Federal Practitioner

The recent Food and Drug Administration (FDA) approval of ensifentrine marks the first new treatment for patients with persistent chronic obstructive pulmonary disease (COPD) in more than a decade, according to manufacturer Verona Pharma.

Ensifentrine offers a new medication and a new delivery method, according to a company press release. Ensifentrine is the first-in-class selective dual inhibitor of both phosphodiesterase 3 (PDE 3) and PDE 4, combining both bronchodilator and nonsteroidal anti-inflammatory effects in a single molecule. The drug is delivered through a standard jet nebulizer.
 

Disease Management Made Easier

Although currently approved therapies for COPD, such as bronchodilators and inhaled corticosteroids (ICS), have benefited many patients, additional treatment options are still needed to help those who remain symptomatic and suffer from frequent exacerbations, said Diego J. Maselli, MD, of the University of Texas Health Science Center, San Antonio.

“Ensifentrine is a new class of medication that inhibits both PDE 3 and PDE 4; this results in both bronchodilation and suppression of the inflammatory response in COPD,” said Dr. Maselli, who was not involved in studies of ensifentrine.

“Large phase III, double-blind, randomized, placebo-controlled studies have demonstrated that ensifentrine improved lung function and reduced the risk of exacerbations in patients with symptomatic moderate to severe COPD,” he said. The study participants were on no long-acting maintenance therapy, or they were receiving long-acting beta agonist (LABA) or long-acting muscarinic antagonist (LAMA) with or without inhaled corticosteroids, he noted.

The FDA approval was supported by data from the phase 3 ENHANCE 1 and 2 trials, which included 760 and 789 adults aged 40-80 years with moderate to severe symptomatic COPD, respectively. Participants were randomized to 3 mg ensifentrine delivered via nebulizer or a placebo twice daily.

In the studies, ensifentrine significantly improved lung function based on the primary outcome of average forced expiratory volume per second within 0-12 hours of administration compared with placebo in both studies. In ENHANCE 1, ensifentrine significantly improved symptoms and quality of life compared with placebo at 24 weeks. The ENHANCE 2 results showed similar trends in favor of ensifentrine, although the differences were not significant at 24 weeks. However, the effects of ensifentrine vs placebo were consistent overall across all symptom and quality of life endpoints at all assessments during the study period, the researchers wrote.

In addition, the inhaled drug was well tolerated, with similar proportions of ensifentrine and placebo patients reporting treatment-emergent adverse events (38.4% and 36.4%, respectively, in ENHANCE 1 and 35.3% and 35.4%, respectively, in ENHANCE 2). The most common treatment-emergent adverse events were nasopharyngitis, hypertension, and back pain, reported in < 3% of the ensifentrine group.

The safety profile of ensifentrine is a plus for patients, said Dr. Maselli. “Ensifentrine was well tolerated in these studies, and the side effect profile was similar to placebo,” he said. The “ensifentrine is delivered via nebulizer and dosed every 12 hours. Some patients may still prefer the use of inhalers, while others may feel more comfortable with this mode of delivery,” he said. 

In clinical practice, “ensifentrine is a welcome addition to the current armamentarium of therapies for COPD as an option for patients who are symptomatic or who have frequent exacerbations,” Dr. Maselli emphasized.

Looking ahead, more studies are needed to evaluate ensifentrine in broader populations of COPD patients, Dr. Maselli said. For example, ensifentrine could be used as an add-on therapy for patients receiving triple therapy (ICS/LABA/LAMA) and for patients with other obstructive inflammatory diseases such as asthma, bronchiectasis, and cystic fibrosis, he noted.

Dr. Maselli disclosed serving as a consultant for GlaxoSmithKline, AstraZeneca, Amgen, and Sanofi/Regeneron; he also serves on the Editorial Board of CHEST Physician.
 

A version of this article appeared on Medscape.com.

The recent Food and Drug Administration (FDA) approval of ensifentrine marks the first new treatment for patients with persistent chronic obstructive pulmonary disease (COPD) in more than a decade, according to manufacturer Verona Pharma.

Ensifentrine offers a new medication and a new delivery method, according to a company press release. Ensifentrine is the first-in-class selective dual inhibitor of both phosphodiesterase 3 (PDE 3) and PDE 4, combining both bronchodilator and nonsteroidal anti-inflammatory effects in a single molecule. The drug is delivered through a standard jet nebulizer.
 

Disease Management Made Easier

Although currently approved therapies for COPD, such as bronchodilators and inhaled corticosteroids (ICS), have benefited many patients, additional treatment options are still needed to help those who remain symptomatic and suffer from frequent exacerbations, said Diego J. Maselli, MD, of the University of Texas Health Science Center, San Antonio.

“Ensifentrine is a new class of medication that inhibits both PDE 3 and PDE 4; this results in both bronchodilation and suppression of the inflammatory response in COPD,” said Dr. Maselli, who was not involved in studies of ensifentrine.

“Large phase III, double-blind, randomized, placebo-controlled studies have demonstrated that ensifentrine improved lung function and reduced the risk of exacerbations in patients with symptomatic moderate to severe COPD,” he said. The study participants were on no long-acting maintenance therapy, or they were receiving long-acting beta agonist (LABA) or long-acting muscarinic antagonist (LAMA) with or without inhaled corticosteroids, he noted.

The FDA approval was supported by data from the phase 3 ENHANCE 1 and 2 trials, which included 760 and 789 adults aged 40-80 years with moderate to severe symptomatic COPD, respectively. Participants were randomized to 3 mg ensifentrine delivered via nebulizer or a placebo twice daily.

In the studies, ensifentrine significantly improved lung function based on the primary outcome of average forced expiratory volume per second within 0-12 hours of administration compared with placebo in both studies. In ENHANCE 1, ensifentrine significantly improved symptoms and quality of life compared with placebo at 24 weeks. The ENHANCE 2 results showed similar trends in favor of ensifentrine, although the differences were not significant at 24 weeks. However, the effects of ensifentrine vs placebo were consistent overall across all symptom and quality of life endpoints at all assessments during the study period, the researchers wrote.

In addition, the inhaled drug was well tolerated, with similar proportions of ensifentrine and placebo patients reporting treatment-emergent adverse events (38.4% and 36.4%, respectively, in ENHANCE 1 and 35.3% and 35.4%, respectively, in ENHANCE 2). The most common treatment-emergent adverse events were nasopharyngitis, hypertension, and back pain, reported in < 3% of the ensifentrine group.

The safety profile of ensifentrine is a plus for patients, said Dr. Maselli. “Ensifentrine was well tolerated in these studies, and the side effect profile was similar to placebo,” he said. The “ensifentrine is delivered via nebulizer and dosed every 12 hours. Some patients may still prefer the use of inhalers, while others may feel more comfortable with this mode of delivery,” he said. 

In clinical practice, “ensifentrine is a welcome addition to the current armamentarium of therapies for COPD as an option for patients who are symptomatic or who have frequent exacerbations,” Dr. Maselli emphasized.

Looking ahead, more studies are needed to evaluate ensifentrine in broader populations of COPD patients, Dr. Maselli said. For example, ensifentrine could be used as an add-on therapy for patients receiving triple therapy (ICS/LABA/LAMA) and for patients with other obstructive inflammatory diseases such as asthma, bronchiectasis, and cystic fibrosis, he noted.

Dr. Maselli disclosed serving as a consultant for GlaxoSmithKline, AstraZeneca, Amgen, and Sanofi/Regeneron; he also serves on the Editorial Board of CHEST Physician.
 

A version of this article appeared on Medscape.com.

The recent Food and Drug Administration (FDA) approval of ensifentrine marks the first new treatment for patients with persistent chronic obstructive pulmonary disease (COPD) in more than a decade, according to manufacturer Verona Pharma.

Ensifentrine offers a new medication and a new delivery method, according to a company press release. Ensifentrine is the first-in-class selective dual inhibitor of both phosphodiesterase 3 (PDE 3) and PDE 4, combining both bronchodilator and nonsteroidal anti-inflammatory effects in a single molecule. The drug is delivered through a standard jet nebulizer.
 

Disease Management Made Easier

Although currently approved therapies for COPD, such as bronchodilators and inhaled corticosteroids (ICS), have benefited many patients, additional treatment options are still needed to help those who remain symptomatic and suffer from frequent exacerbations, said Diego J. Maselli, MD, of the University of Texas Health Science Center, San Antonio.

“Ensifentrine is a new class of medication that inhibits both PDE 3 and PDE 4; this results in both bronchodilation and suppression of the inflammatory response in COPD,” said Dr. Maselli, who was not involved in studies of ensifentrine.

“Large phase III, double-blind, randomized, placebo-controlled studies have demonstrated that ensifentrine improved lung function and reduced the risk of exacerbations in patients with symptomatic moderate to severe COPD,” he said. The study participants were on no long-acting maintenance therapy, or they were receiving long-acting beta agonist (LABA) or long-acting muscarinic antagonist (LAMA) with or without inhaled corticosteroids, he noted.

The FDA approval was supported by data from the phase 3 ENHANCE 1 and 2 trials, which included 760 and 789 adults aged 40-80 years with moderate to severe symptomatic COPD, respectively. Participants were randomized to 3 mg ensifentrine delivered via nebulizer or a placebo twice daily.

In the studies, ensifentrine significantly improved lung function based on the primary outcome of average forced expiratory volume per second within 0-12 hours of administration compared with placebo in both studies. In ENHANCE 1, ensifentrine significantly improved symptoms and quality of life compared with placebo at 24 weeks. The ENHANCE 2 results showed similar trends in favor of ensifentrine, although the differences were not significant at 24 weeks. However, the effects of ensifentrine vs placebo were consistent overall across all symptom and quality of life endpoints at all assessments during the study period, the researchers wrote.

In addition, the inhaled drug was well tolerated, with similar proportions of ensifentrine and placebo patients reporting treatment-emergent adverse events (38.4% and 36.4%, respectively, in ENHANCE 1 and 35.3% and 35.4%, respectively, in ENHANCE 2). The most common treatment-emergent adverse events were nasopharyngitis, hypertension, and back pain, reported in < 3% of the ensifentrine group.

The safety profile of ensifentrine is a plus for patients, said Dr. Maselli. “Ensifentrine was well tolerated in these studies, and the side effect profile was similar to placebo,” he said. The “ensifentrine is delivered via nebulizer and dosed every 12 hours. Some patients may still prefer the use of inhalers, while others may feel more comfortable with this mode of delivery,” he said. 

In clinical practice, “ensifentrine is a welcome addition to the current armamentarium of therapies for COPD as an option for patients who are symptomatic or who have frequent exacerbations,” Dr. Maselli emphasized.

Looking ahead, more studies are needed to evaluate ensifentrine in broader populations of COPD patients, Dr. Maselli said. For example, ensifentrine could be used as an add-on therapy for patients receiving triple therapy (ICS/LABA/LAMA) and for patients with other obstructive inflammatory diseases such as asthma, bronchiectasis, and cystic fibrosis, he noted.

Dr. Maselli disclosed serving as a consultant for GlaxoSmithKline, AstraZeneca, Amgen, and Sanofi/Regeneron; he also serves on the Editorial Board of CHEST Physician.
 

A version of this article appeared on Medscape.com.

Eight commonly used antidepressants have been ranked by their weight gain potential. 

Results of a large observational study showed small differences in short- and long-term weight change in patients prescribed one of eight antidepressants, with bupropion associated with the lowest weight gain and escitalopram, paroxetine, and duloxetine associated with the greatest. 

Escitalopram, paroxetine, and duloxetine users were 10%-15% more likely to gain at least 5% of their baseline weight compared with those taking sertraline, which was used as a comparator. 

Investigators noted that the more clinicians and patients know about how a particular antidepressant may affect patients’ weight, the better informed they can be about which antidepressants to prescribe. 

“Patients and their clinicians often have several options when starting an antidepressant for the first time. This study provides important real-world evidence regarding the amount of weight gain that should be expected after starting some of the most common antidepressants,” lead author Joshua Petimar, ScD, assistant professor of population medicine in the Harvard Pilgrim Health Care Institute at Harvard Medical School, Boston, said in a press release. 

The findings were published online in Annals of Internal Medicine. 


 

Real-World Data

Though weight gain is a commonly reported side effect of antidepressant use and may lead to medication nonadherence and worse outcomes, there is a lack of real-world data about weight change across specific medications. 

Investigators used electronic health records from eight health care systems across the United States spanning from 2010 to 2019. The analysis included information on 183,118 adults aged 20-80 years who were new users of one of eight common first-line antidepressants. Investigators measured their weight at baseline and at 6, 12, and 24 months after initiation to estimate intention-to-treat (ITT) effects of weight change.

At baseline, participants were randomly assigned to begin sertraline, citalopram, escitalopram, fluoxetine, paroxetine, bupropion, duloxetine, or venlafaxine. 

The most common antidepressants prescribed were sertraline, citalopram, and bupropion. Approximately 36% of participants had a diagnosis of depression, and 39% were diagnosed with anxiety.

Among selective serotonin reuptake inhibitors (SSRIs), escitalopram and paroxetine were associated with the greatest 6-month weight gain, whereas bupropion was associated with the least weight gain across all analyses.

Using sertraline as a comparator, 6-month weight change was lower for bupropion (difference, 0.22 kg) and higher for escitalopram (difference, 0.41 kg), duloxetine (difference, 0.34 kg), paroxetine (difference, 0.37 kg), and venlafaxine (difference, 0.17 kg).

Escitalopram, paroxetine, and duloxetine users were 10%-15% more likely to gain at least 5% of their baseline weight compared with sertraline users.

Investigators noted little difference in adherence levels between medications during the study except at 6 months, when it was higher for those who took bupropion (41%) than for those taking other antidepressants (28%-36%).

The study included data only on prescriptions and investigators could not verify whether the medications were dispensed or taken as prescribed. Other limitations included missing weight information because most patients did not encounter the health system at exactly 6, 12, and 24 months; only 15%-30% had weight measurements in those months. 

