 79.6% in the gefitinib arm. Patients were followed for PFS for a median of 22.1 months. “We have relatively mature data,” said Dr. Mok, except for overall survival, with only 36.9% of events occurring at the time of the data cutoff.
The primary endpoint in the open-label trial was PFS in the intention-to-treat population, as assessed by an independent, blinded reviewer. Dr. Mok said that the study was powered to see at least 256 PFS events, and to see an improvement in PFS for dacomitinib that equated to an HR of no more than 0.667. This would translate to median PFS for dacomitinib of 14.3 months versus 9.5 months for gefitinib, values Dr. Mok said were “reasonable.” And, he pointed out, the study results fell almost exactly in line with these predictions, though the actual HR was a bit lower than predicted.
An analysis of PFS by subgroup, also conducted by independent review, found that dacomitinib was favored for all subgroups except for non-Asian patients, for whom the HR was 0.89 but did not reach statistical significance. Since these patients made up about one-fourth of the study population, said Dr. Mok, small sample size was a potential issue. “But we have to ask ourselves the question, do they really perform worse than the Asians, if they have a response?”
To attempt to answer this question, the investigators performed an exploratory analysis of the 72 non-Asian patients who had responded to therapy. Among this group, they saw data similar to that of the overall group, with an HR of 0.547 (95% CI, 0.321-0.933, P less than .0123).
Secondary endpoints included investigator-assessed PFS, overall survival, objective response rate, duration of response, quality of life, and safety assessments.
Objective response rates were similar between arms, at 74.9% for dacomitinib and 71.6% for gefitinib (P = .3883). However, the median duration of response was significantly longer for those on dacomitinib (14.8 versus 8.3 months, P less than .0001).
“This may be best explained by looking into the depth of the response,” said Dr. Mok. Patient-level data showed that dacomitinib patients had a larger reduction in target lesion size; “this may reflect a more potent inhibition of EGFR,” he said.
With the more potent inhibition, however, came more frequent grade 3 adverse events involving diarrhea, dermatitis, stomatitis, and paronychia for those on dacomitinib; however, noted Dr. Mok, serious transaminase elevations were more common in the gefitinib group. “There is no new signal” for concerning toxicity, he said. Dose reductions were more common in dacomitinib than in gefitinib (66.1% versus 18%), but there are two tiers of dose reductions permissible with dacomitinib, giving some flexibility.
Dr. Mok reported financial relationships with multiple pharmaceutical companies, including Pfizer and SFJ Pharmaceuticals, which sponsored the study.
koakes@frontlinemedcom.com
On Twitter @karioakes
CHICAGO – The clear advantage goes to the second-generation tyrosine kinase inhibitor in a new trial comparing dacomitinib to gefitinib for advanced non–small cell lung cancer.
In a randomized, open-label phase III trial designed as a head-to-head comparison of the two drugs for the first-line treatment of advanced non–small cell lung cancer (NSCLC), “the blinded, independent review showed that we have a median progression-free survival (PFS) of 14.7 months versus 9.2 months,” said first author Tony Mok, MD, professor and chair of the department of clinical oncology at the Chinese University of Hong Kong. This PFS rate, he said, “is among the highest of randomized phase III trials in the first-line setting.”
Two years into the study, those taking dacomitinib had triple the PFS rate of those on gefitinib (30.6% versus 9.6%). The overall hazard ratio (HR) for PFS with dacomitinib compared to gefitinib was 0.59 (95% confidence interval [CI], 0.47-0.74, P less than .0001).
A previous single-arm phase II trial of the drug, ARCHER 2017, showed a response rate of 75.6% and a median PFS of 18.2 months for patients with NSCLC and an EGFR-activating mutation.
“Based on these data, we thought it was likely that we could have a hypothesis for dacomitinib to be superior to gefitinib, a first-generation TKI [tyrosine kinase inhibitor], in terms of progression-free survival,” Dr. Mok said in a press conference at the annual meeting of the American Society of Clinical Oncology. Dacomitinib is a second-generation TKI.
Patients in the new study, ARCHER 1050, had advanced NSCLC with EGFR-activating mutations and no prior systemic treatment for their advanced disease. In addition, patients had good performance status, could not have had prior TKI exposure, and could not have CNS metastases. This last exclusion, explained Dr. Mok, was because investigators were uncertain about dacomitinib’s CNS penetration at the time of study design, and because gefitinib may also not be the best therapeutic choice for CNS metastases.
Patients were randomized 1:1 to receive either dacomitinib 45 mg orally daily (n = 227), or gefitinib 250 mg orally daily (n = 225). Patients were stratified by whether or not they were ethnically Asian, and by whether they had EGFR mutation of exon 19 or exon 21. Patients were balanced in terms of age, gender, ethnicity, smoking, and performance status between arms. About 75% of the patients were Asian, and 65% were nonsmokers.
The international study enrolled patients from 71 centers in Asia and Europe. At the time of the data cutoff, investigators saw PFS events totaling 59.9% in the dacomitinib arm and 79.6% in the gefitinib arm. Patients were followed for PFS for a median of 22.1 months. “We have relatively mature data,” said Dr. Mok, except for overall survival, with only 36.9% of events occurring at the time of the data cutoff.
The primary endpoint in the open-label trial was PFS in the intention-to-treat population, as assessed by an independent, blinded reviewer. Dr. Mok said that the study was powered to see at least 256 PFS events, and to see an improvement in PFS for dacomitinib that equated to an HR of no more than 0.667. This would translate to median PFS for dacomitinib of 14.3 months versus 9.5 months for gefitinib, values Dr. Mok said were “reasonable.” And, he pointed out, the study results fell almost exactly in line with these predictions, though the actual HR was a bit lower than predicted.
An analysis of PFS by subgroup, also conducted by independent review, found that dacomitinib was favored for all subgroups except for non-Asian patients, for whom the HR was 0.89 but did not reach statistical significance. Since these patients made up about one-fourth of the study population, said Dr. Mok, small sample size was a potential issue. “But we have to ask ourselves the question, do they really perform worse than the Asians, if they have a response?”
To attempt to answer this question, the investigators performed an exploratory analysis of the 72 non-Asian patients who had responded to therapy. Among this group, they saw data similar to that of the overall group, with an HR of 0.547 (95% CI, 0.321-0.933, P less than .0123).
Secondary endpoints included investigator-assessed PFS, overall survival, objective response rate, duration of response, quality of life, and safety assessments.
Objective response rates were similar between arms, at 74.9% for dacomitinib and 71.6% for gefitinib (P = .3883). However, the median duration of response was significantly longer for those on dacomitinib (14.8 versus 8.3 months, P less than .0001).
“This may be best explained by looking into the depth of the response,” said Dr. Mok. Patient-level data showed that dacomitinib patients had a larger reduction in target lesion size; “this may reflect a more potent inhibition of EGFR,” he said.
With the more potent inhibition, however, came more frequent grade 3 adverse events involving diarrhea, dermatitis, stomatitis, and paronychia for those on dacomitinib; however, noted Dr. Mok, serious transaminase elevations were more common in the gefitinib group. “There is no new signal” for concerning toxicity, he said. Dose reductions were more common in dacomitinib than in gefitinib (66.1% versus 18%), but there are two tiers of dose reductions permissible with dacomitinib, giving some flexibility.
