TOPLINE:

Women who use cocaine, cannabis, or other substances during pregnancy have increased risks of acute cardiovascular (CV) events while in the hospital for delivery, including more than double the risk of maternal mortality, a new study shows.

METHODOLOGY:

• Using the National Inpatient Sample database to identify hospital deliveries between 2004 and 2018 and diagnostic codes to identify maternal substance use, researchers compared 955,531 pregnancies with accompanying substance use – the most common substances being cannabis and opioids, followed by stimulants – to over 60 million pregnancies in which there was no substance use.
• The primary outcome was any CV event, including acute myocardial infarction, stroke, arrhythmia, endocarditis, any acute cardiomyopathy or heart failure, or cardiac arrest; other outcomes included maternal mortality and major adverse cardiac events (MACE).

TAKEAWAY:

• Deliveries complicated by substance use increased from 1,126 per 100,000 deliveries in 2004 to 1,547 per 100,000 in 2018, peaking at 2,187 per 100,000 in 2014.
• After the researchers controlled for patient demographics and CVD risk factors, results showed that pregnant women who used any substance (cannabis, opioids, methamphetamine, alcohol, tobacco, or cocaine) were more likely to experience a CVD event (adjusted odds ratio [aOR], 1.61; 95% confidence interval [CI], 1.53-1.70; P < .001), MACE (aOR, 1.53; 95% CI, 1.46-1.61; P < .001), or maternal mortality (aOR, 2.65; 95% CI, 2.15-3.25; P < .001) during hospitalization for delivery.
• Those using amphetamine/methamphetamine had ninefold higher odds of cardiomyopathy or heart failure and more than sevenfold higher odds of cardiac arrest.

IN PRACTICE:

“For the wellbeing of pregnant women and their children, substance use needs to be considered an independent risk factor for CV events in pregnancy,” the authors wrote. They called for prenatal assessments by a multidisciplinary cardio-obstetrics team to try to decrease cardiac complications.

In an accompanying editorial by Abha Khandelwal, MD, department of medicine, Stanford (Calif.) University, and others, the authors said the findings “highlight the critical support required during pregnancy and postpartum” for substance users, which should include comprehensive medical care and social services as well as access to addiction medicine and treatment of co-occurring mental health disorders.

SOURCE:

The study was carried out by Kari Evans, MD, division of maternal fetal medicine, department of obstetrics and gynecology, University of Arizona, Phoenix. It was published online in the Journal of the American College of Cardiology: Advances.

LIMITATIONS:

Use of administrative databases may have resulted in underreporting of diagnoses. The researchers could not assess the association of dose, duration, method, or timing of use for any substance with CV events. They also could not examine the effect of vaping on maternal CV events or differentiate hospitalizations for delivery that were complicated by CV events from hospitalizations for CV events that prompted delivery. The data did not reflect the postpartum period, during which a high rate of adverse CV events occurs.

DISCLOSURES:

The authors and editorial writers have no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Women who use cocaine, cannabis, or other substances during pregnancy have increased risks of acute cardiovascular (CV) events while in the hospital for delivery, including more than double the risk of maternal mortality, a new study shows.

METHODOLOGY:

• Using the National Inpatient Sample database to identify hospital deliveries between 2004 and 2018 and diagnostic codes to identify maternal substance use, researchers compared 955,531 pregnancies with accompanying substance use – the most common substances being cannabis and opioids, followed by stimulants – to over 60 million pregnancies in which there was no substance use.
• The primary outcome was any CV event, including acute myocardial infarction, stroke, arrhythmia, endocarditis, any acute cardiomyopathy or heart failure, or cardiac arrest; other outcomes included maternal mortality and major adverse cardiac events (MACE).

TAKEAWAY:

• Deliveries complicated by substance use increased from 1,126 per 100,000 deliveries in 2004 to 1,547 per 100,000 in 2018, peaking at 2,187 per 100,000 in 2014.
• After the researchers controlled for patient demographics and CVD risk factors, results showed that pregnant women who used any substance (cannabis, opioids, methamphetamine, alcohol, tobacco, or cocaine) were more likely to experience a CVD event (adjusted odds ratio [aOR], 1.61; 95% confidence interval [CI], 1.53-1.70; P < .001), MACE (aOR, 1.53; 95% CI, 1.46-1.61; P < .001), or maternal mortality (aOR, 2.65; 95% CI, 2.15-3.25; P < .001) during hospitalization for delivery.
• Those using amphetamine/methamphetamine had ninefold higher odds of cardiomyopathy or heart failure and more than sevenfold higher odds of cardiac arrest.

IN PRACTICE:

“For the wellbeing of pregnant women and their children, substance use needs to be considered an independent risk factor for CV events in pregnancy,” the authors wrote. They called for prenatal assessments by a multidisciplinary cardio-obstetrics team to try to decrease cardiac complications.

In an accompanying editorial by Abha Khandelwal, MD, department of medicine, Stanford (Calif.) University, and others, the authors said the findings “highlight the critical support required during pregnancy and postpartum” for substance users, which should include comprehensive medical care and social services as well as access to addiction medicine and treatment of co-occurring mental health disorders.

SOURCE:

The study was carried out by Kari Evans, MD, division of maternal fetal medicine, department of obstetrics and gynecology, University of Arizona, Phoenix. It was published online in the Journal of the American College of Cardiology: Advances.

LIMITATIONS:

Use of administrative databases may have resulted in underreporting of diagnoses. The researchers could not assess the association of dose, duration, method, or timing of use for any substance with CV events. They also could not examine the effect of vaping on maternal CV events or differentiate hospitalizations for delivery that were complicated by CV events from hospitalizations for CV events that prompted delivery. The data did not reflect the postpartum period, during which a high rate of adverse CV events occurs.

DISCLOSURES:

The authors and editorial writers have no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Women who use cocaine, cannabis, or other substances during pregnancy have increased risks of acute cardiovascular (CV) events while in the hospital for delivery, including more than double the risk of maternal mortality, a new study shows.

METHODOLOGY:

• Using the National Inpatient Sample database to identify hospital deliveries between 2004 and 2018 and diagnostic codes to identify maternal substance use, researchers compared 955,531 pregnancies with accompanying substance use – the most common substances being cannabis and opioids, followed by stimulants – to over 60 million pregnancies in which there was no substance use.
• The primary outcome was any CV event, including acute myocardial infarction, stroke, arrhythmia, endocarditis, any acute cardiomyopathy or heart failure, or cardiac arrest; other outcomes included maternal mortality and major adverse cardiac events (MACE).

TAKEAWAY:

• Deliveries complicated by substance use increased from 1,126 per 100,000 deliveries in 2004 to 1,547 per 100,000 in 2018, peaking at 2,187 per 100,000 in 2014.
• After the researchers controlled for patient demographics and CVD risk factors, results showed that pregnant women who used any substance (cannabis, opioids, methamphetamine, alcohol, tobacco, or cocaine) were more likely to experience a CVD event (adjusted odds ratio [aOR], 1.61; 95% confidence interval [CI], 1.53-1.70; P < .001), MACE (aOR, 1.53; 95% CI, 1.46-1.61; P < .001), or maternal mortality (aOR, 2.65; 95% CI, 2.15-3.25; P < .001) during hospitalization for delivery.
• Those using amphetamine/methamphetamine had ninefold higher odds of cardiomyopathy or heart failure and more than sevenfold higher odds of cardiac arrest.

IN PRACTICE:

“For the wellbeing of pregnant women and their children, substance use needs to be considered an independent risk factor for CV events in pregnancy,” the authors wrote. They called for prenatal assessments by a multidisciplinary cardio-obstetrics team to try to decrease cardiac complications.

In an accompanying editorial by Abha Khandelwal, MD, department of medicine, Stanford (Calif.) University, and others, the authors said the findings “highlight the critical support required during pregnancy and postpartum” for substance users, which should include comprehensive medical care and social services as well as access to addiction medicine and treatment of co-occurring mental health disorders.

SOURCE:

The study was carried out by Kari Evans, MD, division of maternal fetal medicine, department of obstetrics and gynecology, University of Arizona, Phoenix. It was published online in the Journal of the American College of Cardiology: Advances.

LIMITATIONS:

Use of administrative databases may have resulted in underreporting of diagnoses. The researchers could not assess the association of dose, duration, method, or timing of use for any substance with CV events. They also could not examine the effect of vaping on maternal CV events or differentiate hospitalizations for delivery that were complicated by CV events from hospitalizations for CV events that prompted delivery. The data did not reflect the postpartum period, during which a high rate of adverse CV events occurs.

DISCLOSURES:

The authors and editorial writers have no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Women with node-negative breast cancers 2 cm or smaller and negative preoperative axillary ultrasound results may be safely spared sentinel lymph node (SLN) biopsy, new research suggests.

METHODOLOGY:

• SLN biopsy is standard for axillary staging in early breast cancer, but whether this biopsy is necessary and whether imaging could replace it remain uncertain.
• In the prospective SOUND trial, researchers randomized 1,405 women with node-negative breast cancers up to 2 cm and negative preoperative axillary ultrasound 1:1 to SLN biopsy or no axillary surgery.
• The primary outcome was 5-year distant disease-free survival (DFS), analyzed as intention-to-treat in 708 women randomized to SLN biopsy and 697 to no axillary surgery.
• Most patients (87.8%) had ER-positive ERBB2-negative disease, were postmenopausal (78%), and had T1 tumors (95%). In the biopsy group, 13.7% of patients had positive axillary nodes.
• Secondary end points were the cumulative incidence of distant recurrences and axillary recurrences, disease-free survival (DFS), and overall survival.

TAKEAWAY:

• Overall, omitting SLN biopsy did not appear to affect outcomes, with patients demonstrating similar 5-year locoregional relapse rates with and without SLN biopsy (1.7% vs. 1.6%), 5-year distant metastases (1.8% with vs. 2.0% without), and 5-year distant DFS (97.7% with vs. 98.0% without).
• Five-year overall survival was also similar between the two groups: 98.2% among those who received SLN biopsy and 98.4% among those who did not.
• Overall, 21 (3.0%) deaths were observed in the SLNB group and 18 (2.6%) deaths in the no axillary surgery group.
• The authors reported no significant differences in adjuvant treatment recommendations between the two groups.

IN PRACTICE:

“The results of this trial support the safety of omitting axillary surgery in older postmenopausal women with ER-positive ERBB2-negative [breast cancer] who met the SOUND eligibility criteria,” the study authors concluded.

In an accompanying editorial, Seema A. Khan, MD, agreed that the outcome data support “the argument that sentinel node positivity is not, in and of itself, a critical parameter that determines therapeutic plans and outcomes in patients with stage I breast cancer.”

SOURCE:

The study, led by Oreste Davide Gentilini, MD, San Raffaele Scientific and Research Hospital, Milan, was published online in JAMA Oncology, with an editorial by Seema Khan, MD, Northwestern University, Chicago.

LIMITATIONS:

The study enrolled patients who could be considered low risk for recurrence in the short-term (median tumor size of 1.1 cm and 87.8% of patients had hormone-receptor positive, ERBB2-negative disease). The authors noted that differences in outcomes might appear over a longer follow-up period.

DISCLOSURES:

The SOUND trial was funded by the European Institute of Oncology Foundation. Some authors report personal fees from pharmaceutical companies.

A version of this article appeared on Medscape.com.

TOPLINE:

Women with node-negative breast cancers 2 cm or smaller and negative preoperative axillary ultrasound results may be safely spared sentinel lymph node (SLN) biopsy, new research suggests.

METHODOLOGY:

• SLN biopsy is standard for axillary staging in early breast cancer, but whether this biopsy is necessary and whether imaging could replace it remain uncertain.
• In the prospective SOUND trial, researchers randomized 1,405 women with node-negative breast cancers up to 2 cm and negative preoperative axillary ultrasound 1:1 to SLN biopsy or no axillary surgery.
• The primary outcome was 5-year distant disease-free survival (DFS), analyzed as intention-to-treat in 708 women randomized to SLN biopsy and 697 to no axillary surgery.
• Most patients (87.8%) had ER-positive ERBB2-negative disease, were postmenopausal (78%), and had T1 tumors (95%). In the biopsy group, 13.7% of patients had positive axillary nodes.
• Secondary end points were the cumulative incidence of distant recurrences and axillary recurrences, disease-free survival (DFS), and overall survival.

TAKEAWAY:

• Overall, omitting SLN biopsy did not appear to affect outcomes, with patients demonstrating similar 5-year locoregional relapse rates with and without SLN biopsy (1.7% vs. 1.6%), 5-year distant metastases (1.8% with vs. 2.0% without), and 5-year distant DFS (97.7% with vs. 98.0% without).
• Five-year overall survival was also similar between the two groups: 98.2% among those who received SLN biopsy and 98.4% among those who did not.
• Overall, 21 (3.0%) deaths were observed in the SLNB group and 18 (2.6%) deaths in the no axillary surgery group.
• The authors reported no significant differences in adjuvant treatment recommendations between the two groups.

IN PRACTICE:

“The results of this trial support the safety of omitting axillary surgery in older postmenopausal women with ER-positive ERBB2-negative [breast cancer] who met the SOUND eligibility criteria,” the study authors concluded.

In an accompanying editorial, Seema A. Khan, MD, agreed that the outcome data support “the argument that sentinel node positivity is not, in and of itself, a critical parameter that determines therapeutic plans and outcomes in patients with stage I breast cancer.”

SOURCE:

The study, led by Oreste Davide Gentilini, MD, San Raffaele Scientific and Research Hospital, Milan, was published online in JAMA Oncology, with an editorial by Seema Khan, MD, Northwestern University, Chicago.

LIMITATIONS:

The study enrolled patients who could be considered low risk for recurrence in the short-term (median tumor size of 1.1 cm and 87.8% of patients had hormone-receptor positive, ERBB2-negative disease). The authors noted that differences in outcomes might appear over a longer follow-up period.

DISCLOSURES:

The SOUND trial was funded by the European Institute of Oncology Foundation. Some authors report personal fees from pharmaceutical companies.

A version of this article appeared on Medscape.com.

TOPLINE:

Women with node-negative breast cancers 2 cm or smaller and negative preoperative axillary ultrasound results may be safely spared sentinel lymph node (SLN) biopsy, new research suggests.

METHODOLOGY:

• SLN biopsy is standard for axillary staging in early breast cancer, but whether this biopsy is necessary and whether imaging could replace it remain uncertain.
• In the prospective SOUND trial, researchers randomized 1,405 women with node-negative breast cancers up to 2 cm and negative preoperative axillary ultrasound 1:1 to SLN biopsy or no axillary surgery.
• The primary outcome was 5-year distant disease-free survival (DFS), analyzed as intention-to-treat in 708 women randomized to SLN biopsy and 697 to no axillary surgery.
• Most patients (87.8%) had ER-positive ERBB2-negative disease, were postmenopausal (78%), and had T1 tumors (95%). In the biopsy group, 13.7% of patients had positive axillary nodes.
• Secondary end points were the cumulative incidence of distant recurrences and axillary recurrences, disease-free survival (DFS), and overall survival.