Finally, the low adherence rates made it difficult to attribute relative weight change at the 12- and 24-month time points to the specific medications of interest.

“Clinicians and patients could consider these differences when making decisions about specific antidepressants, especially given the complex relationships of obesity and depression with health, quality of life, and stigma,” the authors wrote. 

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Disclosures are noted in the original article. 

A version of this article appeared on Medscape.com.

Eight commonly used antidepressants have been ranked by their weight gain potential. 

Results of a large observational study showed small differences in short- and long-term weight change in patients prescribed one of eight antidepressants, with bupropion associated with the lowest weight gain and escitalopram, paroxetine, and duloxetine associated with the greatest. 

Escitalopram, paroxetine, and duloxetine users were 10%-15% more likely to gain at least 5% of their baseline weight compared with those taking sertraline, which was used as a comparator. 

Investigators noted that the more clinicians and patients know about how a particular antidepressant may affect patients’ weight, the better informed they can be about which antidepressants to prescribe. 

“Patients and their clinicians often have several options when starting an antidepressant for the first time. This study provides important real-world evidence regarding the amount of weight gain that should be expected after starting some of the most common antidepressants,” lead author Joshua Petimar, ScD, assistant professor of population medicine in the Harvard Pilgrim Health Care Institute at Harvard Medical School, Boston, said in a press release. 

The findings were published online in Annals of Internal Medicine. 


 

Real-World Data

Though weight gain is a commonly reported side effect of antidepressant use and may lead to medication nonadherence and worse outcomes, there is a lack of real-world data about weight change across specific medications. 

Investigators used electronic health records from eight health care systems across the United States spanning from 2010 to 2019. The analysis included information on 183,118 adults aged 20-80 years who were new users of one of eight common first-line antidepressants. Investigators measured their weight at baseline and at 6, 12, and 24 months after initiation to estimate intention-to-treat (ITT) effects of weight change.

At baseline, participants were randomly assigned to begin sertraline, citalopram, escitalopram, fluoxetine, paroxetine, bupropion, duloxetine, or venlafaxine. 

The most common antidepressants prescribed were sertraline, citalopram, and bupropion. Approximately 36% of participants had a diagnosis of depression, and 39% were diagnosed with anxiety.

Among selective serotonin reuptake inhibitors (SSRIs), escitalopram and paroxetine were associated with the greatest 6-month weight gain, whereas bupropion was associated with the least weight gain across all analyses.

Using sertraline as a comparator, 6-month weight change was lower for bupropion (difference, 0.22 kg) and higher for escitalopram (difference, 0.41 kg), duloxetine (difference, 0.34 kg), paroxetine (difference, 0.37 kg), and venlafaxine (difference, 0.17 kg).

Escitalopram, paroxetine, and duloxetine users were 10%-15% more likely to gain at least 5% of their baseline weight compared with sertraline users.

Investigators noted little difference in adherence levels between medications during the study except at 6 months, when it was higher for those who took bupropion (41%) than for those taking other antidepressants (28%-36%).

The study included data only on prescriptions and investigators could not verify whether the medications were dispensed or taken as prescribed. Other limitations included missing weight information because most patients did not encounter the health system at exactly 6, 12, and 24 months; only 15%-30% had weight measurements in those months. 

Finally, the low adherence rates made it difficult to attribute relative weight change at the 12- and 24-month time points to the specific medications of interest.

“Clinicians and patients could consider these differences when making decisions about specific antidepressants, especially given the complex relationships of obesity and depression with health, quality of life, and stigma,” the authors wrote. 

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Disclosures are noted in the original article. 

A version of this article appeared on Medscape.com.

Eight commonly used antidepressants have been ranked by their weight gain potential. 

Results of a large observational study showed small differences in short- and long-term weight change in patients prescribed one of eight antidepressants, with bupropion associated with the lowest weight gain and escitalopram, paroxetine, and duloxetine associated with the greatest. 

Escitalopram, paroxetine, and duloxetine users were 10%-15% more likely to gain at least 5% of their baseline weight compared with those taking sertraline, which was used as a comparator. 

Investigators noted that the more clinicians and patients know about how a particular antidepressant may affect patients’ weight, the better informed they can be about which antidepressants to prescribe. 

“Patients and their clinicians often have several options when starting an antidepressant for the first time. This study provides important real-world evidence regarding the amount of weight gain that should be expected after starting some of the most common antidepressants,” lead author Joshua Petimar, ScD, assistant professor of population medicine in the Harvard Pilgrim Health Care Institute at Harvard Medical School, Boston, said in a press release. 

The findings were published online in Annals of Internal Medicine. 


 

Real-World Data

Though weight gain is a commonly reported side effect of antidepressant use and may lead to medication nonadherence and worse outcomes, there is a lack of real-world data about weight change across specific medications. 

Investigators used electronic health records from eight health care systems across the United States spanning from 2010 to 2019. The analysis included information on 183,118 adults aged 20-80 years who were new users of one of eight common first-line antidepressants. Investigators measured their weight at baseline and at 6, 12, and 24 months after initiation to estimate intention-to-treat (ITT) effects of weight change.

At baseline, participants were randomly assigned to begin sertraline, citalopram, escitalopram, fluoxetine, paroxetine, bupropion, duloxetine, or venlafaxine. 

The most common antidepressants prescribed were sertraline, citalopram, and bupropion. Approximately 36% of participants had a diagnosis of depression, and 39% were diagnosed with anxiety.

Among selective serotonin reuptake inhibitors (SSRIs), escitalopram and paroxetine were associated with the greatest 6-month weight gain, whereas bupropion was associated with the least weight gain across all analyses.

Using sertraline as a comparator, 6-month weight change was lower for bupropion (difference, 0.22 kg) and higher for escitalopram (difference, 0.41 kg), duloxetine (difference, 0.34 kg), paroxetine (difference, 0.37 kg), and venlafaxine (difference, 0.17 kg).

Escitalopram, paroxetine, and duloxetine users were 10%-15% more likely to gain at least 5% of their baseline weight compared with sertraline users.

Investigators noted little difference in adherence levels between medications during the study except at 6 months, when it was higher for those who took bupropion (41%) than for those taking other antidepressants (28%-36%).

The study included data only on prescriptions and investigators could not verify whether the medications were dispensed or taken as prescribed. Other limitations included missing weight information because most patients did not encounter the health system at exactly 6, 12, and 24 months; only 15%-30% had weight measurements in those months. 

Finally, the low adherence rates made it difficult to attribute relative weight change at the 12- and 24-month time points to the specific medications of interest.

“Clinicians and patients could consider these differences when making decisions about specific antidepressants, especially given the complex relationships of obesity and depression with health, quality of life, and stigma,” the authors wrote. 

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Disclosures are noted in the original article. 

A version of this article appeared on Medscape.com.

TOPLINE:

Compared with placebo, administration of vocacapsaicin during bunionectomy reduces pain and decreases opioid consumption in the first 96 hours after surgery, with no local or systemic toxicity.

METHODOLOGY:

• This triple-blind, randomized, placebo-controlled trial included 147 patients undergoing bunionectomy.
• Patients were randomly assigned to receive 14 mL of either 0.05 mg/mL vocacapsaicin, 0.15 mg/mL vocacapsaicin, 0.30 mg/mL vocacapsaicin, or placebo at the surgical site during wound closure. Except for the study drug, all patients received identical perioperative analgesics.
• Patients were observed for 96 hours post-surgery, with follow-up visits on days 8, 15, and 29 to monitor for pain and adverse events.
• The primary endpoint was overall levels of pain at rest through the first 96 hours after surgery for the 0.30-mg/mL vocacapsaicin group.
• The secondary endpoints included the percentage of patients who did not require opioids and total opioid consumption through 96 hours, as well as pain scores during the first postoperative week.

TAKEAWAY:

• Vocacapsaicin (0.30 mg/mL) reduced pain at rest by 33% over the first 96 hours, compared with placebo (P = .005).
• Overall, 26% of patients who received the 0.30-mg/mL dose of vocacapsaicin did not require opioids through 96 hours compared with 5% of patients receiving placebo (P = .025).
• The researchers reported no difference in the rate, type, or severity of adverse events in the four study groups, consistent with typical recovery from bunionectomy.

IN PRACTICE:

“These data suggest that intraoperative administration of vocacapsaicin may provide substantial benefits in other surgical procedures,” the authors wrote.

SOURCE:

The study was led by Steven L. Shafer, MD, of the Department of Anesthesiology, Perioperative and Pain Medicine at Stanford University in Stanford, California, and published in the June 2024 issue of Anesthesiology.

LIMITATIONS:

The use of opioids was restricted from 0 to 96 hours after surgery, which did not reflect typical clinical practice. The range of vocacapsaicin concentrations tested may not have been extensive enough, as concentrations > 0.30 mg/mL might have provided better analgesia.

DISCLOSURES:

The study was supported by Concentric Analgesics. Two authors declared being employed by Concentric Analgesics. Other authors declared having several ties with many sources, including the funding agency.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article appeared on Medscape.com.

TOPLINE:

Compared with placebo, administration of vocacapsaicin during bunionectomy reduces pain and decreases opioid consumption in the first 96 hours after surgery, with no local or systemic toxicity.

METHODOLOGY:

• This triple-blind, randomized, placebo-controlled trial included 147 patients undergoing bunionectomy.
• Patients were randomly assigned to receive 14 mL of either 0.05 mg/mL vocacapsaicin, 0.15 mg/mL vocacapsaicin, 0.30 mg/mL vocacapsaicin, or placebo at the surgical site during wound closure. Except for the study drug, all patients received identical perioperative analgesics.
• Patients were observed for 96 hours post-surgery, with follow-up visits on days 8, 15, and 29 to monitor for pain and adverse events.
• The primary endpoint was overall levels of pain at rest through the first 96 hours after surgery for the 0.30-mg/mL vocacapsaicin group.
• The secondary endpoints included the percentage of patients who did not require opioids and total opioid consumption through 96 hours, as well as pain scores during the first postoperative week.

TAKEAWAY:

• Vocacapsaicin (0.30 mg/mL) reduced pain at rest by 33% over the first 96 hours, compared with placebo (P = .005).
• Overall, 26% of patients who received the 0.30-mg/mL dose of vocacapsaicin did not require opioids through 96 hours compared with 5% of patients receiving placebo (P = .025).
• The researchers reported no difference in the rate, type, or severity of adverse events in the four study groups, consistent with typical recovery from bunionectomy.

IN PRACTICE:

“These data suggest that intraoperative administration of vocacapsaicin may provide substantial benefits in other surgical procedures,” the authors wrote.

SOURCE:

The study was led by Steven L. Shafer, MD, of the Department of Anesthesiology, Perioperative and Pain Medicine at Stanford University in Stanford, California, and published in the June 2024 issue of Anesthesiology.

LIMITATIONS:

The use of opioids was restricted from 0 to 96 hours after surgery, which did not reflect typical clinical practice. The range of vocacapsaicin concentrations tested may not have been extensive enough, as concentrations > 0.30 mg/mL might have provided better analgesia.

DISCLOSURES:

The study was supported by Concentric Analgesics. Two authors declared being employed by Concentric Analgesics. Other authors declared having several ties with many sources, including the funding agency.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article appeared on Medscape.com.

TOPLINE:

Compared with placebo, administration of vocacapsaicin during bunionectomy reduces pain and decreases opioid consumption in the first 96 hours after surgery, with no local or systemic toxicity.

METHODOLOGY:

• This triple-blind, randomized, placebo-controlled trial included 147 patients undergoing bunionectomy.
• Patients were randomly assigned to receive 14 mL of either 0.05 mg/mL vocacapsaicin, 0.15 mg/mL vocacapsaicin, 0.30 mg/mL vocacapsaicin, or placebo at the surgical site during wound closure. Except for the study drug, all patients received identical perioperative analgesics.
• Patients were observed for 96 hours post-surgery, with follow-up visits on days 8, 15, and 29 to monitor for pain and adverse events.
• The primary endpoint was overall levels of pain at rest through the first 96 hours after surgery for the 0.30-mg/mL vocacapsaicin group.
• The secondary endpoints included the percentage of patients who did not require opioids and total opioid consumption through 96 hours, as well as pain scores during the first postoperative week.

TAKEAWAY:

• Vocacapsaicin (0.30 mg/mL) reduced pain at rest by 33% over the first 96 hours, compared with placebo (P = .005).
• Overall, 26% of patients who received the 0.30-mg/mL dose of vocacapsaicin did not require opioids through 96 hours compared with 5% of patients receiving placebo (P = .025).
• The researchers reported no difference in the rate, type, or severity of adverse events in the four study groups, consistent with typical recovery from bunionectomy.

IN PRACTICE:

“These data suggest that intraoperative administration of vocacapsaicin may provide substantial benefits in other surgical procedures,” the authors wrote.

SOURCE:

The study was led by Steven L. Shafer, MD, of the Department of Anesthesiology, Perioperative and Pain Medicine at Stanford University in Stanford, California, and published in the June 2024 issue of Anesthesiology.

LIMITATIONS:

The use of opioids was restricted from 0 to 96 hours after surgery, which did not reflect typical clinical practice. The range of vocacapsaicin concentrations tested may not have been extensive enough, as concentrations > 0.30 mg/mL might have provided better analgesia.

DISCLOSURES:

The study was supported by Concentric Analgesics. Two authors declared being employed by Concentric Analgesics. Other authors declared having several ties with many sources, including the funding agency.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article appeared on Medscape.com.

TOPLINE:

Sedentary behavior, particularly sitting and watching television, is linked to lower odds of healthy aging, but substituting it with any physical activity — or even sleeping, in case of women with inadequate sleep — may lead to better overall health.

