AVAHO

PHOENIX — Patients with head and neck cancer face high rates of malnutrition during treatment, and oral supplements are often recommended. But they are not the entire answer, a dietician told colleagues at the Association of Veterans Affairs (VA) Hematology/Oncology annual meeting.

“Patients should consume the most liberal diet possible throughout treatment,” said advanced practice oncology dietician Brittany Leneweaver, RD, CSO, CES, at the VA Washington DC Healthcare System. “This means not solely relying on oral nutrition supplements like Ensure if possible.”

While Leneweaver said many patients will need supplements, she stressed these products “are meant to supplement the diet and not be the sole source of nutrition, ideally.” Encouraging the intake of whole foods “is really key to make the transition back to solid foods after they’re done with treatment. This makes it so much easier when they’re already swallowing those thicker textures, rather than just liquid the entire time.”

Malnutrition: Common and Damaging

As Leneweaver noted, malnutrition is common in patients with head and neck cancer, and can lead to “increased treatment toxicity, increased risk of infection, decreased survival, increased surgical complication, delayed healing, decreased physical function, and decreased quality of life.”

Malnutrition data in patients with head and neck cancer in the US is sparse. However, a 2024 study found malnutrition in 20% of patients undergoing head and neck cancer surgery and linked the condition to increased length of stay (β, 5.20 additional days), higher costs (β, $15,722) higher odds of potentially preventable complications (adjusted odds ratio [aOR], 2.04), and lower odds of discharge to home (aOR, 0.34).

Leneweaver said her role involves addressing “nutrition impact symptoms” that reduce veteran food intake such as difficulty swallowing, taste disorders, dry mouth, and inflammation of the mucus membranes.

“I can’t tell you how much time I spend just talking to the patient about their medication regimens, making sure they have antiemetics on board, letting the radiation oncologist know, ‘Hey, it’s probably time for medicine,’” she said. “We’re constantly looking at side effects and addressing to alert the team as quickly as possible so that we can prevent further weight loss.”

Better Diets Lead to Better Outcomes

Leneweaver noted that “many times, patients will continue to rely on oral supplements as their primary source of nutrition over the long term. They may be missing out on several health benefits as a result.”

Research shows that high-quality diets matter in this patient group, she said. They’re associated with “decreased symptoms during treatment, reduced head and neck cancer risk, and reduced risk of those chronic nutrition impact symptoms,” Leneweaver said.

Diets before and after cancer diagnosis can make a difference. A 2019 study examined patient diets prior to diagnosis of head and neck cancer. It found that patients with better diet quality were less likely to experience overall nutrition impact symptoms (OR 0.45). However, “studies have found that the majority of our patients with head and neck cancer have an inadequate diet prior to diagnosis,” Leneweaver said. 

As for postdiagnosis nutrition, a 2022 study linked healthier diets in patients with head and neck cancer to 93% lower 3-year risk of all-cause mortality and 85% lower risk of cancer-specific mortality. 

What’s in a High-Quality Diet?

Regarding specific food recommendations, Leneweaver prefers the American Institute for Cancer Research (AICR) nutrition guidelines over the US Department of Agriculture’s Dietary Guidelines for Americans. The AICR “more clearly recommends plant-based diet with at least two-thirds of each meal coming from a variety of plant sources” and recommends avoiding alcohol entirely and limiting red meat, she said. 

Leneweaver said she recognizes that dietary change can be gradual.

“It’s not going to happen overnight,” she said. “We know that lifestyle change takes a lot of work.”

Basic interventions can be effective, she said: “This can be just as simple as recommending a plant-based diet to your patient or recommending they eat the rainbow. And I don’t mean Skittles, I mean actual plants. If you just mention these couple of things to the patients, this can really go a long way, especially if they’re hearing that consistent messaging.”

Team-Based Follow-Up Is Key

Leneweaver emphasized the importance of following up over time even if patients do not initially accept referrals to nutritional services. Dieticians ideally see patients before or during initial treatment and then weekly during radiation therapy. Posttreatment follow-up continues “until they’re nutritionally stable. This can be anywhere from weekly to monthly.”

Leneweaver emphasized collaborating with other team members. For example, she works with a speech pathologist at joint visits, either weekly or monthly, “so that they can get off of that feeding tube or get back to a solid consistency diet, typically before that 3-month PET scan.”

It is also important to understand barriers to healthy eating in the veteran population, including transportation challenges and poor access to healthy food, Leneweaver said.