TAKEAWAY:

• Overall, omitting SLN biopsy did not appear to affect outcomes, with patients demonstrating similar 5-year locoregional relapse rates with and without SLN biopsy (1.7% vs. 1.6%), 5-year distant metastases (1.8% with vs. 2.0% without), and 5-year distant DFS (97.7% with vs. 98.0% without).
• Five-year overall survival was also similar between the two groups: 98.2% among those who received SLN biopsy and 98.4% among those who did not.
• Overall, 21 (3.0%) deaths were observed in the SLNB group and 18 (2.6%) deaths in the no axillary surgery group.
• The authors reported no significant differences in adjuvant treatment recommendations between the two groups.

IN PRACTICE:

“The results of this trial support the safety of omitting axillary surgery in older postmenopausal women with ER-positive ERBB2-negative [breast cancer] who met the SOUND eligibility criteria,” the study authors concluded.

In an accompanying editorial, Seema A. Khan, MD, agreed that the outcome data support “the argument that sentinel node positivity is not, in and of itself, a critical parameter that determines therapeutic plans and outcomes in patients with stage I breast cancer.”

SOURCE:

The study, led by Oreste Davide Gentilini, MD, San Raffaele Scientific and Research Hospital, Milan, was published online in JAMA Oncology, with an editorial by Seema Khan, MD, Northwestern University, Chicago.

LIMITATIONS:

The study enrolled patients who could be considered low risk for recurrence in the short-term (median tumor size of 1.1 cm and 87.8% of patients had hormone-receptor positive, ERBB2-negative disease). The authors noted that differences in outcomes might appear over a longer follow-up period.

DISCLOSURES:

The SOUND trial was funded by the European Institute of Oncology Foundation. Some authors report personal fees from pharmaceutical companies.

A version of this article appeared on Medscape.com.

Patients with breast cancer often stay on endocrine therapy for 5-10 years.

For many, however, long-term use is a challenge. Studies show about half of breast cancer patients don’t take their hormone therapy as prescribed, and as many as 40% discontinue treatment early.

Stopping adjuvant endocrine therapy prematurely can have major consequences. These patients are more likely to experience cancer recurrence and to die earlier, research shows.

“Given that suboptimal adjuvant endocrine therapy adherence is common and is associated with breast cancer recurrence and mortality, there is a vital need for effective interventions to promote adherence,” Joanna J. Arch, PhD, from the University of Colorado Boulder, and colleagues write in a recent meta-analysis.

Experts discuss why it’s so challenging for patients to adhere to adjuvant endocrine therapy as well as which strategies may help boost long-term use and which likely will not.
 

The adherence problem

To improve adherence to adjuvant endocrine therapy, clinicians first need to understand the barriers patients face.

Studies indicate that a host of issues play into long-term adherence. Medication side effects, such as insomnia, fatigue, anxiety, depression, joint pain, and hot flashes, can deter patients from continuing endocrine therapy.

Tamoxifen, in particular, is known for its severe adverse events. Research suggests it may even increase patients’ risk for endometrial cancer and other uterine diseases.

Recent approvals of aromatase inhibitors – such as anastrozole, exemestane, and letrozole – have provided patients a tamoxifen alterative, but these agents come with their own issues, which include bone loss and vaginal dryness.

Common and severe side effects that affect adherence “should absolutely be addressed sooner, more frequently, and by any provider, not just the medical oncologist,” said Anna Weiss, MD, a breast cancer surgeon with the Wilmot Cancer Center, University of Rochester Medical Center, N.Y.

Other barriers to long-term use include the burden of managing comorbidities and drug costs as well as patients’ uncertainty about the value of long-term cancer therapy.

The issues that take center stage for individual patients may also vary by age. For older patients, comorbidities, cognitive function, and lack of social support may be key barriers to adherence, while for younger patients, fertility and sexual health issues are more pressing.

Clinicians should especially not underestimate the effects of hormonal suppression on adherence, explained Dr. Weiss, who recently published practice pearls on managing side effects of adjunctive endocrine therapy. “I do believe that we have been ignoring the sexual wellness aspect of breast cancer survivorship care for too long,” she said.
 

An array of fixes needed

Given the array of potential obstacles to endocrine therapy adherence, improving long-term use may be equally complex.

In a recent meta-analysis, Dr. Arch and colleagues combed the literature for studies exploring a host of strategies to improve endocrine therapy adherence. The team focused on 25 studies involving 367,873 women with breast cancer who were prescribed tamoxifen or an aromatase inhibitor.

The studies assessed a variety of interventions – disease management and exercise programs to lower side effects, medication reminders via phone or letter to limit missed doses, online educational materials to highlight the importance of adherence, as well as medication changes to reduce drug costs.

Overall, these interventions were of modest benefit in improving adherence. The findings indicate that “a variety of approaches” can be effective, Dr. Arch said.

But, she noted, aside from cost-cutting strategies, “no single approach stood out as more effective than others,” and some studies found minimal or inconsistent benefits to specific interventions.

One analysis, for instance, explored a text message intervention that involved sending patients several texts per week reminding them to take their medication, exercise more, or monitor their side effects. Overall, participants who received text messages missed fewer endocrine therapy doses, compared with those who didn’t – 7.1% versus 17.0% – and for about two-thirds of participants, the text messages motivated lifestyle changes.

Another study included in the meta-analysis, however, found that “twice-weekly text reminders did not improve adherence to aromatase inhibitors.”

Studies in which patients received educational materials about the importance of adherence or how to manage side effects found that effectiveness varied as well. Other analyses indicated that integrating relaxation techniques or other cognitive-behavioral approaches into patient care may have small beneficial effects on adherence.

Dr. Arch’s meta-analysis did, however, find a consistent benefit for cost-cutting interventions. Three large studies reported that medication adherence improved following policy changes that were focused on reducing costs of adjuvant endocrine therapy, either through legislation limiting out-of-pocket costs for oral drugs or by switching to generic formulations.

Xuanzi Qin, PhD, first author on one of the studies, explained that after generic aromatase inhibitor options became available, patients who switched to these options had lower out-of-pocket costs and higher rates of drug adherence.

The take-home message of the study is that “clinicians should know the out-of-pocket costs of the drugs and discuss the costs with patients,” Dr. Qin, of the University of Maryland School of Public Health, College Park, told this news organization.

Dr. Arch pointed out that although the meta-analysis found a consistent benefit to cost-cutting strategies, that does not necessarily translate to a strong benefit.

And overall, the body of research indicates that “we need to develop and test new strategies and hone existing ones,” Dr. Arch said, “so that we can boost adherence even more and help more women benefit fully from these life-extending medications.”

However, Dr. Weiss explained, seemingly small measures may still make important clinical differences for individual patients, even if studies don’t show a statistically significant impact overall on endocrine therapy adherence.

For Dr. Weiss, “even getting one patient to continue their endocrine therapy is a win in my book.”

Dr. Arch reported a consulting or advisory role with AbbVie/Genentech and Bristol-Meyers Squibb and research funding from NCCN/Astrazeneca. Dr. Weiss reports being on the advisory board for Merck and Myriad. Dr. Qin has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Patients with breast cancer often stay on endocrine therapy for 5-10 years.

For many, however, long-term use is a challenge. Studies show about half of breast cancer patients don’t take their hormone therapy as prescribed, and as many as 40% discontinue treatment early.

Stopping adjuvant endocrine therapy prematurely can have major consequences. These patients are more likely to experience cancer recurrence and to die earlier, research shows.

“Given that suboptimal adjuvant endocrine therapy adherence is common and is associated with breast cancer recurrence and mortality, there is a vital need for effective interventions to promote adherence,” Joanna J. Arch, PhD, from the University of Colorado Boulder, and colleagues write in a recent meta-analysis.

Experts discuss why it’s so challenging for patients to adhere to adjuvant endocrine therapy as well as which strategies may help boost long-term use and which likely will not.
 

The adherence problem

To improve adherence to adjuvant endocrine therapy, clinicians first need to understand the barriers patients face.

Studies indicate that a host of issues play into long-term adherence. Medication side effects, such as insomnia, fatigue, anxiety, depression, joint pain, and hot flashes, can deter patients from continuing endocrine therapy.

Tamoxifen, in particular, is known for its severe adverse events. Research suggests it may even increase patients’ risk for endometrial cancer and other uterine diseases.

Recent approvals of aromatase inhibitors – such as anastrozole, exemestane, and letrozole – have provided patients a tamoxifen alterative, but these agents come with their own issues, which include bone loss and vaginal dryness.

Common and severe side effects that affect adherence “should absolutely be addressed sooner, more frequently, and by any provider, not just the medical oncologist,” said Anna Weiss, MD, a breast cancer surgeon with the Wilmot Cancer Center, University of Rochester Medical Center, N.Y.

Other barriers to long-term use include the burden of managing comorbidities and drug costs as well as patients’ uncertainty about the value of long-term cancer therapy.

The issues that take center stage for individual patients may also vary by age. For older patients, comorbidities, cognitive function, and lack of social support may be key barriers to adherence, while for younger patients, fertility and sexual health issues are more pressing.

Clinicians should especially not underestimate the effects of hormonal suppression on adherence, explained Dr. Weiss, who recently published practice pearls on managing side effects of adjunctive endocrine therapy. “I do believe that we have been ignoring the sexual wellness aspect of breast cancer survivorship care for too long,” she said.
 

An array of fixes needed

Given the array of potential obstacles to endocrine therapy adherence, improving long-term use may be equally complex.

In a recent meta-analysis, Dr. Arch and colleagues combed the literature for studies exploring a host of strategies to improve endocrine therapy adherence. The team focused on 25 studies involving 367,873 women with breast cancer who were prescribed tamoxifen or an aromatase inhibitor.

The studies assessed a variety of interventions – disease management and exercise programs to lower side effects, medication reminders via phone or letter to limit missed doses, online educational materials to highlight the importance of adherence, as well as medication changes to reduce drug costs.

Overall, these interventions were of modest benefit in improving adherence. The findings indicate that “a variety of approaches” can be effective, Dr. Arch said.

But, she noted, aside from cost-cutting strategies, “no single approach stood out as more effective than others,” and some studies found minimal or inconsistent benefits to specific interventions.

One analysis, for instance, explored a text message intervention that involved sending patients several texts per week reminding them to take their medication, exercise more, or monitor their side effects. Overall, participants who received text messages missed fewer endocrine therapy doses, compared with those who didn’t – 7.1% versus 17.0% – and for about two-thirds of participants, the text messages motivated lifestyle changes.

Another study included in the meta-analysis, however, found that “twice-weekly text reminders did not improve adherence to aromatase inhibitors.”

Studies in which patients received educational materials about the importance of adherence or how to manage side effects found that effectiveness varied as well. Other analyses indicated that integrating relaxation techniques or other cognitive-behavioral approaches into patient care may have small beneficial effects on adherence.

Dr. Arch’s meta-analysis did, however, find a consistent benefit for cost-cutting interventions. Three large studies reported that medication adherence improved following policy changes that were focused on reducing costs of adjuvant endocrine therapy, either through legislation limiting out-of-pocket costs for oral drugs or by switching to generic formulations.

Xuanzi Qin, PhD, first author on one of the studies, explained that after generic aromatase inhibitor options became available, patients who switched to these options had lower out-of-pocket costs and higher rates of drug adherence.

The take-home message of the study is that “clinicians should know the out-of-pocket costs of the drugs and discuss the costs with patients,” Dr. Qin, of the University of Maryland School of Public Health, College Park, told this news organization.

Dr. Arch pointed out that although the meta-analysis found a consistent benefit to cost-cutting strategies, that does not necessarily translate to a strong benefit.

And overall, the body of research indicates that “we need to develop and test new strategies and hone existing ones,” Dr. Arch said, “so that we can boost adherence even more and help more women benefit fully from these life-extending medications.”

However, Dr. Weiss explained, seemingly small measures may still make important clinical differences for individual patients, even if studies don’t show a statistically significant impact overall on endocrine therapy adherence.

For Dr. Weiss, “even getting one patient to continue their endocrine therapy is a win in my book.”

Dr. Arch reported a consulting or advisory role with AbbVie/Genentech and Bristol-Meyers Squibb and research funding from NCCN/Astrazeneca. Dr. Weiss reports being on the advisory board for Merck and Myriad. Dr. Qin has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Patients with breast cancer often stay on endocrine therapy for 5-10 years.

For many, however, long-term use is a challenge. Studies show about half of breast cancer patients don’t take their hormone therapy as prescribed, and as many as 40% discontinue treatment early.

Stopping adjuvant endocrine therapy prematurely can have major consequences. These patients are more likely to experience cancer recurrence and to die earlier, research shows.

“Given that suboptimal adjuvant endocrine therapy adherence is common and is associated with breast cancer recurrence and mortality, there is a vital need for effective interventions to promote adherence,” Joanna J. Arch, PhD, from the University of Colorado Boulder, and colleagues write in a recent meta-analysis.

Experts discuss why it’s so challenging for patients to adhere to adjuvant endocrine therapy as well as which strategies may help boost long-term use and which likely will not.
 

The adherence problem

To improve adherence to adjuvant endocrine therapy, clinicians first need to understand the barriers patients face.

Studies indicate that a host of issues play into long-term adherence. Medication side effects, such as insomnia, fatigue, anxiety, depression, joint pain, and hot flashes, can deter patients from continuing endocrine therapy.

Tamoxifen, in particular, is known for its severe adverse events. Research suggests it may even increase patients’ risk for endometrial cancer and other uterine diseases.

Recent approvals of aromatase inhibitors – such as anastrozole, exemestane, and letrozole – have provided patients a tamoxifen alterative, but these agents come with their own issues, which include bone loss and vaginal dryness.

Common and severe side effects that affect adherence “should absolutely be addressed sooner, more frequently, and by any provider, not just the medical oncologist,” said Anna Weiss, MD, a breast cancer surgeon with the Wilmot Cancer Center, University of Rochester Medical Center, N.Y.

Other barriers to long-term use include the burden of managing comorbidities and drug costs as well as patients’ uncertainty about the value of long-term cancer therapy.

The issues that take center stage for individual patients may also vary by age. For older patients, comorbidities, cognitive function, and lack of social support may be key barriers to adherence, while for younger patients, fertility and sexual health issues are more pressing.

Clinicians should especially not underestimate the effects of hormonal suppression on adherence, explained Dr. Weiss, who recently published practice pearls on managing side effects of adjunctive endocrine therapy. “I do believe that we have been ignoring the sexual wellness aspect of breast cancer survivorship care for too long,” she said.
 

An array of fixes needed

Given the array of potential obstacles to endocrine therapy adherence, improving long-term use may be equally complex.

In a recent meta-analysis, Dr. Arch and colleagues combed the literature for studies exploring a host of strategies to improve endocrine therapy adherence. The team focused on 25 studies involving 367,873 women with breast cancer who were prescribed tamoxifen or an aromatase inhibitor.

The studies assessed a variety of interventions – disease management and exercise programs to lower side effects, medication reminders via phone or letter to limit missed doses, online educational materials to highlight the importance of adherence, as well as medication changes to reduce drug costs.

Overall, these interventions were of modest benefit in improving adherence. The findings indicate that “a variety of approaches” can be effective, Dr. Arch said.

But, she noted, aside from cost-cutting strategies, “no single approach stood out as more effective than others,” and some studies found minimal or inconsistent benefits to specific interventions.