Dr. Mok reported financial relationships with multiple pharmaceutical companies, including Pfizer and SFJ Pharmaceuticals, which sponsored the study.
koakes@frontlinemedcom.com
On Twitter @karioakes
AT ASCO 2017
Key clinical point:
Major finding: At 2 years, the dacomitinib arm had triple the PFS rate of the gefitinib arm (30.6% versus 9.6%).
Data source: Randomized, open-label phase III clinical trial of 452 patients who received dacomitinib or gefitinib for first-line therapy for advanced non–small cell lung cancer.
Disclosures: Dr. Mok reported financial relationships with multiple pharmaceutical companies, including Pfizer and SFJ Pharmaceuticals, which funded the study.
Endosonography can help eliminate false negatives
BOSTON – Patients at high risk for non–small cell lung cancer (NSCLC) metastases were found to have a significant rate of unsuspected lymph node metastases upon endosonographic assessment, even in the presence of radiologically normal mediastinal lymph nodes, according to a study reported by Pravachan Hegde, MD, of the University of Montreal. Dr. Hegde presented the results at the 2017 AATS Centennial meeting.
Positron-emission tomography (PET) with computed tomography (CT) is routinely utilized to investigate lymph node (LN) metastases in non-small cell lung cancer, according to Dr. Hegde. However, this method has been found to be less sensitive in normal-sized LNs.
Dr. Hegde and his colleagues retrospectively reviewed a single-institution prospectively maintained database. Patients were identified from a cohort between January 2009 and December 2014. Consecutive patients with NSCLC were identified in whom both the pre-endosonography CT and PET-CT were negative for mediastinal LN metastases.
Patients were staged if they had central tumor, tumor size greater than 3 cm, N1 lymph node involvement on PET-CT/CT, or if there was low SUV in the primary tumor. Combined endosonography (EBUS+EUS-FNA) was performed in all patients.
A total of 22 out of 161 patients with radiologically normal mediastinum were found to be positive on combined EBUS/EUS staging. Out of 21 patients upstaged, 71% had tumor size greater than 3 cm; 28% had N1 disease; 61% had N2 disease; and 9% had adrenal involvement. None of the patients that were upstaged had N1 LN involvement on PET-CT or CT scan, according to Dr. Hegde.
A total of 416 lymph nodes were biopsied in the 161 patients by combined endosonography, 147 by EBUS and 269 by EUS. Of the 22 patients upstaged with endosonography, 12 were upstaged with EBUS and 10 were upstaged with EUS.
“Given the significant rate of unsuspected lymph node metastases, combined endosonographic lymph node staging should be routinely performed in staging of NSCLC in high risk patients even in the presence of radiologically normal mediastinal lymph nodes,” Dr. Hegde concluded.
In an interview, Moishe Liberman, MD, a coauthor of the study stated: “Pre-operative lymph node staging of lung cancer has dramatically changed over the last decade due to the availability and improvements in technology in PET, CT, EBUS, and EUS. While imaging (CT and PET) definitely help in staging, these tests are imperfect with significant false-negative rates as seen in our study.
“Minimally invasive, endoscopic techniques can help to significantly decrease these false- negative rates by providing biopsy of the target lymph nodes. Surprise intra-operative findings not accurately picked up by PET and CT should be almost nonexistant in 2017 with aggressive endosonographic pre-operative staging. This ensures that patients who actually benefit from surgery undergo resection and those with higher stage disease get appropriate treatment,” Dr. Liberman added. ■
BOSTON – Patients at high risk for non–small cell lung cancer (NSCLC) metastases were found to have a significant rate of unsuspected lymph node metastases upon endosonographic assessment, even in the presence of radiologically normal mediastinal lymph nodes, according to a study reported by Pravachan Hegde, MD, of the University of Montreal. Dr. Hegde presented the results at the 2017 AATS Centennial meeting.
Positron-emission tomography (PET) with computed tomography (CT) is routinely utilized to investigate lymph node (LN) metastases in non-small cell lung cancer, according to Dr. Hegde. However, this method has been found to be less sensitive in normal-sized LNs.
Dr. Hegde and his colleagues retrospectively reviewed a single-institution prospectively maintained database. Patients were identified from a cohort between January 2009 and December 2014. Consecutive patients with NSCLC were identified in whom both the pre-endosonography CT and PET-CT were negative for mediastinal LN metastases.
Patients were staged if they had central tumor, tumor size greater than 3 cm, N1 lymph node involvement on PET-CT/CT, or if there was low SUV in the primary tumor. Combined endosonography (EBUS+EUS-FNA) was performed in all patients.
A total of 22 out of 161 patients with radiologically normal mediastinum were found to be positive on combined EBUS/EUS staging. Out of 21 patients upstaged, 71% had tumor size greater than 3 cm; 28% had N1 disease; 61% had N2 disease; and 9% had adrenal involvement. None of the patients that were upstaged had N1 LN involvement on PET-CT or CT scan, according to Dr. Hegde.
A total of 416 lymph nodes were biopsied in the 161 patients by combined endosonography, 147 by EBUS and 269 by EUS. Of the 22 patients upstaged with endosonography, 12 were upstaged with EBUS and 10 were upstaged with EUS.
“Given the significant rate of unsuspected lymph node metastases, combined endosonographic lymph node staging should be routinely performed in staging of NSCLC in high risk patients even in the presence of radiologically normal mediastinal lymph nodes,” Dr. Hegde concluded.
In an interview, Moishe Liberman, MD, a coauthor of the study stated: “Pre-operative lymph node staging of lung cancer has dramatically changed over the last decade due to the availability and improvements in technology in PET, CT, EBUS, and EUS. While imaging (CT and PET) definitely help in staging, these tests are imperfect with significant false-negative rates as seen in our study.
“Minimally invasive, endoscopic techniques can help to significantly decrease these false- negative rates by providing biopsy of the target lymph nodes. Surprise intra-operative findings not accurately picked up by PET and CT should be almost nonexistant in 2017 with aggressive endosonographic pre-operative staging. This ensures that patients who actually benefit from surgery undergo resection and those with higher stage disease get appropriate treatment,” Dr. Liberman added. ■
BOSTON – Patients at high risk for non–small cell lung cancer (NSCLC) metastases were found to have a significant rate of unsuspected lymph node metastases upon endosonographic assessment, even in the presence of radiologically normal mediastinal lymph nodes, according to a study reported by Pravachan Hegde, MD, of the University of Montreal. Dr. Hegde presented the results at the 2017 AATS Centennial meeting.
Positron-emission tomography (PET) with computed tomography (CT) is routinely utilized to investigate lymph node (LN) metastases in non-small cell lung cancer, according to Dr. Hegde. However, this method has been found to be less sensitive in normal-sized LNs.
Dr. Hegde and his colleagues retrospectively reviewed a single-institution prospectively maintained database. Patients were identified from a cohort between January 2009 and December 2014. Consecutive patients with NSCLC were identified in whom both the pre-endosonography CT and PET-CT were negative for mediastinal LN metastases.
Patients were staged if they had central tumor, tumor size greater than 3 cm, N1 lymph node involvement on PET-CT/CT, or if there was low SUV in the primary tumor. Combined endosonography (EBUS+EUS-FNA) was performed in all patients.