“Make sure you’re utilizing your social worker, your psychologist, other resources, and food pantries, if you have them.” 

Even when the most ideal choices are not available, she said, “if they only have access to canned vegetables, I’d much rather them eat that than have nothing.”

No disclosures for Leneweaver were provided. 

PHOENIX — Patients with head and neck cancer face high rates of malnutrition during treatment, and oral supplements are often recommended. But they are not the entire answer, a dietician told colleagues at the Association of Veterans Affairs (VA) Hematology/Oncology annual meeting.

“Patients should consume the most liberal diet possible throughout treatment,” said advanced practice oncology dietician Brittany Leneweaver, RD, CSO, CES, at the VA Washington DC Healthcare System. “This means not solely relying on oral nutrition supplements like Ensure if possible.”

While Leneweaver said many patients will need supplements, she stressed these products “are meant to supplement the diet and not be the sole source of nutrition, ideally.” Encouraging the intake of whole foods “is really key to make the transition back to solid foods after they’re done with treatment. This makes it so much easier when they’re already swallowing those thicker textures, rather than just liquid the entire time.”

Malnutrition: Common and Damaging

As Leneweaver noted, malnutrition is common in patients with head and neck cancer, and can lead to “increased treatment toxicity, increased risk of infection, decreased survival, increased surgical complication, delayed healing, decreased physical function, and decreased quality of life.”

Malnutrition data in patients with head and neck cancer in the US is sparse. However, a 2024 study found malnutrition in 20% of patients undergoing head and neck cancer surgery and linked the condition to increased length of stay (β, 5.20 additional days), higher costs (β, $15,722) higher odds of potentially preventable complications (adjusted odds ratio [aOR], 2.04), and lower odds of discharge to home (aOR, 0.34).

Leneweaver said her role involves addressing “nutrition impact symptoms” that reduce veteran food intake such as difficulty swallowing, taste disorders, dry mouth, and inflammation of the mucus membranes.

“I can’t tell you how much time I spend just talking to the patient about their medication regimens, making sure they have antiemetics on board, letting the radiation oncologist know, ‘Hey, it’s probably time for medicine,’” she said. “We’re constantly looking at side effects and addressing to alert the team as quickly as possible so that we can prevent further weight loss.”

Better Diets Lead to Better Outcomes

Leneweaver noted that “many times, patients will continue to rely on oral supplements as their primary source of nutrition over the long term. They may be missing out on several health benefits as a result.”

Research shows that high-quality diets matter in this patient group, she said. They’re associated with “decreased symptoms during treatment, reduced head and neck cancer risk, and reduced risk of those chronic nutrition impact symptoms,” Leneweaver said.

Diets before and after cancer diagnosis can make a difference. A 2019 study examined patient diets prior to diagnosis of head and neck cancer. It found that patients with better diet quality were less likely to experience overall nutrition impact symptoms (OR 0.45). However, “studies have found that the majority of our patients with head and neck cancer have an inadequate diet prior to diagnosis,” Leneweaver said. 

As for postdiagnosis nutrition, a 2022 study linked healthier diets in patients with head and neck cancer to 93% lower 3-year risk of all-cause mortality and 85% lower risk of cancer-specific mortality. 

What’s in a High-Quality Diet?

Regarding specific food recommendations, Leneweaver prefers the American Institute for Cancer Research (AICR) nutrition guidelines over the US Department of Agriculture’s Dietary Guidelines for Americans. The AICR “more clearly recommends plant-based diet with at least two-thirds of each meal coming from a variety of plant sources” and recommends avoiding alcohol entirely and limiting red meat, she said. 

Leneweaver said she recognizes that dietary change can be gradual.

“It’s not going to happen overnight,” she said. “We know that lifestyle change takes a lot of work.”

Basic interventions can be effective, she said: “This can be just as simple as recommending a plant-based diet to your patient or recommending they eat the rainbow. And I don’t mean Skittles, I mean actual plants. If you just mention these couple of things to the patients, this can really go a long way, especially if they’re hearing that consistent messaging.”

Team-Based Follow-Up Is Key

Leneweaver emphasized the importance of following up over time even if patients do not initially accept referrals to nutritional services. Dieticians ideally see patients before or during initial treatment and then weekly during radiation therapy. Posttreatment follow-up continues “until they’re nutritionally stable. This can be anywhere from weekly to monthly.”

