News

TOPLINE:

Emergency department (ED) visits by veterans for low-acuity conditions declined following the US Department of Veterans Affairs (VA) virtual care expansion in March 2020 and remained 12% below the baseline rate through February 2023.

METHODOLOGY:

• Researchers conducted a retrospective cross-sectional analysis using data from the VA Corporate Data Warehouse, including 10,364,893 ED visits (54.3% low-acuity visits) by about 2.6 million veterans (mean age, 60.8 years; 89.6% men; 63.7% White individuals) between March 2017 and February 2023.
• They evaluated the impact of the virtual care expansion — defined as the transition to virtual visits, including telephone and video care — which was implemented from March to May 2020, and assessed outcomes through that period.
• The primary outcome was the change in monthly counts of low-acuity visits to VA EDs, assessed using an interrupted time series analysis. The analysis focused on two intervention points: March 2020 (the start of the pandemic and virtual care scale-up) and May 2020 (when virtual care plateaued).
• A secondary analysis assessed the characteristics of ED users with low-acuity visits before and after the virtual care expansion, using 2 years of data — baseline pre-expansion year 3 (March 2019 to February 2020) and post-expansion year 3 (March 2022 to February 2023).

TAKEAWAY:

• Low-acuity ED utilization dropped by 24,514 visits (P < .001) in March 2020, followed by a modest increase of 7863 visits per month (P = .047) after May 2020, but remained 12.4% below the baseline rate by the end of February 2023.
• High-acuity visits showed similar patterns, with an initial decrease of 22,197 visits in March 2020 (P < .001) and a subsequent increase of 4180 visits per month in the post-expansion period (P = .05).
• Increased virtual care utilization was not significantly associated with reduced ED use for selected low-acuity conditions. The largest relative reductions were observed for major depression (42.4%), gastroenteritis (38.3%), and conjunctivitis (35.6%), whereas the largest absolute reductions occurred in low back pain, knee pain, and cellulitis.
• ED users with low-acuity ED visits in the post-expansion period were more likely to have 100% VA service connection (20.2% vs 14.6%), less medically complex (mean Elixhauser comorbidity score, 3.8 vs 4.2), and more likely to be classified as highly disabled (55.0% vs 48.1%) compared with those in the pre-expansion period.

IN PRACTICE:

“In this national, cross-sectional study, low-acuity ED utilization declined after the VA’s expansion of virtual care. While shifting low-acuity care away from ED settings toward virtual options may improve the value and efficiency of services, questions remain about the effects on quality and patient satisfaction,” the authors wrote. “Further research should be directed at exploring patient- and system-level factors that influence care-seeking decisions for low-acuity conditions,” they added.

SOURCE:

The study was led by Anu Ramachandran, MD, MPH, VA Palo Alto Health Care System, Menlo Park, California. It was published online on JAMA Network Open.

LIMITATIONS:

The classification of visits as low acuity in this study was based on International Classification of Diseases, Tenth Revision codes and discharge disposition; this classification did not imply inappropriate ED use as factors such as symptom severity, medical comorbidities, and access to care — which can influence care-seeking decisions — were not captured. The study did not assess all potential alternatives, including VA Urgent Care centers. Additionally, although virtual care use increased as ED visits declined, the models did not provide evidence of direct substitution.

DISCLOSURES:

The study received support from grants from the Department of VA, Veterans Health Administration, Office of Health Systems Research and Development. One author reported receiving research support through Department of VA Office of Health Systems Research and Development interagency agreement, whereas another reported receiving grant support from the VA Health Services Research program and being employed by the Veterans Affairs during the study.

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 first appeared on Medscape.com.

TOPLINE:

Emergency department (ED) visits by veterans for low-acuity conditions declined following the US Department of Veterans Affairs (VA) virtual care expansion in March 2020 and remained 12% below the baseline rate through February 2023.

METHODOLOGY:

• Researchers conducted a retrospective cross-sectional analysis using data from the VA Corporate Data Warehouse, including 10,364,893 ED visits (54.3% low-acuity visits) by about 2.6 million veterans (mean age, 60.8 years; 89.6% men; 63.7% White individuals) between March 2017 and February 2023.
• They evaluated the impact of the virtual care expansion — defined as the transition to virtual visits, including telephone and video care — which was implemented from March to May 2020, and assessed outcomes through that period.
• The primary outcome was the change in monthly counts of low-acuity visits to VA EDs, assessed using an interrupted time series analysis. The analysis focused on two intervention points: March 2020 (the start of the pandemic and virtual care scale-up) and May 2020 (when virtual care plateaued).
• A secondary analysis assessed the characteristics of ED users with low-acuity visits before and after the virtual care expansion, using 2 years of data — baseline pre-expansion year 3 (March 2019 to February 2020) and post-expansion year 3 (March 2022 to February 2023).

TAKEAWAY:

• Low-acuity ED utilization dropped by 24,514 visits (P < .001) in March 2020, followed by a modest increase of 7863 visits per month (P = .047) after May 2020, but remained 12.4% below the baseline rate by the end of February 2023.
• High-acuity visits showed similar patterns, with an initial decrease of 22,197 visits in March 2020 (P < .001) and a subsequent increase of 4180 visits per month in the post-expansion period (P = .05).
• Increased virtual care utilization was not significantly associated with reduced ED use for selected low-acuity conditions. The largest relative reductions were observed for major depression (42.4%), gastroenteritis (38.3%), and conjunctivitis (35.6%), whereas the largest absolute reductions occurred in low back pain, knee pain, and cellulitis.
• ED users with low-acuity ED visits in the post-expansion period were more likely to have 100% VA service connection (20.2% vs 14.6%), less medically complex (mean Elixhauser comorbidity score, 3.8 vs 4.2), and more likely to be classified as highly disabled (55.0% vs 48.1%) compared with those in the pre-expansion period.

IN PRACTICE:

“In this national, cross-sectional study, low-acuity ED utilization declined after the VA’s expansion of virtual care. While shifting low-acuity care away from ED settings toward virtual options may improve the value and efficiency of services, questions remain about the effects on quality and patient satisfaction,” the authors wrote. “Further research should be directed at exploring patient- and system-level factors that influence care-seeking decisions for low-acuity conditions,” they added.

SOURCE:

The study was led by Anu Ramachandran, MD, MPH, VA Palo Alto Health Care System, Menlo Park, California. It was published online on JAMA Network Open.

LIMITATIONS:

The classification of visits as low acuity in this study was based on International Classification of Diseases, Tenth Revision codes and discharge disposition; this classification did not imply inappropriate ED use as factors such as symptom severity, medical comorbidities, and access to care — which can influence care-seeking decisions — were not captured. The study did not assess all potential alternatives, including VA Urgent Care centers. Additionally, although virtual care use increased as ED visits declined, the models did not provide evidence of direct substitution.

DISCLOSURES:

The study received support from grants from the Department of VA, Veterans Health Administration, Office of Health Systems Research and Development. One author reported receiving research support through Department of VA Office of Health Systems Research and Development interagency agreement, whereas another reported receiving grant support from the VA Health Services Research program and being employed by the Veterans Affairs during the study.

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 first appeared on Medscape.com.

TOPLINE:

Emergency department (ED) visits by veterans for low-acuity conditions declined following the US Department of Veterans Affairs (VA) virtual care expansion in March 2020 and remained 12% below the baseline rate through February 2023.

METHODOLOGY:

• Researchers conducted a retrospective cross-sectional analysis using data from the VA Corporate Data Warehouse, including 10,364,893 ED visits (54.3% low-acuity visits) by about 2.6 million veterans (mean age, 60.8 years; 89.6% men; 63.7% White individuals) between March 2017 and February 2023.
• They evaluated the impact of the virtual care expansion — defined as the transition to virtual visits, including telephone and video care — which was implemented from March to May 2020, and assessed outcomes through that period.
• The primary outcome was the change in monthly counts of low-acuity visits to VA EDs, assessed using an interrupted time series analysis. The analysis focused on two intervention points: March 2020 (the start of the pandemic and virtual care scale-up) and May 2020 (when virtual care plateaued).
• A secondary analysis assessed the characteristics of ED users with low-acuity visits before and after the virtual care expansion, using 2 years of data — baseline pre-expansion year 3 (March 2019 to February 2020) and post-expansion year 3 (March 2022 to February 2023).

TAKEAWAY:

• Low-acuity ED utilization dropped by 24,514 visits (P < .001) in March 2020, followed by a modest increase of 7863 visits per month (P = .047) after May 2020, but remained 12.4% below the baseline rate by the end of February 2023.
• High-acuity visits showed similar patterns, with an initial decrease of 22,197 visits in March 2020 (P < .001) and a subsequent increase of 4180 visits per month in the post-expansion period (P = .05).
• Increased virtual care utilization was not significantly associated with reduced ED use for selected low-acuity conditions. The largest relative reductions were observed for major depression (42.4%), gastroenteritis (38.3%), and conjunctivitis (35.6%), whereas the largest absolute reductions occurred in low back pain, knee pain, and cellulitis.
• ED users with low-acuity ED visits in the post-expansion period were more likely to have 100% VA service connection (20.2% vs 14.6%), less medically complex (mean Elixhauser comorbidity score, 3.8 vs 4.2), and more likely to be classified as highly disabled (55.0% vs 48.1%) compared with those in the pre-expansion period.

IN PRACTICE:

“In this national, cross-sectional study, low-acuity ED utilization declined after the VA’s expansion of virtual care. While shifting low-acuity care away from ED settings toward virtual options may improve the value and efficiency of services, questions remain about the effects on quality and patient satisfaction,” the authors wrote. “Further research should be directed at exploring patient- and system-level factors that influence care-seeking decisions for low-acuity conditions,” they added.

SOURCE:

The study was led by Anu Ramachandran, MD, MPH, VA Palo Alto Health Care System, Menlo Park, California. It was published online on JAMA Network Open.

LIMITATIONS:

The classification of visits as low acuity in this study was based on International Classification of Diseases, Tenth Revision codes and discharge disposition; this classification did not imply inappropriate ED use as factors such as symptom severity, medical comorbidities, and access to care — which can influence care-seeking decisions — were not captured. The study did not assess all potential alternatives, including VA Urgent Care centers. Additionally, although virtual care use increased as ED visits declined, the models did not provide evidence of direct substitution.

DISCLOSURES:

The study received support from grants from the Department of VA, Veterans Health Administration, Office of Health Systems Research and Development. One author reported receiving research support through Department of VA Office of Health Systems Research and Development interagency agreement, whereas another reported receiving grant support from the VA Health Services Research program and being employed by the Veterans Affairs during the study.

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 first appeared on Medscape.com.

TOPLINE:

Veterans received a diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CM) a median of 490 days after heart failure (HF) diagnosis. Those who had atrial fibrillation, coronary artery disease, or chronic kidney disease experienced longer diagnostic delays, whereas older or Black patients experienced shorter delays.

METHODOLOGY:

• Researchers conducted a retrospective cohort study using data from the US Veterans Health Administration to quantify the time from HF diagnosis to ATTR-CM diagnosis and identify predictors of delays in diagnosis.
• They included veterans with HF and incident ATTR-CM diagnosed between 2016 and 2022; these veterans were identified using an algorithm based on diagnoses and medications.
• The final analysis included 2557 veterans, with a median age of 80.5 years; 99.5% were men, and 56.3% were White individuals.
• Assessments captured the time from the first HF diagnosis, the first outpatient prescription for a loop diuretic, and the first hospitalization for HF to the first ATTR-CM diagnosis, along with demographics and comorbidities.
• The primary outcome was the number of days from incident HF diagnosis to incident ATTR-CM diagnosis; a delay of > 6 months was considered meaningful.

TAKEAWAY:

• The median time from HF diagnosis to ATTR-CM diagnosis was 490 days. Overall, 65% of veterans experienced diagnostic delays > 6 months, and > 25% had delays longer than 3 years.
• Factors associated with a shorter time to ATTR-CM diagnosis included Black race (adjusted odds ratio [aOR], 0.71; 95% CI, 0.57-0.88) and older age (aOR per 10 years, 0.66; 95% CI, 0.59-0.73).
• The likelihood of longer diagnostic delays was higher in patients with coronary artery disease (aOR, 1.38; 95% CI, 1.15-1.64) and chronic kidney disease (aOR, 1.79; 95% CI, 1.50-2.15). Those with atrial fibrillation were more likely to have longer delays, although the lower bound of 95% CI was borderline (aOR, 1.21; 95% CI, 1.00-1.45).
• Among veterans with prior prescriptions of loop diuretics, the median time from the first prescription to ATTR-CM diagnosis was 835 days. Among those with a prior hospitalization for HF, the median time from hospitalization to ATTR-CM diagnosis was 300 days.

IN PRACTICE:

“This study supports the need for increased testing for ATTR-CM, thorough evaluation of cardiomyopathy etiologies at the time of HF diagnosis, and the need for new interventions that shorten the diagnostic delay in ATTR-CM,” the researchers reported.