A total of 22 out of 161 patients with radiologically normal mediastinum were found to be positive on combined EBUS/EUS staging. Out of 21 patients upstaged, 71% had tumor size greater than 3 cm; 28% had N1 disease; 61% had N2 disease; and 9% had adrenal involvement. None of the patients that were upstaged had N1 LN involvement on PET-CT or CT scan, according to Dr. Hegde.
A total of 416 lymph nodes were biopsied in the 161 patients by combined endosonography, 147 by EBUS and 269 by EUS. Of the 22 patients upstaged with endosonography, 12 were upstaged with EBUS and 10 were upstaged with EUS.
“Given the significant rate of unsuspected lymph node metastases, combined endosonographic lymph node staging should be routinely performed in staging of NSCLC in high risk patients even in the presence of radiologically normal mediastinal lymph nodes,” Dr. Hegde concluded.
In an interview, Moishe Liberman, MD, a coauthor of the study stated: “Pre-operative lymph node staging of lung cancer has dramatically changed over the last decade due to the availability and improvements in technology in PET, CT, EBUS, and EUS. While imaging (CT and PET) definitely help in staging, these tests are imperfect with significant false-negative rates as seen in our study.
“Minimally invasive, endoscopic techniques can help to significantly decrease these false- negative rates by providing biopsy of the target lymph nodes. Surprise intra-operative findings not accurately picked up by PET and CT should be almost nonexistant in 2017 with aggressive endosonographic pre-operative staging. This ensures that patients who actually benefit from surgery undergo resection and those with higher stage disease get appropriate treatment,” Dr. Liberman added. ■
FDA approves dabrafenib and trametinib for BRAF V600E+ metastatic NSCLC
The FDA also approved a diagnostic, the Oncomine Dx Target Test, a next-generation sequencing test to detect gene mutations or alterations, including BRAF, from a single tissue specimen, the FDA reported in a statement.
The approvals are based on overall response rate (ORR) for the combination in a phase II, nonrandomized, noncomparative, open-label trial of patients with locally confirmed BRAF V600E mutation-positive metastatic NSCLC. The ORR for the combination treatment was 61% (95% confidence interval, 44%-77%) among 36 patients who had received no prior systemic therapy for metastatic NSCLC, and 63% (95% CI, 49%-76%) among 57 patients who had received at least one platinum-based chemotherapy regimen with demonstrated disease progression before enrollment. Those 93 patients were all treated with the combination of dabrafenib (150 mg orally twice daily) and trametinib (2 mg orally once daily).
The ORR was 27% (95% CI, 18%-38%) among a third cohort of 78 patients with previously treated BRAF V600E mutation-positive NSCLC who received single-agent dabrafenib.
The most common adverse reactions were similar to those reported in prior approvals for patients with melanoma, including pyrexia, fatigue, nausea, vomiting, diarrhea, dry skin, decreased appetite, edema, rash, chills, hemorrhage, cough, and dyspnea. The most common grade 3-4 adverse reactions were pyrexia, fatigue, dyspnea, vomiting, rash, hemorrhage, and diarrhea. The most common grade 3-4 laboratory abnormalities were hyponatremia, lymphopenia, anemia, hyperglycemia, neutropenia, leukopenia, hypophosphatemia, and increased alanine aminotransferase. Dabrafenib and trametinib were discontinued for adverse reactions in 18% and 19% of patients, respectively, the FDA said.
Novartis is marketing Dabrafenib as Tafinlar and trametinib as Mekinist.
The recommended doses are dabrafenib 150 mg orally twice daily, approximately 12 hours apart, with trametinib 2 mg orally once daily, following confirmation of BRAF V600E mutation in a tumor specimen by an FDA-approved test.
The FDA also approved a diagnostic, the Oncomine Dx Target Test, a next-generation sequencing test to detect gene mutations or alterations, including BRAF, from a single tissue specimen, the FDA reported in a statement.
The approvals are based on overall response rate (ORR) for the combination in a phase II, nonrandomized, noncomparative, open-label trial of patients with locally confirmed BRAF V600E mutation-positive metastatic NSCLC. The ORR for the combination treatment was 61% (95% confidence interval, 44%-77%) among 36 patients who had received no prior systemic therapy for metastatic NSCLC, and 63% (95% CI, 49%-76%) among 57 patients who had received at least one platinum-based chemotherapy regimen with demonstrated disease progression before enrollment. Those 93 patients were all treated with the combination of dabrafenib (150 mg orally twice daily) and trametinib (2 mg orally once daily).
The ORR was 27% (95% CI, 18%-38%) among a third cohort of 78 patients with previously treated BRAF V600E mutation-positive NSCLC who received single-agent dabrafenib.
The most common adverse reactions were similar to those reported in prior approvals for patients with melanoma, including pyrexia, fatigue, nausea, vomiting, diarrhea, dry skin, decreased appetite, edema, rash, chills, hemorrhage, cough, and dyspnea. The most common grade 3-4 adverse reactions were pyrexia, fatigue, dyspnea, vomiting, rash, hemorrhage, and diarrhea. The most common grade 3-4 laboratory abnormalities were hyponatremia, lymphopenia, anemia, hyperglycemia, neutropenia, leukopenia, hypophosphatemia, and increased alanine aminotransferase. Dabrafenib and trametinib were discontinued for adverse reactions in 18% and 19% of patients, respectively, the FDA said.
Novartis is marketing Dabrafenib as Tafinlar and trametinib as Mekinist.
The recommended doses are dabrafenib 150 mg orally twice daily, approximately 12 hours apart, with trametinib 2 mg orally once daily, following confirmation of BRAF V600E mutation in a tumor specimen by an FDA-approved test.
The FDA also approved a diagnostic, the Oncomine Dx Target Test, a next-generation sequencing test to detect gene mutations or alterations, including BRAF, from a single tissue specimen, the FDA reported in a statement.
The approvals are based on overall response rate (ORR) for the combination in a phase II, nonrandomized, noncomparative, open-label trial of patients with locally confirmed BRAF V600E mutation-positive metastatic NSCLC. The ORR for the combination treatment was 61% (95% confidence interval, 44%-77%) among 36 patients who had received no prior systemic therapy for metastatic NSCLC, and 63% (95% CI, 49%-76%) among 57 patients who had received at least one platinum-based chemotherapy regimen with demonstrated disease progression before enrollment. Those 93 patients were all treated with the combination of dabrafenib (150 mg orally twice daily) and trametinib (2 mg orally once daily).
The ORR was 27% (95% CI, 18%-38%) among a third cohort of 78 patients with previously treated BRAF V600E mutation-positive NSCLC who received single-agent dabrafenib.
The most common adverse reactions were similar to those reported in prior approvals for patients with melanoma, including pyrexia, fatigue, nausea, vomiting, diarrhea, dry skin, decreased appetite, edema, rash, chills, hemorrhage, cough, and dyspnea. The most common grade 3-4 adverse reactions were pyrexia, fatigue, dyspnea, vomiting, rash, hemorrhage, and diarrhea. The most common grade 3-4 laboratory abnormalities were hyponatremia, lymphopenia, anemia, hyperglycemia, neutropenia, leukopenia, hypophosphatemia, and increased alanine aminotransferase. Dabrafenib and trametinib were discontinued for adverse reactions in 18% and 19% of patients, respectively, the FDA said.
Novartis is marketing Dabrafenib as Tafinlar and trametinib as Mekinist.