One analysis, for instance, explored a text message intervention that involved sending patients several texts per week reminding them to take their medication, exercise more, or monitor their side effects. Overall, participants who received text messages missed fewer endocrine therapy doses, compared with those who didn’t – 7.1% versus 17.0% – and for about two-thirds of participants, the text messages motivated lifestyle changes.

Another study included in the meta-analysis, however, found that “twice-weekly text reminders did not improve adherence to aromatase inhibitors.”

Studies in which patients received educational materials about the importance of adherence or how to manage side effects found that effectiveness varied as well. Other analyses indicated that integrating relaxation techniques or other cognitive-behavioral approaches into patient care may have small beneficial effects on adherence.

Dr. Arch’s meta-analysis did, however, find a consistent benefit for cost-cutting interventions. Three large studies reported that medication adherence improved following policy changes that were focused on reducing costs of adjuvant endocrine therapy, either through legislation limiting out-of-pocket costs for oral drugs or by switching to generic formulations.

Xuanzi Qin, PhD, first author on one of the studies, explained that after generic aromatase inhibitor options became available, patients who switched to these options had lower out-of-pocket costs and higher rates of drug adherence.

The take-home message of the study is that “clinicians should know the out-of-pocket costs of the drugs and discuss the costs with patients,” Dr. Qin, of the University of Maryland School of Public Health, College Park, told this news organization.

Dr. Arch pointed out that although the meta-analysis found a consistent benefit to cost-cutting strategies, that does not necessarily translate to a strong benefit.

And overall, the body of research indicates that “we need to develop and test new strategies and hone existing ones,” Dr. Arch said, “so that we can boost adherence even more and help more women benefit fully from these life-extending medications.”

However, Dr. Weiss explained, seemingly small measures may still make important clinical differences for individual patients, even if studies don’t show a statistically significant impact overall on endocrine therapy adherence.

For Dr. Weiss, “even getting one patient to continue their endocrine therapy is a win in my book.”

Dr. Arch reported a consulting or advisory role with AbbVie/Genentech and Bristol-Meyers Squibb and research funding from NCCN/Astrazeneca. Dr. Weiss reports being on the advisory board for Merck and Myriad. Dr. Qin has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

New research suggests that the presence of high-risk colon polyps at screening colonoscopy is significantly associated with an increased risk for death from hepatobiliary cancer.

METHODOLOGY:

• Researchers conducted a retrospective analysis of 343,838 screening colonoscopies performed in Austria from 2007 to 2020. National death registry data were used to identify deaths from gastrointestinal cancers among patients in the cohort.
• Risk for hepatobiliary cancer death by colon polyp risk profile was assessed.
• A cause-specific Cox regression model was used to estimate the association of time to death with polyp risk group at screening colonoscopy.

TAKEAWAY:

• Of the screening colonoscopies, 17,678 (5.1%) revealed high-risk polyps: that is, polyps of at least 10 mm, adenomas with high-grade dysplasia, serrated polyps with dysplasia, or five or more adenomas.
• The cumulative incidence of hepatobiliary cancer death was 0.19% at 6 years and 0.44% at 12 years in the high-risk polyp group versus 0.07% and 0.18%, respectively, in the negative colonoscopy group.
• Overall hepatobiliary cancer mortality was more than twice as high in patients with high-risk polyps compared with peers who had negative colonoscopy (cumulative incidence, 0.39% vs 0.17%).
• After adjustment for age and sex, the presence of high-risk polyps at screening colonoscopy was significantly associated with death from any hepatobiliary cancer (hazard ratio [HR], 1.83); the HRs for death from hepatocellular carcinoma (HCC) and non-HCC hepatobiliary cancer were 1.79 and 1.88, respectively.
• There was no significant association of low-risk polyps with hepatobiliary cancer death (HR, 1.23).

IN PRACTICE:

“Hepatobiliary cancers share risk factors with colorectal cancer, but there are no combined screening programs for these conditions,” the researchers write. “Our findings imply that risk stratification at colonoscopy might be helping to identify patients at need for liver cancer surveillance. However, further studies will be needed to address whether a targeted surveillance of these patients will be cost effective.”

SOURCE:

The study, with first author Jasmin Zessner-Spitzenberg, MD, of the Medical University of Vienna, was published online in Digestive and Liver Disease.

LIMITATIONS:

Some liver cancer deaths might have been falsely classified as other hepatic cancers. The authors lacked information on modifiable cancer risk factors. The generalizability of the findings outside of the screening setting is limited.

DISCLOSURES:

Support for data collection was provided by the Main Association of Statutory Insurance Institutions, the Austrian Society for Gastroenterology and Hepatology, and Austrian Cancer Aid. One author reported relationships with various pharmaceutical companies.

A version of this article appeared on Medscape.com.

TOPLINE:

New research suggests that the presence of high-risk colon polyps at screening colonoscopy is significantly associated with an increased risk for death from hepatobiliary cancer.

METHODOLOGY:

• Researchers conducted a retrospective analysis of 343,838 screening colonoscopies performed in Austria from 2007 to 2020. National death registry data were used to identify deaths from gastrointestinal cancers among patients in the cohort.
• Risk for hepatobiliary cancer death by colon polyp risk profile was assessed.
• A cause-specific Cox regression model was used to estimate the association of time to death with polyp risk group at screening colonoscopy.

TAKEAWAY:

• Of the screening colonoscopies, 17,678 (5.1%) revealed high-risk polyps: that is, polyps of at least 10 mm, adenomas with high-grade dysplasia, serrated polyps with dysplasia, or five or more adenomas.
• The cumulative incidence of hepatobiliary cancer death was 0.19% at 6 years and 0.44% at 12 years in the high-risk polyp group versus 0.07% and 0.18%, respectively, in the negative colonoscopy group.
• Overall hepatobiliary cancer mortality was more than twice as high in patients with high-risk polyps compared with peers who had negative colonoscopy (cumulative incidence, 0.39% vs 0.17%).
• After adjustment for age and sex, the presence of high-risk polyps at screening colonoscopy was significantly associated with death from any hepatobiliary cancer (hazard ratio [HR], 1.83); the HRs for death from hepatocellular carcinoma (HCC) and non-HCC hepatobiliary cancer were 1.79 and 1.88, respectively.
• There was no significant association of low-risk polyps with hepatobiliary cancer death (HR, 1.23).

IN PRACTICE:

“Hepatobiliary cancers share risk factors with colorectal cancer, but there are no combined screening programs for these conditions,” the researchers write. “Our findings imply that risk stratification at colonoscopy might be helping to identify patients at need for liver cancer surveillance. However, further studies will be needed to address whether a targeted surveillance of these patients will be cost effective.”

SOURCE:

The study, with first author Jasmin Zessner-Spitzenberg, MD, of the Medical University of Vienna, was published online in Digestive and Liver Disease.

LIMITATIONS:

Some liver cancer deaths might have been falsely classified as other hepatic cancers. The authors lacked information on modifiable cancer risk factors. The generalizability of the findings outside of the screening setting is limited.

DISCLOSURES:

Support for data collection was provided by the Main Association of Statutory Insurance Institutions, the Austrian Society for Gastroenterology and Hepatology, and Austrian Cancer Aid. One author reported relationships with various pharmaceutical companies.

A version of this article appeared on Medscape.com.

TOPLINE:

New research suggests that the presence of high-risk colon polyps at screening colonoscopy is significantly associated with an increased risk for death from hepatobiliary cancer.

METHODOLOGY:

• Researchers conducted a retrospective analysis of 343,838 screening colonoscopies performed in Austria from 2007 to 2020. National death registry data were used to identify deaths from gastrointestinal cancers among patients in the cohort.
• Risk for hepatobiliary cancer death by colon polyp risk profile was assessed.
• A cause-specific Cox regression model was used to estimate the association of time to death with polyp risk group at screening colonoscopy.

TAKEAWAY:

• Of the screening colonoscopies, 17,678 (5.1%) revealed high-risk polyps: that is, polyps of at least 10 mm, adenomas with high-grade dysplasia, serrated polyps with dysplasia, or five or more adenomas.
• The cumulative incidence of hepatobiliary cancer death was 0.19% at 6 years and 0.44% at 12 years in the high-risk polyp group versus 0.07% and 0.18%, respectively, in the negative colonoscopy group.
• Overall hepatobiliary cancer mortality was more than twice as high in patients with high-risk polyps compared with peers who had negative colonoscopy (cumulative incidence, 0.39% vs 0.17%).
• After adjustment for age and sex, the presence of high-risk polyps at screening colonoscopy was significantly associated with death from any hepatobiliary cancer (hazard ratio [HR], 1.83); the HRs for death from hepatocellular carcinoma (HCC) and non-HCC hepatobiliary cancer were 1.79 and 1.88, respectively.
• There was no significant association of low-risk polyps with hepatobiliary cancer death (HR, 1.23).

IN PRACTICE:

“Hepatobiliary cancers share risk factors with colorectal cancer, but there are no combined screening programs for these conditions,” the researchers write. “Our findings imply that risk stratification at colonoscopy might be helping to identify patients at need for liver cancer surveillance. However, further studies will be needed to address whether a targeted surveillance of these patients will be cost effective.”

SOURCE:

The study, with first author Jasmin Zessner-Spitzenberg, MD, of the Medical University of Vienna, was published online in Digestive and Liver Disease.

LIMITATIONS:

Some liver cancer deaths might have been falsely classified as other hepatic cancers. The authors lacked information on modifiable cancer risk factors. The generalizability of the findings outside of the screening setting is limited.

DISCLOSURES:

Support for data collection was provided by the Main Association of Statutory Insurance Institutions, the Austrian Society for Gastroenterology and Hepatology, and Austrian Cancer Aid. One author reported relationships with various pharmaceutical companies.

A version of this article appeared on Medscape.com.

Recent data suggest that the incidence of early-onset cancer, defined as cancer diagnosed in people younger than 50 years, is on the rise in several countries. Two recent studies confirm this trend, including one published in early September in BMJ Oncology that presents worldwide data on the matter.

Early-onset cancer

The article published in BMJ Oncology shows that over the past 30 years (1990 to 2019), new cancer cases in patients younger than 50 years have increased by 79% worldwide, reaching 3.26 million cases. Among them, early-onset breast cancer had the highest incidence (13.7) and mortality (3.5 per 100k) rates in the global population.

Tracheal (nasopharyngeal) and prostate cancer have increased the most rapidly since 1990, with annual percentage changes estimated at 2.28% and 2.23%, respectively. At the other end of the scale, cases of early-onset liver cancer dropped by around 2.88% year on year.
 

Increase in deaths

There were more than a million (1.06) cancer deaths among patients younger than 50 years in 2019, which is an increase of slightly less than 28% compared with the figures from 1990.

The top four early-onset cancers with the highest mortality and disability-adjusted life year rates among young adults in 2019 were early-onset breast; tracheal, bronchus and lung; stomach; and colorectal cancers. The mortality rates of early-onset kidney cancer and ovarian cancer showed the fastest increasing trends.

“These results contrast with a more traditionally held view of ‘typical’ cancers in adults aged under 50 years,” Ashleigh C. Hamilton, MD, an academic clinical lecturer, and Helen G. Coleman, PhD, a professor, both at Queen’s University Belfast’s Centre for Public Health in the United Kingdom, explained in an accompanying editorial. An important aspect of this study is that it tackled the issue of increasing cancer rates among young people on a global scale, they added. Here, the researchers made use of 2019 data from the Global Burden of Disease database for 29 types of cancer in 204 countries and regions.
 

Industrialized countries

The highest rates of early-onset cancer in 2019 were reported in North America, Australasia, and Western Europe. However, the burden of early-onset cancers in low- to middle-income countries is also of major public health concern. The highest death rates among patients younger than 50 years were in Oceania, Eastern Europe, and Central Asia.

In low- or middle-income regions, early-onset cancer had a significantly higher impact on women than on men in terms of mortality and disease burden, the researchers reported.

On the basis of trends observed over the past 30 years, they estimate that the global incidence and deaths of early-onset cancer would increase by 31% and 21% in 2030, respectively, with 40-year-olds being the most affected.
 

Hypotheses and limitations

How can this increase in the incidence of cancer among patients younger than 50 years be explained? For the authors, genetic factors likely play a role. But dietary risk factors (diet high in red meat, low in fruits, high in sodium, and low in milk, etc.), alcohol consumption, and tobacco use are the main risk factors underlying early-onset cancers in patients under age 50 years. Physical inactivity, excess weight, and hyperglycemia were shown to be contributing factors.

The researchers recognized several limitations to their conclusions. First, the accuracy of Global Burden of Disease data was compromised by the quality of cancer registry data in different countries, which may have led to underreporting and underdiagnosis. Also, questions remain about how screening and early exposure to environmental factors can affect the observed trends.

For the authors of the editorial, “Full understanding of the reasons driving the observed trends remains elusive, although lifestyle factors are likely contributing, and novel areas of research such as antibiotic usage, the gut microbiome, outdoor air pollution, and early life exposures are being explored.”

They concluded, “Prevention and early detection measures are urgently required, along with identifying optimal treatment strategies for early-onset cancers, which should include a holistic approach addressing the unique supportive care needs of younger patients.”

The authors added, “It is worth exploring whether early screening and prevention programs for early-onset cancer should be expanded to include individuals aged 40-44 and 45-49, but further systematic studies and randomized trials are necessary to make a definitive determination.”
 

Trend in the United States

Between 2010 and 2019, although the incidence of cancer dropped in people over age 50 years in the United States, a study published in JAMA Network Open in August showed that the standardized incidence rate of early-onset cancer increased overall. More specifically, the rate increased in women but decreased in men.

In 2019, most early-onset cancer cases involved breast cancer. Between 2010 and 2019, gastrointestinal cancers saw the fastest rise. And among gastrointestinal cancers, those whose incidence rate increased the most rapidly were those affecting the appendix, the intrahepatic bile ducts, and the pancreas.
 

This article was translated from the Medscape French Edition. A version of this article appeared on Medscape.com.

Recent data suggest that the incidence of early-onset cancer, defined as cancer diagnosed in people younger than 50 years, is on the rise in several countries. Two recent studies confirm this trend, including one published in early September in BMJ Oncology that presents worldwide data on the matter.

Early-onset cancer

The article published in BMJ Oncology shows that over the past 30 years (1990 to 2019), new cancer cases in patients younger than 50 years have increased by 79% worldwide, reaching 3.26 million cases. Among them, early-onset breast cancer had the highest incidence (13.7) and mortality (3.5 per 100k) rates in the global population.

Tracheal (nasopharyngeal) and prostate cancer have increased the most rapidly since 1990, with annual percentage changes estimated at 2.28% and 2.23%, respectively. At the other end of the scale, cases of early-onset liver cancer dropped by around 2.88% year on year.
 

Increase in deaths

There were more than a million (1.06) cancer deaths among patients younger than 50 years in 2019, which is an increase of slightly less than 28% compared with the figures from 1990.

The top four early-onset cancers with the highest mortality and disability-adjusted life year rates among young adults in 2019 were early-onset breast; tracheal, bronchus and lung; stomach; and colorectal cancers. The mortality rates of early-onset kidney cancer and ovarian cancer showed the fastest increasing trends.