SOURCE:

This study was led by Gabriela Spencer-Bonilla, MD, MSc, of Stanford University School of Medicine in Stanford, California. It was published online on JACC .

LIMITATIONS:

The analysis was limited to veterans engaged long enough for diagnoses of both HF and ATTR-CM. The findings may not be generalized to women given the predominantly male cohort. Echocardiography and ATTR subtype or genetic data were unavailable.

DISCLOSURES:

This study received funding from AstraZeneca. Four authors reported being the employees and stockholders of AstraZeneca. Several authors reported receiving research funding, consulting fees, and/or having equity in multiple pharmaceutical and healthcare companies, including Novo Nordisk, Bridge Bio, and Pfizer. Two authors reported receiving support from the American Heart Association, with one of them also receiving support from the National Institutes of Health.

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 first appeared on Medscape.com.

TOPLINE:

Veterans received a diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CM) a median of 490 days after heart failure (HF) diagnosis. Those who had atrial fibrillation, coronary artery disease, or chronic kidney disease experienced longer diagnostic delays, whereas older or Black patients experienced shorter delays.

METHODOLOGY:

• Researchers conducted a retrospective cohort study using data from the US Veterans Health Administration to quantify the time from HF diagnosis to ATTR-CM diagnosis and identify predictors of delays in diagnosis.
• They included veterans with HF and incident ATTR-CM diagnosed between 2016 and 2022; these veterans were identified using an algorithm based on diagnoses and medications.
• The final analysis included 2557 veterans, with a median age of 80.5 years; 99.5% were men, and 56.3% were White individuals.
• Assessments captured the time from the first HF diagnosis, the first outpatient prescription for a loop diuretic, and the first hospitalization for HF to the first ATTR-CM diagnosis, along with demographics and comorbidities.
• The primary outcome was the number of days from incident HF diagnosis to incident ATTR-CM diagnosis; a delay of > 6 months was considered meaningful.

TAKEAWAY:

• The median time from HF diagnosis to ATTR-CM diagnosis was 490 days. Overall, 65% of veterans experienced diagnostic delays > 6 months, and > 25% had delays longer than 3 years.
• Factors associated with a shorter time to ATTR-CM diagnosis included Black race (adjusted odds ratio [aOR], 0.71; 95% CI, 0.57-0.88) and older age (aOR per 10 years, 0.66; 95% CI, 0.59-0.73).
• The likelihood of longer diagnostic delays was higher in patients with coronary artery disease (aOR, 1.38; 95% CI, 1.15-1.64) and chronic kidney disease (aOR, 1.79; 95% CI, 1.50-2.15). Those with atrial fibrillation were more likely to have longer delays, although the lower bound of 95% CI was borderline (aOR, 1.21; 95% CI, 1.00-1.45).
• Among veterans with prior prescriptions of loop diuretics, the median time from the first prescription to ATTR-CM diagnosis was 835 days. Among those with a prior hospitalization for HF, the median time from hospitalization to ATTR-CM diagnosis was 300 days.

IN PRACTICE:

“This study supports the need for increased testing for ATTR-CM, thorough evaluation of cardiomyopathy etiologies at the time of HF diagnosis, and the need for new interventions that shorten the diagnostic delay in ATTR-CM,” the researchers reported.

SOURCE:

This study was led by Gabriela Spencer-Bonilla, MD, MSc, of Stanford University School of Medicine in Stanford, California. It was published online on JACC .

LIMITATIONS:

The analysis was limited to veterans engaged long enough for diagnoses of both HF and ATTR-CM. The findings may not be generalized to women given the predominantly male cohort. Echocardiography and ATTR subtype or genetic data were unavailable.

DISCLOSURES:

This study received funding from AstraZeneca. Four authors reported being the employees and stockholders of AstraZeneca. Several authors reported receiving research funding, consulting fees, and/or having equity in multiple pharmaceutical and healthcare companies, including Novo Nordisk, Bridge Bio, and Pfizer. Two authors reported receiving support from the American Heart Association, with one of them also receiving support from the National Institutes of Health.

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 first appeared on Medscape.com.

TOPLINE:

Veterans received a diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CM) a median of 490 days after heart failure (HF) diagnosis. Those who had atrial fibrillation, coronary artery disease, or chronic kidney disease experienced longer diagnostic delays, whereas older or Black patients experienced shorter delays.

METHODOLOGY:

• Researchers conducted a retrospective cohort study using data from the US Veterans Health Administration to quantify the time from HF diagnosis to ATTR-CM diagnosis and identify predictors of delays in diagnosis.
• They included veterans with HF and incident ATTR-CM diagnosed between 2016 and 2022; these veterans were identified using an algorithm based on diagnoses and medications.
• The final analysis included 2557 veterans, with a median age of 80.5 years; 99.5% were men, and 56.3% were White individuals.
• Assessments captured the time from the first HF diagnosis, the first outpatient prescription for a loop diuretic, and the first hospitalization for HF to the first ATTR-CM diagnosis, along with demographics and comorbidities.
• The primary outcome was the number of days from incident HF diagnosis to incident ATTR-CM diagnosis; a delay of > 6 months was considered meaningful.

TAKEAWAY:

• The median time from HF diagnosis to ATTR-CM diagnosis was 490 days. Overall, 65% of veterans experienced diagnostic delays > 6 months, and > 25% had delays longer than 3 years.
• Factors associated with a shorter time to ATTR-CM diagnosis included Black race (adjusted odds ratio [aOR], 0.71; 95% CI, 0.57-0.88) and older age (aOR per 10 years, 0.66; 95% CI, 0.59-0.73).
• The likelihood of longer diagnostic delays was higher in patients with coronary artery disease (aOR, 1.38; 95% CI, 1.15-1.64) and chronic kidney disease (aOR, 1.79; 95% CI, 1.50-2.15). Those with atrial fibrillation were more likely to have longer delays, although the lower bound of 95% CI was borderline (aOR, 1.21; 95% CI, 1.00-1.45).
• Among veterans with prior prescriptions of loop diuretics, the median time from the first prescription to ATTR-CM diagnosis was 835 days. Among those with a prior hospitalization for HF, the median time from hospitalization to ATTR-CM diagnosis was 300 days.

IN PRACTICE:

“This study supports the need for increased testing for ATTR-CM, thorough evaluation of cardiomyopathy etiologies at the time of HF diagnosis, and the need for new interventions that shorten the diagnostic delay in ATTR-CM,” the researchers reported.

SOURCE:

This study was led by Gabriela Spencer-Bonilla, MD, MSc, of Stanford University School of Medicine in Stanford, California. It was published online on JACC .

LIMITATIONS:

The analysis was limited to veterans engaged long enough for diagnoses of both HF and ATTR-CM. The findings may not be generalized to women given the predominantly male cohort. Echocardiography and ATTR subtype or genetic data were unavailable.

DISCLOSURES:

This study received funding from AstraZeneca. Four authors reported being the employees and stockholders of AstraZeneca. Several authors reported receiving research funding, consulting fees, and/or having equity in multiple pharmaceutical and healthcare companies, including Novo Nordisk, Bridge Bio, and Pfizer. Two authors reported receiving support from the American Heart Association, with one of them also receiving support from the National Institutes of Health.

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 first appeared on Medscape.com.

The carol promises partridges and pears. The reality, every December, is a predictable spike in injuries, illness, and emergency care.

Framed around the familiar “12 Days of Christmas,” this seasonal guide sets out the most common festive hazards — many of them preventable — and the practical advice clinicians can share to help patients enjoy a safer holiday.

1. Fire

Candles, open fires, and busy kitchens make December the most dangerous month for house fires. Home fires rise 10% in December and peak on Christmas Day at 53% above average, according to the National Fire Chiefs Council.

Alcohol, distraction, and festive cooking all add to the risk.

• Check for fire hazards before Christmas.
• Never leave cookers or candle unattended.
• Check Christmas lights and avoid overloading sockets.
• Ensure a working smoke alarm on each floor and keep escape routes clear.
• Remember that emollient residues on fabrics are highly flammable.

2. Christmas Trees and Decorations

Trees and trimmings bring their own risk. Christmas trees injure about 1000 people each year, according to the Royal Society for the Prevention of Accidents (RoSPA).

A National Accident Helpline (NAH) survey found that 2.7% of respondents had experienced electric shock from faulty lights. Artificial trees, chosen by 76% of households, carry a sixfold higher injury risk. Real trees dry out and become highly flammable — “a giant bundle of kindling covered in electrical wires,” warned safety analysts TapRooT.

• Water live trees regularly — unplug lights first.
• Keep trees stable and at least 3 feet from heat sources.
• Switch off lights before bed or leaving the house.
• Do not hang stockings near open flames.
• Hang fragile decorations high up.
• Supervise children and pets.

3. Slips, Trips, and Falls

The third danger is underfoot. Falls, burns, and cuts send around 80,000 people to A&E each Christmas, according to RoSPA.

One in 50 people fall from their loft while retrieving decorations, the NAH warned.

• Use sturdy ladders and wear footwear with good grip.
• Keep floors clear of presents, wrapping, cables, and spills.
• Never melt ice with boiling water; refreezing can make surfaces more treacherous.

4. Food and Drug Interactions

Festive eating can interfere with medicines. The Medicines and Healthcare products Regulatory Agency (MHRA) warned that drug-food interactions are not always listed on packaging.

• Grapefruit interacts with multiple drugs.
• Cranberries can enhance warfarin's anticoagulant effect, while vitamin K-rich foods, including sprouts, may reduce it.
• Rich desserts can destabilize blood glucose.
• Tyramine-rich foods, including cheeses and dark chocolate, may trigger migraines or hypertensive crises with monoamine oxidase inhibitors.

5. Alcohol

Up to 70% of weekend A&E attendances are alcohol-related, with numbers rising over Christmas. The MHRA warned that mixing alcohol with medicines can cause drowsiness, impaired coordination, and accidents.

• Avoid drinking on an empty stomach.
• Be cautious of unfamiliar drinks.
• Alternate alcoholic and soft drinks.
• Avoid potentially aggressive intoxicated people.

6. Kitchen Calamities

The festive kitchen is a frequent source of injury. NAH data showed that 49% of people reported accidents while preparing Christmas food. Cuts accounted for 18%, and burns from hot fat 11%. In addition, the Food Standards Agency said that 46% of Christmas cooks do not check use-by dates.

• Keep children and trip hazards out of the kitchen.
• Use back hobs and turn saucepan handles inward.
• Never leave ovens or pans unattended.
• Discard out-of-date food.
• Refrigerate leftovers within 2 hours.

7. Children's Vulnerabilities

Christmas presents bring hidden dangers for children. Button batteries and magnets can inflict serious gastrointestinal damage if swallowed.

• Choose age-appropriate, well-made toys.
• Store batteries, magnets, medicines, and chemicals out of reach.
• Avoid sharp or breakable decorations.
• Place holly, mistletoe, and poinsettias well out of reach.

8. Eye Injuries

Eye injuries surge over Christmas. Champagne corks can travel at nearly 50 mph, risking globe rupture or retinal detachment.

Conifer needles, glitter, and artificial snow can all cause corneal injury.

• Point champagne bottles and party poppers away from people's faces.
• Take care when handling Christmas trees.
• Avoid hanging ornaments at children's eye level.
• Rinse glitter-contaminated eyes with sterile saline.

9. Existing Ailments

By the ninth day, routine has often collapsed. Festive excess, stress and disrupted schedules can destabilize chronic disease.

• Ensure adequate medicines and testing supplies.
• Let hosts know dietary needs in advance.
• Avoid excess salt and alcohol in cardiovascular disease, and excess potassium in kidney disease.
• Increase blood glucose monitoring in diabetes.

10. Presents

Not all gifts are benign. The Child Accident Prevention Trust warned that cheap or counterfeit products may bypass safety standards.

UK safety authorities report that counterfeit Labubu dolls have made up a large share of the roughly 259,000 counterfeit toys seized at UK borders this year, and many have failed safety tests.

• Be cautious when buying for toddlers.
• Look for recognized safety markings.
• Avoid toys with strong magnets or button batteries.
• Laser pointers can cause permanent damage to vision.

11. Stress

As Christmas approaches, pressure mounts. In an NAH survey, 12% of men and 20% of women said they felt rushed, 32% of women were stressed, and 18% overwhelmed.

• Prioritize sleep.
• Get outdoors for early morning light.
• Ask for help and delegate chores.

12. Other People

The final hazard is often the most familiar: Family tension is almost traditional. In one survey, 37% of people said Christmas "wouldn't be the same" without arguments, and 54% admitted enjoying them.

• Set boundaries and agree expectations early.
• Stick to a budget.
• Avoid known flashpoint topics, such as politics.
• Create a quiet space for time out.
• One in 9 people spend Christmas alone. Plan ahead to make it a special day.

The hazards may feel seasonal, but the outcomes are not. For clinicians, the 12 risks offer a reminder that small interventions before Christmas can prevent significant harm after it.

Dr Sheena Meredith is an established medical writer, editor, and consultant in healthcare communications, with extensive experience writing for medical professionals and the general public. She is qualified in medicine and in law and medical ethics. 