METHODOLOGY:

• Previous studies have shown that replacing sedentary behavior with physical activity may improve mortality outcomes, but whether this increased lifespan is accompanied by better overall health remains an unanswered question.
• To understand the impact of sedentary behavior and physical activity on healthy aging, researchers analyzed data from the prospective cohort Nurses’ Health Study.
• They included 45,176 women aged > 50 years in 1992 (mean age, 59.2 years) who were free of major chronic diseases and were followed up for 20 years.
• In 1992, validated questionnaires were used to record exposure to sedentary behavior, different levels of physical activity, and sleep. The time spent watching television was the primary exposure in the sedentary behavior category.
• The main outcome was healthy aging, defined as survival to ≥ 70 years of age and maintenance of four domains of health — being free of 11 main chronic diseases and having no impairment of subjective memory, physical function, or mental health.

TAKEAWAY:

• At 20 years of follow-up, 8.6% of the women achieved healthy aging, while 41.4% had none of the 11 chronic diseases, 16.1% had no physical function impairment, 44.1% had no mental health limitation, and 51.9% reported no memory impairment.
• For each increase of 2 hours per day spent sitting and watching television, the odds of healthy aging dropped by 12% (95% confidence interval [CI], 7%-17%).
• Conversely, every additional 2 hours per day of low-level physical activity at work upped the odds of healthy aging by 6% (95% CI, 3%-9%); furthermore, each extra hour per day of standardized moderate to vigorous physical activity (normal pace walking or the equivalent) was associated with 14% higher odds (95% CI, 11%-16%) of healthy aging.
• In a theoretical modeling analysis, individuals could increase their odds of healthy aging by replacing 1 hour of television time per day with low levels of physical activity at home and work or with moderate to vigorous levels of physical activity — or even sleeping, for those who slept for ≤ 7 hours.

IN PRACTICE:

“These findings expand on the literature reporting that replacing sedentary behavior with light or moderate to vigorous physical activity is associated with decreased mortality by suggesting that this increased lifespan might be accompanied by better overall health,” the authors wrote.

SOURCE:

Hongying Shi, PhD, Department of Epidemiology and Health Statistics, School of Public Health, Wenzhou Medical University, Wenzhou, China, led this study, which was published online in JAMA Network Open.

LIMITATIONS:

The measures of different behaviors were self-reported and may, therefore, be less accurate than objective measurement methods. Measurement error may have attenuated the effect of low levels of physical activity. The single exposure assessment at baseline may not reflect the long-term pattern of these activities.

DISCLOSURES:

The lead author was supported by the National Social Science Foundation Project of China and the Zhejiang Provincial Philosophy and Social Sciences Planning Project. A co-author and the Nurses’ Health Study were supported by the US National Institutes of Health. The authors declared no conflicts of interest.

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

TOPLINE:

Sedentary behavior, particularly sitting and watching television, is linked to lower odds of healthy aging, but substituting it with any physical activity — or even sleeping, in case of women with inadequate sleep — may lead to better overall health.

METHODOLOGY:

• Previous studies have shown that replacing sedentary behavior with physical activity may improve mortality outcomes, but whether this increased lifespan is accompanied by better overall health remains an unanswered question.
• To understand the impact of sedentary behavior and physical activity on healthy aging, researchers analyzed data from the prospective cohort Nurses’ Health Study.
• They included 45,176 women aged > 50 years in 1992 (mean age, 59.2 years) who were free of major chronic diseases and were followed up for 20 years.
• In 1992, validated questionnaires were used to record exposure to sedentary behavior, different levels of physical activity, and sleep. The time spent watching television was the primary exposure in the sedentary behavior category.
• The main outcome was healthy aging, defined as survival to ≥ 70 years of age and maintenance of four domains of health — being free of 11 main chronic diseases and having no impairment of subjective memory, physical function, or mental health.

TAKEAWAY:

• At 20 years of follow-up, 8.6% of the women achieved healthy aging, while 41.4% had none of the 11 chronic diseases, 16.1% had no physical function impairment, 44.1% had no mental health limitation, and 51.9% reported no memory impairment.
• For each increase of 2 hours per day spent sitting and watching television, the odds of healthy aging dropped by 12% (95% confidence interval [CI], 7%-17%).
• Conversely, every additional 2 hours per day of low-level physical activity at work upped the odds of healthy aging by 6% (95% CI, 3%-9%); furthermore, each extra hour per day of standardized moderate to vigorous physical activity (normal pace walking or the equivalent) was associated with 14% higher odds (95% CI, 11%-16%) of healthy aging.
• In a theoretical modeling analysis, individuals could increase their odds of healthy aging by replacing 1 hour of television time per day with low levels of physical activity at home and work or with moderate to vigorous levels of physical activity — or even sleeping, for those who slept for ≤ 7 hours.

IN PRACTICE:

“These findings expand on the literature reporting that replacing sedentary behavior with light or moderate to vigorous physical activity is associated with decreased mortality by suggesting that this increased lifespan might be accompanied by better overall health,” the authors wrote.

SOURCE:

Hongying Shi, PhD, Department of Epidemiology and Health Statistics, School of Public Health, Wenzhou Medical University, Wenzhou, China, led this study, which was published online in JAMA Network Open.

LIMITATIONS:

The measures of different behaviors were self-reported and may, therefore, be less accurate than objective measurement methods. Measurement error may have attenuated the effect of low levels of physical activity. The single exposure assessment at baseline may not reflect the long-term pattern of these activities.

DISCLOSURES:

The lead author was supported by the National Social Science Foundation Project of China and the Zhejiang Provincial Philosophy and Social Sciences Planning Project. A co-author and the Nurses’ Health Study were supported by the US National Institutes of Health. The authors declared no conflicts of interest.

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

TOPLINE:

Sedentary behavior, particularly sitting and watching television, is linked to lower odds of healthy aging, but substituting it with any physical activity — or even sleeping, in case of women with inadequate sleep — may lead to better overall health.

METHODOLOGY:

• Previous studies have shown that replacing sedentary behavior with physical activity may improve mortality outcomes, but whether this increased lifespan is accompanied by better overall health remains an unanswered question.
• To understand the impact of sedentary behavior and physical activity on healthy aging, researchers analyzed data from the prospective cohort Nurses’ Health Study.
• They included 45,176 women aged > 50 years in 1992 (mean age, 59.2 years) who were free of major chronic diseases and were followed up for 20 years.
• In 1992, validated questionnaires were used to record exposure to sedentary behavior, different levels of physical activity, and sleep. The time spent watching television was the primary exposure in the sedentary behavior category.
• The main outcome was healthy aging, defined as survival to ≥ 70 years of age and maintenance of four domains of health — being free of 11 main chronic diseases and having no impairment of subjective memory, physical function, or mental health.

TAKEAWAY:

• At 20 years of follow-up, 8.6% of the women achieved healthy aging, while 41.4% had none of the 11 chronic diseases, 16.1% had no physical function impairment, 44.1% had no mental health limitation, and 51.9% reported no memory impairment.
• For each increase of 2 hours per day spent sitting and watching television, the odds of healthy aging dropped by 12% (95% confidence interval [CI], 7%-17%).
• Conversely, every additional 2 hours per day of low-level physical activity at work upped the odds of healthy aging by 6% (95% CI, 3%-9%); furthermore, each extra hour per day of standardized moderate to vigorous physical activity (normal pace walking or the equivalent) was associated with 14% higher odds (95% CI, 11%-16%) of healthy aging.
• In a theoretical modeling analysis, individuals could increase their odds of healthy aging by replacing 1 hour of television time per day with low levels of physical activity at home and work or with moderate to vigorous levels of physical activity — or even sleeping, for those who slept for ≤ 7 hours.

IN PRACTICE:

“These findings expand on the literature reporting that replacing sedentary behavior with light or moderate to vigorous physical activity is associated with decreased mortality by suggesting that this increased lifespan might be accompanied by better overall health,” the authors wrote.

SOURCE:

Hongying Shi, PhD, Department of Epidemiology and Health Statistics, School of Public Health, Wenzhou Medical University, Wenzhou, China, led this study, which was published online in JAMA Network Open.

LIMITATIONS:

The measures of different behaviors were self-reported and may, therefore, be less accurate than objective measurement methods. Measurement error may have attenuated the effect of low levels of physical activity. The single exposure assessment at baseline may not reflect the long-term pattern of these activities.

DISCLOSURES:

The lead author was supported by the National Social Science Foundation Project of China and the Zhejiang Provincial Philosophy and Social Sciences Planning Project. A co-author and the Nurses’ Health Study were supported by the US National Institutes of Health. The authors declared no conflicts of interest.

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

In a shifting landscape in dementia risk factors, cardiovascular health is now taking precedence.

That’s according to researchers from University College London (UCL) in the United Kingdom who analyzed 27 papers about dementia that had data collected over more than 70 years. They calculated what share of dementia cases were due to different risk factors. Their findings were recently published in the Lancet Public Health.

Top risk factors for dementia over the years have been hypertension, obesity, diabetes, education, and smoking, according to a news release on the findings. But the prevalence of risk factors has changed over the decades.

Researchers said smoking and education have become less important risk factors because of “population-level interventions,” such as stop-smoking campaigns and compulsory public education. On the other hand, obesity and diabetes rates have increased and become bigger risk factors.

Hypertension remains the greatest risk factor, even though doctors and public health groups are putting more emphasis on managing the condition, the study said.

“Cardiovascular risk factors may have contributed more to dementia risk over time, so these deserve more targeted action for future dementia prevention efforts,” said Naaheed Mukadam, PhD, an associate professor at UCL and the lead author of the study.

Eliminating modifiable risk factors could theoretically prevent 40% of dementia cases, the release said. 

The CDC says that an estimated 5.8 million people in the United States have Alzheimer’s disease and related dementias, including 5.6 million people ages 65 and older and about 200,000 under age 65. The UCL release said an estimated 944,000 in the U.K. have dementia. 

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

In a shifting landscape in dementia risk factors, cardiovascular health is now taking precedence.

That’s according to researchers from University College London (UCL) in the United Kingdom who analyzed 27 papers about dementia that had data collected over more than 70 years. They calculated what share of dementia cases were due to different risk factors. Their findings were recently published in the Lancet Public Health.

Top risk factors for dementia over the years have been hypertension, obesity, diabetes, education, and smoking, according to a news release on the findings. But the prevalence of risk factors has changed over the decades.

Researchers said smoking and education have become less important risk factors because of “population-level interventions,” such as stop-smoking campaigns and compulsory public education. On the other hand, obesity and diabetes rates have increased and become bigger risk factors.

Hypertension remains the greatest risk factor, even though doctors and public health groups are putting more emphasis on managing the condition, the study said.

“Cardiovascular risk factors may have contributed more to dementia risk over time, so these deserve more targeted action for future dementia prevention efforts,” said Naaheed Mukadam, PhD, an associate professor at UCL and the lead author of the study.

Eliminating modifiable risk factors could theoretically prevent 40% of dementia cases, the release said. 

The CDC says that an estimated 5.8 million people in the United States have Alzheimer’s disease and related dementias, including 5.6 million people ages 65 and older and about 200,000 under age 65. The UCL release said an estimated 944,000 in the U.K. have dementia. 

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

In a shifting landscape in dementia risk factors, cardiovascular health is now taking precedence.

That’s according to researchers from University College London (UCL) in the United Kingdom who analyzed 27 papers about dementia that had data collected over more than 70 years. They calculated what share of dementia cases were due to different risk factors. Their findings were recently published in the Lancet Public Health.

Top risk factors for dementia over the years have been hypertension, obesity, diabetes, education, and smoking, according to a news release on the findings. But the prevalence of risk factors has changed over the decades.

Researchers said smoking and education have become less important risk factors because of “population-level interventions,” such as stop-smoking campaigns and compulsory public education. On the other hand, obesity and diabetes rates have increased and become bigger risk factors.

Hypertension remains the greatest risk factor, even though doctors and public health groups are putting more emphasis on managing the condition, the study said.

“Cardiovascular risk factors may have contributed more to dementia risk over time, so these deserve more targeted action for future dementia prevention efforts,” said Naaheed Mukadam, PhD, an associate professor at UCL and the lead author of the study.

Eliminating modifiable risk factors could theoretically prevent 40% of dementia cases, the release said. 

The CDC says that an estimated 5.8 million people in the United States have Alzheimer’s disease and related dementias, including 5.6 million people ages 65 and older and about 200,000 under age 65. The UCL release said an estimated 944,000 in the U.K. have dementia. 

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

A few years ago, Kim Lori Sandler, MD, realized many patients newly diagnosed with lung cancer had never been screened for the disease — they received CT scans only because they were symptomatic.

But Dr. Sandler, a radiologist at Vanderbilt University Medical Center in Nashville, Tennessee, could see in medical charts that most of these patients had been eligible for a screening before becoming symptomatic. And for women, most had received decades worth of mammograms. She saw an opportunity and launched a study to find out if an intervention would work.

Low-dose CT and mammography services often are available in the same imaging facility, so women who qualified for a lung cancer screening were offered the scan during their mammography visit. Over a 3-year period, monthly rates of lung scans in women rose by 50% at one facility and 36% at the other.

“What we found is that women are really receptive, if you talk to them about it,” Dr. Sandler said. “I don’t think that lung cancer is thought of as a disease in women.”

Although lung cancer is the leading cause of cancer deaths in the United States, a recent study in JAMA Internal Medicine found only 18% of eligible patients were screened in 2022, a far cry from the rates of 72% for colon cancer — which itself falls short of goals from US medical groups like the American Cancer Society (ACS). Among those eligible, rates of lung screenings were lowest among younger people without comorbid conditions, who did not have health insurance or a usual source of care, and those living in southern states and states that did not expand Medicaid as part of the Affordable Care Act.

But researchers and clinicians, from those working in an urban health center for the homeless to clinics in the poorest counties in the tobacco belt, have used strategies to raise their rates of screening for lung cancer.

Getting patients screened is lifesaving: 27% of people with lung cancer survive 5 years after diagnosis. But the survival rate rises to 63% when cases are diagnosed at an early stage.
 