The recommended doses are dabrafenib 150 mg orally twice daily, approximately 12 hours apart, with trametinib 2 mg orally once daily, following confirmation of BRAF V600E mutation in a tumor specimen by an FDA-approved test.
Personalized snoring video boosts CPAP adherence
BOSTON – Showing patients videos of themselves having apneic episodes may convince them to use continuous positive airway pressure (CPAP), suggests the first results of an ongoing randomized clinical trial.
The investigators based their research project design on a previous pilot study that showed improved adherence to CPAP in patients who were shown videos of themselves sleeping while participating in a sleep study, Mark S. Aloia, PhD, said in a presentation at the annual meeting of the Associated Professional Sleep Societies.
In the new study, patients who had been recently diagnosed with sleep apnea were randomly assigned to participate in one of the three treatment groups. All three groups received sleep apnea and CPAP education prior to the use of CPAP. One group also watched videos of themselves sleeping, snoring, and gasping for air, and another group watched videos of a stranger sleeping and having apneic events.
After adjustment for age, educational level, and baseline sleep apnea severity, those who watched videos of themselves still used their CPAP devices more than 2 hours per night longer than did patients in each of the groups receiving the other two interventions (P = .02).
Both video interventions involved watching 30 minutes of sleep footage shown to each patient once before starting CPAP therapy. CPAP adherence was measured by downloaded data from PAP devices over the first 90 days of use.
The average age of the patients was 50 years, and they had moderate or severe sleep apnea, with mean apnea hypopnea indices ranging from 26.5 to 33.3 in the three study arms. The majority of patients had body mass indexes over 30.
Adherence to CPAP treatment is often poor, with many patients failing to use the device for even 4 hours per night, said Dr. Aloia, a psychologist at National Jewish Health in Denver. Many patients prescribed CPAP for OSA will undergo an educational component that may include watching a video of someone with OSA sleeping and having apneic events, he added. They often have “dramatic responses” to these videos, but then fail to positively change their own behavior.
“Many times we think that if our patient just knew what we know, he or she would use CPAP more, but there is evidence that doctors don’t take their medications any more than patients do, so it is not just a matter of education, it is a little bit deeper than that and it has to be personalized,” he said.
“The use of a personalized video is promising … we hope to present more data next year,” said Dr. Aloia, who has board certification in behavioral sleep medicine,
He noted that the video technique used may be jeopardized as more and more patients partake in home-based rather than lab-based sleep studies. That said, he also reported that the research team had to exclude several patients from the study because they had already viewed videos of themselves sleeping and snoring that had been recorded by their partners.
If the intervention proves effective, Dr. Aloia said he thinks it can be modified for use in home testing.
The study is supported by a grant from the National Heart, Lung, and Blood Institute. Dr. Aloia disclosed that he is a paid employee of Phillips, but that the study used both Phillips and ResMed CPAP devices.
BOSTON – Showing patients videos of themselves having apneic episodes may convince them to use continuous positive airway pressure (CPAP), suggests the first results of an ongoing randomized clinical trial.
The investigators based their research project design on a previous pilot study that showed improved adherence to CPAP in patients who were shown videos of themselves sleeping while participating in a sleep study, Mark S. Aloia, PhD, said in a presentation at the annual meeting of the Associated Professional Sleep Societies.
In the new study, patients who had been recently diagnosed with sleep apnea were randomly assigned to participate in one of the three treatment groups. All three groups received sleep apnea and CPAP education prior to the use of CPAP. One group also watched videos of themselves sleeping, snoring, and gasping for air, and another group watched videos of a stranger sleeping and having apneic events.
After adjustment for age, educational level, and baseline sleep apnea severity, those who watched videos of themselves still used their CPAP devices more than 2 hours per night longer than did patients in each of the groups receiving the other two interventions (P = .02).
Both video interventions involved watching 30 minutes of sleep footage shown to each patient once before starting CPAP therapy. CPAP adherence was measured by downloaded data from PAP devices over the first 90 days of use.
The average age of the patients was 50 years, and they had moderate or severe sleep apnea, with mean apnea hypopnea indices ranging from 26.5 to 33.3 in the three study arms. The majority of patients had body mass indexes over 30.
Adherence to CPAP treatment is often poor, with many patients failing to use the device for even 4 hours per night, said Dr. Aloia, a psychologist at National Jewish Health in Denver. Many patients prescribed CPAP for OSA will undergo an educational component that may include watching a video of someone with OSA sleeping and having apneic events, he added. They often have “dramatic responses” to these videos, but then fail to positively change their own behavior.
“Many times we think that if our patient just knew what we know, he or she would use CPAP more, but there is evidence that doctors don’t take their medications any more than patients do, so it is not just a matter of education, it is a little bit deeper than that and it has to be personalized,” he said.
“The use of a personalized video is promising … we hope to present more data next year,” said Dr. Aloia, who has board certification in behavioral sleep medicine,
He noted that the video technique used may be jeopardized as more and more patients partake in home-based rather than lab-based sleep studies. That said, he also reported that the research team had to exclude several patients from the study because they had already viewed videos of themselves sleeping and snoring that had been recorded by their partners.
If the intervention proves effective, Dr. Aloia said he thinks it can be modified for use in home testing.
The study is supported by a grant from the National Heart, Lung, and Blood Institute. Dr. Aloia disclosed that he is a paid employee of Phillips, but that the study used both Phillips and ResMed CPAP devices.
BOSTON – Showing patients videos of themselves having apneic episodes may convince them to use continuous positive airway pressure (CPAP), suggests the first results of an ongoing randomized clinical trial.
The investigators based their research project design on a previous pilot study that showed improved adherence to CPAP in patients who were shown videos of themselves sleeping while participating in a sleep study, Mark S. Aloia, PhD, said in a presentation at the annual meeting of the Associated Professional Sleep Societies.
In the new study, patients who had been recently diagnosed with sleep apnea were randomly assigned to participate in one of the three treatment groups. All three groups received sleep apnea and CPAP education prior to the use of CPAP. One group also watched videos of themselves sleeping, snoring, and gasping for air, and another group watched videos of a stranger sleeping and having apneic events.
After adjustment for age, educational level, and baseline sleep apnea severity, those who watched videos of themselves still used their CPAP devices more than 2 hours per night longer than did patients in each of the groups receiving the other two interventions (P = .02).
Both video interventions involved watching 30 minutes of sleep footage shown to each patient once before starting CPAP therapy. CPAP adherence was measured by downloaded data from PAP devices over the first 90 days of use.
The average age of the patients was 50 years, and they had moderate or severe sleep apnea, with mean apnea hypopnea indices ranging from 26.5 to 33.3 in the three study arms. The majority of patients had body mass indexes over 30.
Adherence to CPAP treatment is often poor, with many patients failing to use the device for even 4 hours per night, said Dr. Aloia, a psychologist at National Jewish Health in Denver. Many patients prescribed CPAP for OSA will undergo an educational component that may include watching a video of someone with OSA sleeping and having apneic events, he added. They often have “dramatic responses” to these videos, but then fail to positively change their own behavior.
“Many times we think that if our patient just knew what we know, he or she would use CPAP more, but there is evidence that doctors don’t take their medications any more than patients do, so it is not just a matter of education, it is a little bit deeper than that and it has to be personalized,” he said.