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

The carol promises partridges and pears. The reality, every December, is a predictable spike in injuries, illness, and emergency care.

Framed around the familiar “12 Days of Christmas,” this seasonal guide sets out the most common festive hazards — many of them preventable — and the practical advice clinicians can share to help patients enjoy a safer holiday.

1. Fire

Candles, open fires, and busy kitchens make December the most dangerous month for house fires. Home fires rise 10% in December and peak on Christmas Day at 53% above average, according to the National Fire Chiefs Council.

Alcohol, distraction, and festive cooking all add to the risk.

• Check for fire hazards before Christmas.
• Never leave cookers or candle unattended.
• Check Christmas lights and avoid overloading sockets.
• Ensure a working smoke alarm on each floor and keep escape routes clear.
• Remember that emollient residues on fabrics are highly flammable.

2. Christmas Trees and Decorations

Trees and trimmings bring their own risk. Christmas trees injure about 1000 people each year, according to the Royal Society for the Prevention of Accidents (RoSPA).

A National Accident Helpline (NAH) survey found that 2.7% of respondents had experienced electric shock from faulty lights. Artificial trees, chosen by 76% of households, carry a sixfold higher injury risk. Real trees dry out and become highly flammable — “a giant bundle of kindling covered in electrical wires,” warned safety analysts TapRooT.

• Water live trees regularly — unplug lights first.
• Keep trees stable and at least 3 feet from heat sources.
• Switch off lights before bed or leaving the house.
• Do not hang stockings near open flames.
• Hang fragile decorations high up.
• Supervise children and pets.

3. Slips, Trips, and Falls

The third danger is underfoot. Falls, burns, and cuts send around 80,000 people to A&E each Christmas, according to RoSPA.

One in 50 people fall from their loft while retrieving decorations, the NAH warned.

• Use sturdy ladders and wear footwear with good grip.
• Keep floors clear of presents, wrapping, cables, and spills.
• Never melt ice with boiling water; refreezing can make surfaces more treacherous.

4. Food and Drug Interactions

Festive eating can interfere with medicines. The Medicines and Healthcare products Regulatory Agency (MHRA) warned that drug-food interactions are not always listed on packaging.

• Grapefruit interacts with multiple drugs.
• Cranberries can enhance warfarin's anticoagulant effect, while vitamin K-rich foods, including sprouts, may reduce it.
• Rich desserts can destabilize blood glucose.
• Tyramine-rich foods, including cheeses and dark chocolate, may trigger migraines or hypertensive crises with monoamine oxidase inhibitors.

5. Alcohol

Up to 70% of weekend A&E attendances are alcohol-related, with numbers rising over Christmas. The MHRA warned that mixing alcohol with medicines can cause drowsiness, impaired coordination, and accidents.

• Avoid drinking on an empty stomach.
• Be cautious of unfamiliar drinks.
• Alternate alcoholic and soft drinks.
• Avoid potentially aggressive intoxicated people.

6. Kitchen Calamities

The festive kitchen is a frequent source of injury. NAH data showed that 49% of people reported accidents while preparing Christmas food. Cuts accounted for 18%, and burns from hot fat 11%. In addition, the Food Standards Agency said that 46% of Christmas cooks do not check use-by dates.

• Keep children and trip hazards out of the kitchen.
• Use back hobs and turn saucepan handles inward.
• Never leave ovens or pans unattended.
• Discard out-of-date food.
• Refrigerate leftovers within 2 hours.

7. Children's Vulnerabilities

Christmas presents bring hidden dangers for children. Button batteries and magnets can inflict serious gastrointestinal damage if swallowed.

• Choose age-appropriate, well-made toys.
• Store batteries, magnets, medicines, and chemicals out of reach.
• Avoid sharp or breakable decorations.
• Place holly, mistletoe, and poinsettias well out of reach.

8. Eye Injuries

Eye injuries surge over Christmas. Champagne corks can travel at nearly 50 mph, risking globe rupture or retinal detachment.

Conifer needles, glitter, and artificial snow can all cause corneal injury.

• Point champagne bottles and party poppers away from people's faces.
• Take care when handling Christmas trees.
• Avoid hanging ornaments at children's eye level.
• Rinse glitter-contaminated eyes with sterile saline.

9. Existing Ailments

By the ninth day, routine has often collapsed. Festive excess, stress and disrupted schedules can destabilize chronic disease.

• Ensure adequate medicines and testing supplies.
• Let hosts know dietary needs in advance.
• Avoid excess salt and alcohol in cardiovascular disease, and excess potassium in kidney disease.
• Increase blood glucose monitoring in diabetes.

10. Presents

Not all gifts are benign. The Child Accident Prevention Trust warned that cheap or counterfeit products may bypass safety standards.

UK safety authorities report that counterfeit Labubu dolls have made up a large share of the roughly 259,000 counterfeit toys seized at UK borders this year, and many have failed safety tests.

• Be cautious when buying for toddlers.
• Look for recognized safety markings.
• Avoid toys with strong magnets or button batteries.
• Laser pointers can cause permanent damage to vision.

11. Stress

As Christmas approaches, pressure mounts. In an NAH survey, 12% of men and 20% of women said they felt rushed, 32% of women were stressed, and 18% overwhelmed.

• Prioritize sleep.
• Get outdoors for early morning light.
• Ask for help and delegate chores.

12. Other People

The final hazard is often the most familiar: Family tension is almost traditional. In one survey, 37% of people said Christmas "wouldn't be the same" without arguments, and 54% admitted enjoying them.

• Set boundaries and agree expectations early.
• Stick to a budget.
• Avoid known flashpoint topics, such as politics.
• Create a quiet space for time out.
• One in 9 people spend Christmas alone. Plan ahead to make it a special day.

The hazards may feel seasonal, but the outcomes are not. For clinicians, the 12 risks offer a reminder that small interventions before Christmas can prevent significant harm after it.

Dr Sheena Meredith is an established medical writer, editor, and consultant in healthcare communications, with extensive experience writing for medical professionals and the general public. She is qualified in medicine and in law and medical ethics. 

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

The carol promises partridges and pears. The reality, every December, is a predictable spike in injuries, illness, and emergency care.

Framed around the familiar “12 Days of Christmas,” this seasonal guide sets out the most common festive hazards — many of them preventable — and the practical advice clinicians can share to help patients enjoy a safer holiday.

1. Fire

Candles, open fires, and busy kitchens make December the most dangerous month for house fires. Home fires rise 10% in December and peak on Christmas Day at 53% above average, according to the National Fire Chiefs Council.

Alcohol, distraction, and festive cooking all add to the risk.

• Check for fire hazards before Christmas.
• Never leave cookers or candle unattended.
• Check Christmas lights and avoid overloading sockets.
• Ensure a working smoke alarm on each floor and keep escape routes clear.
• Remember that emollient residues on fabrics are highly flammable.

2. Christmas Trees and Decorations

Trees and trimmings bring their own risk. Christmas trees injure about 1000 people each year, according to the Royal Society for the Prevention of Accidents (RoSPA).

A National Accident Helpline (NAH) survey found that 2.7% of respondents had experienced electric shock from faulty lights. Artificial trees, chosen by 76% of households, carry a sixfold higher injury risk. Real trees dry out and become highly flammable — “a giant bundle of kindling covered in electrical wires,” warned safety analysts TapRooT.

• Water live trees regularly — unplug lights first.
• Keep trees stable and at least 3 feet from heat sources.
• Switch off lights before bed or leaving the house.
• Do not hang stockings near open flames.
• Hang fragile decorations high up.
• Supervise children and pets.

3. Slips, Trips, and Falls

The third danger is underfoot. Falls, burns, and cuts send around 80,000 people to A&E each Christmas, according to RoSPA.

One in 50 people fall from their loft while retrieving decorations, the NAH warned.

• Use sturdy ladders and wear footwear with good grip.
• Keep floors clear of presents, wrapping, cables, and spills.
• Never melt ice with boiling water; refreezing can make surfaces more treacherous.

4. Food and Drug Interactions

Festive eating can interfere with medicines. The Medicines and Healthcare products Regulatory Agency (MHRA) warned that drug-food interactions are not always listed on packaging.

• Grapefruit interacts with multiple drugs.
• Cranberries can enhance warfarin's anticoagulant effect, while vitamin K-rich foods, including sprouts, may reduce it.
• Rich desserts can destabilize blood glucose.
• Tyramine-rich foods, including cheeses and dark chocolate, may trigger migraines or hypertensive crises with monoamine oxidase inhibitors.

5. Alcohol

Up to 70% of weekend A&E attendances are alcohol-related, with numbers rising over Christmas. The MHRA warned that mixing alcohol with medicines can cause drowsiness, impaired coordination, and accidents.

• Avoid drinking on an empty stomach.
• Be cautious of unfamiliar drinks.
• Alternate alcoholic and soft drinks.
• Avoid potentially aggressive intoxicated people.

6. Kitchen Calamities

The festive kitchen is a frequent source of injury. NAH data showed that 49% of people reported accidents while preparing Christmas food. Cuts accounted for 18%, and burns from hot fat 11%. In addition, the Food Standards Agency said that 46% of Christmas cooks do not check use-by dates.

• Keep children and trip hazards out of the kitchen.
• Use back hobs and turn saucepan handles inward.
• Never leave ovens or pans unattended.
• Discard out-of-date food.
• Refrigerate leftovers within 2 hours.

7. Children's Vulnerabilities

Christmas presents bring hidden dangers for children. Button batteries and magnets can inflict serious gastrointestinal damage if swallowed.

• Choose age-appropriate, well-made toys.
• Store batteries, magnets, medicines, and chemicals out of reach.
• Avoid sharp or breakable decorations.
• Place holly, mistletoe, and poinsettias well out of reach.

8. Eye Injuries

Eye injuries surge over Christmas. Champagne corks can travel at nearly 50 mph, risking globe rupture or retinal detachment.

Conifer needles, glitter, and artificial snow can all cause corneal injury.

• Point champagne bottles and party poppers away from people's faces.
• Take care when handling Christmas trees.
• Avoid hanging ornaments at children's eye level.
• Rinse glitter-contaminated eyes with sterile saline.

9. Existing Ailments

By the ninth day, routine has often collapsed. Festive excess, stress and disrupted schedules can destabilize chronic disease.

• Ensure adequate medicines and testing supplies.
• Let hosts know dietary needs in advance.
• Avoid excess salt and alcohol in cardiovascular disease, and excess potassium in kidney disease.
• Increase blood glucose monitoring in diabetes.

10. Presents

Not all gifts are benign. The Child Accident Prevention Trust warned that cheap or counterfeit products may bypass safety standards.

UK safety authorities report that counterfeit Labubu dolls have made up a large share of the roughly 259,000 counterfeit toys seized at UK borders this year, and many have failed safety tests.

• Be cautious when buying for toddlers.
• Look for recognized safety markings.
• Avoid toys with strong magnets or button batteries.
• Laser pointers can cause permanent damage to vision.

11. Stress

As Christmas approaches, pressure mounts. In an NAH survey, 12% of men and 20% of women said they felt rushed, 32% of women were stressed, and 18% overwhelmed.

• Prioritize sleep.
• Get outdoors for early morning light.
• Ask for help and delegate chores.

12. Other People

The final hazard is often the most familiar: Family tension is almost traditional. In one survey, 37% of people said Christmas "wouldn't be the same" without arguments, and 54% admitted enjoying them.

• Set boundaries and agree expectations early.
• Stick to a budget.
• Avoid known flashpoint topics, such as politics.
• Create a quiet space for time out.
• One in 9 people spend Christmas alone. Plan ahead to make it a special day.

The hazards may feel seasonal, but the outcomes are not. For clinicians, the 12 risks offer a reminder that small interventions before Christmas can prevent significant harm after it.

Dr Sheena Meredith is an established medical writer, editor, and consultant in healthcare communications, with extensive experience writing for medical professionals and the general public. She is qualified in medicine and in law and medical ethics. 

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

TOPLINE:

The use of services for mental health involving video chats with medical professionals increased in female veterans from 2019 to 2022, with women living in urban areas more likely to use the services than their rural counterparts. Black and Hispanic women showed the largest increases.

METHODOLOGY:

• Researchers analyzed trends in video telemental health utilization among female veterans within an observational cohort of Veterans Health Administration (VHA) mental health outpatient visits, by rurality and race, from 2019 to 2022.
• The study included 470,863 female veterans (mean age, 43 years; 51% White individuals) who had ≥ 1 outpatient mental health visit; a subsample of 141,349 veterans with mental health visits in both 2019 and 2022 was analyzed for changes in telemental health use.
• Video telemental health encounters were identified using specific codes for synchronous, video-based mental health care and included both visits at clinics and those at home through the VA Video Connect system.
• The researchers categorized race into 5 groups and classified veterans’ residences as rural and urban using commuting area codes.