Leneweaver emphasized collaborating with other team members. For example, she works with a speech pathologist at joint visits, either weekly or monthly, “so that they can get off of that feeding tube or get back to a solid consistency diet, typically before that 3-month PET scan.”

It is also important to understand barriers to healthy eating in the veteran population, including transportation challenges and poor access to healthy food, Leneweaver said.

“Make sure you’re utilizing your social worker, your psychologist, other resources, and food pantries, if you have them.” 

Even when the most ideal choices are not available, she said, “if they only have access to canned vegetables, I’d much rather them eat that than have nothing.”

No disclosures for Leneweaver were provided. 

PHOENIX — Patients with head and neck cancer face high rates of malnutrition during treatment, and oral supplements are often recommended. But they are not the entire answer, a dietician told colleagues at the Association of Veterans Affairs (VA) Hematology/Oncology annual meeting.

“Patients should consume the most liberal diet possible throughout treatment,” said advanced practice oncology dietician Brittany Leneweaver, RD, CSO, CES, at the VA Washington DC Healthcare System. “This means not solely relying on oral nutrition supplements like Ensure if possible.”

While Leneweaver said many patients will need supplements, she stressed these products “are meant to supplement the diet and not be the sole source of nutrition, ideally.” Encouraging the intake of whole foods “is really key to make the transition back to solid foods after they’re done with treatment. This makes it so much easier when they’re already swallowing those thicker textures, rather than just liquid the entire time.”

Malnutrition: Common and Damaging

As Leneweaver noted, malnutrition is common in patients with head and neck cancer, and can lead to “increased treatment toxicity, increased risk of infection, decreased survival, increased surgical complication, delayed healing, decreased physical function, and decreased quality of life.”

Malnutrition data in patients with head and neck cancer in the US is sparse. However, a 2024 study found malnutrition in 20% of patients undergoing head and neck cancer surgery and linked the condition to increased length of stay (β, 5.20 additional days), higher costs (β, $15,722) higher odds of potentially preventable complications (adjusted odds ratio [aOR], 2.04), and lower odds of discharge to home (aOR, 0.34).

Leneweaver said her role involves addressing “nutrition impact symptoms” that reduce veteran food intake such as difficulty swallowing, taste disorders, dry mouth, and inflammation of the mucus membranes.

“I can’t tell you how much time I spend just talking to the patient about their medication regimens, making sure they have antiemetics on board, letting the radiation oncologist know, ‘Hey, it’s probably time for medicine,’” she said. “We’re constantly looking at side effects and addressing to alert the team as quickly as possible so that we can prevent further weight loss.”

Better Diets Lead to Better Outcomes

Leneweaver noted that “many times, patients will continue to rely on oral supplements as their primary source of nutrition over the long term. They may be missing out on several health benefits as a result.”

Research shows that high-quality diets matter in this patient group, she said. They’re associated with “decreased symptoms during treatment, reduced head and neck cancer risk, and reduced risk of those chronic nutrition impact symptoms,” Leneweaver said.

Diets before and after cancer diagnosis can make a difference. A 2019 study examined patient diets prior to diagnosis of head and neck cancer. It found that patients with better diet quality were less likely to experience overall nutrition impact symptoms (OR 0.45). However, “studies have found that the majority of our patients with head and neck cancer have an inadequate diet prior to diagnosis,” Leneweaver said. 

As for postdiagnosis nutrition, a 2022 study linked healthier diets in patients with head and neck cancer to 93% lower 3-year risk of all-cause mortality and 85% lower risk of cancer-specific mortality. 

What’s in a High-Quality Diet?

Regarding specific food recommendations, Leneweaver prefers the American Institute for Cancer Research (AICR) nutrition guidelines over the US Department of Agriculture’s Dietary Guidelines for Americans. The AICR “more clearly recommends plant-based diet with at least two-thirds of each meal coming from a variety of plant sources” and recommends avoiding alcohol entirely and limiting red meat, she said. 

Leneweaver said she recognizes that dietary change can be gradual.

“It’s not going to happen overnight,” she said. “We know that lifestyle change takes a lot of work.”

Basic interventions can be effective, she said: “This can be just as simple as recommending a plant-based diet to your patient or recommending they eat the rainbow. And I don’t mean Skittles, I mean actual plants. If you just mention these couple of things to the patients, this can really go a long way, especially if they’re hearing that consistent messaging.”