“The use of a personalized video is promising … we hope to present more data next year,” said Dr. Aloia, who has board certification in behavioral sleep medicine,
He noted that the video technique used may be jeopardized as more and more patients partake in home-based rather than lab-based sleep studies. That said, he also reported that the research team had to exclude several patients from the study because they had already viewed videos of themselves sleeping and snoring that had been recorded by their partners.
If the intervention proves effective, Dr. Aloia said he thinks it can be modified for use in home testing.
The study is supported by a grant from the National Heart, Lung, and Blood Institute. Dr. Aloia disclosed that he is a paid employee of Phillips, but that the study used both Phillips and ResMed CPAP devices.
AT SLEEP 2017
Key clinical point: Showing patients videos of themselves having an apneic event during CPAP initiation resulted in greater treatment adherence over 3 months, compared to standard ways of initiating CPAP therapy.
Major finding: Patients who watched personalized sleep videos used their CPAP devices more than 2 hours per night longer, compared with those who were not shown a personalized video.
Data source: Randomized controlled trial with 3-month data on 24 individuals out of a planned enrollment of 300 patients.
Disclosures: This ongoing study is supported by a grant from the National Heart, Lung, and Blood Institute. Dr. Aloia disclosed that he is a paid employee of Phillips, but that the study used both Phillips and ResMed CPAP devices.
T-DMI doesn’t wow in HER2-overexpressing NSCLC
CHICAGO –Beyond its role in advanced breast cancer, the antibody-drug conjugate ado-trastuzumab-emtansine (T-DM1; Kadcyla) showed modest activity in some patients with metastatic non–small cell lung cancer (mNSCLC) overexpressing the human epidermal growth factor-2 (HER2) receptor, investigators reported.
In an ongoing phase II study, 4 of 20 patients with mNSCLC whose tumors expressed the highest levels of HER2 had partial responses. In contrast, none of the 20 patients with tumors overexpressing HER2 at lower levels had responses, reported Thomas E. Stinchcombe, MD, of Duke University, Durham, N.C.
Previous studies have shown that HER2 overexpression by immunohistochemistry (IHC) is associated with poor prognosis in patients with NSCLC, but in contrast to breast and gastric cancers, HER2 overexpression in NSCLC is not always accompanied by HER2 amplifications.
“HER2 amplifications and HER2 mutations are generally mutually exclusive in NSCLC. Given the known mechanism of action of T-DM1, HER2 overexpression was chosen as an inclusion criterion for this study,” Dr. Stinchcombe said.
They enrolled patients with HER2-overexpressing mNSCLC who had disease progression following platinum-based chemotherapy. The patients were assigned to one of two 20-patient cohorts based on IHC2+ (10% or more of cells stained with 2+ intensity), or IHC3+ (10% or more of cells stained with 3+intensity).
For the primary endpoint of treatment response none of the patients in the IHC2+ cohort had objective responses by Response Evaluation Criteria in Solid Tumors (RECIST), although eight patients in this cohort had stable disease, including one patient who remained in stable disease status on treatment out to 21 months at last follow-up.
In the IHC3+ cohort, four patients had partial responses, for an objective response rate of 20%. The median duration of response was 7.3 months. Two patients in this cohort had stable disease.
Median PFS was similar between the cohorts, at 2.6 months for IHC2+ and 2.7 months for IHC3+. The respective median OS durations were 12.2 and 12.1 months.
The safety profile of T-DM1 in this population was similar to that seen in breast cancer. There were two grade 3 serious adverse events: one infusion-related hypersensitivity reaction, and one case of thrombocytopenia. There were 10 grade 3 events of any kind, 1 grade 4 event, and 1 treatment withdrawal due to a grade 2 infusion reaction.
“I think it’s honestly a little hard to tell from this study, which is very small, whether there is really a role of [HER2] overexpression in actually driving oncogenesis and being a target for T-DM1,” she said.
Dr. Stinchcombe reported institutional research funding from Hoffmann-LaRoche, which sponsored the trial, and several coauthors are employees of the company.
CHICAGO –Beyond its role in advanced breast cancer, the antibody-drug conjugate ado-trastuzumab-emtansine (T-DM1; Kadcyla) showed modest activity in some patients with metastatic non–small cell lung cancer (mNSCLC) overexpressing the human epidermal growth factor-2 (HER2) receptor, investigators reported.
In an ongoing phase II study, 4 of 20 patients with mNSCLC whose tumors expressed the highest levels of HER2 had partial responses. In contrast, none of the 20 patients with tumors overexpressing HER2 at lower levels had responses, reported Thomas E. Stinchcombe, MD, of Duke University, Durham, N.C.
Previous studies have shown that HER2 overexpression by immunohistochemistry (IHC) is associated with poor prognosis in patients with NSCLC, but in contrast to breast and gastric cancers, HER2 overexpression in NSCLC is not always accompanied by HER2 amplifications.
“HER2 amplifications and HER2 mutations are generally mutually exclusive in NSCLC. Given the known mechanism of action of T-DM1, HER2 overexpression was chosen as an inclusion criterion for this study,” Dr. Stinchcombe said.
They enrolled patients with HER2-overexpressing mNSCLC who had disease progression following platinum-based chemotherapy. The patients were assigned to one of two 20-patient cohorts based on IHC2+ (10% or more of cells stained with 2+ intensity), or IHC3+ (10% or more of cells stained with 3+intensity).
For the primary endpoint of treatment response none of the patients in the IHC2+ cohort had objective responses by Response Evaluation Criteria in Solid Tumors (RECIST), although eight patients in this cohort had stable disease, including one patient who remained in stable disease status on treatment out to 21 months at last follow-up.
In the IHC3+ cohort, four patients had partial responses, for an objective response rate of 20%. The median duration of response was 7.3 months. Two patients in this cohort had stable disease.
Median PFS was similar between the cohorts, at 2.6 months for IHC2+ and 2.7 months for IHC3+. The respective median OS durations were 12.2 and 12.1 months.
The safety profile of T-DM1 in this population was similar to that seen in breast cancer. There were two grade 3 serious adverse events: one infusion-related hypersensitivity reaction, and one case of thrombocytopenia. There were 10 grade 3 events of any kind, 1 grade 4 event, and 1 treatment withdrawal due to a grade 2 infusion reaction.
“I think it’s honestly a little hard to tell from this study, which is very small, whether there is really a role of [HER2] overexpression in actually driving oncogenesis and being a target for T-DM1,” she said.
Dr. Stinchcombe reported institutional research funding from Hoffmann-LaRoche, which sponsored the trial, and several coauthors are employees of the company.
CHICAGO –Beyond its role in advanced breast cancer, the antibody-drug conjugate ado-trastuzumab-emtansine (T-DM1; Kadcyla) showed modest activity in some patients with metastatic non–small cell lung cancer (mNSCLC) overexpressing the human epidermal growth factor-2 (HER2) receptor, investigators reported.
In an ongoing phase II study, 4 of 20 patients with mNSCLC whose tumors expressed the highest levels of HER2 had partial responses. In contrast, none of the 20 patients with tumors overexpressing HER2 at lower levels had responses, reported Thomas E. Stinchcombe, MD, of Duke University, Durham, N.C.
Previous studies have shown that HER2 overexpression by immunohistochemistry (IHC) is associated with poor prognosis in patients with NSCLC, but in contrast to breast and gastric cancers, HER2 overexpression in NSCLC is not always accompanied by HER2 amplifications.