TAKEAWAY:

• The use of synchronous video telemental health services among female veterans increased from < 7% to 32% from 2019 to 2022, with stable in-person care rates.
• In 2019, female veterans living in rural areas had an increased likelihood of using video telemental health. However, by 2022, this difference decreased, and female veterans living in urban areas showed equivalent or higher usage. Female veterans living in urban areas had a greater increase in the number of visits in 2022 than their peers living in rural areas.
• Black and Hispanic female veterans showed greater increases in video tele-mental health usage in both urban and rural areas. No significant change in telemental health visits was noted for American Indian and Alaska Native female veterans between 2019 and 2022.
• In the analysis of the subsample, female veterans living in urban areas were 21-35 times more likely to use video telemental health in 2022 vs 2019, whereas female veterans living in rural areas were 7-11 times more likely.

IN PRACTICE:

“The rapid changes observed in SVT-MH [synchronous video telehealth for mental health] use over a relatively short time period underscore the potential for achieving equity through intentional system-level efforts. However, our findings also highlight the risk of overgeneralizing telehealth utilization patterns,” the authors wrote. “Our findings underscore the need for targeted digital care strategies — especially for rural and AIAN [American Indian and Alaska Native] women veterans — to ensure that all veterans benefit equally from virtual care options,” they added.

SOURCE:

This study was led by Michelle A. Mengeling, PhD, MS, of the VHA Office of Rural Health at the Veterans Rural Health Resource Center in Iowa City, Iowa. It was published online on December 10, 2025, in The Journal of Rural Health.

LIMITATIONS:

Female veterans older than 60 years were excluded to avoid confounding with Medicare service usage. Rurality was classified as urban or rural, which may overlook variations in highly rural or isolated areas. The focus on VHA-delivered mental health care might not fully capture the use of video-based telemental health services.

DISCLOSURES:

This study was supported by grants from the US Department of Veterans Affairs, VHA, Office of Rural Health, Veterans Rural Health Resource Center - Iowa City. The authors declared having no conflicts of interest.

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 story first appeared on Medscape.com.

TOPLINE:

The use of services for mental health involving video chats with medical professionals increased in female veterans from 2019 to 2022, with women living in urban areas more likely to use the services than their rural counterparts. Black and Hispanic women showed the largest increases.

METHODOLOGY:

• Researchers analyzed trends in video telemental health utilization among female veterans within an observational cohort of Veterans Health Administration (VHA) mental health outpatient visits, by rurality and race, from 2019 to 2022.
• The study included 470,863 female veterans (mean age, 43 years; 51% White individuals) who had ≥ 1 outpatient mental health visit; a subsample of 141,349 veterans with mental health visits in both 2019 and 2022 was analyzed for changes in telemental health use.
• Video telemental health encounters were identified using specific codes for synchronous, video-based mental health care and included both visits at clinics and those at home through the VA Video Connect system.
• The researchers categorized race into 5 groups and classified veterans’ residences as rural and urban using commuting area codes.

TAKEAWAY:

• The use of synchronous video telemental health services among female veterans increased from < 7% to 32% from 2019 to 2022, with stable in-person care rates.
• In 2019, female veterans living in rural areas had an increased likelihood of using video telemental health. However, by 2022, this difference decreased, and female veterans living in urban areas showed equivalent or higher usage. Female veterans living in urban areas had a greater increase in the number of visits in 2022 than their peers living in rural areas.
• Black and Hispanic female veterans showed greater increases in video tele-mental health usage in both urban and rural areas. No significant change in telemental health visits was noted for American Indian and Alaska Native female veterans between 2019 and 2022.
• In the analysis of the subsample, female veterans living in urban areas were 21-35 times more likely to use video telemental health in 2022 vs 2019, whereas female veterans living in rural areas were 7-11 times more likely.

IN PRACTICE:

“The rapid changes observed in SVT-MH [synchronous video telehealth for mental health] use over a relatively short time period underscore the potential for achieving equity through intentional system-level efforts. However, our findings also highlight the risk of overgeneralizing telehealth utilization patterns,” the authors wrote. “Our findings underscore the need for targeted digital care strategies — especially for rural and AIAN [American Indian and Alaska Native] women veterans — to ensure that all veterans benefit equally from virtual care options,” they added.

SOURCE:

This study was led by Michelle A. Mengeling, PhD, MS, of the VHA Office of Rural Health at the Veterans Rural Health Resource Center in Iowa City, Iowa. It was published online on December 10, 2025, in The Journal of Rural Health.

LIMITATIONS:

Female veterans older than 60 years were excluded to avoid confounding with Medicare service usage. Rurality was classified as urban or rural, which may overlook variations in highly rural or isolated areas. The focus on VHA-delivered mental health care might not fully capture the use of video-based telemental health services.

DISCLOSURES:

This study was supported by grants from the US Department of Veterans Affairs, VHA, Office of Rural Health, Veterans Rural Health Resource Center - Iowa City. The authors declared having no conflicts of interest.

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 story first appeared on Medscape.com.

TOPLINE:

The use of services for mental health involving video chats with medical professionals increased in female veterans from 2019 to 2022, with women living in urban areas more likely to use the services than their rural counterparts. Black and Hispanic women showed the largest increases.

METHODOLOGY:

• Researchers analyzed trends in video telemental health utilization among female veterans within an observational cohort of Veterans Health Administration (VHA) mental health outpatient visits, by rurality and race, from 2019 to 2022.
• The study included 470,863 female veterans (mean age, 43 years; 51% White individuals) who had ≥ 1 outpatient mental health visit; a subsample of 141,349 veterans with mental health visits in both 2019 and 2022 was analyzed for changes in telemental health use.
• Video telemental health encounters were identified using specific codes for synchronous, video-based mental health care and included both visits at clinics and those at home through the VA Video Connect system.
• The researchers categorized race into 5 groups and classified veterans’ residences as rural and urban using commuting area codes.

TAKEAWAY:

• The use of synchronous video telemental health services among female veterans increased from < 7% to 32% from 2019 to 2022, with stable in-person care rates.
• In 2019, female veterans living in rural areas had an increased likelihood of using video telemental health. However, by 2022, this difference decreased, and female veterans living in urban areas showed equivalent or higher usage. Female veterans living in urban areas had a greater increase in the number of visits in 2022 than their peers living in rural areas.
• Black and Hispanic female veterans showed greater increases in video tele-mental health usage in both urban and rural areas. No significant change in telemental health visits was noted for American Indian and Alaska Native female veterans between 2019 and 2022.
• In the analysis of the subsample, female veterans living in urban areas were 21-35 times more likely to use video telemental health in 2022 vs 2019, whereas female veterans living in rural areas were 7-11 times more likely.

IN PRACTICE:

“The rapid changes observed in SVT-MH [synchronous video telehealth for mental health] use over a relatively short time period underscore the potential for achieving equity through intentional system-level efforts. However, our findings also highlight the risk of overgeneralizing telehealth utilization patterns,” the authors wrote. “Our findings underscore the need for targeted digital care strategies — especially for rural and AIAN [American Indian and Alaska Native] women veterans — to ensure that all veterans benefit equally from virtual care options,” they added.

SOURCE:

This study was led by Michelle A. Mengeling, PhD, MS, of the VHA Office of Rural Health at the Veterans Rural Health Resource Center in Iowa City, Iowa. It was published online on December 10, 2025, in The Journal of Rural Health.

LIMITATIONS:

Female veterans older than 60 years were excluded to avoid confounding with Medicare service usage. Rurality was classified as urban or rural, which may overlook variations in highly rural or isolated areas. The focus on VHA-delivered mental health care might not fully capture the use of video-based telemental health services.

DISCLOSURES:

This study was supported by grants from the US Department of Veterans Affairs, VHA, Office of Rural Health, Veterans Rural Health Resource Center - Iowa City. The authors declared having no conflicts of interest.

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 story first appeared on Medscape.com.

Adding teclistamab to daratumumab dramatically improved progression-free survival and overall survival vs standard-of-care (SOC) therapy in patients with relapsed or refractory multiple myeloma (RRMM) in the phase 3 MajesTEC-3 trial.

At median follow-up of 34.5 months, progression-free survival was not reached in study participants randomized to receive teclistamab plus daratumumab (Tec-Dara). Starkly contrasting that was the 18.1 months progression-free survival among those randomized to a control group who received the standard of care: investigator’s choice of daratumumab and dexamethasone plus either pomalidomide or bortezomib (DPd/DVd (hazard ratio [HR], 0.17). Overall survival also significantly favored Tec-Dara (HR, 0.46).

Lead investigator María-Victoria Mateos, MD, PhD, reported the findings in a late-breaking abstract session at American Society of Hematology (ASH) 2025 Annual Meeting. They were published simultaneously in The New England Journal of Medicine.

“[Tec-Dara in this setting] generated the greatest progression-free survival treatment effect to date [in RRMR] with a plateau phase after 6 months of therapy, suggesting potential for functional cure,” said Mateos, a consultant physician and associate professor at the University of Salamanca, Salamanca, Spain.

“We consider that this synergistic immunotherapy combination…is a new potential standard of care for relapsed or refractory multiple myeloma after at least on prior line of therapy, with broad potential across academic and community settings,” added Mateos, who also directs the Multiple Myeloma Program at the University.

Based on the MajesTEC-3 findings, the FDA proactively awarded a national priority voucher to Tec-Dara under the Commissioner’s National Priority Voucher pilot program designed to accelerate the review of certain promising products.

About Tec-Dara

Teclistamab (Tecvayli) is an off-the-shelf first-in-class bispecific monoclonal antibody shown in the MajesTEC-1 trial to provide deep, durable responses in RRMM, with improved efficacy and safety with earlier lines of therapy. The FDA approved the agent for use in 4th or greater lines of therapy in 2022 based on those findings.

Daratumumab (Darzalex) is a widely used anti-CD38 monoclonal antibody currently considered the SOC therapy for RRMM. Both agents are products of the Janssen Pharmaceutical Companies of Johnson & Johnson.

Although front-line therapy for multiple myeloma has dramatically improved, there is a need for new, more effective treatment strategies in patients with disease progression, Mateos noted.

Therefore, she and her colleagues conducted MajesTEC-3, a randomized trial exploring the fully immunotherapy-based regimen of Tec-Dara vs daratumumab-based SOC in patients who had received one to three prior lines of therapy, including a proteasome inhibitor and lenalidomide (Len).

The study was the first to test a bispecific monoclonal antibody as early as the first relapse after initial treatment, she noted.

About MajesTEC-3

Study participants were 587 adults aged 25-88 years. Those with one prior line of therapy were required to be Len-refractory with progressive disease on or after the last therapy. Prior anti-CD-38 Patients with prior B-cell maturation antigen-directed therapy or who were refractory to anti-CD38 treatment were excluded.

The 291 patients randomized to the Tec-Dara treatment group and 296 randomized to the control group were treated in 28-day cycles according to the standard daratumumab schedule: weekly treatment during cycles 1 and 2, biweekly treatment during cycles 3-6, and monthly treatments beginning with cycle 7.

Teclistamab was initiated with an approved step-up dose school followed by 1.5 mg/kg weekly in cycles 1 and 2, 3 mg/kg biweekly in cycles 3-6, and 3 mg/kg monthly beginning with cycle 7.

The 36-month progression-free survival rates with Tec-Dara vs DPd/DVd were 83.4% and 29.7%, with the 36-month overall survival rates having been 83.3% and 65.0%. More than 90% of patients in the Tec-Dara group who were alive at 6 months were also alive at 30 months, Mateos noted.

For both progression-free survival and overall survival, the “clinically remarkable and statistically significant” differences were apparent across all prespecified and clinically relevant subgroups, she added. These included patients who were 75 years or older, Len-refractory patients, and those with high-risk cytogenetics, ≥ 60% bone marrow plasma cells, soft-tissue plasmacytomas, and anti-CD38 exposure.

Patients receiving Tec-Dara also had significantly higher rates of complete or better responses (81.8% vs 32.1%; odds ratio [OR], 9.56), overall response (89.0% vs 75.3%; OR, 2.65), and minimal residual disease-negativity (58.4% vs 17.1%; OR, 6.78).

The median time to first response and first complete or better response was similar in the two groups, but 36-month duration of response was 88.5 vs 36.4 months. At data cutoff, 49.4% of patients remained on study treatment — 71.0% in the Tec-Dara group and 28.3% in the DPd/DVd group, and median treatment duration was twice as long with Tec-Dara (32.4 vs 16.1 months), she said.

Serious adverse events occurred at similar rates in the treatment and control groups (70.7% and 62.4%) and most (44.2%) were grade 1 cytokine release syndrome (CRS). No grade 3 CRS occurred, and all CRS cases resolved.

Immune effector-cell-associated neurotoxicity occurred in 1.1% of patients, and all cases resolved.

Treatment-related adverse events leading to discontinuation occurred in 4.6% and 5.5% of patients in the Tec-Dara and DPd/DVd groups. The rates of deaths due to treatment-emergent adverse events were also similar in the groups (7.1% vs 5.9%).