Increasing Uptake

The formal recommendation to use low-dose chest CT to screen for lung cancer is only a decade old. The approach was first endorsed by the United States Preventive Services Task Force (USPSTF) on the basis of an influential trial that found such testing was linked to a 20% reduction in mortality from the disease. Updated 2021 USPSTF guidelines call for annual screening of people aged 50-80 years who have a 20 pack-year history of smoking and currently smoke or have quit within the past 15 years.

But implementing the recommendation is not always simple. Unlike a colorectal or breast cancer screening, which is recommended primarily on patient age, eligibility for a lung cancer screening requires calculating pack-years of smoking, and, for past smokers, knowledge of when they quit.

The structured fields in most electronic medical records (EMRs) inquire about current or past use of cigarettes and the number of daily packs smoked. But few EMRs can calculate when a patient starts smoking two cigarettes a day but then increases to a pack a day and cuts down again. EMRs also do not track when a patient has stopped smoking permanently. Individual clinicians or health systems must identify patients who are eligible for screening, but the lack of automated calculations makes that job more difficult.

Dr. Sandler and colleagues turned to the informatics team at Vanderbilt to develop a natural language processing approach that extracts smoking data directly from clinician notes instead of using standard variables in their EMR.

The number of patients identified as needing a screening using the algorithm nearly doubled from baseline, from 5887 to 10,231 over a 3-year period, according to results from another study that Dr. Sandler published.

Although the algorithm may occasionally flag someone who does not need screening as eligible, “you can always have a conversation with the patient to determine if they actually meet eligibility criteria,” Dr. Sandler said.
 

Patient Navigators to the Rescue?

About a decade ago, Travis Baggett, MD, MPH, an associate professor of internal medicine at Harvard Medical School, Boston, Massachusetts, received pilot funding from the ACS to study cancer epidemiology among patients at Boston Health Care for the Homeless Program (BHCHP), which serves nearly 10,000 patients at a variety of Boston-area clinics each year.

“We found that both the incidence and mortality rates for lung cancer were more than twofold higher than in the general population,” Dr. Baggett, who is also the director of research at BHCHP, said.

He also discovered that BHCHP patients were diagnosed at significantly later stages than people in the general population for malignancies like breast and colorectal cancer.

Screening for lung cancer was a new recommendation at the time. With additional funding from the ACS, he launched a clinical trial in 2020 that randomized patients who were eligible for lung cancer screening to either work with a patient navigator or receive usual care.

The navigators eased the burden on primary care clinicians: They facilitated shared decision-making visits, helped participants make and attend appointments for low-dose CT, assisted with transportation, and arranged follow-up as needed.

The 3-year study found 43% of patients who received navigation services underwent screening for lung cancer, compared with 9% in the usual-care arm. Participants said the navigators played a critical role in educating them about the importance of screening, coordinating care, and providing emotional support.

“At the root of it all, it was quite clear that one thing that made the navigator successful was their interpersonal qualities and having someone that the patient could trust to help guide them through the process,” Dr. Baggett said.

The navigator program, however, stopped when the funding for the study ended.

But another health system has implemented navigators in a sustainable way through a quality improvement project. Michael Gieske, MD, director of lung cancer screening at St. Elizabeth Healthcare in Edgewood, Kentucky, starts his Friday morning meeting with a multidisciplinary group, including a thoracic surgeon, radiologist, pulmonologist, and several screening nurse navigators. They review the week’s chest CTs, with approximately one-third from patients who underwent lung cancer screening.

Nurse navigators at St. Elizabeth Healthcare follow up with any patient whose scan is suspicious for lung cancer and guide them through the process of seeing specialists and obtaining additional testing.

“They essentially hold the patient’s hand through this scary time in their life and make sure that everything flows smoothly and efficiently,” said Dr. Gieske, a family medicine physician.

St. Elizabeth’s program also draws on several evidence-based strategies used for other cancer screening programs, such as patient and provider education and quarterly feedback to their 194 primary care clinicians on rates of lung cancer screening among their eligible patients.

Several requirements for reimbursement for a lung cancer screening from the US Centers for Medicare & Medicaid Services can also serve as barriers to getting patients screened: Clinicians must identify who is eligible, provide tobacco cessation counseling, and document the shared decision-making process.

To streamline the steps, St. Elizabeth’s clinicians use an EMR smart set that reminds clinicians to verify smoking history and helps them document the required counseling.

Last year, 47% of eligible patients received their recommended screening, and Dr. Gieske said he expects even more improvement.

“We’re on track this year to complete 60% uptake if things continue,” he said, adding that 76% of the new cases of lung cancer are now diagnosed in stage I, with only 5% diagnosed in stage IV.

Dr. Gieske has shared his experience with many clinics in Appalachia, home to some of the highest rates of mortality from lung cancer in the country. A major part of his role with the Appalachian Community Cancer Alliance is helping educate primary care clinicians in the region about the importance of early detection of lung cancer.

“I think one of the most important things is just to convey a message of hope,” he said. “We’re trying to get the good word out there that if you screen individuals, you’re going to catch it early, when you have an extremely high chance of curing the lung cancer.”

Dr. Baggett reported support from grants from the ACS and the Massachusetts General Hospital Research Scholars Program. Dr. Sandler and Dr. Gieske reported no financial conflicts.

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

A few years ago, Kim Lori Sandler, MD, realized many patients newly diagnosed with lung cancer had never been screened for the disease — they received CT scans only because they were symptomatic.

But Dr. Sandler, a radiologist at Vanderbilt University Medical Center in Nashville, Tennessee, could see in medical charts that most of these patients had been eligible for a screening before becoming symptomatic. And for women, most had received decades worth of mammograms. She saw an opportunity and launched a study to find out if an intervention would work.

Low-dose CT and mammography services often are available in the same imaging facility, so women who qualified for a lung cancer screening were offered the scan during their mammography visit. Over a 3-year period, monthly rates of lung scans in women rose by 50% at one facility and 36% at the other.

“What we found is that women are really receptive, if you talk to them about it,” Dr. Sandler said. “I don’t think that lung cancer is thought of as a disease in women.”

Although lung cancer is the leading cause of cancer deaths in the United States, a recent study in JAMA Internal Medicine found only 18% of eligible patients were screened in 2022, a far cry from the rates of 72% for colon cancer — which itself falls short of goals from US medical groups like the American Cancer Society (ACS). Among those eligible, rates of lung screenings were lowest among younger people without comorbid conditions, who did not have health insurance or a usual source of care, and those living in southern states and states that did not expand Medicaid as part of the Affordable Care Act.

But researchers and clinicians, from those working in an urban health center for the homeless to clinics in the poorest counties in the tobacco belt, have used strategies to raise their rates of screening for lung cancer.

Getting patients screened is lifesaving: 27% of people with lung cancer survive 5 years after diagnosis. But the survival rate rises to 63% when cases are diagnosed at an early stage.
 

Increasing Uptake

The formal recommendation to use low-dose chest CT to screen for lung cancer is only a decade old. The approach was first endorsed by the United States Preventive Services Task Force (USPSTF) on the basis of an influential trial that found such testing was linked to a 20% reduction in mortality from the disease. Updated 2021 USPSTF guidelines call for annual screening of people aged 50-80 years who have a 20 pack-year history of smoking and currently smoke or have quit within the past 15 years.

But implementing the recommendation is not always simple. Unlike a colorectal or breast cancer screening, which is recommended primarily on patient age, eligibility for a lung cancer screening requires calculating pack-years of smoking, and, for past smokers, knowledge of when they quit.

The structured fields in most electronic medical records (EMRs) inquire about current or past use of cigarettes and the number of daily packs smoked. But few EMRs can calculate when a patient starts smoking two cigarettes a day but then increases to a pack a day and cuts down again. EMRs also do not track when a patient has stopped smoking permanently. Individual clinicians or health systems must identify patients who are eligible for screening, but the lack of automated calculations makes that job more difficult.

Dr. Sandler and colleagues turned to the informatics team at Vanderbilt to develop a natural language processing approach that extracts smoking data directly from clinician notes instead of using standard variables in their EMR.

The number of patients identified as needing a screening using the algorithm nearly doubled from baseline, from 5887 to 10,231 over a 3-year period, according to results from another study that Dr. Sandler published.

Although the algorithm may occasionally flag someone who does not need screening as eligible, “you can always have a conversation with the patient to determine if they actually meet eligibility criteria,” Dr. Sandler said.
 

Patient Navigators to the Rescue?

About a decade ago, Travis Baggett, MD, MPH, an associate professor of internal medicine at Harvard Medical School, Boston, Massachusetts, received pilot funding from the ACS to study cancer epidemiology among patients at Boston Health Care for the Homeless Program (BHCHP), which serves nearly 10,000 patients at a variety of Boston-area clinics each year.

“We found that both the incidence and mortality rates for lung cancer were more than twofold higher than in the general population,” Dr. Baggett, who is also the director of research at BHCHP, said.

He also discovered that BHCHP patients were diagnosed at significantly later stages than people in the general population for malignancies like breast and colorectal cancer.

Screening for lung cancer was a new recommendation at the time. With additional funding from the ACS, he launched a clinical trial in 2020 that randomized patients who were eligible for lung cancer screening to either work with a patient navigator or receive usual care.

The navigators eased the burden on primary care clinicians: They facilitated shared decision-making visits, helped participants make and attend appointments for low-dose CT, assisted with transportation, and arranged follow-up as needed.

The 3-year study found 43% of patients who received navigation services underwent screening for lung cancer, compared with 9% in the usual-care arm. Participants said the navigators played a critical role in educating them about the importance of screening, coordinating care, and providing emotional support.

“At the root of it all, it was quite clear that one thing that made the navigator successful was their interpersonal qualities and having someone that the patient could trust to help guide them through the process,” Dr. Baggett said.

The navigator program, however, stopped when the funding for the study ended.

But another health system has implemented navigators in a sustainable way through a quality improvement project. Michael Gieske, MD, director of lung cancer screening at St. Elizabeth Healthcare in Edgewood, Kentucky, starts his Friday morning meeting with a multidisciplinary group, including a thoracic surgeon, radiologist, pulmonologist, and several screening nurse navigators. They review the week’s chest CTs, with approximately one-third from patients who underwent lung cancer screening.

Nurse navigators at St. Elizabeth Healthcare follow up with any patient whose scan is suspicious for lung cancer and guide them through the process of seeing specialists and obtaining additional testing.

“They essentially hold the patient’s hand through this scary time in their life and make sure that everything flows smoothly and efficiently,” said Dr. Gieske, a family medicine physician.

St. Elizabeth’s program also draws on several evidence-based strategies used for other cancer screening programs, such as patient and provider education and quarterly feedback to their 194 primary care clinicians on rates of lung cancer screening among their eligible patients.

Several requirements for reimbursement for a lung cancer screening from the US Centers for Medicare & Medicaid Services can also serve as barriers to getting patients screened: Clinicians must identify who is eligible, provide tobacco cessation counseling, and document the shared decision-making process.

To streamline the steps, St. Elizabeth’s clinicians use an EMR smart set that reminds clinicians to verify smoking history and helps them document the required counseling.

Last year, 47% of eligible patients received their recommended screening, and Dr. Gieske said he expects even more improvement.

“We’re on track this year to complete 60% uptake if things continue,” he said, adding that 76% of the new cases of lung cancer are now diagnosed in stage I, with only 5% diagnosed in stage IV.

Dr. Gieske has shared his experience with many clinics in Appalachia, home to some of the highest rates of mortality from lung cancer in the country. A major part of his role with the Appalachian Community Cancer Alliance is helping educate primary care clinicians in the region about the importance of early detection of lung cancer.

“I think one of the most important things is just to convey a message of hope,” he said. “We’re trying to get the good word out there that if you screen individuals, you’re going to catch it early, when you have an extremely high chance of curing the lung cancer.”

Dr. Baggett reported support from grants from the ACS and the Massachusetts General Hospital Research Scholars Program. Dr. Sandler and Dr. Gieske reported no financial conflicts.

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

A few years ago, Kim Lori Sandler, MD, realized many patients newly diagnosed with lung cancer had never been screened for the disease — they received CT scans only because they were symptomatic.

But Dr. Sandler, a radiologist at Vanderbilt University Medical Center in Nashville, Tennessee, could see in medical charts that most of these patients had been eligible for a screening before becoming symptomatic. And for women, most had received decades worth of mammograms. She saw an opportunity and launched a study to find out if an intervention would work.

Low-dose CT and mammography services often are available in the same imaging facility, so women who qualified for a lung cancer screening were offered the scan during their mammography visit. Over a 3-year period, monthly rates of lung scans in women rose by 50% at one facility and 36% at the other.

“What we found is that women are really receptive, if you talk to them about it,” Dr. Sandler said. “I don’t think that lung cancer is thought of as a disease in women.”

Although lung cancer is the leading cause of cancer deaths in the United States, a recent study in JAMA Internal Medicine found only 18% of eligible patients were screened in 2022, a far cry from the rates of 72% for colon cancer — which itself falls short of goals from US medical groups like the American Cancer Society (ACS). Among those eligible, rates of lung screenings were lowest among younger people without comorbid conditions, who did not have health insurance or a usual source of care, and those living in southern states and states that did not expand Medicaid as part of the Affordable Care Act.

But researchers and clinicians, from those working in an urban health center for the homeless to clinics in the poorest counties in the tobacco belt, have used strategies to raise their rates of screening for lung cancer.

Getting patients screened is lifesaving: 27% of people with lung cancer survive 5 years after diagnosis. But the survival rate rises to 63% when cases are diagnosed at an early stage.
 

Increasing Uptake

The formal recommendation to use low-dose chest CT to screen for lung cancer is only a decade old. The approach was first endorsed by the United States Preventive Services Task Force (USPSTF) on the basis of an influential trial that found such testing was linked to a 20% reduction in mortality from the disease. Updated 2021 USPSTF guidelines call for annual screening of people aged 50-80 years who have a 20 pack-year history of smoking and currently smoke or have quit within the past 15 years.