Team-Based Follow-Up Is Key

Leneweaver emphasized the importance of following up over time even if patients do not initially accept referrals to nutritional services. Dieticians ideally see patients before or during initial treatment and then weekly during radiation therapy. Posttreatment follow-up continues “until they’re nutritionally stable. This can be anywhere from weekly to monthly.”

Leneweaver emphasized collaborating with other team members. For example, she works with a speech pathologist at joint visits, either weekly or monthly, “so that they can get off of that feeding tube or get back to a solid consistency diet, typically before that 3-month PET scan.”

It is also important to understand barriers to healthy eating in the veteran population, including transportation challenges and poor access to healthy food, Leneweaver said.

“Make sure you’re utilizing your social worker, your psychologist, other resources, and food pantries, if you have them.” 

Even when the most ideal choices are not available, she said, “if they only have access to canned vegetables, I’d much rather them eat that than have nothing.”

No disclosures for Leneweaver were provided. 

TOPLINE:

A comprehensive review of 92 studies found that 15% to 20% of lung cancers occurred among nonsmokers and were associated with environmental and germline risk factors. These cancers frequently harbored actionable genomic drivers, and targeted EGFR and ALK therapies produced significant diseasefree survival (DFS) and overall survival benefits.

METHODOLOGY:

• Lung cancer continues to be the leading cause of cancer death worldwide, causing about 1.8 million deaths in 2022, with smoking remaining the predominant risk factor. However, the incidence of lung cancer among nonsmokers (those who have smoked less than 100 cigarettes in their lifetime) is rising, varies by sex and geography, and is linked to environmental exposures and family history. The misperception that lung cancer is almost invariably caused by smoking may delay assessment and diagnosis.
• Researchers conducted a review of 92 studies on lung cancer in nonsmokers: 6 meta-analyses or systematic reviews, 16 randomized clinical trials, eight prospective cohort studies, seven retrospective cohort studies, three cross-sectional studies, four observational or case-control studies, 13 genomic studies, and 35 other studies.
• Overall, lung cancer among nonsmokers accounted for 15% to 20% of all lung cancer cases. Most lung cancers in nonsmokers were adenocarcinomas (60% to 80%), with a median age at diagnosis of 67 years in this group compared with 70 years in people with a history of smoking.
• Data analysis from three US hospital networks showed that the proportion of lung cancer among nonsmokers increased from 8.0% to 14.9% between 1990 and 2013. A pooled analysis of seven Finnish cohorts reported an absolute increase in lung cancer among nonsmokers from 6.9 per 100,000 person-years in 1972 to 12.9 per 100,000 person-years in 2015.
• The age-adjusted incidence rate of lung cancer in the US between 2000 and 2013 was 17.5 per 100,000 individuals among Asian female nonsmokers compared with 10.1 per 100,000 among non-Hispanic White female nonsmokers.

TAKEAWAY:

• Environmental and occupational risk factors were secondhand smoke, residential radon, outdoor and household air pollution (PM_2.5), asbestos and silica exposure, and prior thoracic radiotherapy. Having a first-degree relative with lung cancer increased the risk of developing lung cancer, and genome-wide association studies identified susceptibility loci associated with lung cancer risk in nonsmokers.
• Family history and inherited susceptibility increased lung cancer risk in never smokers (odds ratio [OR] for lung cancer in those with a first–degree relative, 1.51), and clonal hematopoiesis was also associated with higher risk (OR, 1.43). Importantly, tumors in nonsmokers were frequently driven by actionable somatic alterations (EGFR mutations, 40% to 60% in nonsmokers compared with 10% in smokers) and enrichment of ALK/ROS1/RET/ERBB2/NTRK/NRG1 fusions; 78% to 92% of adenocarcinomas in nonsmokers harbored actionable drivers (compared with 49.5% in ever smokers), and nonsmokers had a substantially lower tumor mutational burden (10–fold lower).
• Similar to individuals with a history of smoking, nonsmokers with lung cancer presented with cough, pain, dyspnea, or weight loss or had disease detected incidentally. Surgical resection remained the preferred treatment for anatomically resectable lung cancer (stages I-III) in medically eligible patients, with follow-up CT screening recommended every 6 months for 2 to 3 years and then annually.
• Targeted adjuvant therapy substantially improved outcomes for resected EGFR–mutant or ALK–rearranged non-small cell lung cancer (NSCLC). Four-year DFS was increased to 70% with osimertinib compared with 29% with placebo (hazard ratio [HR], 0.23) and 5–year overall survival was increased to 85% compared with 73% (HR, 0.49). Two–year DFS was 93.8% with alectinib compared with 63% with placebo (HR, 0.24). In unresectable EGFR-mutated stage III NSCLC, median progression-free survival was 39.1 months with adjuvant osimertinib compared with 5.6 months with placebo. For resected ALKpositive disease, 2–year DFS was 93.8% with adjuvant alectinib compared with 63.0% with chemotherapy (HR, 0.24).
• However, singleagent single agent programmed cell death protein 1 inhibitors or programmed death-ligand 1 inhibitors demonstrated limited efficacy in EGFR or ALK–driven tumors, and benefit was attenuated in never smokers. Regarding screening and early detection, the US Preventive Services Task Force did not recommend lowdose CT screening for nonsmokers, whereas Taiwan implemented a biennial screening program for selected nonsmoking high–risk groups.