Infections of any grade occurred in 96.5% and 84.1% of Tec-Dara and DPd/DVd patients, and grade 3/4 infections occurred in 54.1% and 43.4%. New-onset grade 3 or greater infections decreased over time.

“It’s important to acknowledge that patients with infections needed to be supported with adequate prophylaxis and immunoglobulins,” Mateo stressed.

Implications for Patients With RRMM

Teclistamab is currently only approved after three prior lines of therapy, but under the FDA Commissioner’s National Priority Voucher program, the agency will aim to complete its review of Tec-Dara for earlier treatment within 1-2 months following submission of an application for approval by Johnson & Johnson.

If an approval for that indication were to occur, it would be transformative for patients with RRMM, said Michael Rosenzweig, MD, of City of Hope, Duarte, California, in an interview with Medscape Medical News.

The [MajesTEC-3] findings suggest that Tec-Dar “really gives patients a chance at long-term disease control,” added Rosenzweig, chief of the Division of Multiple Myeloma, and an associate professor in the Department of Hematology & Hematopoietic Cell Transplantation at City of Hope.

MajesTEC-3 was funded by Johnson & Johnson. Mateos disclosed relationships with numerous pharmaceutical companies, including Johnson & Johnson. Rosenzweig reported consulting for Johnson & Johnson and was previously on the company’s speakers bureau.

Sharon Worcester, MA, is an award-winning medical journalist based in Birmingham, Alabama, writing for Medscape, MDedge, and other affiliate sites. She currently covers oncology, but she has also written on a variety of other medical specialties and health care topics. She can be reached at [email protected] or on X: @SW_MedReporter.

Adding teclistamab to daratumumab dramatically improved progression-free survival and overall survival vs standard-of-care (SOC) therapy in patients with relapsed or refractory multiple myeloma (RRMM) in the phase 3 MajesTEC-3 trial.

At median follow-up of 34.5 months, progression-free survival was not reached in study participants randomized to receive teclistamab plus daratumumab (Tec-Dara). Starkly contrasting that was the 18.1 months progression-free survival among those randomized to a control group who received the standard of care: investigator’s choice of daratumumab and dexamethasone plus either pomalidomide or bortezomib (DPd/DVd (hazard ratio [HR], 0.17). Overall survival also significantly favored Tec-Dara (HR, 0.46).

Lead investigator María-Victoria Mateos, MD, PhD, reported the findings in a late-breaking abstract session at American Society of Hematology (ASH) 2025 Annual Meeting. They were published simultaneously in The New England Journal of Medicine.

“[Tec-Dara in this setting] generated the greatest progression-free survival treatment effect to date [in RRMR] with a plateau phase after 6 months of therapy, suggesting potential for functional cure,” said Mateos, a consultant physician and associate professor at the University of Salamanca, Salamanca, Spain.

“We consider that this synergistic immunotherapy combination…is a new potential standard of care for relapsed or refractory multiple myeloma after at least on prior line of therapy, with broad potential across academic and community settings,” added Mateos, who also directs the Multiple Myeloma Program at the University.

Based on the MajesTEC-3 findings, the FDA proactively awarded a national priority voucher to Tec-Dara under the Commissioner’s National Priority Voucher pilot program designed to accelerate the review of certain promising products.

About Tec-Dara

Teclistamab (Tecvayli) is an off-the-shelf first-in-class bispecific monoclonal antibody shown in the MajesTEC-1 trial to provide deep, durable responses in RRMM, with improved efficacy and safety with earlier lines of therapy. The FDA approved the agent for use in 4th or greater lines of therapy in 2022 based on those findings.

Daratumumab (Darzalex) is a widely used anti-CD38 monoclonal antibody currently considered the SOC therapy for RRMM. Both agents are products of the Janssen Pharmaceutical Companies of Johnson & Johnson.

Although front-line therapy for multiple myeloma has dramatically improved, there is a need for new, more effective treatment strategies in patients with disease progression, Mateos noted.

Therefore, she and her colleagues conducted MajesTEC-3, a randomized trial exploring the fully immunotherapy-based regimen of Tec-Dara vs daratumumab-based SOC in patients who had received one to three prior lines of therapy, including a proteasome inhibitor and lenalidomide (Len).

The study was the first to test a bispecific monoclonal antibody as early as the first relapse after initial treatment, she noted.

About MajesTEC-3

Study participants were 587 adults aged 25-88 years. Those with one prior line of therapy were required to be Len-refractory with progressive disease on or after the last therapy. Prior anti-CD-38 Patients with prior B-cell maturation antigen-directed therapy or who were refractory to anti-CD38 treatment were excluded.

The 291 patients randomized to the Tec-Dara treatment group and 296 randomized to the control group were treated in 28-day cycles according to the standard daratumumab schedule: weekly treatment during cycles 1 and 2, biweekly treatment during cycles 3-6, and monthly treatments beginning with cycle 7.

Teclistamab was initiated with an approved step-up dose school followed by 1.5 mg/kg weekly in cycles 1 and 2, 3 mg/kg biweekly in cycles 3-6, and 3 mg/kg monthly beginning with cycle 7.

The 36-month progression-free survival rates with Tec-Dara vs DPd/DVd were 83.4% and 29.7%, with the 36-month overall survival rates having been 83.3% and 65.0%. More than 90% of patients in the Tec-Dara group who were alive at 6 months were also alive at 30 months, Mateos noted.

For both progression-free survival and overall survival, the “clinically remarkable and statistically significant” differences were apparent across all prespecified and clinically relevant subgroups, she added. These included patients who were 75 years or older, Len-refractory patients, and those with high-risk cytogenetics, ≥ 60% bone marrow plasma cells, soft-tissue plasmacytomas, and anti-CD38 exposure.

Patients receiving Tec-Dara also had significantly higher rates of complete or better responses (81.8% vs 32.1%; odds ratio [OR], 9.56), overall response (89.0% vs 75.3%; OR, 2.65), and minimal residual disease-negativity (58.4% vs 17.1%; OR, 6.78).

The median time to first response and first complete or better response was similar in the two groups, but 36-month duration of response was 88.5 vs 36.4 months. At data cutoff, 49.4% of patients remained on study treatment — 71.0% in the Tec-Dara group and 28.3% in the DPd/DVd group, and median treatment duration was twice as long with Tec-Dara (32.4 vs 16.1 months), she said.

Serious adverse events occurred at similar rates in the treatment and control groups (70.7% and 62.4%) and most (44.2%) were grade 1 cytokine release syndrome (CRS). No grade 3 CRS occurred, and all CRS cases resolved.

Immune effector-cell-associated neurotoxicity occurred in 1.1% of patients, and all cases resolved.

Treatment-related adverse events leading to discontinuation occurred in 4.6% and 5.5% of patients in the Tec-Dara and DPd/DVd groups. The rates of deaths due to treatment-emergent adverse events were also similar in the groups (7.1% vs 5.9%).

Infections of any grade occurred in 96.5% and 84.1% of Tec-Dara and DPd/DVd patients, and grade 3/4 infections occurred in 54.1% and 43.4%. New-onset grade 3 or greater infections decreased over time.

“It’s important to acknowledge that patients with infections needed to be supported with adequate prophylaxis and immunoglobulins,” Mateo stressed.

Implications for Patients With RRMM

Teclistamab is currently only approved after three prior lines of therapy, but under the FDA Commissioner’s National Priority Voucher program, the agency will aim to complete its review of Tec-Dara for earlier treatment within 1-2 months following submission of an application for approval by Johnson & Johnson.

If an approval for that indication were to occur, it would be transformative for patients with RRMM, said Michael Rosenzweig, MD, of City of Hope, Duarte, California, in an interview with Medscape Medical News.

The [MajesTEC-3] findings suggest that Tec-Dar “really gives patients a chance at long-term disease control,” added Rosenzweig, chief of the Division of Multiple Myeloma, and an associate professor in the Department of Hematology & Hematopoietic Cell Transplantation at City of Hope.

MajesTEC-3 was funded by Johnson & Johnson. Mateos disclosed relationships with numerous pharmaceutical companies, including Johnson & Johnson. Rosenzweig reported consulting for Johnson & Johnson and was previously on the company’s speakers bureau.

Sharon Worcester, MA, is an award-winning medical journalist based in Birmingham, Alabama, writing for Medscape, MDedge, and other affiliate sites. She currently covers oncology, but she has also written on a variety of other medical specialties and health care topics. She can be reached at [email protected] or on X: @SW_MedReporter.

Adding teclistamab to daratumumab dramatically improved progression-free survival and overall survival vs standard-of-care (SOC) therapy in patients with relapsed or refractory multiple myeloma (RRMM) in the phase 3 MajesTEC-3 trial.

At median follow-up of 34.5 months, progression-free survival was not reached in study participants randomized to receive teclistamab plus daratumumab (Tec-Dara). Starkly contrasting that was the 18.1 months progression-free survival among those randomized to a control group who received the standard of care: investigator’s choice of daratumumab and dexamethasone plus either pomalidomide or bortezomib (DPd/DVd (hazard ratio [HR], 0.17). Overall survival also significantly favored Tec-Dara (HR, 0.46).

Lead investigator María-Victoria Mateos, MD, PhD, reported the findings in a late-breaking abstract session at American Society of Hematology (ASH) 2025 Annual Meeting. They were published simultaneously in The New England Journal of Medicine.

“[Tec-Dara in this setting] generated the greatest progression-free survival treatment effect to date [in RRMR] with a plateau phase after 6 months of therapy, suggesting potential for functional cure,” said Mateos, a consultant physician and associate professor at the University of Salamanca, Salamanca, Spain.

“We consider that this synergistic immunotherapy combination…is a new potential standard of care for relapsed or refractory multiple myeloma after at least on prior line of therapy, with broad potential across academic and community settings,” added Mateos, who also directs the Multiple Myeloma Program at the University.

Based on the MajesTEC-3 findings, the FDA proactively awarded a national priority voucher to Tec-Dara under the Commissioner’s National Priority Voucher pilot program designed to accelerate the review of certain promising products.

About Tec-Dara

Teclistamab (Tecvayli) is an off-the-shelf first-in-class bispecific monoclonal antibody shown in the MajesTEC-1 trial to provide deep, durable responses in RRMM, with improved efficacy and safety with earlier lines of therapy. The FDA approved the agent for use in 4th or greater lines of therapy in 2022 based on those findings.

Daratumumab (Darzalex) is a widely used anti-CD38 monoclonal antibody currently considered the SOC therapy for RRMM. Both agents are products of the Janssen Pharmaceutical Companies of Johnson & Johnson.

Although front-line therapy for multiple myeloma has dramatically improved, there is a need for new, more effective treatment strategies in patients with disease progression, Mateos noted.

Therefore, she and her colleagues conducted MajesTEC-3, a randomized trial exploring the fully immunotherapy-based regimen of Tec-Dara vs daratumumab-based SOC in patients who had received one to three prior lines of therapy, including a proteasome inhibitor and lenalidomide (Len).

The study was the first to test a bispecific monoclonal antibody as early as the first relapse after initial treatment, she noted.

About MajesTEC-3

Study participants were 587 adults aged 25-88 years. Those with one prior line of therapy were required to be Len-refractory with progressive disease on or after the last therapy. Prior anti-CD-38 Patients with prior B-cell maturation antigen-directed therapy or who were refractory to anti-CD38 treatment were excluded.

The 291 patients randomized to the Tec-Dara treatment group and 296 randomized to the control group were treated in 28-day cycles according to the standard daratumumab schedule: weekly treatment during cycles 1 and 2, biweekly treatment during cycles 3-6, and monthly treatments beginning with cycle 7.

Teclistamab was initiated with an approved step-up dose school followed by 1.5 mg/kg weekly in cycles 1 and 2, 3 mg/kg biweekly in cycles 3-6, and 3 mg/kg monthly beginning with cycle 7.

The 36-month progression-free survival rates with Tec-Dara vs DPd/DVd were 83.4% and 29.7%, with the 36-month overall survival rates having been 83.3% and 65.0%. More than 90% of patients in the Tec-Dara group who were alive at 6 months were also alive at 30 months, Mateos noted.

For both progression-free survival and overall survival, the “clinically remarkable and statistically significant” differences were apparent across all prespecified and clinically relevant subgroups, she added. These included patients who were 75 years or older, Len-refractory patients, and those with high-risk cytogenetics, ≥ 60% bone marrow plasma cells, soft-tissue plasmacytomas, and anti-CD38 exposure.

Patients receiving Tec-Dara also had significantly higher rates of complete or better responses (81.8% vs 32.1%; odds ratio [OR], 9.56), overall response (89.0% vs 75.3%; OR, 2.65), and minimal residual disease-negativity (58.4% vs 17.1%; OR, 6.78).

The median time to first response and first complete or better response was similar in the two groups, but 36-month duration of response was 88.5 vs 36.4 months. At data cutoff, 49.4% of patients remained on study treatment — 71.0% in the Tec-Dara group and 28.3% in the DPd/DVd group, and median treatment duration was twice as long with Tec-Dara (32.4 vs 16.1 months), she said.