“These results contrast with a more traditionally held view of ‘typical’ cancers in adults aged under 50 years,” Ashleigh C. Hamilton, MD, an academic clinical lecturer, and Helen G. Coleman, PhD, a professor, both at Queen’s University Belfast’s Centre for Public Health in the United Kingdom, explained in an accompanying editorial. An important aspect of this study is that it tackled the issue of increasing cancer rates among young people on a global scale, they added. Here, the researchers made use of 2019 data from the Global Burden of Disease database for 29 types of cancer in 204 countries and regions.
 

Industrialized countries

The highest rates of early-onset cancer in 2019 were reported in North America, Australasia, and Western Europe. However, the burden of early-onset cancers in low- to middle-income countries is also of major public health concern. The highest death rates among patients younger than 50 years were in Oceania, Eastern Europe, and Central Asia.

In low- or middle-income regions, early-onset cancer had a significantly higher impact on women than on men in terms of mortality and disease burden, the researchers reported.

On the basis of trends observed over the past 30 years, they estimate that the global incidence and deaths of early-onset cancer would increase by 31% and 21% in 2030, respectively, with 40-year-olds being the most affected.
 

Hypotheses and limitations

How can this increase in the incidence of cancer among patients younger than 50 years be explained? For the authors, genetic factors likely play a role. But dietary risk factors (diet high in red meat, low in fruits, high in sodium, and low in milk, etc.), alcohol consumption, and tobacco use are the main risk factors underlying early-onset cancers in patients under age 50 years. Physical inactivity, excess weight, and hyperglycemia were shown to be contributing factors.

The researchers recognized several limitations to their conclusions. First, the accuracy of Global Burden of Disease data was compromised by the quality of cancer registry data in different countries, which may have led to underreporting and underdiagnosis. Also, questions remain about how screening and early exposure to environmental factors can affect the observed trends.

For the authors of the editorial, “Full understanding of the reasons driving the observed trends remains elusive, although lifestyle factors are likely contributing, and novel areas of research such as antibiotic usage, the gut microbiome, outdoor air pollution, and early life exposures are being explored.”

They concluded, “Prevention and early detection measures are urgently required, along with identifying optimal treatment strategies for early-onset cancers, which should include a holistic approach addressing the unique supportive care needs of younger patients.”

The authors added, “It is worth exploring whether early screening and prevention programs for early-onset cancer should be expanded to include individuals aged 40-44 and 45-49, but further systematic studies and randomized trials are necessary to make a definitive determination.”
 

Trend in the United States

Between 2010 and 2019, although the incidence of cancer dropped in people over age 50 years in the United States, a study published in JAMA Network Open in August showed that the standardized incidence rate of early-onset cancer increased overall. More specifically, the rate increased in women but decreased in men.

In 2019, most early-onset cancer cases involved breast cancer. Between 2010 and 2019, gastrointestinal cancers saw the fastest rise. And among gastrointestinal cancers, those whose incidence rate increased the most rapidly were those affecting the appendix, the intrahepatic bile ducts, and the pancreas.
 

This article was translated from the Medscape French Edition. A version of this article appeared on Medscape.com.

Recent data suggest that the incidence of early-onset cancer, defined as cancer diagnosed in people younger than 50 years, is on the rise in several countries. Two recent studies confirm this trend, including one published in early September in BMJ Oncology that presents worldwide data on the matter.

Early-onset cancer

The article published in BMJ Oncology shows that over the past 30 years (1990 to 2019), new cancer cases in patients younger than 50 years have increased by 79% worldwide, reaching 3.26 million cases. Among them, early-onset breast cancer had the highest incidence (13.7) and mortality (3.5 per 100k) rates in the global population.

Tracheal (nasopharyngeal) and prostate cancer have increased the most rapidly since 1990, with annual percentage changes estimated at 2.28% and 2.23%, respectively. At the other end of the scale, cases of early-onset liver cancer dropped by around 2.88% year on year.
 

Increase in deaths

There were more than a million (1.06) cancer deaths among patients younger than 50 years in 2019, which is an increase of slightly less than 28% compared with the figures from 1990.

The top four early-onset cancers with the highest mortality and disability-adjusted life year rates among young adults in 2019 were early-onset breast; tracheal, bronchus and lung; stomach; and colorectal cancers. The mortality rates of early-onset kidney cancer and ovarian cancer showed the fastest increasing trends.

“These results contrast with a more traditionally held view of ‘typical’ cancers in adults aged under 50 years,” Ashleigh C. Hamilton, MD, an academic clinical lecturer, and Helen G. Coleman, PhD, a professor, both at Queen’s University Belfast’s Centre for Public Health in the United Kingdom, explained in an accompanying editorial. An important aspect of this study is that it tackled the issue of increasing cancer rates among young people on a global scale, they added. Here, the researchers made use of 2019 data from the Global Burden of Disease database for 29 types of cancer in 204 countries and regions.
 

Industrialized countries

The highest rates of early-onset cancer in 2019 were reported in North America, Australasia, and Western Europe. However, the burden of early-onset cancers in low- to middle-income countries is also of major public health concern. The highest death rates among patients younger than 50 years were in Oceania, Eastern Europe, and Central Asia.

In low- or middle-income regions, early-onset cancer had a significantly higher impact on women than on men in terms of mortality and disease burden, the researchers reported.

On the basis of trends observed over the past 30 years, they estimate that the global incidence and deaths of early-onset cancer would increase by 31% and 21% in 2030, respectively, with 40-year-olds being the most affected.
 

Hypotheses and limitations

How can this increase in the incidence of cancer among patients younger than 50 years be explained? For the authors, genetic factors likely play a role. But dietary risk factors (diet high in red meat, low in fruits, high in sodium, and low in milk, etc.), alcohol consumption, and tobacco use are the main risk factors underlying early-onset cancers in patients under age 50 years. Physical inactivity, excess weight, and hyperglycemia were shown to be contributing factors.

The researchers recognized several limitations to their conclusions. First, the accuracy of Global Burden of Disease data was compromised by the quality of cancer registry data in different countries, which may have led to underreporting and underdiagnosis. Also, questions remain about how screening and early exposure to environmental factors can affect the observed trends.

For the authors of the editorial, “Full understanding of the reasons driving the observed trends remains elusive, although lifestyle factors are likely contributing, and novel areas of research such as antibiotic usage, the gut microbiome, outdoor air pollution, and early life exposures are being explored.”

They concluded, “Prevention and early detection measures are urgently required, along with identifying optimal treatment strategies for early-onset cancers, which should include a holistic approach addressing the unique supportive care needs of younger patients.”

The authors added, “It is worth exploring whether early screening and prevention programs for early-onset cancer should be expanded to include individuals aged 40-44 and 45-49, but further systematic studies and randomized trials are necessary to make a definitive determination.”
 

Trend in the United States

Between 2010 and 2019, although the incidence of cancer dropped in people over age 50 years in the United States, a study published in JAMA Network Open in August showed that the standardized incidence rate of early-onset cancer increased overall. More specifically, the rate increased in women but decreased in men.

In 2019, most early-onset cancer cases involved breast cancer. Between 2010 and 2019, gastrointestinal cancers saw the fastest rise. And among gastrointestinal cancers, those whose incidence rate increased the most rapidly were those affecting the appendix, the intrahepatic bile ducts, and the pancreas.
 

This article was translated from the Medscape French Edition. A version of this article appeared on Medscape.com.

At a glance, “health literacy” sounds like it has something specifically to do with the ability to read. Mary Laudon Thomas, MS, CNS, AOCN, a former president of Association of VA Hematology/Oncology, knows better.

“It’s not the same as reading level, and it’s not the same as educational level,” Thomas told Federal Practitioner. “Even educated people can think men can’t get breast cancer or misunderstand how to properly take their medications.”

Instead, health literacy is a broader topic: Do patients understand what’s going on when they get medical care? Can they use the information they get to make informed decisions about their health? Low health literacy is associated with lower use of preventative care of poorer adherence, poorer ability to navigate the health system and contributes to social inequities. In cancer care, low health literacy is associated with lower levels of screening, longer lag times in symptom identification, impairments in risk perception, fewer questions, lower perceived quality of life, and less follow-up.

Thomas and colleagues explored strategies to improve health literacy in cancer care during a half-day session on September 28th, kicking off the AVAHO 2023 annual meeting in Chicago. 

There are countless examples of patients who fail to understand aspects of their care, said Thomas, a retired clinical nurse specialist in hematology at California’s VA Palo Alto Health Care System who now serves as cochair of the AVAHO education committee. A patient may not realize that high blood pressure and hypertension are the same thing, for instance, or not understand that they need to go to the radiology department for a computed tomography.

“That’s our problem,” Thomas said. “We’re so fluent in our medical-speak that we forget we’re speaking a foreign language to other people.”

The goal of the AVAHO 2023 workshop is to “help people develop awareness of the scope of the problem and give them tools they can use to simplify how they speak to patients, teach patients and inform patients,” Thomas said.

In the first segment of the program, Angela Kumar, MPH, national program manager for Veterans Health Education and Information, discussed the VA organizational approach to health literacy. She noted that building a health-literate care organization aligns with the VA goal to be a high reliability organization. Veterans who have questions and concerns will need additional information throughout their cancer journey. The role for VA clinicians is to help answer veterans’ questions. “Rather than assume patients know what we are talking about, we have to make sure they understand,” Kumar explained. Institutional support will lead to better health outcomes and patient satisfaction throughout the system. VA is in the process of creating a patient centered learning program, Kumar noted. The program will be open to veterans, their families, caregivers, and provide training for VA health care professionals.

In the workshop’s 2 other sessions Janet Papadakos, PhD, MEd, a scientist at the University of Toronto’s Institute for Education Research, discussed the impact of health literacy on cancer treatment and outcomes and Fatemeh Youssefi, PhD, RN, OCN, director at large and committee member of the Oncology Nursing Society, discussed the roles of health literacy and patient education in empowering patients. Both speakers noted that patients with cancer are undergoing intense emotional stress, which can significantly impact their ability to understanding their treatment. Importantly, Papadakos explained, people can change and improve their health literacy, so clinicians have an opportunity to help influence and improve comprehension for their patient, by taking basic steps shown to improve health literacy.

“We know that in general, people with low health literacy report worse health, and they also have historically have poor outcomes,” Thomas said. Indeed, a 2021 systematic review of 66 papers found that “lower health literacy was associated with greater difficulties understanding and processing cancer related information, poorer quality of life and poorer experience of care.” Just 12% of US adults have proficient health literacy and one-third of adults have difficulty with common health tasks.

Papadakos and Youssefi provided some guidance for better communication with patients. Teach back, for example, is a tool to ensure patients understand topics when discussed. The key, Papadakos explained, is that it is not a test of the patient but rather a test of how well the information was communicated. Youssefi and Papadakos also emphasized the importance of using plain language. Clear and precise words that avoid technical terms avoid miscommunication and confusion. Finally, they urged clinicians to never assume health literacy and to approach all patients using clear language to ensure that they understand and can provide back the content covered.

Thomas said 3 more virtual sessions about health literacy will be offered over the coming year. Organizers will develop the specific topics after engaging in a discussion with attendees at the end of the AVAHO session. Meanwhile, advocates are developing a section of the AVAHO website that will be devoted to health literacy.

The workshop received support from Genentech.

At a glance, “health literacy” sounds like it has something specifically to do with the ability to read. Mary Laudon Thomas, MS, CNS, AOCN, a former president of Association of VA Hematology/Oncology, knows better.

“It’s not the same as reading level, and it’s not the same as educational level,” Thomas told Federal Practitioner. “Even educated people can think men can’t get breast cancer or misunderstand how to properly take their medications.”

Instead, health literacy is a broader topic: Do patients understand what’s going on when they get medical care? Can they use the information they get to make informed decisions about their health? Low health literacy is associated with lower use of preventative care of poorer adherence, poorer ability to navigate the health system and contributes to social inequities. In cancer care, low health literacy is associated with lower levels of screening, longer lag times in symptom identification, impairments in risk perception, fewer questions, lower perceived quality of life, and less follow-up.

Thomas and colleagues explored strategies to improve health literacy in cancer care during a half-day session on September 28th, kicking off the AVAHO 2023 annual meeting in Chicago. 

There are countless examples of patients who fail to understand aspects of their care, said Thomas, a retired clinical nurse specialist in hematology at California’s VA Palo Alto Health Care System who now serves as cochair of the AVAHO education committee. A patient may not realize that high blood pressure and hypertension are the same thing, for instance, or not understand that they need to go to the radiology department for a computed tomography.

“That’s our problem,” Thomas said. “We’re so fluent in our medical-speak that we forget we’re speaking a foreign language to other people.”

The goal of the AVAHO 2023 workshop is to “help people develop awareness of the scope of the problem and give them tools they can use to simplify how they speak to patients, teach patients and inform patients,” Thomas said.

In the first segment of the program, Angela Kumar, MPH, national program manager for Veterans Health Education and Information, discussed the VA organizational approach to health literacy. She noted that building a health-literate care organization aligns with the VA goal to be a high reliability organization. Veterans who have questions and concerns will need additional information throughout their cancer journey. The role for VA clinicians is to help answer veterans’ questions. “Rather than assume patients know what we are talking about, we have to make sure they understand,” Kumar explained. Institutional support will lead to better health outcomes and patient satisfaction throughout the system. VA is in the process of creating a patient centered learning program, Kumar noted. The program will be open to veterans, their families, caregivers, and provide training for VA health care professionals.

In the workshop’s 2 other sessions Janet Papadakos, PhD, MEd, a scientist at the University of Toronto’s Institute for Education Research, discussed the impact of health literacy on cancer treatment and outcomes and Fatemeh Youssefi, PhD, RN, OCN, director at large and committee member of the Oncology Nursing Society, discussed the roles of health literacy and patient education in empowering patients. Both speakers noted that patients with cancer are undergoing intense emotional stress, which can significantly impact their ability to understanding their treatment. Importantly, Papadakos explained, people can change and improve their health literacy, so clinicians have an opportunity to help influence and improve comprehension for their patient, by taking basic steps shown to improve health literacy.

“We know that in general, people with low health literacy report worse health, and they also have historically have poor outcomes,” Thomas said. Indeed, a 2021 systematic review of 66 papers found that “lower health literacy was associated with greater difficulties understanding and processing cancer related information, poorer quality of life and poorer experience of care.” Just 12% of US adults have proficient health literacy and one-third of adults have difficulty with common health tasks.

Papadakos and Youssefi provided some guidance for better communication with patients. Teach back, for example, is a tool to ensure patients understand topics when discussed. The key, Papadakos explained, is that it is not a test of the patient but rather a test of how well the information was communicated. Youssefi and Papadakos also emphasized the importance of using plain language. Clear and precise words that avoid technical terms avoid miscommunication and confusion. Finally, they urged clinicians to never assume health literacy and to approach all patients using clear language to ensure that they understand and can provide back the content covered.

Thomas said 3 more virtual sessions about health literacy will be offered over the coming year. Organizers will develop the specific topics after engaging in a discussion with attendees at the end of the AVAHO session. Meanwhile, advocates are developing a section of the AVAHO website that will be devoted to health literacy.

The workshop received support from Genentech.

At a glance, “health literacy” sounds like it has something specifically to do with the ability to read. Mary Laudon Thomas, MS, CNS, AOCN, a former president of Association of VA Hematology/Oncology, knows better.