“HER2 amplifications and HER2 mutations are generally mutually exclusive in NSCLC. Given the known mechanism of action of T-DM1, HER2 overexpression was chosen as an inclusion criterion for this study,” Dr. Stinchcombe said.
They enrolled patients with HER2-overexpressing mNSCLC who had disease progression following platinum-based chemotherapy. The patients were assigned to one of two 20-patient cohorts based on IHC2+ (10% or more of cells stained with 2+ intensity), or IHC3+ (10% or more of cells stained with 3+intensity).
For the primary endpoint of treatment response none of the patients in the IHC2+ cohort had objective responses by Response Evaluation Criteria in Solid Tumors (RECIST), although eight patients in this cohort had stable disease, including one patient who remained in stable disease status on treatment out to 21 months at last follow-up.
In the IHC3+ cohort, four patients had partial responses, for an objective response rate of 20%. The median duration of response was 7.3 months. Two patients in this cohort had stable disease.
Median PFS was similar between the cohorts, at 2.6 months for IHC2+ and 2.7 months for IHC3+. The respective median OS durations were 12.2 and 12.1 months.
The safety profile of T-DM1 in this population was similar to that seen in breast cancer. There were two grade 3 serious adverse events: one infusion-related hypersensitivity reaction, and one case of thrombocytopenia. There were 10 grade 3 events of any kind, 1 grade 4 event, and 1 treatment withdrawal due to a grade 2 infusion reaction.
“I think it’s honestly a little hard to tell from this study, which is very small, whether there is really a role of [HER2] overexpression in actually driving oncogenesis and being a target for T-DM1,” she said.
Dr. Stinchcombe reported institutional research funding from Hoffmann-LaRoche, which sponsored the trial, and several coauthors are employees of the company.
AT ASCO 2017
Key clinical point: Some non–small cell lung cancer (NSCLC) tumors overexpress HER2, suggesting the use of T-DM1, an anti-HER2 antibody drug conjugate.
Major finding: Four of 20 patients with HER2-overexpressing NSCLC has partial responses to T-DM1 therapy.
Data source: Open-label prospective trial of 40 patients with NSCLC positive for HER2.
Disclosures: Dr. Stinchcombe reported institutional research funding from Hoffmann-LaRoche, which sponsored the trial, and several coauthors are employees of the company.
Mild OSA linked to hypertension
BOSTON – Sleep apnea doesn’t have to be severe or even symptomatic to increase the risk of hypertension and diabetes, according to a pair of new studies.
“We found that even mild sleep apnea was strongly associated with increased risk of developing hypertension by four times, compared to individuals without sleep apnea,” said principal investigator and top sleep researcher Alexandros N. Vgontzas, MD, of Pennsylvania State University College of Medicine in a SLEEP press release. “Similarly, moderate sleep apnea was associated with increased risk of developing diabetes by almost three times, compared to individuals without sleep apnea.”
Dr. Vgontzas presented his team’s results on the link between mild to moderate OSA and hypertension at the annual meeting of the American Academy of Sleep Medicine. In a separate session, his colleague at Penn State, Yun Li, MD, presented the diabetes-related findings of the same study.
After multivariate adjustment, including controlling for change in body mass index over time, both mild and moderate OSA were significantly associated with increased odds for developing hypertension, compared with controls without OSA (odds ratios, 4.36 and 3.46, respectively.).
The researchers found their test for an age interaction was also significant, indicating that younger adults with nonsevere OSA were at increased risk of hypertension, while those over 60 years of age were not.
[polldaddy:9792720]
“In young and middle-aged adults, our findings suggest that early detection and treatment of mild to moderate sleep apnea is warranted in order to prevent future cardiometabolic disease,” said Dr. Li in a press release. “Given the stronger association of sleep apnea with metabolic abnormalities in this age group, emphasis should be placed on yearly monitoring of indices of metabolic symptoms and lifestyle interventions, such as weight control, healthy diet, regular exercise, and stress management.”
For diabetes, moderate OSA was significantly associated with an almost threefold increased odds for developing diabetes after adjusting for a range of baseline and follow-up variables (OR, 2.78), but mild OSA was not associated with incident diabetes (OR, 0.47).
Both studies utilized data from the Penn State Adult Cohort, a random general population sample of 1,741 adults who underwent an overnight polysomnography sleep study and had a detailed medical history interview at baseline. Mild and moderate OSA were defined as an apnea hypopnea index from 5 to 14.9 and from 15 to 29.9, respectively. The presence of hypertension or diabetes at baseline and follow-up was defined by a self-report of receiving treatment for or having a physician diagnosis of either condition.
The age range of the studied population was wide (20-84 years), with a mean age of about 47 years. The incidence of diabetes was 10.2% at follow-up, while hypertension was found in 34.2% of patients. Dr. Vgontzas said the percentage of patients with hypertension was roughly what he had expected for this population.
“Our conclusion is that, the younger a person is, the stronger is the need for detection and treatment of sleep apnea,” said Dr. Vgontzas, though he acknowledged that putting these millions of people on continuous positive airway pressure therapy is not an easy proposition.
The study was supported by National Institutes of Health grants. Dr. Vgontzas reported no conflicts of interest.
BOSTON – Sleep apnea doesn’t have to be severe or even symptomatic to increase the risk of hypertension and diabetes, according to a pair of new studies.
“We found that even mild sleep apnea was strongly associated with increased risk of developing hypertension by four times, compared to individuals without sleep apnea,” said principal investigator and top sleep researcher Alexandros N. Vgontzas, MD, of Pennsylvania State University College of Medicine in a SLEEP press release. “Similarly, moderate sleep apnea was associated with increased risk of developing diabetes by almost three times, compared to individuals without sleep apnea.”
Dr. Vgontzas presented his team’s results on the link between mild to moderate OSA and hypertension at the annual meeting of the American Academy of Sleep Medicine. In a separate session, his colleague at Penn State, Yun Li, MD, presented the diabetes-related findings of the same study.
After multivariate adjustment, including controlling for change in body mass index over time, both mild and moderate OSA were significantly associated with increased odds for developing hypertension, compared with controls without OSA (odds ratios, 4.36 and 3.46, respectively.).
The researchers found their test for an age interaction was also significant, indicating that younger adults with nonsevere OSA were at increased risk of hypertension, while those over 60 years of age were not.
[polldaddy:9792720]
“In young and middle-aged adults, our findings suggest that early detection and treatment of mild to moderate sleep apnea is warranted in order to prevent future cardiometabolic disease,” said Dr. Li in a press release. “Given the stronger association of sleep apnea with metabolic abnormalities in this age group, emphasis should be placed on yearly monitoring of indices of metabolic symptoms and lifestyle interventions, such as weight control, healthy diet, regular exercise, and stress management.”
For diabetes, moderate OSA was significantly associated with an almost threefold increased odds for developing diabetes after adjusting for a range of baseline and follow-up variables (OR, 2.78), but mild OSA was not associated with incident diabetes (OR, 0.47).
Both studies utilized data from the Penn State Adult Cohort, a random general population sample of 1,741 adults who underwent an overnight polysomnography sleep study and had a detailed medical history interview at baseline. Mild and moderate OSA were defined as an apnea hypopnea index from 5 to 14.9 and from 15 to 29.9, respectively. The presence of hypertension or diabetes at baseline and follow-up was defined by a self-report of receiving treatment for or having a physician diagnosis of either condition.