IN PRACTICE:

“Among patients with lung cancer, nonsmoking individuals are more likely to have genomic alterations, such as EGFR mutations or ALK gene rearrangements, and these patients have improved survival when treated with TKIs compared with chemotherapy,” the authors of the study wrote.

SOURCE:

The study, led by Cian Murphy, PhD, Cancer Evolution and Genome Instability Laboratory, Francis Crick Institute, London, England, was published online in JAMA.

LIMITATIONS:

Becausesmoking history was often not included in many databases, cancer registries, and trials, the incidence and prevalence of lung cancer in nonsmokers could not be accurately determined. Additionally, accurate quantification of environmental exposures, such as air pollution, presented significant challenges. The quality of the evidence was not formally evaluated, and some relevant articles may have been missed in the literature review.

DISCLOSURES:

The study received support from multiple organizations, including the Rosetrees Trust, Ruth Strauss Foundation, Cancer Research UK, and the National Health and Medical Research Council. Several authors reported receiving grants or personal fees from 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:

A comprehensive review of 92 studies found that 15% to 20% of lung cancers occurred among nonsmokers and were associated with environmental and germline risk factors. These cancers frequently harbored actionable genomic drivers, and targeted EGFR and ALK therapies produced significant diseasefree survival (DFS) and overall survival benefits.

METHODOLOGY:

• Lung cancer continues to be the leading cause of cancer death worldwide, causing about 1.8 million deaths in 2022, with smoking remaining the predominant risk factor. However, the incidence of lung cancer among nonsmokers (those who have smoked less than 100 cigarettes in their lifetime) is rising, varies by sex and geography, and is linked to environmental exposures and family history. The misperception that lung cancer is almost invariably caused by smoking may delay assessment and diagnosis.
• Researchers conducted a review of 92 studies on lung cancer in nonsmokers: 6 meta-analyses or systematic reviews, 16 randomized clinical trials, eight prospective cohort studies, seven retrospective cohort studies, three cross-sectional studies, four observational or case-control studies, 13 genomic studies, and 35 other studies.
• Overall, lung cancer among nonsmokers accounted for 15% to 20% of all lung cancer cases. Most lung cancers in nonsmokers were adenocarcinomas (60% to 80%), with a median age at diagnosis of 67 years in this group compared with 70 years in people with a history of smoking.
• Data analysis from three US hospital networks showed that the proportion of lung cancer among nonsmokers increased from 8.0% to 14.9% between 1990 and 2013. A pooled analysis of seven Finnish cohorts reported an absolute increase in lung cancer among nonsmokers from 6.9 per 100,000 person-years in 1972 to 12.9 per 100,000 person-years in 2015.
• The age-adjusted incidence rate of lung cancer in the US between 2000 and 2013 was 17.5 per 100,000 individuals among Asian female nonsmokers compared with 10.1 per 100,000 among non-Hispanic White female nonsmokers.

TAKEAWAY:

• Environmental and occupational risk factors were secondhand smoke, residential radon, outdoor and household air pollution (PM_2.5), asbestos and silica exposure, and prior thoracic radiotherapy. Having a first-degree relative with lung cancer increased the risk of developing lung cancer, and genome-wide association studies identified susceptibility loci associated with lung cancer risk in nonsmokers.
• Family history and inherited susceptibility increased lung cancer risk in never smokers (odds ratio [OR] for lung cancer in those with a first–degree relative, 1.51), and clonal hematopoiesis was also associated with higher risk (OR, 1.43). Importantly, tumors in nonsmokers were frequently driven by actionable somatic alterations (EGFR mutations, 40% to 60% in nonsmokers compared with 10% in smokers) and enrichment of ALK/ROS1/RET/ERBB2/NTRK/NRG1 fusions; 78% to 92% of adenocarcinomas in nonsmokers harbored actionable drivers (compared with 49.5% in ever smokers), and nonsmokers had a substantially lower tumor mutational burden (10–fold lower).
• Similar to individuals with a history of smoking, nonsmokers with lung cancer presented with cough, pain, dyspnea, or weight loss or had disease detected incidentally. Surgical resection remained the preferred treatment for anatomically resectable lung cancer (stages I-III) in medically eligible patients, with follow-up CT screening recommended every 6 months for 2 to 3 years and then annually.
• Targeted adjuvant therapy substantially improved outcomes for resected EGFR–mutant or ALK–rearranged non-small cell lung cancer (NSCLC). Four-year DFS was increased to 70% with osimertinib compared with 29% with placebo (hazard ratio [HR], 0.23) and 5–year overall survival was increased to 85% compared with 73% (HR, 0.49). Two–year DFS was 93.8% with alectinib compared with 63% with placebo (HR, 0.24). In unresectable EGFR-mutated stage III NSCLC, median progression-free survival was 39.1 months with adjuvant osimertinib compared with 5.6 months with placebo. For resected ALKpositive disease, 2–year DFS was 93.8% with adjuvant alectinib compared with 63.0% with chemotherapy (HR, 0.24).
• However, singleagent single agent programmed cell death protein 1 inhibitors or programmed death-ligand 1 inhibitors demonstrated limited efficacy in EGFR or ALK–driven tumors, and benefit was attenuated in never smokers. Regarding screening and early detection, the US Preventive Services Task Force did not recommend lowdose CT screening for nonsmokers, whereas Taiwan implemented a biennial screening program for selected nonsmoking high–risk groups.

IN PRACTICE:

“Among patients with lung cancer, nonsmoking individuals are more likely to have genomic alterations, such as EGFR mutations or ALK gene rearrangements, and these patients have improved survival when treated with TKIs compared with chemotherapy,” the authors of the study wrote.

SOURCE:

The study, led by Cian Murphy, PhD, Cancer Evolution and Genome Instability Laboratory, Francis Crick Institute, London, England, was published online in JAMA.

LIMITATIONS:

Becausesmoking history was often not included in many databases, cancer registries, and trials, the incidence and prevalence of lung cancer in nonsmokers could not be accurately determined. Additionally, accurate quantification of environmental exposures, such as air pollution, presented significant challenges. The quality of the evidence was not formally evaluated, and some relevant articles may have been missed in the literature review.

DISCLOSURES:

The study received support from multiple organizations, including the Rosetrees Trust, Ruth Strauss Foundation, Cancer Research UK, and the National Health and Medical Research Council. Several authors reported receiving grants or personal fees from 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:

A comprehensive review of 92 studies found that 15% to 20% of lung cancers occurred among nonsmokers and were associated with environmental and germline risk factors. These cancers frequently harbored actionable genomic drivers, and targeted EGFR and ALK therapies produced significant diseasefree survival (DFS) and overall survival benefits.

METHODOLOGY:

• Lung cancer continues to be the leading cause of cancer death worldwide, causing about 1.8 million deaths in 2022, with smoking remaining the predominant risk factor. However, the incidence of lung cancer among nonsmokers (those who have smoked less than 100 cigarettes in their lifetime) is rising, varies by sex and geography, and is linked to environmental exposures and family history. The misperception that lung cancer is almost invariably caused by smoking may delay assessment and diagnosis.
• Researchers conducted a review of 92 studies on lung cancer in nonsmokers: 6 meta-analyses or systematic reviews, 16 randomized clinical trials, eight prospective cohort studies, seven retrospective cohort studies, three cross-sectional studies, four observational or case-control studies, 13 genomic studies, and 35 other studies.
• Overall, lung cancer among nonsmokers accounted for 15% to 20% of all lung cancer cases. Most lung cancers in nonsmokers were adenocarcinomas (60% to 80%), with a median age at diagnosis of 67 years in this group compared with 70 years in people with a history of smoking.
• Data analysis from three US hospital networks showed that the proportion of lung cancer among nonsmokers increased from 8.0% to 14.9% between 1990 and 2013. A pooled analysis of seven Finnish cohorts reported an absolute increase in lung cancer among nonsmokers from 6.9 per 100,000 person-years in 1972 to 12.9 per 100,000 person-years in 2015.
• The age-adjusted incidence rate of lung cancer in the US between 2000 and 2013 was 17.5 per 100,000 individuals among Asian female nonsmokers compared with 10.1 per 100,000 among non-Hispanic White female nonsmokers.