“It’s not the same as reading level, and it’s not the same as educational level,” Thomas told Federal Practitioner. “Even educated people can think men can’t get breast cancer or misunderstand how to properly take their medications.”

Instead, health literacy is a broader topic: Do patients understand what’s going on when they get medical care? Can they use the information they get to make informed decisions about their health? Low health literacy is associated with lower use of preventative care of poorer adherence, poorer ability to navigate the health system and contributes to social inequities. In cancer care, low health literacy is associated with lower levels of screening, longer lag times in symptom identification, impairments in risk perception, fewer questions, lower perceived quality of life, and less follow-up.

Thomas and colleagues explored strategies to improve health literacy in cancer care during a half-day session on September 28th, kicking off the AVAHO 2023 annual meeting in Chicago. 

There are countless examples of patients who fail to understand aspects of their care, said Thomas, a retired clinical nurse specialist in hematology at California’s VA Palo Alto Health Care System who now serves as cochair of the AVAHO education committee. A patient may not realize that high blood pressure and hypertension are the same thing, for instance, or not understand that they need to go to the radiology department for a computed tomography.

“That’s our problem,” Thomas said. “We’re so fluent in our medical-speak that we forget we’re speaking a foreign language to other people.”

The goal of the AVAHO 2023 workshop is to “help people develop awareness of the scope of the problem and give them tools they can use to simplify how they speak to patients, teach patients and inform patients,” Thomas said.

In the first segment of the program, Angela Kumar, MPH, national program manager for Veterans Health Education and Information, discussed the VA organizational approach to health literacy. She noted that building a health-literate care organization aligns with the VA goal to be a high reliability organization. Veterans who have questions and concerns will need additional information throughout their cancer journey. The role for VA clinicians is to help answer veterans’ questions. “Rather than assume patients know what we are talking about, we have to make sure they understand,” Kumar explained. Institutional support will lead to better health outcomes and patient satisfaction throughout the system. VA is in the process of creating a patient centered learning program, Kumar noted. The program will be open to veterans, their families, caregivers, and provide training for VA health care professionals.

In the workshop’s 2 other sessions Janet Papadakos, PhD, MEd, a scientist at the University of Toronto’s Institute for Education Research, discussed the impact of health literacy on cancer treatment and outcomes and Fatemeh Youssefi, PhD, RN, OCN, director at large and committee member of the Oncology Nursing Society, discussed the roles of health literacy and patient education in empowering patients. Both speakers noted that patients with cancer are undergoing intense emotional stress, which can significantly impact their ability to understanding their treatment. Importantly, Papadakos explained, people can change and improve their health literacy, so clinicians have an opportunity to help influence and improve comprehension for their patient, by taking basic steps shown to improve health literacy.

“We know that in general, people with low health literacy report worse health, and they also have historically have poor outcomes,” Thomas said. Indeed, a 2021 systematic review of 66 papers found that “lower health literacy was associated with greater difficulties understanding and processing cancer related information, poorer quality of life and poorer experience of care.” Just 12% of US adults have proficient health literacy and one-third of adults have difficulty with common health tasks.

Papadakos and Youssefi provided some guidance for better communication with patients. Teach back, for example, is a tool to ensure patients understand topics when discussed. The key, Papadakos explained, is that it is not a test of the patient but rather a test of how well the information was communicated. Youssefi and Papadakos also emphasized the importance of using plain language. Clear and precise words that avoid technical terms avoid miscommunication and confusion. Finally, they urged clinicians to never assume health literacy and to approach all patients using clear language to ensure that they understand and can provide back the content covered.

Thomas said 3 more virtual sessions about health literacy will be offered over the coming year. Organizers will develop the specific topics after engaging in a discussion with attendees at the end of the AVAHO session. Meanwhile, advocates are developing a section of the AVAHO website that will be devoted to health literacy.

The workshop received support from Genentech.

Approximately 4 in 10 cases of type 1 diabetes in adults are diagnosed at age 30 years and older, based on data from nearly 1,000 individuals.

New-onset type 1 diabetes in adults is often misdiagnosed as type 2 diabetes, which may lead to inappropriate care, wrote Michael Fang, PhD, of Johns Hopkins University, Baltimore, and colleagues.

Previous research suggests that more than half of type 1 diabetes cases develop in adults, but data on variations in clinical characteristics and age at diagnosis are limited, the researchers said. “Clarifying the burden of adult-onset type 1 diabetes in the general population may help reduce misdiagnosis.”

In a study published in Annals of Internal Medicine, the researchers identified 947 adults aged 18 years and older with newly diagnosed type 1 diabetes, by using data from the National Health Interview Survey between 2016 and 2022. The subjects’ mean age at the time of the survey was 49 years and 48% were women. The racial/ethnic distribution was 73% non-Hispanic White, 10% non-Hispanic Black, 12% Hispanic, 3%, non-Hispanic Asian, and 3% other race/ethnicity.

Overall, 37% of participants were diagnosed with type 1 diabetes after age 30 years, with an overall median age at diagnosis of 24 years.

Type 1 diabetes was diagnosed later in men than in women, at a median age of 27 years vs. 22 years, respectively, and later in racial/ethnic minorities than in non-Hispanic Whites, with a median age of 26-30 years versus 21 years, respectively.

Autoantibody and C-peptide tests are recommended to confirm type 1 diabetes in adults with a suspected diagnosis, but the best method to identify high-risk adults remains unclear, the researchers wrote in their discussion.

“Traditional markers used to differentiate type 1 and type 2 diabetes, such as body mass index, may have limited utility, especially because obesity is now common in the type 1 diabetes population,” they said. New tools combining clinical features and biomarkers may improve accuracy of diagnosis of type 1 diabetes in the adult population, but more research is needed.

The findings were limited by several factors including misclassification based on self-reports of diagnosis and age, the researchers noted. Other limitations included lack of data on diagnostic measures such as levels of autoantibodies, C-peptides, and other indicators of diabetes, as well as inexact subgroup estimates because of small sample sizes.

“We extended existing research by characterizing the age at diagnosis in a nationally representative sample and by documenting variation across race/ethnicity and clinical characteristics,” they said.

The study was supported by grants from the National Heart, Lung, and Blood Institute. The lead authors had no financial conflicts to disclose. Corresponding author Elizabeth Selvin, PhD, disclosed grants from NIH and FNIH, personal fees from Novo Nordisk, other financial relationships with Wolters Kluwer, and nonfinancial support from many pharmaceutical companies outside the current study; she also serves as deputy editor of Diabetes Care and a member of the editorial board of Diabetologia.

Approximately 4 in 10 cases of type 1 diabetes in adults are diagnosed at age 30 years and older, based on data from nearly 1,000 individuals.

New-onset type 1 diabetes in adults is often misdiagnosed as type 2 diabetes, which may lead to inappropriate care, wrote Michael Fang, PhD, of Johns Hopkins University, Baltimore, and colleagues.

Previous research suggests that more than half of type 1 diabetes cases develop in adults, but data on variations in clinical characteristics and age at diagnosis are limited, the researchers said. “Clarifying the burden of adult-onset type 1 diabetes in the general population may help reduce misdiagnosis.”

In a study published in Annals of Internal Medicine, the researchers identified 947 adults aged 18 years and older with newly diagnosed type 1 diabetes, by using data from the National Health Interview Survey between 2016 and 2022. The subjects’ mean age at the time of the survey was 49 years and 48% were women. The racial/ethnic distribution was 73% non-Hispanic White, 10% non-Hispanic Black, 12% Hispanic, 3%, non-Hispanic Asian, and 3% other race/ethnicity.

Overall, 37% of participants were diagnosed with type 1 diabetes after age 30 years, with an overall median age at diagnosis of 24 years.

Type 1 diabetes was diagnosed later in men than in women, at a median age of 27 years vs. 22 years, respectively, and later in racial/ethnic minorities than in non-Hispanic Whites, with a median age of 26-30 years versus 21 years, respectively.

Autoantibody and C-peptide tests are recommended to confirm type 1 diabetes in adults with a suspected diagnosis, but the best method to identify high-risk adults remains unclear, the researchers wrote in their discussion.

“Traditional markers used to differentiate type 1 and type 2 diabetes, such as body mass index, may have limited utility, especially because obesity is now common in the type 1 diabetes population,” they said. New tools combining clinical features and biomarkers may improve accuracy of diagnosis of type 1 diabetes in the adult population, but more research is needed.

The findings were limited by several factors including misclassification based on self-reports of diagnosis and age, the researchers noted. Other limitations included lack of data on diagnostic measures such as levels of autoantibodies, C-peptides, and other indicators of diabetes, as well as inexact subgroup estimates because of small sample sizes.

“We extended existing research by characterizing the age at diagnosis in a nationally representative sample and by documenting variation across race/ethnicity and clinical characteristics,” they said.

The study was supported by grants from the National Heart, Lung, and Blood Institute. The lead authors had no financial conflicts to disclose. Corresponding author Elizabeth Selvin, PhD, disclosed grants from NIH and FNIH, personal fees from Novo Nordisk, other financial relationships with Wolters Kluwer, and nonfinancial support from many pharmaceutical companies outside the current study; she also serves as deputy editor of Diabetes Care and a member of the editorial board of Diabetologia.

Approximately 4 in 10 cases of type 1 diabetes in adults are diagnosed at age 30 years and older, based on data from nearly 1,000 individuals.

New-onset type 1 diabetes in adults is often misdiagnosed as type 2 diabetes, which may lead to inappropriate care, wrote Michael Fang, PhD, of Johns Hopkins University, Baltimore, and colleagues.

Previous research suggests that more than half of type 1 diabetes cases develop in adults, but data on variations in clinical characteristics and age at diagnosis are limited, the researchers said. “Clarifying the burden of adult-onset type 1 diabetes in the general population may help reduce misdiagnosis.”

In a study published in Annals of Internal Medicine, the researchers identified 947 adults aged 18 years and older with newly diagnosed type 1 diabetes, by using data from the National Health Interview Survey between 2016 and 2022. The subjects’ mean age at the time of the survey was 49 years and 48% were women. The racial/ethnic distribution was 73% non-Hispanic White, 10% non-Hispanic Black, 12% Hispanic, 3%, non-Hispanic Asian, and 3% other race/ethnicity.

Overall, 37% of participants were diagnosed with type 1 diabetes after age 30 years, with an overall median age at diagnosis of 24 years.

Type 1 diabetes was diagnosed later in men than in women, at a median age of 27 years vs. 22 years, respectively, and later in racial/ethnic minorities than in non-Hispanic Whites, with a median age of 26-30 years versus 21 years, respectively.

Autoantibody and C-peptide tests are recommended to confirm type 1 diabetes in adults with a suspected diagnosis, but the best method to identify high-risk adults remains unclear, the researchers wrote in their discussion.

“Traditional markers used to differentiate type 1 and type 2 diabetes, such as body mass index, may have limited utility, especially because obesity is now common in the type 1 diabetes population,” they said. New tools combining clinical features and biomarkers may improve accuracy of diagnosis of type 1 diabetes in the adult population, but more research is needed.

The findings were limited by several factors including misclassification based on self-reports of diagnosis and age, the researchers noted. Other limitations included lack of data on diagnostic measures such as levels of autoantibodies, C-peptides, and other indicators of diabetes, as well as inexact subgroup estimates because of small sample sizes.

“We extended existing research by characterizing the age at diagnosis in a nationally representative sample and by documenting variation across race/ethnicity and clinical characteristics,” they said.

The study was supported by grants from the National Heart, Lung, and Blood Institute. The lead authors had no financial conflicts to disclose. Corresponding author Elizabeth Selvin, PhD, disclosed grants from NIH and FNIH, personal fees from Novo Nordisk, other financial relationships with Wolters Kluwer, and nonfinancial support from many pharmaceutical companies outside the current study; she also serves as deputy editor of Diabetes Care and a member of the editorial board of Diabetologia.

For patients with acute myeloid leukemia (AML), especially those who are older or have relapsed/refractory disease, standard chemotherapy treatments often fail to change their poor clinical trajectories. These days, however, a new era of targeted therapy is improving prognoses somewhat – and raising hopes that even bigger advancements are on the horizon.

“We went almost 3 decades with nothing, then all of a sudden we’ve had nine approvals in 5 or 6 years,” said Harvard Medical School, Boston, leukemia specialist Amir Fathi, MD, in an interview. “We’ve had a lot of advancement and a number of good options emerge.”

However, Dr. Fathi and other hematologists cautioned that the treatment landscape is becoming more complex to navigate. And they noted that prognoses for many older patients with AML remain grim. The expensive new treatments may only extend their lifespans by a matter of months, although some are surviving for years.

As the specialists explained, there are a variety of reasons why AML is especially difficult to treat.

“AML is one of the fastest growing human cancers, with tumor cell doubling times measured in mere hours in some patients. Therefore patients can present critically ill with white blood cell counts in the [hundreds of thousands of white blood cells per microliter instead of the normal range of 4,000-11,000]," said leukemia specialist Eunice S. Wang, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, N.Y. “Because blood cells are found in every organ of the body, the sheer volume of rapidly growing cancer cells can overwhelm multiple organ systems in a very short amount of time. These rapid growing cells and the fact that the median age of diagnosis with AML is 67-70 years old makes this a clinically challenging cancer to treat. Chemotherapy strong enough to kill cancer cells run the risk of also harming the patient as well.”

Also, older patients often have comorbidities, and they face risks of infection from both the disease and its treatments, said AML specialist Nicole R. Grieselhuber, MD, PhD, of the Ohio State University, Columbus, in an interview.

Enter targeted therapy, which “has allowed individuals who previously were not candidates for cytotoxic chemotherapy because of their age or possible toxicities to receive effective therapy for AML,” Dr. Wang said. “Therapy directed at specific biological features of AML cells such as mutations (FLT3, IDH1, IDH2) or surface proteins (CD33) can augment the efficacy of conventional chemotherapy or in some cases (i.e., FLT3 inhibitors) be more effective than chemotherapy in controlling AML.”

Targeted therapy drugs “are expected to more selectively kill cancer cells and spare normal counterparts,” she added.

The FDA has approved nine targeted therapy drugs for AML in the last few years.

Retinoic acid and arsenic trioxide therapy for acute promyelocytic leukemia “has transformed this AML subtype into one of the most curable AML diseases,” Dr. Wang said. A 2017 long-term analysis of the drug combination found that complete remission was reached in 96% of 54 high-risk patients and 133 low-risk patients; the 5-year survival rate was 88%. (Some patients also received gemtuzumab ozogamicin, a CD33 antibody-drug conjugate.)

According to Dr. Wang, three FLT3 inhibitors have been approved for AML with the FLT3 mutation: midostaurin and quizartinib in the frontline setting in conjunction with intensive chemotherapy and gilteritinib for relapsed/refractory FLT3-mutant AML.

A 2017 study linked midostaurin plus chemotherapy to longer survival (hazard ratio for death = 0.78; P = .009), versus placebo plus chemotherapy, in patients aged 18-59. This year, a phase 3 randomized trial of quizartinib versus placebo linked the drug to longer survival median overall (31.9 months versus 15.1 months; P = .032) In a 2019 trial, patients who took gilteritinib had longer median overall survival (9.3 months versus 5.6 months; HR for death = 0.64; P < .001).