Serious adverse events occurred at similar rates in the treatment and control groups (70.7% and 62.4%) and most (44.2%) were grade 1 cytokine release syndrome (CRS). No grade 3 CRS occurred, and all CRS cases resolved.

Immune effector-cell-associated neurotoxicity occurred in 1.1% of patients, and all cases resolved.

Treatment-related adverse events leading to discontinuation occurred in 4.6% and 5.5% of patients in the Tec-Dara and DPd/DVd groups. The rates of deaths due to treatment-emergent adverse events were also similar in the groups (7.1% vs 5.9%).

Infections of any grade occurred in 96.5% and 84.1% of Tec-Dara and DPd/DVd patients, and grade 3/4 infections occurred in 54.1% and 43.4%. New-onset grade 3 or greater infections decreased over time.

“It’s important to acknowledge that patients with infections needed to be supported with adequate prophylaxis and immunoglobulins,” Mateo stressed.

Implications for Patients With RRMM

Teclistamab is currently only approved after three prior lines of therapy, but under the FDA Commissioner’s National Priority Voucher program, the agency will aim to complete its review of Tec-Dara for earlier treatment within 1-2 months following submission of an application for approval by Johnson & Johnson.

If an approval for that indication were to occur, it would be transformative for patients with RRMM, said Michael Rosenzweig, MD, of City of Hope, Duarte, California, in an interview with Medscape Medical News.

The [MajesTEC-3] findings suggest that Tec-Dar “really gives patients a chance at long-term disease control,” added Rosenzweig, chief of the Division of Multiple Myeloma, and an associate professor in the Department of Hematology & Hematopoietic Cell Transplantation at City of Hope.

MajesTEC-3 was funded by Johnson & Johnson. Mateos disclosed relationships with numerous pharmaceutical companies, including Johnson & Johnson. Rosenzweig reported consulting for Johnson & Johnson and was previously on the company’s speakers bureau.

Sharon Worcester, MA, is an award-winning medical journalist based in Birmingham, Alabama, writing for Medscape, MDedge, and other affiliate sites. She currently covers oncology, but she has also written on a variety of other medical specialties and health care topics. She can be reached at [email protected] or on X: @SW_MedReporter.

The National Institute for Health and Care Excellence (NICE) has recommended amivantamab (Rybrevant) plus lazertinib (Lazcluze) as a first-line option for adults with previously untreated advanced non–small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations.

In final draft guidance, NICE said the combination therapy should be funded by the NHS in England for eligible patients when it is the most appropriate option. Around 1115 people are expected to benefit.

Lung cancer is the third most common cancer and the leading cause of cancer mortality in the UK. It accounted for 10% of all new cancer diagnoses and 20% of cancer deaths in 2020. Approximately 31,000 people received NSCLC diagnoses in England in 2021, comprising 91% of all lung cancer cases. EGFR mutation-positive NSCLC is more common in women, non-smokers, and individuals from Asian ethnic backgrounds.

Welcoming the decision, Virginia Harrison, research trustee, EGFR+ UK, said, “This is a meaningful advance for patients and their families facing this diagnosis. [It] provides something the EGFR community urgently needs: more choice in first-line treatment.”

How Practice May Shift

The recommendation adds an alternative to existing standards, including osimertinib monotherapy or osimertinib plus pemetrexed/platinum-based chemotherapy. Clinical specialists noted that no single standard care exists for this patient group.

Younger patients and those willing to accept greater side effects may choose between amivantamab plus lazertinib or osimertinib plus chemotherapy. Patients older than 80 years might prefer osimertinib monotherapy due to adverse event considerations.

Mechanism of Action and Clinical Evidence

Amivantamab is a bispecific antibody that simultaneously binds EGFR and mesenchymal-epithelial transition receptors, blocking downstream signaling pathways that drive tumor growth and promoting immune-mediated cancer cell killing. Lazertinib is an oral third-generation EGFR TKI that selectively inhibits mutant EGFR signaling. Together, the agents provides complementary suppression of EGFR-driven tumour growth and resistance mechanisms.

The NICE recommendation is supported by results from the phase 3 MARIPOSA trial, which met its primary endpoint of progression-free survival (PFS). Treatment with amivantamab plus lazertinib significantly prolonged median PFS to 23.7 months compared with 16.6 months with osimertinib. The combination also demonstrated a significant improvement in overall survival, reducing the risk for death by 25% vs osimertinib. Median OS was not reached in the combination arm and was 36.7 months with osimertinib.

The most common adverse reactions with the combination included rash, nail toxicity, hypoalbuminaemia, hepatotoxicity, and stomatitis. 

A Medicines and Healthcare products Regulatory Agency-approved subcutaneous  formulation of amivantamab, authorized after the committee’s initial meeting, may further improve tolerability and convenience. Administration-related reactions occurred in 63% of patients with the intravenous formulation vs 14% with the subcutaneous formulation. Clinicians expect subcutaneous dosing to replace intravenous use in practice.

Dosing, Access, and Implementation

Amivantamab is administered every 2 weeks, either intravenously or subcutaneously. Lazertinib is taken as a daily oral tablet. 

Rybrevant costs £1079 for a 350-mg per 7-mL vial. Lazcluze is priced at £4128.50 for 56 x 80-mg tablets and £6192.75 for 28 x 240-mg tablets. Confidential NHS discounts are available through simple patient access schemes.

Integrated care boards, NHS England, and local authorities must implement the guidance within 90 days of publication. For drugs receiving positive draft recommendations for routine commissioning, interim funding becomes accessible from the Cancer Drugs Fund budget starting from the point of marketing authorisation or publication of draft guidance.

The National Institute for Health and Care Excellence (NICE) has recommended amivantamab (Rybrevant) plus lazertinib (Lazcluze) as a first-line option for adults with previously untreated advanced non–small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations.

In final draft guidance, NICE said the combination therapy should be funded by the NHS in England for eligible patients when it is the most appropriate option. Around 1115 people are expected to benefit.

Lung cancer is the third most common cancer and the leading cause of cancer mortality in the UK. It accounted for 10% of all new cancer diagnoses and 20% of cancer deaths in 2020. Approximately 31,000 people received NSCLC diagnoses in England in 2021, comprising 91% of all lung cancer cases. EGFR mutation-positive NSCLC is more common in women, non-smokers, and individuals from Asian ethnic backgrounds.

Welcoming the decision, Virginia Harrison, research trustee, EGFR+ UK, said, “This is a meaningful advance for patients and their families facing this diagnosis. [It] provides something the EGFR community urgently needs: more choice in first-line treatment.”

How Practice May Shift

The recommendation adds an alternative to existing standards, including osimertinib monotherapy or osimertinib plus pemetrexed/platinum-based chemotherapy. Clinical specialists noted that no single standard care exists for this patient group.

Younger patients and those willing to accept greater side effects may choose between amivantamab plus lazertinib or osimertinib plus chemotherapy. Patients older than 80 years might prefer osimertinib monotherapy due to adverse event considerations.

Mechanism of Action and Clinical Evidence

Amivantamab is a bispecific antibody that simultaneously binds EGFR and mesenchymal-epithelial transition receptors, blocking downstream signaling pathways that drive tumor growth and promoting immune-mediated cancer cell killing. Lazertinib is an oral third-generation EGFR TKI that selectively inhibits mutant EGFR signaling. Together, the agents provides complementary suppression of EGFR-driven tumour growth and resistance mechanisms.

The NICE recommendation is supported by results from the phase 3 MARIPOSA trial, which met its primary endpoint of progression-free survival (PFS). Treatment with amivantamab plus lazertinib significantly prolonged median PFS to 23.7 months compared with 16.6 months with osimertinib. The combination also demonstrated a significant improvement in overall survival, reducing the risk for death by 25% vs osimertinib. Median OS was not reached in the combination arm and was 36.7 months with osimertinib.

The most common adverse reactions with the combination included rash, nail toxicity, hypoalbuminaemia, hepatotoxicity, and stomatitis. 

A Medicines and Healthcare products Regulatory Agency-approved subcutaneous  formulation of amivantamab, authorized after the committee’s initial meeting, may further improve tolerability and convenience. Administration-related reactions occurred in 63% of patients with the intravenous formulation vs 14% with the subcutaneous formulation. Clinicians expect subcutaneous dosing to replace intravenous use in practice.

Dosing, Access, and Implementation

Amivantamab is administered every 2 weeks, either intravenously or subcutaneously. Lazertinib is taken as a daily oral tablet. 

Rybrevant costs £1079 for a 350-mg per 7-mL vial. Lazcluze is priced at £4128.50 for 56 x 80-mg tablets and £6192.75 for 28 x 240-mg tablets. Confidential NHS discounts are available through simple patient access schemes.

Integrated care boards, NHS England, and local authorities must implement the guidance within 90 days of publication. For drugs receiving positive draft recommendations for routine commissioning, interim funding becomes accessible from the Cancer Drugs Fund budget starting from the point of marketing authorisation or publication of draft guidance.

The National Institute for Health and Care Excellence (NICE) has recommended amivantamab (Rybrevant) plus lazertinib (Lazcluze) as a first-line option for adults with previously untreated advanced non–small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations.

In final draft guidance, NICE said the combination therapy should be funded by the NHS in England for eligible patients when it is the most appropriate option. Around 1115 people are expected to benefit.

Lung cancer is the third most common cancer and the leading cause of cancer mortality in the UK. It accounted for 10% of all new cancer diagnoses and 20% of cancer deaths in 2020. Approximately 31,000 people received NSCLC diagnoses in England in 2021, comprising 91% of all lung cancer cases. EGFR mutation-positive NSCLC is more common in women, non-smokers, and individuals from Asian ethnic backgrounds.

Welcoming the decision, Virginia Harrison, research trustee, EGFR+ UK, said, “This is a meaningful advance for patients and their families facing this diagnosis. [It] provides something the EGFR community urgently needs: more choice in first-line treatment.”

How Practice May Shift

The recommendation adds an alternative to existing standards, including osimertinib monotherapy or osimertinib plus pemetrexed/platinum-based chemotherapy. Clinical specialists noted that no single standard care exists for this patient group.

Younger patients and those willing to accept greater side effects may choose between amivantamab plus lazertinib or osimertinib plus chemotherapy. Patients older than 80 years might prefer osimertinib monotherapy due to adverse event considerations.

Mechanism of Action and Clinical Evidence

Amivantamab is a bispecific antibody that simultaneously binds EGFR and mesenchymal-epithelial transition receptors, blocking downstream signaling pathways that drive tumor growth and promoting immune-mediated cancer cell killing. Lazertinib is an oral third-generation EGFR TKI that selectively inhibits mutant EGFR signaling. Together, the agents provides complementary suppression of EGFR-driven tumour growth and resistance mechanisms.

The NICE recommendation is supported by results from the phase 3 MARIPOSA trial, which met its primary endpoint of progression-free survival (PFS). Treatment with amivantamab plus lazertinib significantly prolonged median PFS to 23.7 months compared with 16.6 months with osimertinib. The combination also demonstrated a significant improvement in overall survival, reducing the risk for death by 25% vs osimertinib. Median OS was not reached in the combination arm and was 36.7 months with osimertinib.

The most common adverse reactions with the combination included rash, nail toxicity, hypoalbuminaemia, hepatotoxicity, and stomatitis. 

A Medicines and Healthcare products Regulatory Agency-approved subcutaneous  formulation of amivantamab, authorized after the committee’s initial meeting, may further improve tolerability and convenience. Administration-related reactions occurred in 63% of patients with the intravenous formulation vs 14% with the subcutaneous formulation. Clinicians expect subcutaneous dosing to replace intravenous use in practice.

Dosing, Access, and Implementation

Amivantamab is administered every 2 weeks, either intravenously or subcutaneously. Lazertinib is taken as a daily oral tablet. 

Rybrevant costs £1079 for a 350-mg per 7-mL vial. Lazcluze is priced at £4128.50 for 56 x 80-mg tablets and £6192.75 for 28 x 240-mg tablets. Confidential NHS discounts are available through simple patient access schemes.

Integrated care boards, NHS England, and local authorities must implement the guidance within 90 days of publication. For drugs receiving positive draft recommendations for routine commissioning, interim funding becomes accessible from the Cancer Drugs Fund budget starting from the point of marketing authorisation or publication of draft guidance.

Intensive long-distance running could be a risk for advanced adenomas (AAs) for the colon, a small prospective study reported this summer at the American Society of Clinical Oncology (ASCO) 2025.

Refined screening strategies for this running population are therefore warranted, and pathologic and epidemiologic evaluations should explore causation and ancillary risk factors in this unique population, according to Timothy L. Cannon, MD, oncologist at Inova Schar Cancer Institute in Fairfax, Virginia, and colleagues.

The full study (NCT 05419531), which is currently being reviewed for publication, looked at colonoscopy results from 100 marathon and ultramarathon runners and found that almost half had polyps, and 15% (95% CI, 7.9-22.4) had confirmed AAs).

The AA rate was higher than the 4.5% to 6% seen in adults in their late 40s in the general population and was higher even than the 12% found in Alaska Natives, who are at heightened risk for colon cancer.