TAKEAWAY:

• Environmental and occupational risk factors were secondhand smoke, residential radon, outdoor and household air pollution (PM_2.5), asbestos and silica exposure, and prior thoracic radiotherapy. Having a first-degree relative with lung cancer increased the risk of developing lung cancer, and genome-wide association studies identified susceptibility loci associated with lung cancer risk in nonsmokers.
• Family history and inherited susceptibility increased lung cancer risk in never smokers (odds ratio [OR] for lung cancer in those with a first–degree relative, 1.51), and clonal hematopoiesis was also associated with higher risk (OR, 1.43). Importantly, tumors in nonsmokers were frequently driven by actionable somatic alterations (EGFR mutations, 40% to 60% in nonsmokers compared with 10% in smokers) and enrichment of ALK/ROS1/RET/ERBB2/NTRK/NRG1 fusions; 78% to 92% of adenocarcinomas in nonsmokers harbored actionable drivers (compared with 49.5% in ever smokers), and nonsmokers had a substantially lower tumor mutational burden (10–fold lower).
• Similar to individuals with a history of smoking, nonsmokers with lung cancer presented with cough, pain, dyspnea, or weight loss or had disease detected incidentally. Surgical resection remained the preferred treatment for anatomically resectable lung cancer (stages I-III) in medically eligible patients, with follow-up CT screening recommended every 6 months for 2 to 3 years and then annually.
• Targeted adjuvant therapy substantially improved outcomes for resected EGFR–mutant or ALK–rearranged non-small cell lung cancer (NSCLC). Four-year DFS was increased to 70% with osimertinib compared with 29% with placebo (hazard ratio [HR], 0.23) and 5–year overall survival was increased to 85% compared with 73% (HR, 0.49). Two–year DFS was 93.8% with alectinib compared with 63% with placebo (HR, 0.24). In unresectable EGFR-mutated stage III NSCLC, median progression-free survival was 39.1 months with adjuvant osimertinib compared with 5.6 months with placebo. For resected ALKpositive disease, 2–year DFS was 93.8% with adjuvant alectinib compared with 63.0% with chemotherapy (HR, 0.24).
• However, singleagent single agent programmed cell death protein 1 inhibitors or programmed death-ligand 1 inhibitors demonstrated limited efficacy in EGFR or ALK–driven tumors, and benefit was attenuated in never smokers. Regarding screening and early detection, the US Preventive Services Task Force did not recommend lowdose CT screening for nonsmokers, whereas Taiwan implemented a biennial screening program for selected nonsmoking high–risk groups.

IN PRACTICE:

“Among patients with lung cancer, nonsmoking individuals are more likely to have genomic alterations, such as EGFR mutations or ALK gene rearrangements, and these patients have improved survival when treated with TKIs compared with chemotherapy,” the authors of the study wrote.

SOURCE:

The study, led by Cian Murphy, PhD, Cancer Evolution and Genome Instability Laboratory, Francis Crick Institute, London, England, was published online in JAMA.

LIMITATIONS:

Becausesmoking history was often not included in many databases, cancer registries, and trials, the incidence and prevalence of lung cancer in nonsmokers could not be accurately determined. Additionally, accurate quantification of environmental exposures, such as air pollution, presented significant challenges. The quality of the evidence was not formally evaluated, and some relevant articles may have been missed in the literature review.

DISCLOSURES:

The study received support from multiple organizations, including the Rosetrees Trust, Ruth Strauss Foundation, Cancer Research UK, and the National Health and Medical Research Council. Several authors reported receiving grants or personal fees from 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.

BERLIN — Re-treatment with an antiepidermal growth factor receptor (EGFR) agent is effective in patients with chemorefractory metastatic colorectal cancer (mCRC) with RAS and BRAF wild-type tumors confirmed on circulating tumor DNA (ctDNA), although the sequencing of therapy does not seem to matter, suggest overall survival results from the crossover trial PARERE.

The findings nevertheless indicate that anti-EGFR rechallenge with panitumumab may prolong progression-free survival (PFS) over the multiple kinase inhibitor regorafenib. This suggests that “the most pragmatic choice” would be to give the anti-EGFR before regorafenib, said study presenter Marco Maria Germani, MD, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.