The success of these treatments “has led FLT3 mutant AML to be reclassified from a poor risk AML subtype to intermediate risk AML,” Dr. Wang said.

A 2022 report about FLT3 inhibitors cautioned, however, that “several drug resistance mechanisms have been identified” and added that “the benefit of FLT3 inhibitor maintenance therapy, either post chemotherapy or post transplant, remains controversial, although several studies are ongoing.”

Gemtuzumab ozogamicin is a monoclonal antibody connected to a chemotherapy drug, according to the American Cancer Society. “The addition of gemtuzumab ozogamicin to intensive chemotherapy has enhanced outcomes of favorable and intermediate risk disease,” Dr. Wang said.

Ivosidenib, olutasidenib, and enasidenib target the IDH1 or IDH2 genes in ADL. “These drugs seem to work by helping the leukemia cells mature (differentiate) into more normal cells,” according to the American Cancer Society. “Because of this, they are sometimes referred to as differentiation agents.”

In older adults, a combination treatment with venetoclax, a BCL-2 inhibitor, and a hypomethylating agent has become standard, Ohio State’s Dr. Grieselhuber said. The treatment is FDA approved.

There are caveats to targeted therapy in AML. The treatments can be enormously expensive, “and even patients with insurance are often shocked by the copay,” Dr. Grieselhuber said. It helps to work with pharmacists, social workers, or nurse navigators to help patients afford the treatments, she said.

Side effects vary by therapy and can include QT elongation and differentiation syndrome.

Most challenging of all, many AML patients still face shortened lifespans even if new treatments are available for them.

“Typically for older patients with AML, the lifespan of patients with therapy was 5-7 months and without therapy was 2-3 months,” Dr. Wang said. “Now, with regimens specifically designed for elderly and/or unfit subjects, many individuals are now routinely living more than a year: 14-18 months to 3-4 years.”

But “the vast majority of AML patients will still die of their disease with overall 5-year outcomes still less than 30% in all age categories,” she said. In addition, “fewer than 50% of AML patients are eligible for treatment with FDA-approved targeted therapies, as their disease biology does not express the mutation or protein needed for efficacy.”

Still, she said, “this represents a vast improvement.” And, she added, “in younger individuals, the combination of chemotherapy followed by allogeneic transplant has now permitted more of these individuals to be cured of their disease.” Dr. Grieselhuber noted that transplants are now considered appropriate even for patients in their 60s or early 70s, and they can be combined with targeted therapy.

Dr. Grieselhuber urged colleagues to keep in mind that quality-of-life preferences will play a role in some patient choices. For example, a elderly patient may reject burdensome infusion therapy and choose a pill instead, even if it has less efficacy. “There’s really no one-size-fits-all,” she said.

And, she added, it can be difficult to make choices about treatment because of the lack of randomized, head-to-head data regarding new therapies.

What’s on the horizon? Dr. Wang highlighted a novel class of targeted therapies called menin inhibitors for patients with NPM1-mutated AML, which she said accounts for one-third of patients with the disease. A treatment targeting disease in the 5%-10% patients with the KMT2A gene is also in the works, she said.

For now, Dr. Wang said it’s essential for clinicians “to perform timely comprehensive molecular and genomic tests on all AML patients at diagnosis and relapse to determine which individuals would benefit from targeted therapy versus cytotoxic chemotherapy. And participation in clinical trials at every stage of AML therapy can help accelerate clinical development of new agents for this disease.”

Dr. Fathi discloses relationships with Daiichi Sankyo, Pfizer, Rigel, Autolus, Amgen, Servier, Takeda, Orum, Menarini, Remix, AbbVie, Astellas, BMS, Ibsen, Gilead, Genentech, and AstraZeneca. Dr. Wang discloses ties with AbbVie, Astellas, BMS, CTI Biopharma, Daiichi Sankyo, Gilead, GSK, Johnson & Johnson, Kite, Kura, Novartis, Pfizer, Rigel, Sellas, and Sumitomo Pharma. Dr. Grieselhuber has no disclosures.

For patients with acute myeloid leukemia (AML), especially those who are older or have relapsed/refractory disease, standard chemotherapy treatments often fail to change their poor clinical trajectories. These days, however, a new era of targeted therapy is improving prognoses somewhat – and raising hopes that even bigger advancements are on the horizon.

“We went almost 3 decades with nothing, then all of a sudden we’ve had nine approvals in 5 or 6 years,” said Harvard Medical School, Boston, leukemia specialist Amir Fathi, MD, in an interview. “We’ve had a lot of advancement and a number of good options emerge.”

However, Dr. Fathi and other hematologists cautioned that the treatment landscape is becoming more complex to navigate. And they noted that prognoses for many older patients with AML remain grim. The expensive new treatments may only extend their lifespans by a matter of months, although some are surviving for years.

As the specialists explained, there are a variety of reasons why AML is especially difficult to treat.

“AML is one of the fastest growing human cancers, with tumor cell doubling times measured in mere hours in some patients. Therefore patients can present critically ill with white blood cell counts in the [hundreds of thousands of white blood cells per microliter instead of the normal range of 4,000-11,000]," said leukemia specialist Eunice S. Wang, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, N.Y. “Because blood cells are found in every organ of the body, the sheer volume of rapidly growing cancer cells can overwhelm multiple organ systems in a very short amount of time. These rapid growing cells and the fact that the median age of diagnosis with AML is 67-70 years old makes this a clinically challenging cancer to treat. Chemotherapy strong enough to kill cancer cells run the risk of also harming the patient as well.”

Also, older patients often have comorbidities, and they face risks of infection from both the disease and its treatments, said AML specialist Nicole R. Grieselhuber, MD, PhD, of the Ohio State University, Columbus, in an interview.

Enter targeted therapy, which “has allowed individuals who previously were not candidates for cytotoxic chemotherapy because of their age or possible toxicities to receive effective therapy for AML,” Dr. Wang said. “Therapy directed at specific biological features of AML cells such as mutations (FLT3, IDH1, IDH2) or surface proteins (CD33) can augment the efficacy of conventional chemotherapy or in some cases (i.e., FLT3 inhibitors) be more effective than chemotherapy in controlling AML.”

Targeted therapy drugs “are expected to more selectively kill cancer cells and spare normal counterparts,” she added.

The FDA has approved nine targeted therapy drugs for AML in the last few years.

Retinoic acid and arsenic trioxide therapy for acute promyelocytic leukemia “has transformed this AML subtype into one of the most curable AML diseases,” Dr. Wang said. A 2017 long-term analysis of the drug combination found that complete remission was reached in 96% of 54 high-risk patients and 133 low-risk patients; the 5-year survival rate was 88%. (Some patients also received gemtuzumab ozogamicin, a CD33 antibody-drug conjugate.)

According to Dr. Wang, three FLT3 inhibitors have been approved for AML with the FLT3 mutation: midostaurin and quizartinib in the frontline setting in conjunction with intensive chemotherapy and gilteritinib for relapsed/refractory FLT3-mutant AML.

A 2017 study linked midostaurin plus chemotherapy to longer survival (hazard ratio for death = 0.78; P = .009), versus placebo plus chemotherapy, in patients aged 18-59. This year, a phase 3 randomized trial of quizartinib versus placebo linked the drug to longer survival median overall (31.9 months versus 15.1 months; P = .032) In a 2019 trial, patients who took gilteritinib had longer median overall survival (9.3 months versus 5.6 months; HR for death = 0.64; P < .001).

The success of these treatments “has led FLT3 mutant AML to be reclassified from a poor risk AML subtype to intermediate risk AML,” Dr. Wang said.

A 2022 report about FLT3 inhibitors cautioned, however, that “several drug resistance mechanisms have been identified” and added that “the benefit of FLT3 inhibitor maintenance therapy, either post chemotherapy or post transplant, remains controversial, although several studies are ongoing.”

Gemtuzumab ozogamicin is a monoclonal antibody connected to a chemotherapy drug, according to the American Cancer Society. “The addition of gemtuzumab ozogamicin to intensive chemotherapy has enhanced outcomes of favorable and intermediate risk disease,” Dr. Wang said.

Ivosidenib, olutasidenib, and enasidenib target the IDH1 or IDH2 genes in ADL. “These drugs seem to work by helping the leukemia cells mature (differentiate) into more normal cells,” according to the American Cancer Society. “Because of this, they are sometimes referred to as differentiation agents.”

In older adults, a combination treatment with venetoclax, a BCL-2 inhibitor, and a hypomethylating agent has become standard, Ohio State’s Dr. Grieselhuber said. The treatment is FDA approved.

There are caveats to targeted therapy in AML. The treatments can be enormously expensive, “and even patients with insurance are often shocked by the copay,” Dr. Grieselhuber said. It helps to work with pharmacists, social workers, or nurse navigators to help patients afford the treatments, she said.

Side effects vary by therapy and can include QT elongation and differentiation syndrome.

Most challenging of all, many AML patients still face shortened lifespans even if new treatments are available for them.

“Typically for older patients with AML, the lifespan of patients with therapy was 5-7 months and without therapy was 2-3 months,” Dr. Wang said. “Now, with regimens specifically designed for elderly and/or unfit subjects, many individuals are now routinely living more than a year: 14-18 months to 3-4 years.”

But “the vast majority of AML patients will still die of their disease with overall 5-year outcomes still less than 30% in all age categories,” she said. In addition, “fewer than 50% of AML patients are eligible for treatment with FDA-approved targeted therapies, as their disease biology does not express the mutation or protein needed for efficacy.”

Still, she said, “this represents a vast improvement.” And, she added, “in younger individuals, the combination of chemotherapy followed by allogeneic transplant has now permitted more of these individuals to be cured of their disease.” Dr. Grieselhuber noted that transplants are now considered appropriate even for patients in their 60s or early 70s, and they can be combined with targeted therapy.

Dr. Grieselhuber urged colleagues to keep in mind that quality-of-life preferences will play a role in some patient choices. For example, a elderly patient may reject burdensome infusion therapy and choose a pill instead, even if it has less efficacy. “There’s really no one-size-fits-all,” she said.

And, she added, it can be difficult to make choices about treatment because of the lack of randomized, head-to-head data regarding new therapies.

What’s on the horizon? Dr. Wang highlighted a novel class of targeted therapies called menin inhibitors for patients with NPM1-mutated AML, which she said accounts for one-third of patients with the disease. A treatment targeting disease in the 5%-10% patients with the KMT2A gene is also in the works, she said.

For now, Dr. Wang said it’s essential for clinicians “to perform timely comprehensive molecular and genomic tests on all AML patients at diagnosis and relapse to determine which individuals would benefit from targeted therapy versus cytotoxic chemotherapy. And participation in clinical trials at every stage of AML therapy can help accelerate clinical development of new agents for this disease.”

Dr. Fathi discloses relationships with Daiichi Sankyo, Pfizer, Rigel, Autolus, Amgen, Servier, Takeda, Orum, Menarini, Remix, AbbVie, Astellas, BMS, Ibsen, Gilead, Genentech, and AstraZeneca. Dr. Wang discloses ties with AbbVie, Astellas, BMS, CTI Biopharma, Daiichi Sankyo, Gilead, GSK, Johnson & Johnson, Kite, Kura, Novartis, Pfizer, Rigel, Sellas, and Sumitomo Pharma. Dr. Grieselhuber has no disclosures.

For patients with acute myeloid leukemia (AML), especially those who are older or have relapsed/refractory disease, standard chemotherapy treatments often fail to change their poor clinical trajectories. These days, however, a new era of targeted therapy is improving prognoses somewhat – and raising hopes that even bigger advancements are on the horizon.

“We went almost 3 decades with nothing, then all of a sudden we’ve had nine approvals in 5 or 6 years,” said Harvard Medical School, Boston, leukemia specialist Amir Fathi, MD, in an interview. “We’ve had a lot of advancement and a number of good options emerge.”

However, Dr. Fathi and other hematologists cautioned that the treatment landscape is becoming more complex to navigate. And they noted that prognoses for many older patients with AML remain grim. The expensive new treatments may only extend their lifespans by a matter of months, although some are surviving for years.

As the specialists explained, there are a variety of reasons why AML is especially difficult to treat.

“AML is one of the fastest growing human cancers, with tumor cell doubling times measured in mere hours in some patients. Therefore patients can present critically ill with white blood cell counts in the [hundreds of thousands of white blood cells per microliter instead of the normal range of 4,000-11,000]," said leukemia specialist Eunice S. Wang, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, N.Y. “Because blood cells are found in every organ of the body, the sheer volume of rapidly growing cancer cells can overwhelm multiple organ systems in a very short amount of time. These rapid growing cells and the fact that the median age of diagnosis with AML is 67-70 years old makes this a clinically challenging cancer to treat. Chemotherapy strong enough to kill cancer cells run the risk of also harming the patient as well.”

Also, older patients often have comorbidities, and they face risks of infection from both the disease and its treatments, said AML specialist Nicole R. Grieselhuber, MD, PhD, of the Ohio State University, Columbus, in an interview.

Enter targeted therapy, which “has allowed individuals who previously were not candidates for cytotoxic chemotherapy because of their age or possible toxicities to receive effective therapy for AML,” Dr. Wang said. “Therapy directed at specific biological features of AML cells such as mutations (FLT3, IDH1, IDH2) or surface proteins (CD33) can augment the efficacy of conventional chemotherapy or in some cases (i.e., FLT3 inhibitors) be more effective than chemotherapy in controlling AML.”

Targeted therapy drugs “are expected to more selectively kill cancer cells and spare normal counterparts,” she added.

The FDA has approved nine targeted therapy drugs for AML in the last few years.

Retinoic acid and arsenic trioxide therapy for acute promyelocytic leukemia “has transformed this AML subtype into one of the most curable AML diseases,” Dr. Wang said. A 2017 long-term analysis of the drug combination found that complete remission was reached in 96% of 54 high-risk patients and 133 low-risk patients; the 5-year survival rate was 88%. (Some patients also received gemtuzumab ozogamicin, a CD33 antibody-drug conjugate.)

According to Dr. Wang, three FLT3 inhibitors have been approved for AML with the FLT3 mutation: midostaurin and quizartinib in the frontline setting in conjunction with intensive chemotherapy and gilteritinib for relapsed/refractory FLT3-mutant AML.

A 2017 study linked midostaurin plus chemotherapy to longer survival (hazard ratio for death = 0.78; P = .009), versus placebo plus chemotherapy, in patients aged 18-59. This year, a phase 3 randomized trial of quizartinib versus placebo linked the drug to longer survival median overall (31.9 months versus 15.1 months; P = .032) In a 2019 trial, patients who took gilteritinib had longer median overall survival (9.3 months versus 5.6 months; HR for death = 0.64; P < .001).

The success of these treatments “has led FLT3 mutant AML to be reclassified from a poor risk AML subtype to intermediate risk AML,” Dr. Wang said.

A 2022 report about FLT3 inhibitors cautioned, however, that “several drug resistance mechanisms have been identified” and added that “the benefit of FLT3 inhibitor maintenance therapy, either post chemotherapy or post transplant, remains controversial, although several studies are ongoing.”

Gemtuzumab ozogamicin is a monoclonal antibody connected to a chemotherapy drug, according to the American Cancer Society. “The addition of gemtuzumab ozogamicin to intensive chemotherapy has enhanced outcomes of favorable and intermediate risk disease,” Dr. Wang said.