The age range of the studied population was wide (20-84 years), with a mean age of about 47 years. The incidence of diabetes was 10.2% at follow-up, while hypertension was found in 34.2% of patients. Dr. Vgontzas said the percentage of patients with hypertension was roughly what he had expected for this population.
“Our conclusion is that, the younger a person is, the stronger is the need for detection and treatment of sleep apnea,” said Dr. Vgontzas, though he acknowledged that putting these millions of people on continuous positive airway pressure therapy is not an easy proposition.
The study was supported by National Institutes of Health grants. Dr. Vgontzas reported no conflicts of interest.
BOSTON – Sleep apnea doesn’t have to be severe or even symptomatic to increase the risk of hypertension and diabetes, according to a pair of new studies.
“We found that even mild sleep apnea was strongly associated with increased risk of developing hypertension by four times, compared to individuals without sleep apnea,” said principal investigator and top sleep researcher Alexandros N. Vgontzas, MD, of Pennsylvania State University College of Medicine in a SLEEP press release. “Similarly, moderate sleep apnea was associated with increased risk of developing diabetes by almost three times, compared to individuals without sleep apnea.”
Dr. Vgontzas presented his team’s results on the link between mild to moderate OSA and hypertension at the annual meeting of the American Academy of Sleep Medicine. In a separate session, his colleague at Penn State, Yun Li, MD, presented the diabetes-related findings of the same study.
After multivariate adjustment, including controlling for change in body mass index over time, both mild and moderate OSA were significantly associated with increased odds for developing hypertension, compared with controls without OSA (odds ratios, 4.36 and 3.46, respectively.).
The researchers found their test for an age interaction was also significant, indicating that younger adults with nonsevere OSA were at increased risk of hypertension, while those over 60 years of age were not.
[polldaddy:9792720]
“In young and middle-aged adults, our findings suggest that early detection and treatment of mild to moderate sleep apnea is warranted in order to prevent future cardiometabolic disease,” said Dr. Li in a press release. “Given the stronger association of sleep apnea with metabolic abnormalities in this age group, emphasis should be placed on yearly monitoring of indices of metabolic symptoms and lifestyle interventions, such as weight control, healthy diet, regular exercise, and stress management.”
For diabetes, moderate OSA was significantly associated with an almost threefold increased odds for developing diabetes after adjusting for a range of baseline and follow-up variables (OR, 2.78), but mild OSA was not associated with incident diabetes (OR, 0.47).
Both studies utilized data from the Penn State Adult Cohort, a random general population sample of 1,741 adults who underwent an overnight polysomnography sleep study and had a detailed medical history interview at baseline. Mild and moderate OSA were defined as an apnea hypopnea index from 5 to 14.9 and from 15 to 29.9, respectively. The presence of hypertension or diabetes at baseline and follow-up was defined by a self-report of receiving treatment for or having a physician diagnosis of either condition.
The age range of the studied population was wide (20-84 years), with a mean age of about 47 years. The incidence of diabetes was 10.2% at follow-up, while hypertension was found in 34.2% of patients. Dr. Vgontzas said the percentage of patients with hypertension was roughly what he had expected for this population.
“Our conclusion is that, the younger a person is, the stronger is the need for detection and treatment of sleep apnea,” said Dr. Vgontzas, though he acknowledged that putting these millions of people on continuous positive airway pressure therapy is not an easy proposition.
The study was supported by National Institutes of Health grants. Dr. Vgontzas reported no conflicts of interest.
AT SLEEP 2017
Key clinical point: In a random sample of adults, the presence of mild to moderate OSA was associated with a significantly higher risk of hypertension and diabetes.
Major finding: Individuals with mild to moderate OSA had more than a fourfold increased risk of hypertension over 10 years of follow-up (OR, 4.36). Moderate OSA was significantly associated with incident diabetes risk (OR, 2.78), but mild OSA was not.
Data source: An observational study including a random sample of 1,741 adults between the ages of 20 and 84 years.
Disclosures: The study was supported by National Institutes of Health grants. Dr. Vgontzas reported no conflicts of interest.
Lung cancer linked to suicide
WASHINGTON – U.S. patients diagnosed with lung cancer have had the highest suicide rates among patients diagnosed with any of the other most common, non-skin cancers, and they also had a substantially higher suicide risk, compared with the general U.S. adult population, based on U.S. national data collected during 1973-2013.
Although U.S. lung cancer patients showed a “steep” decline in suicide rates starting in about 1985 that then accelerated beginning in the mid-1990s, as recently as 2010-2013 the rate was roughly twice as high in lung cancer patients when compared with the general U.S. adult population. The rate of lung cancer patients taking their lives was also significantly above the suicide rates among patients with breast, colorectal, or prostate cancer, Mohamed Rahouma, MD, reported at an international conference of the American Thoracic Society.
However, he also stressed that identification of lung cancer patients at especially high suicide risk was important to allow “proper psychological assessment, support, and counseling to reduce [suicide] rates.”
Lung cancer patients with the highest rates included men, widowed individuals, septuagenarians, and Asians, his analysis showed. Standardized mortality ratios (SMRs) for suicide of these highest-risk subgroups were near or exceeding 10 times fold higher than the suicide rates of comparable demographic groups among the general U.S. adult population, according to Dr. Rahouma and his associates.
The overall SMR for all lung cancer patients during the entire four decades studied, compared with the overall U.S. adult population, was 4. Even during the period 2005-2013, when suicide among lung cancer patients had fallen to its lowest level, the SMR for this group was still more than 2.
The investigators used data collected by the U.S. Surveillance Epidemiology and End Results (SEER) Program cancer database maintained by the National Cancer Institute. For suicide rates among the general U.S. population they used data from the National Vital Statistics Reports produced by the Centers for Disease Control and Prevention. The SEER database included entries for more than 3.6 million U.S. cancer patients during 1973-2013, of whom 6,661 patents had committed suicide, an overall SMR of 1.6.
When the researchers drilled down the SMRs for individual cancer types they found that while the SMR for lung cancer patients throughout the period studied was just above 4, the SMRs for breast and colorectal cancer patients were both 1.4, and 1.2 for patients with prostate cancer. This analysis adjusted for patients’ age, sex, race, and year of diagnosis, Dr. Rahouma reported.
The time from diagnosis to suicide was also strikingly quicker among lung cancer patients, at an average of 8 months, compared with average delays from diagnosis to suicide of 40-60 months for patients with breast, colorectal, or prostate cancer. Dr. Rahouma’s time-trend analysis showed that the SMRs for these three other cancer types held more or less steady within the range of 1-2 throughout the 4 decades examined, and by 2010-2013 the three SMRs all were at or just above 1. Lung cancer was the only malignancy in this group that showed a wide range in SMR over time, with the peak some 30-40 years ago.
Among the lung cancer patient subgroups that showed the highest SMRs for suicide during the entire period studied, men had a SMR of 9, Asians had a SMR of nearly 14, those with a deceased spouse had a SMR for suicide of almost 12, and septuagenarians had a SMR of 12, said Dr. Rahouma. The impact of these risk factors was greatest during the first 8 months following lung cancer diagnosis. After 8 months, the strength of the risk factors diminished, with the SMRs within each risk category dropping by roughly half.