But implementing the recommendation is not always simple. Unlike a colorectal or breast cancer screening, which is recommended primarily on patient age, eligibility for a lung cancer screening requires calculating pack-years of smoking, and, for past smokers, knowledge of when they quit.

The structured fields in most electronic medical records (EMRs) inquire about current or past use of cigarettes and the number of daily packs smoked. But few EMRs can calculate when a patient starts smoking two cigarettes a day but then increases to a pack a day and cuts down again. EMRs also do not track when a patient has stopped smoking permanently. Individual clinicians or health systems must identify patients who are eligible for screening, but the lack of automated calculations makes that job more difficult.

Dr. Sandler and colleagues turned to the informatics team at Vanderbilt to develop a natural language processing approach that extracts smoking data directly from clinician notes instead of using standard variables in their EMR.

The number of patients identified as needing a screening using the algorithm nearly doubled from baseline, from 5887 to 10,231 over a 3-year period, according to results from another study that Dr. Sandler published.

Although the algorithm may occasionally flag someone who does not need screening as eligible, “you can always have a conversation with the patient to determine if they actually meet eligibility criteria,” Dr. Sandler said.
 

Patient Navigators to the Rescue?

About a decade ago, Travis Baggett, MD, MPH, an associate professor of internal medicine at Harvard Medical School, Boston, Massachusetts, received pilot funding from the ACS to study cancer epidemiology among patients at Boston Health Care for the Homeless Program (BHCHP), which serves nearly 10,000 patients at a variety of Boston-area clinics each year.

“We found that both the incidence and mortality rates for lung cancer were more than twofold higher than in the general population,” Dr. Baggett, who is also the director of research at BHCHP, said.

He also discovered that BHCHP patients were diagnosed at significantly later stages than people in the general population for malignancies like breast and colorectal cancer.

Screening for lung cancer was a new recommendation at the time. With additional funding from the ACS, he launched a clinical trial in 2020 that randomized patients who were eligible for lung cancer screening to either work with a patient navigator or receive usual care.

The navigators eased the burden on primary care clinicians: They facilitated shared decision-making visits, helped participants make and attend appointments for low-dose CT, assisted with transportation, and arranged follow-up as needed.

The 3-year study found 43% of patients who received navigation services underwent screening for lung cancer, compared with 9% in the usual-care arm. Participants said the navigators played a critical role in educating them about the importance of screening, coordinating care, and providing emotional support.

“At the root of it all, it was quite clear that one thing that made the navigator successful was their interpersonal qualities and having someone that the patient could trust to help guide them through the process,” Dr. Baggett said.

The navigator program, however, stopped when the funding for the study ended.

But another health system has implemented navigators in a sustainable way through a quality improvement project. Michael Gieske, MD, director of lung cancer screening at St. Elizabeth Healthcare in Edgewood, Kentucky, starts his Friday morning meeting with a multidisciplinary group, including a thoracic surgeon, radiologist, pulmonologist, and several screening nurse navigators. They review the week’s chest CTs, with approximately one-third from patients who underwent lung cancer screening.

Nurse navigators at St. Elizabeth Healthcare follow up with any patient whose scan is suspicious for lung cancer and guide them through the process of seeing specialists and obtaining additional testing.

“They essentially hold the patient’s hand through this scary time in their life and make sure that everything flows smoothly and efficiently,” said Dr. Gieske, a family medicine physician.

St. Elizabeth’s program also draws on several evidence-based strategies used for other cancer screening programs, such as patient and provider education and quarterly feedback to their 194 primary care clinicians on rates of lung cancer screening among their eligible patients.

Several requirements for reimbursement for a lung cancer screening from the US Centers for Medicare & Medicaid Services can also serve as barriers to getting patients screened: Clinicians must identify who is eligible, provide tobacco cessation counseling, and document the shared decision-making process.

To streamline the steps, St. Elizabeth’s clinicians use an EMR smart set that reminds clinicians to verify smoking history and helps them document the required counseling.

Last year, 47% of eligible patients received their recommended screening, and Dr. Gieske said he expects even more improvement.

“We’re on track this year to complete 60% uptake if things continue,” he said, adding that 76% of the new cases of lung cancer are now diagnosed in stage I, with only 5% diagnosed in stage IV.

Dr. Gieske has shared his experience with many clinics in Appalachia, home to some of the highest rates of mortality from lung cancer in the country. A major part of his role with the Appalachian Community Cancer Alliance is helping educate primary care clinicians in the region about the importance of early detection of lung cancer.

“I think one of the most important things is just to convey a message of hope,” he said. “We’re trying to get the good word out there that if you screen individuals, you’re going to catch it early, when you have an extremely high chance of curing the lung cancer.”

Dr. Baggett reported support from grants from the ACS and the Massachusetts General Hospital Research Scholars Program. Dr. Sandler and Dr. Gieske reported no financial conflicts.

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

A central aim of prostate cancer treatment is to prolong survival, but trials often overlook another key goal: Improving — or at least maintaining — quality of life (QoL).

The recent American Society of Clinical Oncology (ASCO) 2024 annual meeting dedicated a session to QoL outcomes in men with prostate cancer.

The trials explored the effects of treatment suspension or intensification on health-related QoL as well as interventions to manage side effects in different patient populations.

The first presentation focused on a post hoc analysis of the phase 3 EMBARK trial, which looked at the effect of suspending treatment on health-related QoL in men with nonmetastatic disease at a high risk for biochemical recurrence.

Earlier findings from the trial, presented at ESMO in 2023, showed enzalutamide alone or in combination with androgen deprivation therapy (ADT) was associated with a significant improvement in metastasis-free survival vs placebo plus leuprolide.

The initial trial randomized 1068 patients at a high risk for biochemical recurrence to these three treatment groups and suspended therapy at week 37 if prostate-specific antigen (PSA) levels fell below 0.2 ng/mL. Patients, however, were not randomized into the treatment suspension groups. Treatment resumed if PSA levels rose to ≥ 2.0 ng/mL in patients who had undergone radical prostatectomy or ≥ 5.0 ng/mL in those who had not had surgery.

The post hoc analysis, which assessed patient-reported QoL outcomes following treatment suspension at baseline and every 12 weeks until progression, found no meaningful changes in the worst pain in the past 24 hours, as measured by the Brief Pain Inventory–Short Form.

Patients also reported no meaningful changes in total and physical well-being scores on the Functional Assessment of Cancer Therapy–Prostate (FACT-P) and on the European Quality of Life Five-Dimensions (EuroQol-5D) visual analog scale score, as well as no meaningful changes in sexual activity and urinary and bowel symptoms, based on scores from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Prostate 25 (QLQ-PR25).

Hormone treatment-related symptoms on the QLQ-PR25, however, “quickly improved but eventually began to worsen after week 97,” explained lead author Stephen J. Freedland, MD, from Cedars-Sinai Medical Center, Los Angeles, California, who presented the new findings at ASCO.

Dr. Freedland concluded that the EMBARK results show that enzalutamide, with or without ADT, improves metastasis-free survival vs leuprolide alone, without affecting global health-related QoL during treatment or after treatment suspension.

However, Channing J. Paller, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Medicine, Baltimore, Maryland, who was not involved in the research, pointed out that “patient selection is key” when choosing therapies, given that ADT has distinct adverse effects. Comorbidities and adverse effects “must be taken into consideration to help the doctor and patient make more personalized treatment choices.”
 

Treatment Intensification and QoL

Another presentation explored health-related QoL outcomes from the phase 3 PRESTO trial.

The study examined ADT intensification in 504 patients who had high-risk biochemically relapsed nonmetastatic hormone-sensitive prostate cancer and a PSA doubling time of 9 months or less. Patients were randomized to ADT monotherapy with degarelix or leuprolide, ADT plus apalutamide, or ADT plus apalutamide, abiraterone acetate, and prednisone.

In previous data from PRESTO, the combination therapy groups both had significantly longer median PSA progression-free survival than the ADT monotherapy arm.

The latest data looked at the health-related QoL outcomes in the PRESTO population, measured using the Expanded Prostate Cancer Index Composite, the PROMIS Fatigue tool, the Hot Flash Related Daily Interference Scale, and the EuroQol-5D.

Ronald C. Chen, MD, MPH, of the University of Kansas Medical Center, Kansas City, who presented the new findings at ASCO, reported that ADT plus apalutamide improved PSA progression-free survival over ADT alone and did not meaningfully increase common treatment-related symptoms, such as hormonal symptoms, sexual dysfunction, hot flash interference, and fatigue.

However, treatment intensification with triple androgen regimen did not lead to further improvements in PSA progression-free survival but did increase the rate of serious adverse events, the time to testosterone recover, and increased hot flash interference.

PRESTO as well as EMBARK “provide a strong rationale for intensification of androgen blockade in men with high-risk biochemical recurrence after completing primary local therapy” and could even “reduce the need for subsequent treatment,” concluded Dr. Chen.
 

CBT for Managing ADT Side Effects

Up to 80% of men receiving ADT to treat prostate cancer experience night sweats and hot flashes, which are associated with sleep disturbance, anxiety, low mood, and cognitive impairments.

A third trial presented during the session looked at the impact of cognitive-behavioral therapy (CBT) on these side effects of ADT treatment.

Initial findings from the MANCAN study found that CBT delivered by a psychologist reduced the impact of hot flashes and night sweats at 6 weeks.

The MANCAN2 study assessed QoL at 6 months among 162 patients with localized or advanced prostate cancer who underwent at least 6 months of continuous ADT and who experienced more severe hot flashes and night sweats, defined as a score of ≥ 2 on the hot flashes and night sweats problem rating scale.

Study participants were randomized to CBT plus treatment as usual, or treatment as usual alone, with the intervention consisting of two CBT group sessions 4 weeks apart. Between CBT sessions, patients could refer to a booklet and CD, alongside exercises and CBT strategies.

MANCAN2 confirmed that CBT was associated with a significantly greater reduction in hot flash and night sweat scores over standard care alone at 6 weeks. Patients receiving CBT also reported better QoL, sleep, and functional status but those differences did not reach statistical significance.

By 6 months, those in the CBT group still reported better outcomes in each category, but no differences were statistically significant at this time point. Overall, however, 14% of treatment as usual alone patients discontinued ADT at 6 months vs none in the CBT arm.

“Further research is therefore needed to determine whether or not you can make this effect more durable” and to look at “the potential for CBT to support treatment compliance,” said study presenter Simon J. Crabb, PhD, MBBS, from the University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, England.
 

QoL With Radioligand Crossover

Finally, the phase 3 PSMAfore study compared ¹⁷⁷Lu-PSMA-617 with abiraterone or enzalutamide in 468 taxane-naive patients with metastatic castration-resistant prostate cancer who had progressed on a previous androgen receptor pathway inhibitor.

In earlier analyses, Karim Fizazi, MD, PhD, Institut Gustave Roussy, Université Paris-Saclay, Paris, France, reported that ¹⁷⁷Lu-PSMA-617 improved radiographic progression-free survival by 59% over androgen receptor pathway inhibitor therapy but did not lead to significant differences in overall survival.

In a new interim analysis, Dr. Fizazi and colleagues explored outcomes in patients eligible to cross over to ¹⁷⁷Lu-PSMA-617 following androgen receptor pathway inhibitor therapy. Assessments of health-related QoL revealed that ¹⁷⁷Lu-PSMA-617 led to about a 40% improvement in scores on two QoL tools — 41% with FACT-P and 39% with EuroQol-5D.

On subscales of FACT-P, Dr. Fizazi reported that ¹⁷⁷Lu-PSMA-617 was also associated with a significantly longer time to worsening in physical, functional, and emotional well-being over standard therapy. A pain inventory score indicated that ¹⁷⁷Lu-PSMA-617 led to a 31% improvement in the time to worsening pain intensity, as well as a 33% increase in the time to worsening pain interference.

With the treatment having a “favorable safety profile,” Dr. Fizazi said the results suggest ¹⁷⁷Lu-PSMA-617 is a “treatment option” for patients with metastatic castration-resistant prostate cancer who have undergone androgen receptor pathway inhibitor treatment.

MANCAN2 was funded by the UK National Institute for Health and Care Research. EMBARK was funded by Astellas Pharma and Pfizer, the codevelopers of enzalutamide. PRESTO was funded by Alliance Foundation Trials and Johnson & Johnson. PSMAfore was funded by Novartis. Dr. Freedland declared relationships with Pfizer and Astellas Pharma, among others. Paller declared relationships with AstraZeneca, Dendreon, Exelixis, Janssen Oncology, Omnitura, Lilly, and Bayer. Dr. Chen declared relationships with Astellas Pharma, Pfizer, and others. Dr. Crabb declared relationships with AstraZeneca, Bristol-Myers Squibb, Ipsen, Merck, Amgen, Amphista Therapeutics, Bayer, Janssen, MSD, Pfizer, Astex Pharmaceuticals, Clovis Oncology, and Roche. Dr. Fizazi reported relationships with Novartis, AstraZeneca, and a dozen other companies.

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

A central aim of prostate cancer treatment is to prolong survival, but trials often overlook another key goal: Improving — or at least maintaining — quality of life (QoL).

The recent American Society of Clinical Oncology (ASCO) 2024 annual meeting dedicated a session to QoL outcomes in men with prostate cancer.

The trials explored the effects of treatment suspension or intensification on health-related QoL as well as interventions to manage side effects in different patient populations.

The first presentation focused on a post hoc analysis of the phase 3 EMBARK trial, which looked at the effect of suspending treatment on health-related QoL in men with nonmetastatic disease at a high risk for biochemical recurrence.

Earlier findings from the trial, presented at ESMO in 2023, showed enzalutamide alone or in combination with androgen deprivation therapy (ADT) was associated with a significant improvement in metastasis-free survival vs placebo plus leuprolide.