Ivosidenib, olutasidenib, and enasidenib target the IDH1 or IDH2 genes in ADL. “These drugs seem to work by helping the leukemia cells mature (differentiate) into more normal cells,” according to the American Cancer Society. “Because of this, they are sometimes referred to as differentiation agents.”

In older adults, a combination treatment with venetoclax, a BCL-2 inhibitor, and a hypomethylating agent has become standard, Ohio State’s Dr. Grieselhuber said. The treatment is FDA approved.

There are caveats to targeted therapy in AML. The treatments can be enormously expensive, “and even patients with insurance are often shocked by the copay,” Dr. Grieselhuber said. It helps to work with pharmacists, social workers, or nurse navigators to help patients afford the treatments, she said.

Side effects vary by therapy and can include QT elongation and differentiation syndrome.

Most challenging of all, many AML patients still face shortened lifespans even if new treatments are available for them.

“Typically for older patients with AML, the lifespan of patients with therapy was 5-7 months and without therapy was 2-3 months,” Dr. Wang said. “Now, with regimens specifically designed for elderly and/or unfit subjects, many individuals are now routinely living more than a year: 14-18 months to 3-4 years.”

But “the vast majority of AML patients will still die of their disease with overall 5-year outcomes still less than 30% in all age categories,” she said. In addition, “fewer than 50% of AML patients are eligible for treatment with FDA-approved targeted therapies, as their disease biology does not express the mutation or protein needed for efficacy.”

Still, she said, “this represents a vast improvement.” And, she added, “in younger individuals, the combination of chemotherapy followed by allogeneic transplant has now permitted more of these individuals to be cured of their disease.” Dr. Grieselhuber noted that transplants are now considered appropriate even for patients in their 60s or early 70s, and they can be combined with targeted therapy.

Dr. Grieselhuber urged colleagues to keep in mind that quality-of-life preferences will play a role in some patient choices. For example, a elderly patient may reject burdensome infusion therapy and choose a pill instead, even if it has less efficacy. “There’s really no one-size-fits-all,” she said.

And, she added, it can be difficult to make choices about treatment because of the lack of randomized, head-to-head data regarding new therapies.

What’s on the horizon? Dr. Wang highlighted a novel class of targeted therapies called menin inhibitors for patients with NPM1-mutated AML, which she said accounts for one-third of patients with the disease. A treatment targeting disease in the 5%-10% patients with the KMT2A gene is also in the works, she said.

For now, Dr. Wang said it’s essential for clinicians “to perform timely comprehensive molecular and genomic tests on all AML patients at diagnosis and relapse to determine which individuals would benefit from targeted therapy versus cytotoxic chemotherapy. And participation in clinical trials at every stage of AML therapy can help accelerate clinical development of new agents for this disease.”

Dr. Fathi discloses relationships with Daiichi Sankyo, Pfizer, Rigel, Autolus, Amgen, Servier, Takeda, Orum, Menarini, Remix, AbbVie, Astellas, BMS, Ibsen, Gilead, Genentech, and AstraZeneca. Dr. Wang discloses ties with AbbVie, Astellas, BMS, CTI Biopharma, Daiichi Sankyo, Gilead, GSK, Johnson & Johnson, Kite, Kura, Novartis, Pfizer, Rigel, Sellas, and Sumitomo Pharma. Dr. Grieselhuber has no disclosures.

The complex pathophysiology of obesity requires a multidisciplinary approach that includes lifestyle and medical interventions for successful management. Antiobesity medications (AOMs) have emerged as a powerful and life-changing tool for many individuals with obesity who are unable to sustain long-term weight loss through lifestyle changes alone. As with other chronic diseases such as hypertension and hyperlipidemia, the goal of decades of research has been to develop antiobesity medications with long-term efficacy and safety. Recent groundbreaking findings from a phase 2 trial show immense potential for a new AOM.

Here are five things to know about the role of agonists in the management of obesity.

1. Gut hormone physiology informs the development of AOMs.

The three hormones associated with obesity or diabetes are glucagonlike peptide 1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and glucagon. GLP-1, a peptide released from the intestines in response to food ingestion, increases insulin production, reduces gut motility, and suppresses appetite. GIP is also an intestinal hormone that increases meal-stimulated insulin production and additionally facilitates lipolysis. Glucagon is known to increase hepatic glucose output but will also increase insulin secretion in the setting of hyperglycemia. Glucagon also promotes lipolysis.

Though these hormones are more commonly thought of as incretins, gut hormones that stimulate postprandial insulin secretion, their role in energy physiology is more diverse. Because of multiple mechanisms of action, incretins are increasingly referred to as nutrient-stimulated hormones (NuSH), a term which encompasses other peptides with therapeutic potential (e.g., amylin, oxyntomodulin, peptide tyrosine–tyrosine).

2. Studies have shown that NuSH therapies are highly effective AOMs.

In 2021 the Food and Drug Administration approved subcutaneous semaglutide 2.4 mg, a GLP-1 receptor agonist, for the treatment of obesity. Clinical trials demonstrating an average weight loss of 15% in patients taking semaglutide ushered in a new era of AOMs associated with significant weight loss that not only improve disease activity but also have the potential to achieve diabetes remission. Recent findings from the OASIS I trial demonstrated an average weight loss of 15.1% from baseline in patients treated with oral semaglutide for 68 weeks. Medical societies, including the American Diabetes Association and the American Association for the Study of Liver Diseases, recommend 10%-15% weight loss to fully treat weight-related comorbidities like type 2 diabetes and nonalcoholic fatty liver disease. In 2022, tirzepatide, a dual GLP-1 and GIP receptor agonist, demonstrated an average weight loss of 22.5% in phase 3 of the SURMOUNT-1 trial for obesity – a weight loss approaching that of some bariatric surgeries.

3. Clinical trial data show that the novel triple agonist retatrutide induces significant weight loss.

Preclinical studies on the newest NuSH therapy, triple GLP-1–GIP–glucagon receptor agonist retatrutide, showed predominant activity at the GIP receptor, with less GLP-1– and glucagon-receptor agonism than that of endogenous GLP-1 and GIP. Results from a phase 2 trial published in June 2023 showed a weight loss of 24% at 48 weeks in adults with obesity treated with retatrutide, which is the greatest weight loss reported in an obesity trial so far. Moreover, for the first time in obesity pharmacotherapy research, 100% of participants achieved clinically significant weight loss (defined as ≥ 5% of baseline weight).

4. Retatrutide may improve lipid metabolism.

In the phase 2 trial, retatrutide reduced low-density lipoprotein cholesterol levels by approximately 20%. This degree of reduced plasma LDL-C is dramatic in weight loss studies. Typically, weight loss significantly reduces triglyceride levels, increases high-density lipoprotein cholesterol levels, and has a modest effect on LDL-C reduction of about 5%.

A 20% reduction in LDL-C with retatrutide is hypothesis generating. Preclinical studies have shown glucagon to be an important regulator of proprotein convertase subtilisin/kexin type 9 degradation, with the lack of glucagon resulting in increased PCSK9 levels, decreased LDL receptors, and increased plasma LDL; conversely, treatment with glucagon decreased plasma LDL.

5. The long-term safety of retatrutide still needs to be determined.

In the 48-week phase 2 trial, retatrutide was observed to have a side-effect profile largely similar to other NuSH therapies (e.g., semaglutide 2.4 mg, tirzepatide), with a predominance of gastrointestinal symptoms including nausea, diarrhea, vomiting, and constipation. However, side effects potentially unique to retatrutide also emerged. Cutaneous hyperesthesia and skin sensitivity were reported in 7% of participants in the retatrutide group vs. 1% in the placebo group; none of these effects were associated with physical skin findings. Of note, 17 out of 198 (9%) participants in the retatrutide group developed cardiac arrhythmia vs. two out of 70 (3%) in the placebo group. There was no consistent pattern of arrhythmia type (e.g., supraventricular, ventricular) observed, and some of these events were reported as “palpitations” or “increased heart rate” without further detail. Phase 3 clinical trial data will provide further insight into the long-term safety of retatrutide.

Dr. Tchang is assistant professor of clinical medicine, division of endocrinology, Weill Cornell Medicine and physician, department of medicine, New York-Presbyterian/Weill Cornell Medical Center, both in New York. She has disclosed ties with Gelesis and Novo Nordisk.

A version of this article appeared on Medscape.com.

The complex pathophysiology of obesity requires a multidisciplinary approach that includes lifestyle and medical interventions for successful management. Antiobesity medications (AOMs) have emerged as a powerful and life-changing tool for many individuals with obesity who are unable to sustain long-term weight loss through lifestyle changes alone. As with other chronic diseases such as hypertension and hyperlipidemia, the goal of decades of research has been to develop antiobesity medications with long-term efficacy and safety. Recent groundbreaking findings from a phase 2 trial show immense potential for a new AOM.

Here are five things to know about the role of agonists in the management of obesity.

1. Gut hormone physiology informs the development of AOMs.

The three hormones associated with obesity or diabetes are glucagonlike peptide 1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and glucagon. GLP-1, a peptide released from the intestines in response to food ingestion, increases insulin production, reduces gut motility, and suppresses appetite. GIP is also an intestinal hormone that increases meal-stimulated insulin production and additionally facilitates lipolysis. Glucagon is known to increase hepatic glucose output but will also increase insulin secretion in the setting of hyperglycemia. Glucagon also promotes lipolysis.

Though these hormones are more commonly thought of as incretins, gut hormones that stimulate postprandial insulin secretion, their role in energy physiology is more diverse. Because of multiple mechanisms of action, incretins are increasingly referred to as nutrient-stimulated hormones (NuSH), a term which encompasses other peptides with therapeutic potential (e.g., amylin, oxyntomodulin, peptide tyrosine–tyrosine).

2. Studies have shown that NuSH therapies are highly effective AOMs.

In 2021 the Food and Drug Administration approved subcutaneous semaglutide 2.4 mg, a GLP-1 receptor agonist, for the treatment of obesity. Clinical trials demonstrating an average weight loss of 15% in patients taking semaglutide ushered in a new era of AOMs associated with significant weight loss that not only improve disease activity but also have the potential to achieve diabetes remission. Recent findings from the OASIS I trial demonstrated an average weight loss of 15.1% from baseline in patients treated with oral semaglutide for 68 weeks. Medical societies, including the American Diabetes Association and the American Association for the Study of Liver Diseases, recommend 10%-15% weight loss to fully treat weight-related comorbidities like type 2 diabetes and nonalcoholic fatty liver disease. In 2022, tirzepatide, a dual GLP-1 and GIP receptor agonist, demonstrated an average weight loss of 22.5% in phase 3 of the SURMOUNT-1 trial for obesity – a weight loss approaching that of some bariatric surgeries.

3. Clinical trial data show that the novel triple agonist retatrutide induces significant weight loss.

Preclinical studies on the newest NuSH therapy, triple GLP-1–GIP–glucagon receptor agonist retatrutide, showed predominant activity at the GIP receptor, with less GLP-1– and glucagon-receptor agonism than that of endogenous GLP-1 and GIP. Results from a phase 2 trial published in June 2023 showed a weight loss of 24% at 48 weeks in adults with obesity treated with retatrutide, which is the greatest weight loss reported in an obesity trial so far. Moreover, for the first time in obesity pharmacotherapy research, 100% of participants achieved clinically significant weight loss (defined as ≥ 5% of baseline weight).

4. Retatrutide may improve lipid metabolism.

In the phase 2 trial, retatrutide reduced low-density lipoprotein cholesterol levels by approximately 20%. This degree of reduced plasma LDL-C is dramatic in weight loss studies. Typically, weight loss significantly reduces triglyceride levels, increases high-density lipoprotein cholesterol levels, and has a modest effect on LDL-C reduction of about 5%.

A 20% reduction in LDL-C with retatrutide is hypothesis generating. Preclinical studies have shown glucagon to be an important regulator of proprotein convertase subtilisin/kexin type 9 degradation, with the lack of glucagon resulting in increased PCSK9 levels, decreased LDL receptors, and increased plasma LDL; conversely, treatment with glucagon decreased plasma LDL.

5. The long-term safety of retatrutide still needs to be determined.

In the 48-week phase 2 trial, retatrutide was observed to have a side-effect profile largely similar to other NuSH therapies (e.g., semaglutide 2.4 mg, tirzepatide), with a predominance of gastrointestinal symptoms including nausea, diarrhea, vomiting, and constipation. However, side effects potentially unique to retatrutide also emerged. Cutaneous hyperesthesia and skin sensitivity were reported in 7% of participants in the retatrutide group vs. 1% in the placebo group; none of these effects were associated with physical skin findings. Of note, 17 out of 198 (9%) participants in the retatrutide group developed cardiac arrhythmia vs. two out of 70 (3%) in the placebo group. There was no consistent pattern of arrhythmia type (e.g., supraventricular, ventricular) observed, and some of these events were reported as “palpitations” or “increased heart rate” without further detail. Phase 3 clinical trial data will provide further insight into the long-term safety of retatrutide.

Dr. Tchang is assistant professor of clinical medicine, division of endocrinology, Weill Cornell Medicine and physician, department of medicine, New York-Presbyterian/Weill Cornell Medical Center, both in New York. She has disclosed ties with Gelesis and Novo Nordisk.

A version of this article appeared on Medscape.com.

The complex pathophysiology of obesity requires a multidisciplinary approach that includes lifestyle and medical interventions for successful management. Antiobesity medications (AOMs) have emerged as a powerful and life-changing tool for many individuals with obesity who are unable to sustain long-term weight loss through lifestyle changes alone. As with other chronic diseases such as hypertension and hyperlipidemia, the goal of decades of research has been to develop antiobesity medications with long-term efficacy and safety. Recent groundbreaking findings from a phase 2 trial show immense potential for a new AOM.

Here are five things to know about the role of agonists in the management of obesity.

1. Gut hormone physiology informs the development of AOMs.

The three hormones associated with obesity or diabetes are glucagonlike peptide 1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and glucagon. GLP-1, a peptide released from the intestines in response to food ingestion, increases insulin production, reduces gut motility, and suppresses appetite. GIP is also an intestinal hormone that increases meal-stimulated insulin production and additionally facilitates lipolysis. Glucagon is known to increase hepatic glucose output but will also increase insulin secretion in the setting of hyperglycemia. Glucagon also promotes lipolysis.

Though these hormones are more commonly thought of as incretins, gut hormones that stimulate postprandial insulin secretion, their role in energy physiology is more diverse. Because of multiple mechanisms of action, incretins are increasingly referred to as nutrient-stimulated hormones (NuSH), a term which encompasses other peptides with therapeutic potential (e.g., amylin, oxyntomodulin, peptide tyrosine–tyrosine).

2. Studies have shown that NuSH therapies are highly effective AOMs.

In 2021 the Food and Drug Administration approved subcutaneous semaglutide 2.4 mg, a GLP-1 receptor agonist, for the treatment of obesity. Clinical trials demonstrating an average weight loss of 15% in patients taking semaglutide ushered in a new era of AOMs associated with significant weight loss that not only improve disease activity but also have the potential to achieve diabetes remission. Recent findings from the OASIS I trial demonstrated an average weight loss of 15.1% from baseline in patients treated with oral semaglutide for 68 weeks. Medical societies, including the American Diabetes Association and the American Association for the Study of Liver Diseases, recommend 10%-15% weight loss to fully treat weight-related comorbidities like type 2 diabetes and nonalcoholic fatty liver disease. In 2022, tirzepatide, a dual GLP-1 and GIP receptor agonist, demonstrated an average weight loss of 22.5% in phase 3 of the SURMOUNT-1 trial for obesity – a weight loss approaching that of some bariatric surgeries.