The highest-risk subgroups that the analysis identified should especially be referred for psychiatric support, Dr. Rahouma concluded. “These data will change our practice” at Cornell, he predicted.
Dr. Rahouma had no disclosures.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
WASHINGTON – U.S. patients diagnosed with lung cancer have had the highest suicide rates among patients diagnosed with any of the other most common, non-skin cancers, and they also had a substantially higher suicide risk, compared with the general U.S. adult population, based on U.S. national data collected during 1973-2013.
Although U.S. lung cancer patients showed a “steep” decline in suicide rates starting in about 1985 that then accelerated beginning in the mid-1990s, as recently as 2010-2013 the rate was roughly twice as high in lung cancer patients when compared with the general U.S. adult population. The rate of lung cancer patients taking their lives was also significantly above the suicide rates among patients with breast, colorectal, or prostate cancer, Mohamed Rahouma, MD, reported at an international conference of the American Thoracic Society.
However, he also stressed that identification of lung cancer patients at especially high suicide risk was important to allow “proper psychological assessment, support, and counseling to reduce [suicide] rates.”
Lung cancer patients with the highest rates included men, widowed individuals, septuagenarians, and Asians, his analysis showed. Standardized mortality ratios (SMRs) for suicide of these highest-risk subgroups were near or exceeding 10 times fold higher than the suicide rates of comparable demographic groups among the general U.S. adult population, according to Dr. Rahouma and his associates.
The overall SMR for all lung cancer patients during the entire four decades studied, compared with the overall U.S. adult population, was 4. Even during the period 2005-2013, when suicide among lung cancer patients had fallen to its lowest level, the SMR for this group was still more than 2.
The investigators used data collected by the U.S. Surveillance Epidemiology and End Results (SEER) Program cancer database maintained by the National Cancer Institute. For suicide rates among the general U.S. population they used data from the National Vital Statistics Reports produced by the Centers for Disease Control and Prevention. The SEER database included entries for more than 3.6 million U.S. cancer patients during 1973-2013, of whom 6,661 patents had committed suicide, an overall SMR of 1.6.
When the researchers drilled down the SMRs for individual cancer types they found that while the SMR for lung cancer patients throughout the period studied was just above 4, the SMRs for breast and colorectal cancer patients were both 1.4, and 1.2 for patients with prostate cancer. This analysis adjusted for patients’ age, sex, race, and year of diagnosis, Dr. Rahouma reported.
The time from diagnosis to suicide was also strikingly quicker among lung cancer patients, at an average of 8 months, compared with average delays from diagnosis to suicide of 40-60 months for patients with breast, colorectal, or prostate cancer. Dr. Rahouma’s time-trend analysis showed that the SMRs for these three other cancer types held more or less steady within the range of 1-2 throughout the 4 decades examined, and by 2010-2013 the three SMRs all were at or just above 1. Lung cancer was the only malignancy in this group that showed a wide range in SMR over time, with the peak some 30-40 years ago.
Among the lung cancer patient subgroups that showed the highest SMRs for suicide during the entire period studied, men had a SMR of 9, Asians had a SMR of nearly 14, those with a deceased spouse had a SMR for suicide of almost 12, and septuagenarians had a SMR of 12, said Dr. Rahouma. The impact of these risk factors was greatest during the first 8 months following lung cancer diagnosis. After 8 months, the strength of the risk factors diminished, with the SMRs within each risk category dropping by roughly half.
The highest-risk subgroups that the analysis identified should especially be referred for psychiatric support, Dr. Rahouma concluded. “These data will change our practice” at Cornell, he predicted.
Dr. Rahouma had no disclosures.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
WASHINGTON – U.S. patients diagnosed with lung cancer have had the highest suicide rates among patients diagnosed with any of the other most common, non-skin cancers, and they also had a substantially higher suicide risk, compared with the general U.S. adult population, based on U.S. national data collected during 1973-2013.
Although U.S. lung cancer patients showed a “steep” decline in suicide rates starting in about 1985 that then accelerated beginning in the mid-1990s, as recently as 2010-2013 the rate was roughly twice as high in lung cancer patients when compared with the general U.S. adult population. The rate of lung cancer patients taking their lives was also significantly above the suicide rates among patients with breast, colorectal, or prostate cancer, Mohamed Rahouma, MD, reported at an international conference of the American Thoracic Society.
However, he also stressed that identification of lung cancer patients at especially high suicide risk was important to allow “proper psychological assessment, support, and counseling to reduce [suicide] rates.”
Lung cancer patients with the highest rates included men, widowed individuals, septuagenarians, and Asians, his analysis showed. Standardized mortality ratios (SMRs) for suicide of these highest-risk subgroups were near or exceeding 10 times fold higher than the suicide rates of comparable demographic groups among the general U.S. adult population, according to Dr. Rahouma and his associates.
The overall SMR for all lung cancer patients during the entire four decades studied, compared with the overall U.S. adult population, was 4. Even during the period 2005-2013, when suicide among lung cancer patients had fallen to its lowest level, the SMR for this group was still more than 2.
The investigators used data collected by the U.S. Surveillance Epidemiology and End Results (SEER) Program cancer database maintained by the National Cancer Institute. For suicide rates among the general U.S. population they used data from the National Vital Statistics Reports produced by the Centers for Disease Control and Prevention. The SEER database included entries for more than 3.6 million U.S. cancer patients during 1973-2013, of whom 6,661 patents had committed suicide, an overall SMR of 1.6.
When the researchers drilled down the SMRs for individual cancer types they found that while the SMR for lung cancer patients throughout the period studied was just above 4, the SMRs for breast and colorectal cancer patients were both 1.4, and 1.2 for patients with prostate cancer. This analysis adjusted for patients’ age, sex, race, and year of diagnosis, Dr. Rahouma reported.
The time from diagnosis to suicide was also strikingly quicker among lung cancer patients, at an average of 8 months, compared with average delays from diagnosis to suicide of 40-60 months for patients with breast, colorectal, or prostate cancer. Dr. Rahouma’s time-trend analysis showed that the SMRs for these three other cancer types held more or less steady within the range of 1-2 throughout the 4 decades examined, and by 2010-2013 the three SMRs all were at or just above 1. Lung cancer was the only malignancy in this group that showed a wide range in SMR over time, with the peak some 30-40 years ago.
Among the lung cancer patient subgroups that showed the highest SMRs for suicide during the entire period studied, men had a SMR of 9, Asians had a SMR of nearly 14, those with a deceased spouse had a SMR for suicide of almost 12, and septuagenarians had a SMR of 12, said Dr. Rahouma. The impact of these risk factors was greatest during the first 8 months following lung cancer diagnosis. After 8 months, the strength of the risk factors diminished, with the SMRs within each risk category dropping by roughly half.
The highest-risk subgroups that the analysis identified should especially be referred for psychiatric support, Dr. Rahouma concluded. “These data will change our practice” at Cornell, he predicted.
Dr. Rahouma had no disclosures.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT ATS 2017
Key clinical point:
Major finding: During 1973-2013, suicide among U.S. lung cancer patients was four times higher than the general adult U.S. population.
Data source: Statistics on more than 3.6 million U.S. cancer patients in the SEER Program.
Disclosures: Dr. Rahouma had no disclosures.