"After meeting 3 extreme endurance athletes — 2 who ran 100-mile ultramarathons and 1 lady who ran dozens of triathlons — with stage IV colon cancer before age 40, I began to be suspicious of a link," Cannon told Medscape Medical News. At least 2 of them said they were told that bleeding after long runs was common, which they took to mean as normal. "I could imagine multiple reasons that endurance runners would be predisposed to cancer, with my initial focus on the inflammation and cell turnover incited by the well-described ischemia and runner's colitis."

Study Details

From October 2022 to December 2024, 100 eligible participants aged 35 to 50 years had colonoscopies. The median age was 42.5 years; 55 participants were female and 45 were male. In terms of endurance eligibility, all had completed at ≥ 2 registered ultramarathons (50 km or longer) or 5 registered marathons (26.2 miles). Patients were excluded if they were known or suspected to have inflammatory bowel disease, familial adenomatous polyposis, or Lynch syndrome (hereditary nonpolyposis colorectal cancer).

The historical 1.2% in average-risk individuals aged 40-49 years was used for the expected rate of AAs, defined as lesions > 10 mm, lesions with 25% tubulovillous features, or high-grade dysplasia.

In other findings, 39 had ≥ 1 adenoma and had ≥ 3 adenomas but did not meet AA criteria and were not included in the 15% with AA.

While no colon cancer was detected in the cohort, Cannon said 30% experienced rectal bleeding after exercise, especially those with AAs compared with those without: 53% vs 22%. "While rectal bleeding had a significant association with finding advanced adenomas on the colonoscopy, there were still many with advanced adenomas who reported no bleeding," he said.

Runner's colitis, or trots, is a common condition thought to be related to ischemia, mechanical stress, or adverse impact on the gut microbiome. "Mechanism is the huge question that I certainly can't answer at this point," Cannon said. "At some distance, blood flow gets diverted from the splanchnic circulation to the legs, and gut ischemia seems to ensue. I envision high rates of disorderly cell turnover and more opportunities for mutagenesis. This needs to be studied, and what I am describing is certainly either an oversimplification or simply not related at all."

The authors noted that exercise-induced gastrointestinal injury is likely associated with reduced blood flow to the intestines during long-distance running, but not evidence has linked this bowel ischemia to carcinogenesis.

Diet could be another factor. "I am fascinated with runners' diets. They seem to consume, on average, a huge amount of ultraprocessed bars and goos. They also may drink from plastic bottles far more than the average person. These are just 2 of many possibilities," Cannon said. "Nearly a third of our participants were vegan or vegetarian. We are planning a second, more detailed, survey or our participants. We will really dig down on these questions as well as specifics regarding their training regimens."

Commenting on the study but not involved in it, Thomas F. Imperiale, MD, professor of gastroenterology and hepatology at Indiana University Indianapolis, said that while the findings are provocative, several methodological issues require consideration in subsequent research.

"First, the comparative benchmark of advanced adenoma prevalence of 1.2% is based on screening colonoscopy data from 25 years ago. At the very least, a concurrent benchmark should be used," he told Medscape Medical News. The second issue is the absence of a control group of persons who may exercise but who do not run marathons. "This addition would strengthen study validity more than using a concurrent comparison."

The case group of long-distance runners and a control group of nonmarathon runners could be compared for prevalence of AAs with adjustment for age, sex, race or ethnicity, family history of colorectal cancer, diet, other physical activity, tobacco use history, BMI or waist circumference, ethanol use, and perhaps other early-life exposures and indication for colonoscopy. "Last, it would be interesting to know whether and how often the 100 participants developed symptoms possibly consistent with colonic ischemia either during or after long-distance runs, which might provide indirect support for the presumptive mechanism of action."

In other comments, Hamed Khalili, MD, MPH, gastroenterologist at Massachusetts General Hospital and associate professor at Harvard Medical School, both in Boston, called the results very preliminary. "The sample size is small, and the comparator group is a historical control, so it's unclear whether the observed differences are just a sampling issue," he said.

Cannon has this advice for physicians: "Please don't dismiss symptoms of runner's colitis as benign. This condition requires investigation," he said. While he hasn't seen any expert recommendation to treat postrunning bleeding any differently from other causes of melena or hematochezia, both of which would normally merit a colonoscopy, in practice many gastroenterologists dismiss this type of bleeding as benign. "If larger studies confirm our findings, I don't think it's out of the question that marathoners will have unique screening recommendations. But this study is not robust enough, of course, to merit such a recommendation."

His group is planning a study on the runner's microbiome and on the proteome of the colonic tissue in this group.

Cannon reported having no relevant conflicts of interest to disclose. Imperiale and Khalili reported having no conflicts of interest relevant to their comments on the study.

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

Intensive long-distance running could be a risk for advanced adenomas (AAs) for the colon, a small prospective study reported this summer at the American Society of Clinical Oncology (ASCO) 2025.

Refined screening strategies for this running population are therefore warranted, and pathologic and epidemiologic evaluations should explore causation and ancillary risk factors in this unique population, according to Timothy L. Cannon, MD, oncologist at Inova Schar Cancer Institute in Fairfax, Virginia, and colleagues.

The full study (NCT 05419531), which is currently being reviewed for publication, looked at colonoscopy results from 100 marathon and ultramarathon runners and found that almost half had polyps, and 15% (95% CI, 7.9-22.4) had confirmed AAs).

The AA rate was higher than the 4.5% to 6% seen in adults in their late 40s in the general population and was higher even than the 12% found in Alaska Natives, who are at heightened risk for colon cancer.

"After meeting 3 extreme endurance athletes — 2 who ran 100-mile ultramarathons and 1 lady who ran dozens of triathlons — with stage IV colon cancer before age 40, I began to be suspicious of a link," Cannon told Medscape Medical News. At least 2 of them said they were told that bleeding after long runs was common, which they took to mean as normal. "I could imagine multiple reasons that endurance runners would be predisposed to cancer, with my initial focus on the inflammation and cell turnover incited by the well-described ischemia and runner's colitis."

Study Details

From October 2022 to December 2024, 100 eligible participants aged 35 to 50 years had colonoscopies. The median age was 42.5 years; 55 participants were female and 45 were male. In terms of endurance eligibility, all had completed at ≥ 2 registered ultramarathons (50 km or longer) or 5 registered marathons (26.2 miles). Patients were excluded if they were known or suspected to have inflammatory bowel disease, familial adenomatous polyposis, or Lynch syndrome (hereditary nonpolyposis colorectal cancer).

The historical 1.2% in average-risk individuals aged 40-49 years was used for the expected rate of AAs, defined as lesions > 10 mm, lesions with 25% tubulovillous features, or high-grade dysplasia.

In other findings, 39 had ≥ 1 adenoma and had ≥ 3 adenomas but did not meet AA criteria and were not included in the 15% with AA.

While no colon cancer was detected in the cohort, Cannon said 30% experienced rectal bleeding after exercise, especially those with AAs compared with those without: 53% vs 22%. "While rectal bleeding had a significant association with finding advanced adenomas on the colonoscopy, there were still many with advanced adenomas who reported no bleeding," he said.

Runner's colitis, or trots, is a common condition thought to be related to ischemia, mechanical stress, or adverse impact on the gut microbiome. "Mechanism is the huge question that I certainly can't answer at this point," Cannon said. "At some distance, blood flow gets diverted from the splanchnic circulation to the legs, and gut ischemia seems to ensue. I envision high rates of disorderly cell turnover and more opportunities for mutagenesis. This needs to be studied, and what I am describing is certainly either an oversimplification or simply not related at all."

The authors noted that exercise-induced gastrointestinal injury is likely associated with reduced blood flow to the intestines during long-distance running, but not evidence has linked this bowel ischemia to carcinogenesis.

Diet could be another factor. "I am fascinated with runners' diets. They seem to consume, on average, a huge amount of ultraprocessed bars and goos. They also may drink from plastic bottles far more than the average person. These are just 2 of many possibilities," Cannon said. "Nearly a third of our participants were vegan or vegetarian. We are planning a second, more detailed, survey or our participants. We will really dig down on these questions as well as specifics regarding their training regimens."

Commenting on the study but not involved in it, Thomas F. Imperiale, MD, professor of gastroenterology and hepatology at Indiana University Indianapolis, said that while the findings are provocative, several methodological issues require consideration in subsequent research.

"First, the comparative benchmark of advanced adenoma prevalence of 1.2% is based on screening colonoscopy data from 25 years ago. At the very least, a concurrent benchmark should be used," he told Medscape Medical News. The second issue is the absence of a control group of persons who may exercise but who do not run marathons. "This addition would strengthen study validity more than using a concurrent comparison."

The case group of long-distance runners and a control group of nonmarathon runners could be compared for prevalence of AAs with adjustment for age, sex, race or ethnicity, family history of colorectal cancer, diet, other physical activity, tobacco use history, BMI or waist circumference, ethanol use, and perhaps other early-life exposures and indication for colonoscopy. "Last, it would be interesting to know whether and how often the 100 participants developed symptoms possibly consistent with colonic ischemia either during or after long-distance runs, which might provide indirect support for the presumptive mechanism of action."

In other comments, Hamed Khalili, MD, MPH, gastroenterologist at Massachusetts General Hospital and associate professor at Harvard Medical School, both in Boston, called the results very preliminary. "The sample size is small, and the comparator group is a historical control, so it's unclear whether the observed differences are just a sampling issue," he said.

Cannon has this advice for physicians: "Please don't dismiss symptoms of runner's colitis as benign. This condition requires investigation," he said. While he hasn't seen any expert recommendation to treat postrunning bleeding any differently from other causes of melena or hematochezia, both of which would normally merit a colonoscopy, in practice many gastroenterologists dismiss this type of bleeding as benign. "If larger studies confirm our findings, I don't think it's out of the question that marathoners will have unique screening recommendations. But this study is not robust enough, of course, to merit such a recommendation."

His group is planning a study on the runner's microbiome and on the proteome of the colonic tissue in this group.

Cannon reported having no relevant conflicts of interest to disclose. Imperiale and Khalili reported having no conflicts of interest relevant to their comments on the study.

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

Intensive long-distance running could be a risk for advanced adenomas (AAs) for the colon, a small prospective study reported this summer at the American Society of Clinical Oncology (ASCO) 2025.

Refined screening strategies for this running population are therefore warranted, and pathologic and epidemiologic evaluations should explore causation and ancillary risk factors in this unique population, according to Timothy L. Cannon, MD, oncologist at Inova Schar Cancer Institute in Fairfax, Virginia, and colleagues.

The full study (NCT 05419531), which is currently being reviewed for publication, looked at colonoscopy results from 100 marathon and ultramarathon runners and found that almost half had polyps, and 15% (95% CI, 7.9-22.4) had confirmed AAs).

The AA rate was higher than the 4.5% to 6% seen in adults in their late 40s in the general population and was higher even than the 12% found in Alaska Natives, who are at heightened risk for colon cancer.

"After meeting 3 extreme endurance athletes — 2 who ran 100-mile ultramarathons and 1 lady who ran dozens of triathlons — with stage IV colon cancer before age 40, I began to be suspicious of a link," Cannon told Medscape Medical News. At least 2 of them said they were told that bleeding after long runs was common, which they took to mean as normal. "I could imagine multiple reasons that endurance runners would be predisposed to cancer, with my initial focus on the inflammation and cell turnover incited by the well-described ischemia and runner's colitis."

Study Details

From October 2022 to December 2024, 100 eligible participants aged 35 to 50 years had colonoscopies. The median age was 42.5 years; 55 participants were female and 45 were male. In terms of endurance eligibility, all had completed at ≥ 2 registered ultramarathons (50 km or longer) or 5 registered marathons (26.2 miles). Patients were excluded if they were known or suspected to have inflammatory bowel disease, familial adenomatous polyposis, or Lynch syndrome (hereditary nonpolyposis colorectal cancer).

The historical 1.2% in average-risk individuals aged 40-49 years was used for the expected rate of AAs, defined as lesions > 10 mm, lesions with 25% tubulovillous features, or high-grade dysplasia.

In other findings, 39 had ≥ 1 adenoma and had ≥ 3 adenomas but did not meet AA criteria and were not included in the 15% with AA.

While no colon cancer was detected in the cohort, Cannon said 30% experienced rectal bleeding after exercise, especially those with AAs compared with those without: 53% vs 22%. "While rectal bleeding had a significant association with finding advanced adenomas on the colonoscopy, there were still many with advanced adenomas who reported no bleeding," he said.

Runner's colitis, or trots, is a common condition thought to be related to ischemia, mechanical stress, or adverse impact on the gut microbiome. "Mechanism is the huge question that I certainly can't answer at this point," Cannon said. "At some distance, blood flow gets diverted from the splanchnic circulation to the legs, and gut ischemia seems to ensue. I envision high rates of disorderly cell turnover and more opportunities for mutagenesis. This needs to be studied, and what I am describing is certainly either an oversimplification or simply not related at all."