The initial trial randomized 1068 patients at a high risk for biochemical recurrence to these three treatment groups and suspended therapy at week 37 if prostate-specific antigen (PSA) levels fell below 0.2 ng/mL. Patients, however, were not randomized into the treatment suspension groups. Treatment resumed if PSA levels rose to ≥ 2.0 ng/mL in patients who had undergone radical prostatectomy or ≥ 5.0 ng/mL in those who had not had surgery.

The post hoc analysis, which assessed patient-reported QoL outcomes following treatment suspension at baseline and every 12 weeks until progression, found no meaningful changes in the worst pain in the past 24 hours, as measured by the Brief Pain Inventory–Short Form.

Patients also reported no meaningful changes in total and physical well-being scores on the Functional Assessment of Cancer Therapy–Prostate (FACT-P) and on the European Quality of Life Five-Dimensions (EuroQol-5D) visual analog scale score, as well as no meaningful changes in sexual activity and urinary and bowel symptoms, based on scores from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Prostate 25 (QLQ-PR25).

Hormone treatment-related symptoms on the QLQ-PR25, however, “quickly improved but eventually began to worsen after week 97,” explained lead author Stephen J. Freedland, MD, from Cedars-Sinai Medical Center, Los Angeles, California, who presented the new findings at ASCO.

Dr. Freedland concluded that the EMBARK results show that enzalutamide, with or without ADT, improves metastasis-free survival vs leuprolide alone, without affecting global health-related QoL during treatment or after treatment suspension.

However, Channing J. Paller, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Medicine, Baltimore, Maryland, who was not involved in the research, pointed out that “patient selection is key” when choosing therapies, given that ADT has distinct adverse effects. Comorbidities and adverse effects “must be taken into consideration to help the doctor and patient make more personalized treatment choices.”
 

Treatment Intensification and QoL

Another presentation explored health-related QoL outcomes from the phase 3 PRESTO trial.

The study examined ADT intensification in 504 patients who had high-risk biochemically relapsed nonmetastatic hormone-sensitive prostate cancer and a PSA doubling time of 9 months or less. Patients were randomized to ADT monotherapy with degarelix or leuprolide, ADT plus apalutamide, or ADT plus apalutamide, abiraterone acetate, and prednisone.

In previous data from PRESTO, the combination therapy groups both had significantly longer median PSA progression-free survival than the ADT monotherapy arm.

The latest data looked at the health-related QoL outcomes in the PRESTO population, measured using the Expanded Prostate Cancer Index Composite, the PROMIS Fatigue tool, the Hot Flash Related Daily Interference Scale, and the EuroQol-5D.

Ronald C. Chen, MD, MPH, of the University of Kansas Medical Center, Kansas City, who presented the new findings at ASCO, reported that ADT plus apalutamide improved PSA progression-free survival over ADT alone and did not meaningfully increase common treatment-related symptoms, such as hormonal symptoms, sexual dysfunction, hot flash interference, and fatigue.

However, treatment intensification with triple androgen regimen did not lead to further improvements in PSA progression-free survival but did increase the rate of serious adverse events, the time to testosterone recover, and increased hot flash interference.

PRESTO as well as EMBARK “provide a strong rationale for intensification of androgen blockade in men with high-risk biochemical recurrence after completing primary local therapy” and could even “reduce the need for subsequent treatment,” concluded Dr. Chen.
 

CBT for Managing ADT Side Effects

Up to 80% of men receiving ADT to treat prostate cancer experience night sweats and hot flashes, which are associated with sleep disturbance, anxiety, low mood, and cognitive impairments.

A third trial presented during the session looked at the impact of cognitive-behavioral therapy (CBT) on these side effects of ADT treatment.

Initial findings from the MANCAN study found that CBT delivered by a psychologist reduced the impact of hot flashes and night sweats at 6 weeks.

The MANCAN2 study assessed QoL at 6 months among 162 patients with localized or advanced prostate cancer who underwent at least 6 months of continuous ADT and who experienced more severe hot flashes and night sweats, defined as a score of ≥ 2 on the hot flashes and night sweats problem rating scale.

Study participants were randomized to CBT plus treatment as usual, or treatment as usual alone, with the intervention consisting of two CBT group sessions 4 weeks apart. Between CBT sessions, patients could refer to a booklet and CD, alongside exercises and CBT strategies.

MANCAN2 confirmed that CBT was associated with a significantly greater reduction in hot flash and night sweat scores over standard care alone at 6 weeks. Patients receiving CBT also reported better QoL, sleep, and functional status but those differences did not reach statistical significance.

By 6 months, those in the CBT group still reported better outcomes in each category, but no differences were statistically significant at this time point. Overall, however, 14% of treatment as usual alone patients discontinued ADT at 6 months vs none in the CBT arm.

“Further research is therefore needed to determine whether or not you can make this effect more durable” and to look at “the potential for CBT to support treatment compliance,” said study presenter Simon J. Crabb, PhD, MBBS, from the University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, England.
 

QoL With Radioligand Crossover

Finally, the phase 3 PSMAfore study compared ¹⁷⁷Lu-PSMA-617 with abiraterone or enzalutamide in 468 taxane-naive patients with metastatic castration-resistant prostate cancer who had progressed on a previous androgen receptor pathway inhibitor.

In earlier analyses, Karim Fizazi, MD, PhD, Institut Gustave Roussy, Université Paris-Saclay, Paris, France, reported that ¹⁷⁷Lu-PSMA-617 improved radiographic progression-free survival by 59% over androgen receptor pathway inhibitor therapy but did not lead to significant differences in overall survival.

In a new interim analysis, Dr. Fizazi and colleagues explored outcomes in patients eligible to cross over to ¹⁷⁷Lu-PSMA-617 following androgen receptor pathway inhibitor therapy. Assessments of health-related QoL revealed that ¹⁷⁷Lu-PSMA-617 led to about a 40% improvement in scores on two QoL tools — 41% with FACT-P and 39% with EuroQol-5D.

On subscales of FACT-P, Dr. Fizazi reported that ¹⁷⁷Lu-PSMA-617 was also associated with a significantly longer time to worsening in physical, functional, and emotional well-being over standard therapy. A pain inventory score indicated that ¹⁷⁷Lu-PSMA-617 led to a 31% improvement in the time to worsening pain intensity, as well as a 33% increase in the time to worsening pain interference.

With the treatment having a “favorable safety profile,” Dr. Fizazi said the results suggest ¹⁷⁷Lu-PSMA-617 is a “treatment option” for patients with metastatic castration-resistant prostate cancer who have undergone androgen receptor pathway inhibitor treatment.

MANCAN2 was funded by the UK National Institute for Health and Care Research. EMBARK was funded by Astellas Pharma and Pfizer, the codevelopers of enzalutamide. PRESTO was funded by Alliance Foundation Trials and Johnson & Johnson. PSMAfore was funded by Novartis. Dr. Freedland declared relationships with Pfizer and Astellas Pharma, among others. Paller declared relationships with AstraZeneca, Dendreon, Exelixis, Janssen Oncology, Omnitura, Lilly, and Bayer. Dr. Chen declared relationships with Astellas Pharma, Pfizer, and others. Dr. Crabb declared relationships with AstraZeneca, Bristol-Myers Squibb, Ipsen, Merck, Amgen, Amphista Therapeutics, Bayer, Janssen, MSD, Pfizer, Astex Pharmaceuticals, Clovis Oncology, and Roche. Dr. Fizazi reported relationships with Novartis, AstraZeneca, and a dozen other companies.

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

A central aim of prostate cancer treatment is to prolong survival, but trials often overlook another key goal: Improving — or at least maintaining — quality of life (QoL).

The recent American Society of Clinical Oncology (ASCO) 2024 annual meeting dedicated a session to QoL outcomes in men with prostate cancer.

The trials explored the effects of treatment suspension or intensification on health-related QoL as well as interventions to manage side effects in different patient populations.

The first presentation focused on a post hoc analysis of the phase 3 EMBARK trial, which looked at the effect of suspending treatment on health-related QoL in men with nonmetastatic disease at a high risk for biochemical recurrence.

Earlier findings from the trial, presented at ESMO in 2023, showed enzalutamide alone or in combination with androgen deprivation therapy (ADT) was associated with a significant improvement in metastasis-free survival vs placebo plus leuprolide.

The initial trial randomized 1068 patients at a high risk for biochemical recurrence to these three treatment groups and suspended therapy at week 37 if prostate-specific antigen (PSA) levels fell below 0.2 ng/mL. Patients, however, were not randomized into the treatment suspension groups. Treatment resumed if PSA levels rose to ≥ 2.0 ng/mL in patients who had undergone radical prostatectomy or ≥ 5.0 ng/mL in those who had not had surgery.

The post hoc analysis, which assessed patient-reported QoL outcomes following treatment suspension at baseline and every 12 weeks until progression, found no meaningful changes in the worst pain in the past 24 hours, as measured by the Brief Pain Inventory–Short Form.

Patients also reported no meaningful changes in total and physical well-being scores on the Functional Assessment of Cancer Therapy–Prostate (FACT-P) and on the European Quality of Life Five-Dimensions (EuroQol-5D) visual analog scale score, as well as no meaningful changes in sexual activity and urinary and bowel symptoms, based on scores from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Prostate 25 (QLQ-PR25).

Hormone treatment-related symptoms on the QLQ-PR25, however, “quickly improved but eventually began to worsen after week 97,” explained lead author Stephen J. Freedland, MD, from Cedars-Sinai Medical Center, Los Angeles, California, who presented the new findings at ASCO.

Dr. Freedland concluded that the EMBARK results show that enzalutamide, with or without ADT, improves metastasis-free survival vs leuprolide alone, without affecting global health-related QoL during treatment or after treatment suspension.

However, Channing J. Paller, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Medicine, Baltimore, Maryland, who was not involved in the research, pointed out that “patient selection is key” when choosing therapies, given that ADT has distinct adverse effects. Comorbidities and adverse effects “must be taken into consideration to help the doctor and patient make more personalized treatment choices.”
 

Treatment Intensification and QoL

Another presentation explored health-related QoL outcomes from the phase 3 PRESTO trial.

The study examined ADT intensification in 504 patients who had high-risk biochemically relapsed nonmetastatic hormone-sensitive prostate cancer and a PSA doubling time of 9 months or less. Patients were randomized to ADT monotherapy with degarelix or leuprolide, ADT plus apalutamide, or ADT plus apalutamide, abiraterone acetate, and prednisone.

In previous data from PRESTO, the combination therapy groups both had significantly longer median PSA progression-free survival than the ADT monotherapy arm.

The latest data looked at the health-related QoL outcomes in the PRESTO population, measured using the Expanded Prostate Cancer Index Composite, the PROMIS Fatigue tool, the Hot Flash Related Daily Interference Scale, and the EuroQol-5D.

Ronald C. Chen, MD, MPH, of the University of Kansas Medical Center, Kansas City, who presented the new findings at ASCO, reported that ADT plus apalutamide improved PSA progression-free survival over ADT alone and did not meaningfully increase common treatment-related symptoms, such as hormonal symptoms, sexual dysfunction, hot flash interference, and fatigue.

However, treatment intensification with triple androgen regimen did not lead to further improvements in PSA progression-free survival but did increase the rate of serious adverse events, the time to testosterone recover, and increased hot flash interference.

PRESTO as well as EMBARK “provide a strong rationale for intensification of androgen blockade in men with high-risk biochemical recurrence after completing primary local therapy” and could even “reduce the need for subsequent treatment,” concluded Dr. Chen.
 

CBT for Managing ADT Side Effects

Up to 80% of men receiving ADT to treat prostate cancer experience night sweats and hot flashes, which are associated with sleep disturbance, anxiety, low mood, and cognitive impairments.

A third trial presented during the session looked at the impact of cognitive-behavioral therapy (CBT) on these side effects of ADT treatment.

Initial findings from the MANCAN study found that CBT delivered by a psychologist reduced the impact of hot flashes and night sweats at 6 weeks.

The MANCAN2 study assessed QoL at 6 months among 162 patients with localized or advanced prostate cancer who underwent at least 6 months of continuous ADT and who experienced more severe hot flashes and night sweats, defined as a score of ≥ 2 on the hot flashes and night sweats problem rating scale.

Study participants were randomized to CBT plus treatment as usual, or treatment as usual alone, with the intervention consisting of two CBT group sessions 4 weeks apart. Between CBT sessions, patients could refer to a booklet and CD, alongside exercises and CBT strategies.

MANCAN2 confirmed that CBT was associated with a significantly greater reduction in hot flash and night sweat scores over standard care alone at 6 weeks. Patients receiving CBT also reported better QoL, sleep, and functional status but those differences did not reach statistical significance.

By 6 months, those in the CBT group still reported better outcomes in each category, but no differences were statistically significant at this time point. Overall, however, 14% of treatment as usual alone patients discontinued ADT at 6 months vs none in the CBT arm.

“Further research is therefore needed to determine whether or not you can make this effect more durable” and to look at “the potential for CBT to support treatment compliance,” said study presenter Simon J. Crabb, PhD, MBBS, from the University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, England.
 

QoL With Radioligand Crossover

Finally, the phase 3 PSMAfore study compared ¹⁷⁷Lu-PSMA-617 with abiraterone or enzalutamide in 468 taxane-naive patients with metastatic castration-resistant prostate cancer who had progressed on a previous androgen receptor pathway inhibitor.

In earlier analyses, Karim Fizazi, MD, PhD, Institut Gustave Roussy, Université Paris-Saclay, Paris, France, reported that ¹⁷⁷Lu-PSMA-617 improved radiographic progression-free survival by 59% over androgen receptor pathway inhibitor therapy but did not lead to significant differences in overall survival.

In a new interim analysis, Dr. Fizazi and colleagues explored outcomes in patients eligible to cross over to ¹⁷⁷Lu-PSMA-617 following androgen receptor pathway inhibitor therapy. Assessments of health-related QoL revealed that ¹⁷⁷Lu-PSMA-617 led to about a 40% improvement in scores on two QoL tools — 41% with FACT-P and 39% with EuroQol-5D.