3. Clinical trial data show that the novel triple agonist retatrutide induces significant weight loss.

Preclinical studies on the newest NuSH therapy, triple GLP-1–GIP–glucagon receptor agonist retatrutide, showed predominant activity at the GIP receptor, with less GLP-1– and glucagon-receptor agonism than that of endogenous GLP-1 and GIP. Results from a phase 2 trial published in June 2023 showed a weight loss of 24% at 48 weeks in adults with obesity treated with retatrutide, which is the greatest weight loss reported in an obesity trial so far. Moreover, for the first time in obesity pharmacotherapy research, 100% of participants achieved clinically significant weight loss (defined as ≥ 5% of baseline weight).

4. Retatrutide may improve lipid metabolism.

In the phase 2 trial, retatrutide reduced low-density lipoprotein cholesterol levels by approximately 20%. This degree of reduced plasma LDL-C is dramatic in weight loss studies. Typically, weight loss significantly reduces triglyceride levels, increases high-density lipoprotein cholesterol levels, and has a modest effect on LDL-C reduction of about 5%.

A 20% reduction in LDL-C with retatrutide is hypothesis generating. Preclinical studies have shown glucagon to be an important regulator of proprotein convertase subtilisin/kexin type 9 degradation, with the lack of glucagon resulting in increased PCSK9 levels, decreased LDL receptors, and increased plasma LDL; conversely, treatment with glucagon decreased plasma LDL.

5. The long-term safety of retatrutide still needs to be determined.

In the 48-week phase 2 trial, retatrutide was observed to have a side-effect profile largely similar to other NuSH therapies (e.g., semaglutide 2.4 mg, tirzepatide), with a predominance of gastrointestinal symptoms including nausea, diarrhea, vomiting, and constipation. However, side effects potentially unique to retatrutide also emerged. Cutaneous hyperesthesia and skin sensitivity were reported in 7% of participants in the retatrutide group vs. 1% in the placebo group; none of these effects were associated with physical skin findings. Of note, 17 out of 198 (9%) participants in the retatrutide group developed cardiac arrhythmia vs. two out of 70 (3%) in the placebo group. There was no consistent pattern of arrhythmia type (e.g., supraventricular, ventricular) observed, and some of these events were reported as “palpitations” or “increased heart rate” without further detail. Phase 3 clinical trial data will provide further insight into the long-term safety of retatrutide.

Dr. Tchang is assistant professor of clinical medicine, division of endocrinology, Weill Cornell Medicine and physician, department of medicine, New York-Presbyterian/Weill Cornell Medical Center, both in New York. She has disclosed ties with Gelesis and Novo Nordisk.

A version of this article appeared on Medscape.com.

In early September, startling cancer research findings hit the news.

A study press release headline touted a “global surge” in new cancer cases among younger people over the past 3 decades.

Many major news outlets parroted the “striking” finding. “Cancer cases in under-50s worldwide up nearly 80% in 3 decades, study finds,” The Guardian reported.

The analysis, published in BMJ Oncology, plumbed data from the Global Burden of Disease 2019 study to determine changes in cancer incidence and deaths among people aged 15-49 years across 204 countries.

The team found that, between 1990 and 2019, global cancer cases in this younger group had increased by almost 80% and cancer deaths had risen by nearly 28%. The authors flagged diet, alcohol, and tobacco as “the main risk factors” underlying the early-onset cancer trend.

But the analysis was deeply flawed, experts said. It failed to account for population growth and age.

The global population has increased by 46% between 1990 and 2019, but the study calculations are “based on absolute numbers rather than age-standardized rates,” said Montserrat García-Closas, MD, MPH, PhD, professor of epidemiology at the Institute of Cancer Research, London, who weighed in on the findings via the U.K.-based Science Media Centre. That means “these numbers do not account for changes in demographics such as increases in population size or aging of the population.”

The study researchers reported 1.82 million early-onset cancer cases in 1990 and 3.26 million global cases in 2019, which led to the reported increase of 79.1%.

Similarly, the authors calculated the change in cancer deaths globally using absolute, not population or age-adjusted, numbers: 0.83 million cancer deaths in 1990 and 1.06 million in 2019 led to the reported increase of 27.7%.

But when population growth is considered, the story changes dramatically. The population-adjusted calculations indicate that the global incidence of early-onset cancers only rose about 6% over the past 30 years while cancer deaths actually fell 25% in that time, according to calculations done by Medscape using the study’s supplemental data.

Experts commenting via the BMJ website also noted the flawed calculations. “Epidemic news, but no epidemic of cancer,” Henrik Møller, MD, lead epidemiologist for the Danish Clinical Registries, and colleagues wrote, highlighting the “misleading” 79% figure. When accounting for population growth in Nordic countries, Dr. Møller and colleagues found a 1% average annual increase in the cancer incidence rate and a 2.5% decrease in the cancer mortality rate.

This news organization reached out to the study’s corresponding authors, Kefeng Ding and Xue Li, to ask why they used absolute numbers instead of population-adjusted numbers for their calculations, but they did not respond in time for publication.

In their analysis, however, the researchers did note that “the study still has several limitations” that could affect the results, such as variations in the quality and availability of data provided by different countries.

The study, for instance, compared the Solomon Islands with the other 203 nations and concluded that the Solomons had the highest age-standardized death rate for early-onset cancer (82.9 per 100,000). However, this tiny South Pacific nation, whose population is scattered across 350 islands, did not start collecting cancer data until 2008 and founded its first oncology unit in 2019.

The authors also reported the “sharpest increases” in cancer cases diagnosed between 1990 and 2019 in the United Arab Emirates (1,127.6%), Qatar (1,089.5%), and Saudi Arabia (896.0%); however, those numbers do not seem possible, given population growth during that time, and may instead reflect reporting or other changes in those countries.

Although the overarching conclusion may be misleading, some of the numbers ring true, especially for breast cancer. The researchers found that the incidence of early breast cancer increased nearly 18% – from 11.2 to 13.2 per 100,000 – between 1990 and 2019.

This increase is “consistent with what is happening” in the United Kingdom, said Stephen Duffy of Queen Mary University of London, also weighing in via the Science Media Centre. Since the United Kingdom does not routinely screen women under 50, this rise “is not due to increased diagnostic activity.”

Darren Brenner, MD, associate professor in oncology at the University of Calgary (Alta.), said in an interview he agreed that the breast cancer trends look accurate.

In a 2020 study, Brenner and colleagues found that breast cancer diagnoses in women under 40 had increased significantly between 2000 and 2015, at a rate of 0.66% per year. “Given that breast cancer at a younger age is associated with worse outcomes, the results are troubling,” Brenner and colleagues concluded at the time.

The experts commenting via Science Media Centre reported no conflicts of interest.

A version of this article first appeared on Medscape.com.

In early September, startling cancer research findings hit the news.

A study press release headline touted a “global surge” in new cancer cases among younger people over the past 3 decades.

Many major news outlets parroted the “striking” finding. “Cancer cases in under-50s worldwide up nearly 80% in 3 decades, study finds,” The Guardian reported.

The analysis, published in BMJ Oncology, plumbed data from the Global Burden of Disease 2019 study to determine changes in cancer incidence and deaths among people aged 15-49 years across 204 countries.

The team found that, between 1990 and 2019, global cancer cases in this younger group had increased by almost 80% and cancer deaths had risen by nearly 28%. The authors flagged diet, alcohol, and tobacco as “the main risk factors” underlying the early-onset cancer trend.

But the analysis was deeply flawed, experts said. It failed to account for population growth and age.

The global population has increased by 46% between 1990 and 2019, but the study calculations are “based on absolute numbers rather than age-standardized rates,” said Montserrat García-Closas, MD, MPH, PhD, professor of epidemiology at the Institute of Cancer Research, London, who weighed in on the findings via the U.K.-based Science Media Centre. That means “these numbers do not account for changes in demographics such as increases in population size or aging of the population.”

The study researchers reported 1.82 million early-onset cancer cases in 1990 and 3.26 million global cases in 2019, which led to the reported increase of 79.1%.

Similarly, the authors calculated the change in cancer deaths globally using absolute, not population or age-adjusted, numbers: 0.83 million cancer deaths in 1990 and 1.06 million in 2019 led to the reported increase of 27.7%.

But when population growth is considered, the story changes dramatically. The population-adjusted calculations indicate that the global incidence of early-onset cancers only rose about 6% over the past 30 years while cancer deaths actually fell 25% in that time, according to calculations done by Medscape using the study’s supplemental data.

Experts commenting via the BMJ website also noted the flawed calculations. “Epidemic news, but no epidemic of cancer,” Henrik Møller, MD, lead epidemiologist for the Danish Clinical Registries, and colleagues wrote, highlighting the “misleading” 79% figure. When accounting for population growth in Nordic countries, Dr. Møller and colleagues found a 1% average annual increase in the cancer incidence rate and a 2.5% decrease in the cancer mortality rate.

This news organization reached out to the study’s corresponding authors, Kefeng Ding and Xue Li, to ask why they used absolute numbers instead of population-adjusted numbers for their calculations, but they did not respond in time for publication.

In their analysis, however, the researchers did note that “the study still has several limitations” that could affect the results, such as variations in the quality and availability of data provided by different countries.

The study, for instance, compared the Solomon Islands with the other 203 nations and concluded that the Solomons had the highest age-standardized death rate for early-onset cancer (82.9 per 100,000). However, this tiny South Pacific nation, whose population is scattered across 350 islands, did not start collecting cancer data until 2008 and founded its first oncology unit in 2019.

The authors also reported the “sharpest increases” in cancer cases diagnosed between 1990 and 2019 in the United Arab Emirates (1,127.6%), Qatar (1,089.5%), and Saudi Arabia (896.0%); however, those numbers do not seem possible, given population growth during that time, and may instead reflect reporting or other changes in those countries.

Although the overarching conclusion may be misleading, some of the numbers ring true, especially for breast cancer. The researchers found that the incidence of early breast cancer increased nearly 18% – from 11.2 to 13.2 per 100,000 – between 1990 and 2019.

This increase is “consistent with what is happening” in the United Kingdom, said Stephen Duffy of Queen Mary University of London, also weighing in via the Science Media Centre. Since the United Kingdom does not routinely screen women under 50, this rise “is not due to increased diagnostic activity.”

Darren Brenner, MD, associate professor in oncology at the University of Calgary (Alta.), said in an interview he agreed that the breast cancer trends look accurate.

In a 2020 study, Brenner and colleagues found that breast cancer diagnoses in women under 40 had increased significantly between 2000 and 2015, at a rate of 0.66% per year. “Given that breast cancer at a younger age is associated with worse outcomes, the results are troubling,” Brenner and colleagues concluded at the time.

The experts commenting via Science Media Centre reported no conflicts of interest.

A version of this article first appeared on Medscape.com.

In early September, startling cancer research findings hit the news.

A study press release headline touted a “global surge” in new cancer cases among younger people over the past 3 decades.

Many major news outlets parroted the “striking” finding. “Cancer cases in under-50s worldwide up nearly 80% in 3 decades, study finds,” The Guardian reported.

The analysis, published in BMJ Oncology, plumbed data from the Global Burden of Disease 2019 study to determine changes in cancer incidence and deaths among people aged 15-49 years across 204 countries.

The team found that, between 1990 and 2019, global cancer cases in this younger group had increased by almost 80% and cancer deaths had risen by nearly 28%. The authors flagged diet, alcohol, and tobacco as “the main risk factors” underlying the early-onset cancer trend.

But the analysis was deeply flawed, experts said. It failed to account for population growth and age.

The global population has increased by 46% between 1990 and 2019, but the study calculations are “based on absolute numbers rather than age-standardized rates,” said Montserrat García-Closas, MD, MPH, PhD, professor of epidemiology at the Institute of Cancer Research, London, who weighed in on the findings via the U.K.-based Science Media Centre. That means “these numbers do not account for changes in demographics such as increases in population size or aging of the population.”

The study researchers reported 1.82 million early-onset cancer cases in 1990 and 3.26 million global cases in 2019, which led to the reported increase of 79.1%.

Similarly, the authors calculated the change in cancer deaths globally using absolute, not population or age-adjusted, numbers: 0.83 million cancer deaths in 1990 and 1.06 million in 2019 led to the reported increase of 27.7%.

But when population growth is considered, the story changes dramatically. The population-adjusted calculations indicate that the global incidence of early-onset cancers only rose about 6% over the past 30 years while cancer deaths actually fell 25% in that time, according to calculations done by Medscape using the study’s supplemental data.

Experts commenting via the BMJ website also noted the flawed calculations. “Epidemic news, but no epidemic of cancer,” Henrik Møller, MD, lead epidemiologist for the Danish Clinical Registries, and colleagues wrote, highlighting the “misleading” 79% figure. When accounting for population growth in Nordic countries, Dr. Møller and colleagues found a 1% average annual increase in the cancer incidence rate and a 2.5% decrease in the cancer mortality rate.

This news organization reached out to the study’s corresponding authors, Kefeng Ding and Xue Li, to ask why they used absolute numbers instead of population-adjusted numbers for their calculations, but they did not respond in time for publication.

In their analysis, however, the researchers did note that “the study still has several limitations” that could affect the results, such as variations in the quality and availability of data provided by different countries.

The study, for instance, compared the Solomon Islands with the other 203 nations and concluded that the Solomons had the highest age-standardized death rate for early-onset cancer (82.9 per 100,000). However, this tiny South Pacific nation, whose population is scattered across 350 islands, did not start collecting cancer data until 2008 and founded its first oncology unit in 2019.

The authors also reported the “sharpest increases” in cancer cases diagnosed between 1990 and 2019 in the United Arab Emirates (1,127.6%), Qatar (1,089.5%), and Saudi Arabia (896.0%); however, those numbers do not seem possible, given population growth during that time, and may instead reflect reporting or other changes in those countries.

Although the overarching conclusion may be misleading, some of the numbers ring true, especially for breast cancer. The researchers found that the incidence of early breast cancer increased nearly 18% – from 11.2 to 13.2 per 100,000 – between 1990 and 2019.

This increase is “consistent with what is happening” in the United Kingdom, said Stephen Duffy of Queen Mary University of London, also weighing in via the Science Media Centre. Since the United Kingdom does not routinely screen women under 50, this rise “is not due to increased diagnostic activity.”

Darren Brenner, MD, associate professor in oncology at the University of Calgary (Alta.), said in an interview he agreed that the breast cancer trends look accurate.

In a 2020 study, Brenner and colleagues found that breast cancer diagnoses in women under 40 had increased significantly between 2000 and 2015, at a rate of 0.66% per year. “Given that breast cancer at a younger age is associated with worse outcomes, the results are troubling,” Brenner and colleagues concluded at the time.

The experts commenting via Science Media Centre reported no conflicts of interest.

A version of this article first appeared on Medscape.com.