The authors noted that exercise-induced gastrointestinal injury is likely associated with reduced blood flow to the intestines during long-distance running, but not evidence has linked this bowel ischemia to carcinogenesis.

Diet could be another factor. "I am fascinated with runners' diets. They seem to consume, on average, a huge amount of ultraprocessed bars and goos. They also may drink from plastic bottles far more than the average person. These are just 2 of many possibilities," Cannon said. "Nearly a third of our participants were vegan or vegetarian. We are planning a second, more detailed, survey or our participants. We will really dig down on these questions as well as specifics regarding their training regimens."

Commenting on the study but not involved in it, Thomas F. Imperiale, MD, professor of gastroenterology and hepatology at Indiana University Indianapolis, said that while the findings are provocative, several methodological issues require consideration in subsequent research.

"First, the comparative benchmark of advanced adenoma prevalence of 1.2% is based on screening colonoscopy data from 25 years ago. At the very least, a concurrent benchmark should be used," he told Medscape Medical News. The second issue is the absence of a control group of persons who may exercise but who do not run marathons. "This addition would strengthen study validity more than using a concurrent comparison."

The case group of long-distance runners and a control group of nonmarathon runners could be compared for prevalence of AAs with adjustment for age, sex, race or ethnicity, family history of colorectal cancer, diet, other physical activity, tobacco use history, BMI or waist circumference, ethanol use, and perhaps other early-life exposures and indication for colonoscopy. "Last, it would be interesting to know whether and how often the 100 participants developed symptoms possibly consistent with colonic ischemia either during or after long-distance runs, which might provide indirect support for the presumptive mechanism of action."

In other comments, Hamed Khalili, MD, MPH, gastroenterologist at Massachusetts General Hospital and associate professor at Harvard Medical School, both in Boston, called the results very preliminary. "The sample size is small, and the comparator group is a historical control, so it's unclear whether the observed differences are just a sampling issue," he said.

Cannon has this advice for physicians: "Please don't dismiss symptoms of runner's colitis as benign. This condition requires investigation," he said. While he hasn't seen any expert recommendation to treat postrunning bleeding any differently from other causes of melena or hematochezia, both of which would normally merit a colonoscopy, in practice many gastroenterologists dismiss this type of bleeding as benign. "If larger studies confirm our findings, I don't think it's out of the question that marathoners will have unique screening recommendations. But this study is not robust enough, of course, to merit such a recommendation."

His group is planning a study on the runner's microbiome and on the proteome of the colonic tissue in this group.

Cannon reported having no relevant conflicts of interest to disclose. Imperiale and Khalili reported having no conflicts of interest relevant to their comments on the study.

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

TOPLINE:

Non-operative management achieved 95% distant relapse-free survival at 30 months in patients with stage II-III rectal cancer showing a clinical complete response to total neoadjuvant therapy, while maintaining successful salvage surgery options among 15% of those who experienced local regrowth according to a phase 2 trial.

METHODOLOGY:

• Researchers conducted an investigator-driven, multicentre, single-arm, phase 2 trial enrolling 180 patients (median age, 62 years; 44% women) with stage II-III adenocarcinoma of the lower-to-middle rectum across four cancer centres in Italy from June 2018 to August 2023.
• Treatment consisted of induction chemotherapy with 4 cycles of capecitabine (1000 mg/m² orally twice daily on days 1-14 every 3 weeks) and oxaliplatin (130 mg/m² intravenously on day 1 every 3 weeks), followed by chemoradiotherapy with 50-54 Gy in 25 fractions for 5 weeks.
• The analysis included 179 evaluable patients: 47 (26%) who achieved a clinical complete response were assigned to nonoperative management, 107 (60%) underwent surgery after therapy, and 18 (10%) underwent surgery after study discontinuation.
• The primary outcome was 30-month distant relapse-free survival in the non-operative management group, and secondary outcomes included local relapse-free or regrowth-free survival (local regrowth after non-operative management and local relapse after surgery).

TAKEAWAY:

• After a median follow-up of 35 months, 30-month distant relapse-free survival reached 95% in the non-operative management group vs 74% in the surgery group and 74% in the overall population.
• Among patients undergoing non-operative management, 15% experienced tumour regrowth in the rectal wall within 2 years, corresponding to a 2-year risk for local regrowth of 17%, and cumulative risks for local relapse were 11% at 2 years and 16% at 3 years among those in the surgery group.
• The most common adverse events of grade 3-4 were diarrhoea (4%), lymphopenia (4%), and neutropenia (4%). Overall, 17% of patients had a serious adverse event, with bowel obstruction (4%) and thromboembolism (3%) being the most common adverse events.
• Circulating tumour DNA positivity after total neoadjuvant therapy showed significant prognostic value, with the positive status associated with worse distant relapse-free survival (P = .0032) and progression-free survival (P = .0028) among patients in the non-operative management group.

IN PRACTICE:

“Nonoperative management ensures excellent distant disease control with organ preservation after clinical complete response,” the authors wrote. “As a watch-and-wait approach becomes a recognised standard in international guidelines, the integration of ctDNA [circulating tumour DNA] and possibly other novel biomarkers, adds a crucial dimension to risk stratification and underscores the potential for personalised treatment approaches,” they added.

SOURCE:

This study was led by Alessio Amatu, MD, and Giorgio Patelli, MD, Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy. It was published online in The Lancet Oncology .

LIMITATIONS:

This study was powered only to estimate 30-month distant relapse-free survival for the non-operative management group, potentially limiting statistical power for subgroup and molecular analyses. The single-arm design without randomisation did not directly address whether rectal surgery might provide added value in cases of clinical complete response. The specific induction-based total neoadjuvant therapy strategy used might not have fully reflected evolving practices. Additionally, the racial homogeneity of the study population limited generalisability beyond predominantly White populations.

DISCLOSURES:

This study was funded by Fondazione AIRC ETS, Fondazione Oncologia Niguarda ETS, Grande Ospedale Metropolitano Niguarda, Ministero della Salute, and AIRC 5xMille 2018. Several authors reported receiving grants or honoraria and having other ties with various sources. Full disclosures are noted in the original article.

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 first appeared on Medscape.com.

TOPLINE:

Non-operative management achieved 95% distant relapse-free survival at 30 months in patients with stage II-III rectal cancer showing a clinical complete response to total neoadjuvant therapy, while maintaining successful salvage surgery options among 15% of those who experienced local regrowth according to a phase 2 trial.

METHODOLOGY:

• Researchers conducted an investigator-driven, multicentre, single-arm, phase 2 trial enrolling 180 patients (median age, 62 years; 44% women) with stage II-III adenocarcinoma of the lower-to-middle rectum across four cancer centres in Italy from June 2018 to August 2023.
• Treatment consisted of induction chemotherapy with 4 cycles of capecitabine (1000 mg/m² orally twice daily on days 1-14 every 3 weeks) and oxaliplatin (130 mg/m² intravenously on day 1 every 3 weeks), followed by chemoradiotherapy with 50-54 Gy in 25 fractions for 5 weeks.
• The analysis included 179 evaluable patients: 47 (26%) who achieved a clinical complete response were assigned to nonoperative management, 107 (60%) underwent surgery after therapy, and 18 (10%) underwent surgery after study discontinuation.
• The primary outcome was 30-month distant relapse-free survival in the non-operative management group, and secondary outcomes included local relapse-free or regrowth-free survival (local regrowth after non-operative management and local relapse after surgery).

TAKEAWAY:

• After a median follow-up of 35 months, 30-month distant relapse-free survival reached 95% in the non-operative management group vs 74% in the surgery group and 74% in the overall population.
• Among patients undergoing non-operative management, 15% experienced tumour regrowth in the rectal wall within 2 years, corresponding to a 2-year risk for local regrowth of 17%, and cumulative risks for local relapse were 11% at 2 years and 16% at 3 years among those in the surgery group.
• The most common adverse events of grade 3-4 were diarrhoea (4%), lymphopenia (4%), and neutropenia (4%). Overall, 17% of patients had a serious adverse event, with bowel obstruction (4%) and thromboembolism (3%) being the most common adverse events.
• Circulating tumour DNA positivity after total neoadjuvant therapy showed significant prognostic value, with the positive status associated with worse distant relapse-free survival (P = .0032) and progression-free survival (P = .0028) among patients in the non-operative management group.

IN PRACTICE:

“Nonoperative management ensures excellent distant disease control with organ preservation after clinical complete response,” the authors wrote. “As a watch-and-wait approach becomes a recognised standard in international guidelines, the integration of ctDNA [circulating tumour DNA] and possibly other novel biomarkers, adds a crucial dimension to risk stratification and underscores the potential for personalised treatment approaches,” they added.

SOURCE:

This study was led by Alessio Amatu, MD, and Giorgio Patelli, MD, Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy. It was published online in The Lancet Oncology .

LIMITATIONS:

This study was powered only to estimate 30-month distant relapse-free survival for the non-operative management group, potentially limiting statistical power for subgroup and molecular analyses. The single-arm design without randomisation did not directly address whether rectal surgery might provide added value in cases of clinical complete response. The specific induction-based total neoadjuvant therapy strategy used might not have fully reflected evolving practices. Additionally, the racial homogeneity of the study population limited generalisability beyond predominantly White populations.

DISCLOSURES:

This study was funded by Fondazione AIRC ETS, Fondazione Oncologia Niguarda ETS, Grande Ospedale Metropolitano Niguarda, Ministero della Salute, and AIRC 5xMille 2018. Several authors reported receiving grants or honoraria and having other ties with various sources. Full disclosures are noted in the original article.

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 first appeared on Medscape.com.

TOPLINE:

Non-operative management achieved 95% distant relapse-free survival at 30 months in patients with stage II-III rectal cancer showing a clinical complete response to total neoadjuvant therapy, while maintaining successful salvage surgery options among 15% of those who experienced local regrowth according to a phase 2 trial.

METHODOLOGY:

• Researchers conducted an investigator-driven, multicentre, single-arm, phase 2 trial enrolling 180 patients (median age, 62 years; 44% women) with stage II-III adenocarcinoma of the lower-to-middle rectum across four cancer centres in Italy from June 2018 to August 2023.
• Treatment consisted of induction chemotherapy with 4 cycles of capecitabine (1000 mg/m² orally twice daily on days 1-14 every 3 weeks) and oxaliplatin (130 mg/m² intravenously on day 1 every 3 weeks), followed by chemoradiotherapy with 50-54 Gy in 25 fractions for 5 weeks.
• The analysis included 179 evaluable patients: 47 (26%) who achieved a clinical complete response were assigned to nonoperative management, 107 (60%) underwent surgery after therapy, and 18 (10%) underwent surgery after study discontinuation.
• The primary outcome was 30-month distant relapse-free survival in the non-operative management group, and secondary outcomes included local relapse-free or regrowth-free survival (local regrowth after non-operative management and local relapse after surgery).

TAKEAWAY:

• After a median follow-up of 35 months, 30-month distant relapse-free survival reached 95% in the non-operative management group vs 74% in the surgery group and 74% in the overall population.
• Among patients undergoing non-operative management, 15% experienced tumour regrowth in the rectal wall within 2 years, corresponding to a 2-year risk for local regrowth of 17%, and cumulative risks for local relapse were 11% at 2 years and 16% at 3 years among those in the surgery group.
• The most common adverse events of grade 3-4 were diarrhoea (4%), lymphopenia (4%), and neutropenia (4%). Overall, 17% of patients had a serious adverse event, with bowel obstruction (4%) and thromboembolism (3%) being the most common adverse events.
• Circulating tumour DNA positivity after total neoadjuvant therapy showed significant prognostic value, with the positive status associated with worse distant relapse-free survival (P = .0032) and progression-free survival (P = .0028) among patients in the non-operative management group.

IN PRACTICE:

“Nonoperative management ensures excellent distant disease control with organ preservation after clinical complete response,” the authors wrote. “As a watch-and-wait approach becomes a recognised standard in international guidelines, the integration of ctDNA [circulating tumour DNA] and possibly other novel biomarkers, adds a crucial dimension to risk stratification and underscores the potential for personalised treatment approaches,” they added.

SOURCE:

This study was led by Alessio Amatu, MD, and Giorgio Patelli, MD, Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy. It was published online in The Lancet Oncology .

LIMITATIONS:

This study was powered only to estimate 30-month distant relapse-free survival for the non-operative management group, potentially limiting statistical power for subgroup and molecular analyses. The single-arm design without randomisation did not directly address whether rectal surgery might provide added value in cases of clinical complete response. The specific induction-based total neoadjuvant therapy strategy used might not have fully reflected evolving practices. Additionally, the racial homogeneity of the study population limited generalisability beyond predominantly White populations.

DISCLOSURES:

This study was funded by Fondazione AIRC ETS, Fondazione Oncologia Niguarda ETS, Grande Ospedale Metropolitano Niguarda, Ministero della Salute, and AIRC 5xMille 2018. Several authors reported receiving grants or honoraria and having other ties with various sources. Full disclosures are noted in the original article.

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 first appeared on Medscape.com.