On subscales of FACT-P, Dr. Fizazi reported that ¹⁷⁷Lu-PSMA-617 was also associated with a significantly longer time to worsening in physical, functional, and emotional well-being over standard therapy. A pain inventory score indicated that ¹⁷⁷Lu-PSMA-617 led to a 31% improvement in the time to worsening pain intensity, as well as a 33% increase in the time to worsening pain interference.

With the treatment having a “favorable safety profile,” Dr. Fizazi said the results suggest ¹⁷⁷Lu-PSMA-617 is a “treatment option” for patients with metastatic castration-resistant prostate cancer who have undergone androgen receptor pathway inhibitor treatment.

MANCAN2 was funded by the UK National Institute for Health and Care Research. EMBARK was funded by Astellas Pharma and Pfizer, the codevelopers of enzalutamide. PRESTO was funded by Alliance Foundation Trials and Johnson & Johnson. PSMAfore was funded by Novartis. Dr. Freedland declared relationships with Pfizer and Astellas Pharma, among others. Paller declared relationships with AstraZeneca, Dendreon, Exelixis, Janssen Oncology, Omnitura, Lilly, and Bayer. Dr. Chen declared relationships with Astellas Pharma, Pfizer, and others. Dr. Crabb declared relationships with AstraZeneca, Bristol-Myers Squibb, Ipsen, Merck, Amgen, Amphista Therapeutics, Bayer, Janssen, MSD, Pfizer, Astex Pharmaceuticals, Clovis Oncology, and Roche. Dr. Fizazi reported relationships with Novartis, AstraZeneca, and a dozen other companies.

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

Not too long ago, prostate-cancer genetics didn’t mean much to patient care. But in recent years, the landscape of therapy has transformed as researchers have discovered links between multiple genes and aggressive tumors. 

Now, as a hematologist-oncologist explained to attendees at an Association of VA Hematology/Oncology regional meeting in Detroit, genetic tests can guide treatment for some—but not all—men with prostate cancer.

For patients with mutations, appropriate supplemental medications “can improve overall outcomes and have a long-standing impact on patients” said Scott J. Dawsey, MD, of the John D. Dingell Veterans Affairs Medical Center in Detroit in an interview following the AVAHO meeting, which focused on the management of prostate cancer.

As Dawsey explained, about 10% of patients with prostate cancer appear to have genetic mutations, although the exact percentage is unclear. The mutations are especially common in metastatic forms of prostate cancer. They’re estimated to be present in 11.8%-16.2% of those cases.

While these proportions are relatively small, the number of overall prostate-cancer cases with mutations is large due to the high burden of the disease, Dawsey said. Prostate cancer is by far the most common cancer in men, and estimated 299,010 cases will be diagnosed in the United States this year.

According to Dawsey, genetic mutations seem to boost the risk of more aggressive disease—and the risk of other malignancies—by disrupting DNA repair. This process can lead to even more mutations that may “make the cancer behave and grow more aggressively.”

But not all prostate cancer patients need to undergo genetic testing. Dawsey urged colleagues to figure out which patients should be tested by consulting National Comprehensive Cancer Network (NCCN) guidelines and the newly updated US Department of Veterans Affairs (VA) prostate cancer clinical pathway.

The two sets of recommendations agree on germline testing in patients with cases that are metastatic, very high risk, and high risk. Lower-risk cases should only be tested if patients meet family history criteria. The sets of guidelines also recommend somatic testing in patients with metastatic cancer.

In addition to providing guidance about treatment, genetic test results can have implications regarding other potential malignancies that may affect patients, Dawsey said. The results may also have implications for cancer risk in family members.

Several drugs are now available for patients with genetic mutations, including checkpoint inhibitors and PARP inhibitors. The drugs, which have unique mechanisms of action, are given in addition to standard prostate cancer treatments, he said.

“If a patient doesn’t have one of these genetic changes,” he said, “these drugs aren’t an option.”

A long list of drugs or combinations of drugs are in clinical trials, including the poly(adenosine diphosphate–ribose) polymerase (PARP) inhibitors olaparib, abiraterone, and niraparib and the checkpoint inhibitors nivolumab and cemiplimab.

The drugs generally improve response rates and progression-free survival, Dawsey said, and patients are generally able to tolerate them. In regard to which drugs to choose, he suggested consulting the and NCCN guidelines and the VA oncology clinical pathway for prostate cancer.

Not too long ago, prostate-cancer genetics didn’t mean much to patient care. But in recent years, the landscape of therapy has transformed as researchers have discovered links between multiple genes and aggressive tumors. 

Now, as a hematologist-oncologist explained to attendees at an Association of VA Hematology/Oncology regional meeting in Detroit, genetic tests can guide treatment for some—but not all—men with prostate cancer.

For patients with mutations, appropriate supplemental medications “can improve overall outcomes and have a long-standing impact on patients” said Scott J. Dawsey, MD, of the John D. Dingell Veterans Affairs Medical Center in Detroit in an interview following the AVAHO meeting, which focused on the management of prostate cancer.

As Dawsey explained, about 10% of patients with prostate cancer appear to have genetic mutations, although the exact percentage is unclear. The mutations are especially common in metastatic forms of prostate cancer. They’re estimated to be present in 11.8%-16.2% of those cases.

While these proportions are relatively small, the number of overall prostate-cancer cases with mutations is large due to the high burden of the disease, Dawsey said. Prostate cancer is by far the most common cancer in men, and estimated 299,010 cases will be diagnosed in the United States this year.

According to Dawsey, genetic mutations seem to boost the risk of more aggressive disease—and the risk of other malignancies—by disrupting DNA repair. This process can lead to even more mutations that may “make the cancer behave and grow more aggressively.”

But not all prostate cancer patients need to undergo genetic testing. Dawsey urged colleagues to figure out which patients should be tested by consulting National Comprehensive Cancer Network (NCCN) guidelines and the newly updated US Department of Veterans Affairs (VA) prostate cancer clinical pathway.

The two sets of recommendations agree on germline testing in patients with cases that are metastatic, very high risk, and high risk. Lower-risk cases should only be tested if patients meet family history criteria. The sets of guidelines also recommend somatic testing in patients with metastatic cancer.

In addition to providing guidance about treatment, genetic test results can have implications regarding other potential malignancies that may affect patients, Dawsey said. The results may also have implications for cancer risk in family members.

Several drugs are now available for patients with genetic mutations, including checkpoint inhibitors and PARP inhibitors. The drugs, which have unique mechanisms of action, are given in addition to standard prostate cancer treatments, he said.

“If a patient doesn’t have one of these genetic changes,” he said, “these drugs aren’t an option.”

A long list of drugs or combinations of drugs are in clinical trials, including the poly(adenosine diphosphate–ribose) polymerase (PARP) inhibitors olaparib, abiraterone, and niraparib and the checkpoint inhibitors nivolumab and cemiplimab.

The drugs generally improve response rates and progression-free survival, Dawsey said, and patients are generally able to tolerate them. In regard to which drugs to choose, he suggested consulting the and NCCN guidelines and the VA oncology clinical pathway for prostate cancer.

Not too long ago, prostate-cancer genetics didn’t mean much to patient care. But in recent years, the landscape of therapy has transformed as researchers have discovered links between multiple genes and aggressive tumors. 

Now, as a hematologist-oncologist explained to attendees at an Association of VA Hematology/Oncology regional meeting in Detroit, genetic tests can guide treatment for some—but not all—men with prostate cancer.

For patients with mutations, appropriate supplemental medications “can improve overall outcomes and have a long-standing impact on patients” said Scott J. Dawsey, MD, of the John D. Dingell Veterans Affairs Medical Center in Detroit in an interview following the AVAHO meeting, which focused on the management of prostate cancer.

As Dawsey explained, about 10% of patients with prostate cancer appear to have genetic mutations, although the exact percentage is unclear. The mutations are especially common in metastatic forms of prostate cancer. They’re estimated to be present in 11.8%-16.2% of those cases.

While these proportions are relatively small, the number of overall prostate-cancer cases with mutations is large due to the high burden of the disease, Dawsey said. Prostate cancer is by far the most common cancer in men, and estimated 299,010 cases will be diagnosed in the United States this year.

According to Dawsey, genetic mutations seem to boost the risk of more aggressive disease—and the risk of other malignancies—by disrupting DNA repair. This process can lead to even more mutations that may “make the cancer behave and grow more aggressively.”

But not all prostate cancer patients need to undergo genetic testing. Dawsey urged colleagues to figure out which patients should be tested by consulting National Comprehensive Cancer Network (NCCN) guidelines and the newly updated US Department of Veterans Affairs (VA) prostate cancer clinical pathway.

The two sets of recommendations agree on germline testing in patients with cases that are metastatic, very high risk, and high risk. Lower-risk cases should only be tested if patients meet family history criteria. The sets of guidelines also recommend somatic testing in patients with metastatic cancer.

In addition to providing guidance about treatment, genetic test results can have implications regarding other potential malignancies that may affect patients, Dawsey said. The results may also have implications for cancer risk in family members.

Several drugs are now available for patients with genetic mutations, including checkpoint inhibitors and PARP inhibitors. The drugs, which have unique mechanisms of action, are given in addition to standard prostate cancer treatments, he said.

“If a patient doesn’t have one of these genetic changes,” he said, “these drugs aren’t an option.”

A long list of drugs or combinations of drugs are in clinical trials, including the poly(adenosine diphosphate–ribose) polymerase (PARP) inhibitors olaparib, abiraterone, and niraparib and the checkpoint inhibitors nivolumab and cemiplimab.

The drugs generally improve response rates and progression-free survival, Dawsey said, and patients are generally able to tolerate them. In regard to which drugs to choose, he suggested consulting the and NCCN guidelines and the VA oncology clinical pathway for prostate cancer.

Findings from the phase 3 ESOPEC trial demonstrate an overall survival advantage with a perioperative chemotherapy regimen known as FLOT, compared with a neoadjuvant chemoradiation approach, called CROSS, in patients with resectable, locally advanced esophageal adenocarcinoma.

The study results, presented as a late-breaking abstract at the annual meeting of the American Society of Clinical Oncology (ASCO), help settle a long-standing debate about whether chemotherapy with FLOT — 5-florouracil, leucovorin, oxaliplatin, and docetaxel — before and after surgery, or neoadjuvant radiation plus CROSS — carboplatin and paclitaxel — followed by surgery is the best approach.

There has been “considerable disagreement as to whether giving all adjuvant therapy upfront versus ‘sandwich’ adjuvant therapy before and after surgery is the better standard of care for locally advanced resectable esophageal cancer,” Jennifer Tseng, MD, of Boston Medical Center, Boston, said in an ASCO press release. This randomized clinical trial shows the sandwich approach “provides better outcomes.”

The practice-changing ESOPEC findings will have an important effect on the management of patients with resectable esophageal adenocarcinoma and gastroesophageal junction adenocarcinoma, but local and distant failures remain a challenge in this population, explained invited discussant Karyn A. Goodman, MD.

Advances since the initiation of ESOPEC — such as immunotherapy options and personalized strategies — suggest the esophageal adenocarcinoma story is still evolving, said Dr. Goodman, professor and vice chair of research and quality in the Department of Radiation Oncology at Icahn School of Medicine at Mount Sinai, New York. 
 

The ESOPEC trial

Both the FLOT and CROSS regimens are established standards of care in resectable esophageal adenocarcinoma, and the choice of treatment has largely varied based on geographical location.

The current randomized, prospective, open-label ESOPEC trial, however, demonstrated that FLOT can prolong overall survival, first author Jens Hoeppner, MD, from the University of Bielefeld in Detmold, Germany, reported.

Overall, 438 patients with locally advanced, resectable esophageal adenocarcinoma recruited between February 2016 and April 2020 from 25 sites in Germany and randomized to either FLOT (n = 221) or CROSS (n = 217). The median age was 63 years, and most (89.3%) were men. Patients were followed until November 2023, and median follow-up was 55 months.

Patients in the FLOT arm received four cycles — one every 2 weeks for 8 weeks — followed by surgery 4-6 weeks later. FLOT cycles were reinitiated 4-6 weeks after surgery and given every 2 weeks for 8 weeks.

Those in the CROSS arm received one cycle per week of radiation therapy for 5 weeks plus carboplatin and paclitaxel followed by surgery 4-6 weeks after the last cycle.

Overall, 86% received both neoadjuvant therapy and surgery in the FLOT arm versus 82.9% in the CROSS group. Among these patients, 16.8% in the FLOT group achieved a pathological complete remission versus 10.0% in the CROSS arm.

In the intention-to-treat population, median overall survival was almost twice as long in the FLOT group — 66 months versus 37 months. At 3 years, those who received FLOT had a 30% lower risk of dying (hazard ratio [HR], 0.70), with 57.4% of patients alive at that point, compared with 50.7% patients in the CROSS arm.

The 5-year overall survival was 50.6% in the FLOT group versus 38.7% in the CROSS group.

Patients receiving FLOT also demonstrated improved progression-free survival (PFS), with a median PFS of 38 months versus 16 months. The 3-year PFS was 51.6% with FLOT versus 35.0% with CROSS (HR, 0.66). The exploratory subgroup analyses for sex, age, ECOG status, and clinical T and N stages also favored FLOT.

The 30-day postoperative mortality was 1.0% in the FLOT group and 1.7% in the CROSS group, and the 90-day postoperative mortality rate was 3.2% and 5.6%, respectively.

Based on these findings, perioperative chemotherapy with FLOT should be preferred over neoadjuvant chemoradiation with CROSS, Dr. Hoeppner concluded.

Dr. Goodman agreed, noting that, in the wake of ESOPEC, FLOT will likely be adopted as a more standard approach in the United States for patients who are fit. And, for patients who are not candidates for FLOT, CROSS is a reasonable option, she said.

But, she asked, does it really have to be an either/or situation?

Multiple studies, including Dr. Goodman’s 2021 Alliance/CALGB 80803 study, have demonstrated promising outcomes with combined modalities and adapting therapy based on treatment response. Several trials, for instance, are evaluating combining FLOT and CROSS, with some showing the approach is feasible and comes with manageable toxicity.

It’s also important to look outside of FLOT and CROSS. During ESOPEC, new approaches entered the treatment landscape, including the use of adjuvant immunotherapy following neoadjuvant chemoradiation and surgery for noncomplete response.

Take the CheckMate 577 study, which found that adjuvant nivolumab immunotherapy after preoperative CROSS and surgery significantly reduced metastatic recurrence and doubled disease-free survival in patients who did not achieve a complete response. This approach is now a standard of care for those patients.

FLOT plus neoadjuvant nivolumab may also be a viable option, Dr. Goodman noted, but we haven’t yet seen “any benefit in survival with the combo of chemotherapy and immunotherapy for resectable esophago-gastric cancer.”

Further studies are needed to evaluate the synergy of immunotherapy and radiotherapy. The next chapter of the esophageal adenocarcinoma story may feature a “best-of-both-worlds” approach that combines induction chemotherapy, followed by personalized chemoradiation, surgery, and potentially adjuvant immunotherapy, Dr. Goodman explained.

While the ESOPEC findings are impressive, the 5-year overall survival of only 50% is still suboptimal, she noted. “Given the poor prognosis with this disease, we need to continue to develop clinical trials to identify better targets, novel treatment combinations, and select patients that will respond best to specific treatment.”

ESOPEC was funded by the Deutsche Forschungsgemeinschaft (German Research Foundation). Dr. Hoeppner reported receiving travel, accommodations, and expenses from Intuitive Surgical. Dr. Goodman reported a relationship with the National Cancer Institute and consulting or advisory roles for Novartis, Philips Healthcare, RenovoRX, and Roche/Genentech.

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

Findings from the phase 3 ESOPEC trial demonstrate an overall survival advantage with a perioperative chemotherapy regimen known as FLOT, compared with a neoadjuvant chemoradiation approach, called CROSS, in patients with resectable, locally advanced esophageal adenocarcinoma.

The study results, presented as a late-breaking abstract at the annual meeting of the American Society of Clinical Oncology (ASCO), help settle a long-standing debate about whether chemotherapy with FLOT — 5-florouracil, leucovorin, oxaliplatin, and docetaxel — before and after surgery, or neoadjuvant radiation plus CROSS — carboplatin and paclitaxel — followed by surgery is the best approach.

There has been “considerable disagreement as to whether giving all adjuvant therapy upfront versus ‘sandwich’ adjuvant therapy before and after surgery is the better standard of care for locally advanced resectable esophageal cancer,” Jennifer Tseng, MD, of Boston Medical Center, Boston, said in an ASCO press release. This randomized clinical trial shows the sandwich approach “provides better outcomes.”

The practice-changing ESOPEC findings will have an important effect on the management of patients with resectable esophageal adenocarcinoma and gastroesophageal junction adenocarcinoma, but local and distant failures remain a challenge in this population, explained invited discussant Karyn A. Goodman, MD.

Advances since the initiation of ESOPEC — such as immunotherapy options and personalized strategies — suggest the esophageal adenocarcinoma story is still evolving, said Dr. Goodman, professor and vice chair of research and quality in the Department of Radiation Oncology at Icahn School of Medicine at Mount Sinai, New York. 
 

The ESOPEC trial

Both the FLOT and CROSS regimens are established standards of care in resectable esophageal adenocarcinoma, and the choice of treatment has largely varied based on geographical location.

The current randomized, prospective, open-label ESOPEC trial, however, demonstrated that FLOT can prolong overall survival, first author Jens Hoeppner, MD, from the University of Bielefeld in Detmold, Germany, reported.

Overall, 438 patients with locally advanced, resectable esophageal adenocarcinoma recruited between February 2016 and April 2020 from 25 sites in Germany and randomized to either FLOT (n = 221) or CROSS (n = 217). The median age was 63 years, and most (89.3%) were men. Patients were followed until November 2023, and median follow-up was 55 months.

Patients in the FLOT arm received four cycles — one every 2 weeks for 8 weeks — followed by surgery 4-6 weeks later. FLOT cycles were reinitiated 4-6 weeks after surgery and given every 2 weeks for 8 weeks.

Those in the CROSS arm received one cycle per week of radiation therapy for 5 weeks plus carboplatin and paclitaxel followed by surgery 4-6 weeks after the last cycle.

Overall, 86% received both neoadjuvant therapy and surgery in the FLOT arm versus 82.9% in the CROSS group. Among these patients, 16.8% in the FLOT group achieved a pathological complete remission versus 10.0% in the CROSS arm.

In the intention-to-treat population, median overall survival was almost twice as long in the FLOT group — 66 months versus 37 months. At 3 years, those who received FLOT had a 30% lower risk of dying (hazard ratio [HR], 0.70), with 57.4% of patients alive at that point, compared with 50.7% patients in the CROSS arm.

The 5-year overall survival was 50.6% in the FLOT group versus 38.7% in the CROSS group.

Patients receiving FLOT also demonstrated improved progression-free survival (PFS), with a median PFS of 38 months versus 16 months. The 3-year PFS was 51.6% with FLOT versus 35.0% with CROSS (HR, 0.66). The exploratory subgroup analyses for sex, age, ECOG status, and clinical T and N stages also favored FLOT.

The 30-day postoperative mortality was 1.0% in the FLOT group and 1.7% in the CROSS group, and the 90-day postoperative mortality rate was 3.2% and 5.6%, respectively.

Based on these findings, perioperative chemotherapy with FLOT should be preferred over neoadjuvant chemoradiation with CROSS, Dr. Hoeppner concluded.

Dr. Goodman agreed, noting that, in the wake of ESOPEC, FLOT will likely be adopted as a more standard approach in the United States for patients who are fit. And, for patients who are not candidates for FLOT, CROSS is a reasonable option, she said.

But, she asked, does it really have to be an either/or situation?

Multiple studies, including Dr. Goodman’s 2021 Alliance/CALGB 80803 study, have demonstrated promising outcomes with combined modalities and adapting therapy based on treatment response. Several trials, for instance, are evaluating combining FLOT and CROSS, with some showing the approach is feasible and comes with manageable toxicity.

It’s also important to look outside of FLOT and CROSS. During ESOPEC, new approaches entered the treatment landscape, including the use of adjuvant immunotherapy following neoadjuvant chemoradiation and surgery for noncomplete response.

Take the CheckMate 577 study, which found that adjuvant nivolumab immunotherapy after preoperative CROSS and surgery significantly reduced metastatic recurrence and doubled disease-free survival in patients who did not achieve a complete response. This approach is now a standard of care for those patients.

FLOT plus neoadjuvant nivolumab may also be a viable option, Dr. Goodman noted, but we haven’t yet seen “any benefit in survival with the combo of chemotherapy and immunotherapy for resectable esophago-gastric cancer.”

Further studies are needed to evaluate the synergy of immunotherapy and radiotherapy. The next chapter of the esophageal adenocarcinoma story may feature a “best-of-both-worlds” approach that combines induction chemotherapy, followed by personalized chemoradiation, surgery, and potentially adjuvant immunotherapy, Dr. Goodman explained.

While the ESOPEC findings are impressive, the 5-year overall survival of only 50% is still suboptimal, she noted. “Given the poor prognosis with this disease, we need to continue to develop clinical trials to identify better targets, novel treatment combinations, and select patients that will respond best to specific treatment.”

ESOPEC was funded by the Deutsche Forschungsgemeinschaft (German Research Foundation). Dr. Hoeppner reported receiving travel, accommodations, and expenses from Intuitive Surgical. Dr. Goodman reported a relationship with the National Cancer Institute and consulting or advisory roles for Novartis, Philips Healthcare, RenovoRX, and Roche/Genentech.

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

Findings from the phase 3 ESOPEC trial demonstrate an overall survival advantage with a perioperative chemotherapy regimen known as FLOT, compared with a neoadjuvant chemoradiation approach, called CROSS, in patients with resectable, locally advanced esophageal adenocarcinoma.

The study results, presented as a late-breaking abstract at the annual meeting of the American Society of Clinical Oncology (ASCO), help settle a long-standing debate about whether chemotherapy with FLOT — 5-florouracil, leucovorin, oxaliplatin, and docetaxel — before and after surgery, or neoadjuvant radiation plus CROSS — carboplatin and paclitaxel — followed by surgery is the best approach.

There has been “considerable disagreement as to whether giving all adjuvant therapy upfront versus ‘sandwich’ adjuvant therapy before and after surgery is the better standard of care for locally advanced resectable esophageal cancer,” Jennifer Tseng, MD, of Boston Medical Center, Boston, said in an ASCO press release. This randomized clinical trial shows the sandwich approach “provides better outcomes.”

The practice-changing ESOPEC findings will have an important effect on the management of patients with resectable esophageal adenocarcinoma and gastroesophageal junction adenocarcinoma, but local and distant failures remain a challenge in this population, explained invited discussant Karyn A. Goodman, MD.

Advances since the initiation of ESOPEC — such as immunotherapy options and personalized strategies — suggest the esophageal adenocarcinoma story is still evolving, said Dr. Goodman, professor and vice chair of research and quality in the Department of Radiation Oncology at Icahn School of Medicine at Mount Sinai, New York. 
 

The ESOPEC trial

Both the FLOT and CROSS regimens are established standards of care in resectable esophageal adenocarcinoma, and the choice of treatment has largely varied based on geographical location.

The current randomized, prospective, open-label ESOPEC trial, however, demonstrated that FLOT can prolong overall survival, first author Jens Hoeppner, MD, from the University of Bielefeld in Detmold, Germany, reported.

Overall, 438 patients with locally advanced, resectable esophageal adenocarcinoma recruited between February 2016 and April 2020 from 25 sites in Germany and randomized to either FLOT (n = 221) or CROSS (n = 217). The median age was 63 years, and most (89.3%) were men. Patients were followed until November 2023, and median follow-up was 55 months.

Patients in the FLOT arm received four cycles — one every 2 weeks for 8 weeks — followed by surgery 4-6 weeks later. FLOT cycles were reinitiated 4-6 weeks after surgery and given every 2 weeks for 8 weeks.

Those in the CROSS arm received one cycle per week of radiation therapy for 5 weeks plus carboplatin and paclitaxel followed by surgery 4-6 weeks after the last cycle.

Overall, 86% received both neoadjuvant therapy and surgery in the FLOT arm versus 82.9% in the CROSS group. Among these patients, 16.8% in the FLOT group achieved a pathological complete remission versus 10.0% in the CROSS arm.

In the intention-to-treat population, median overall survival was almost twice as long in the FLOT group — 66 months versus 37 months. At 3 years, those who received FLOT had a 30% lower risk of dying (hazard ratio [HR], 0.70), with 57.4% of patients alive at that point, compared with 50.7% patients in the CROSS arm.

The 5-year overall survival was 50.6% in the FLOT group versus 38.7% in the CROSS group.

Patients receiving FLOT also demonstrated improved progression-free survival (PFS), with a median PFS of 38 months versus 16 months. The 3-year PFS was 51.6% with FLOT versus 35.0% with CROSS (HR, 0.66). The exploratory subgroup analyses for sex, age, ECOG status, and clinical T and N stages also favored FLOT.

The 30-day postoperative mortality was 1.0% in the FLOT group and 1.7% in the CROSS group, and the 90-day postoperative mortality rate was 3.2% and 5.6%, respectively.

Based on these findings, perioperative chemotherapy with FLOT should be preferred over neoadjuvant chemoradiation with CROSS, Dr. Hoeppner concluded.

Dr. Goodman agreed, noting that, in the wake of ESOPEC, FLOT will likely be adopted as a more standard approach in the United States for patients who are fit. And, for patients who are not candidates for FLOT, CROSS is a reasonable option, she said.

But, she asked, does it really have to be an either/or situation?

Multiple studies, including Dr. Goodman’s 2021 Alliance/CALGB 80803 study, have demonstrated promising outcomes with combined modalities and adapting therapy based on treatment response. Several trials, for instance, are evaluating combining FLOT and CROSS, with some showing the approach is feasible and comes with manageable toxicity.

It’s also important to look outside of FLOT and CROSS. During ESOPEC, new approaches entered the treatment landscape, including the use of adjuvant immunotherapy following neoadjuvant chemoradiation and surgery for noncomplete response.

Take the CheckMate 577 study, which found that adjuvant nivolumab immunotherapy after preoperative CROSS and surgery significantly reduced metastatic recurrence and doubled disease-free survival in patients who did not achieve a complete response. This approach is now a standard of care for those patients.

FLOT plus neoadjuvant nivolumab may also be a viable option, Dr. Goodman noted, but we haven’t yet seen “any benefit in survival with the combo of chemotherapy and immunotherapy for resectable esophago-gastric cancer.”

Further studies are needed to evaluate the synergy of immunotherapy and radiotherapy. The next chapter of the esophageal adenocarcinoma story may feature a “best-of-both-worlds” approach that combines induction chemotherapy, followed by personalized chemoradiation, surgery, and potentially adjuvant immunotherapy, Dr. Goodman explained.

While the ESOPEC findings are impressive, the 5-year overall survival of only 50% is still suboptimal, she noted. “Given the poor prognosis with this disease, we need to continue to develop clinical trials to identify better targets, novel treatment combinations, and select patients that will respond best to specific treatment.”

ESOPEC was funded by the Deutsche Forschungsgemeinschaft (German Research Foundation). Dr. Hoeppner reported receiving travel, accommodations, and expenses from Intuitive Surgical. Dr. Goodman reported a relationship with the National Cancer Institute and consulting or advisory roles for Novartis, Philips Healthcare, RenovoRX, and Roche/Genentech.

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