The caveat, however, is in patients who have an anti-EGFR interval since previously receiving the drugs of < 6 months. Those patients appeared to do better if they had regorafenib first and then anti-EGFR rechallenge.

Overall, Germani said that “since [trifluridine/tipiracil] plus bevacizumab is today the third-line standard of care” in this patient population, “anti-EGFR re-treatment might be considered after progression” on that combination.

Germani presented the research on October 18 at the European Society for Medical Oncology (ESMO) Annual Meeting 2025, which was simultaneously published in the Annals of Oncology.

Michel P. Ducreux, MD, PhD, head of the Digestive Cancer Committee at Gustave Roussy, Villejuif, France, and invited discussant for the results, said, despite the study being negative, it is “very important to continue to perform this kind of trial to evaluate the [ideal] sequence in the treatment of our patients.”

He continued that the secondary endpoints in the trial of PFS and objective response and disease control rates were “fairly in favor of the use of rechallenge before regorafenib, and in my opinion, this is really quite convincing.”

Ducreux, who was not involved in PARERE trail, also pointed to the sex difference seen in the study, which suggested that women responded much better to having anti-EGFR retreatment before regorafenib than did men.

Similar findings have been reported in a number of other trials, and previous work has suggested that there are sex differences in the pharmacokinetics of several anticancer drugs. However, while this is “very important,” he said that “we never consider it, because we are not able to really explain [it].”

Overall, he concluded that, on the basis of these results, he would agree with the notion that it is better to propose a rechallenge with anti-EGFR treatment as the fourth-line therapy in this patient population, before administering regorafenib.

Ducreux explained that, after a partial response, tumors acquire resistance to EGFR inhibitors through alterations and mutations that occur during treatment, via nongenetic mechanisms, and through treatment-induced selection for preexisting mutations.

Previous work has shown that mutations, such as in the RAS gene, are detectable early during EGFR inhibitor therapy, but that they then decay exponentially once the drugs are stopped, with the potential that tumors regain their sensitivity to them.

Germani said that this means that ctDNA-guided retreatment with anti-EGFR therapies is a “promising approach” in pretreated patients with RAS and BRAF wild-type mCRC, and that the sequencing of the drugs may be important. Indeed, the REVERCE trial showed that giving regorafenib followed by the anti-EGFR drug cetuzximab was associated with longer overall survival than the other way around in anti-EGFR medication-naive patients.

 

Methods and Results

For PARERE, the researchers enrolled patients aged at least 18 years with RAS and BRAF wild-type mCRC who were previously treated with a first-line anti-EGFR-containing regimen and had at least a partial response or stable disease for at least 6 months.

The patients were also required to have had at least one intervening anti-EGFR-free line of therapy, and to have previously received treatment with fluoropyrimidine, oxaliplatin, irinotecan, and anti-angiogenics. At least 4 months were required to have passed between the end of anti-EGFR administration and screening for the study.

In all, 428 patients were screened between December 2020 and December 2024, with 213 patients with RAS and BRAF wild-type mCRC, as detected on ctDNA, enrolled. They were randomized to panitumumab or regorafenib until first progression, followed by regorafenib, if they started on panitumumab, or panitumumab, if they started on regorafenib, until second progression.

The median age of the patients was 61 years among those who started on panitumumab and 64 years among those initially given regorafenib in the trial, and 63% and 57%, respectively, were male. The median number of prior lines of therapy was two in both groups, and 65% and 69%, respectively, had received pantitumumab as their first-line anti-EGFR.

Initial findings from the study presented at the 2025 ASCO Annual Meeting indicated that, after a median follow-up of 23.5 months, there was no significant difference in the median first PFS between the two treatment arms.

However, patients who started with panitumumab had a significant improvement in both the objective response and disease control rates (P < .001), as well as a signal for a potentially longer median second PFS, than those who started with regorafenib, particularly on the per-protocol analysis.

Presenting the overall survival results, Germani said that there was no significant difference between the groups on the intention-to-treat analysis, at a stratified hazard ratio of 1.13 (P = .440), or on the per-protocol analysis, at a hazard ratio of 1.07 (P = .730).

“We then ran a subgroup analysis,” he continued, “and we found out that an anti-EGFR-free interval before liquid biopsy shorter than 6 months was associated with less benefit from a panitumumab [first] sequence, which is biologically sound.”

It was also observed that women did significantly better when having panitumumab first, whereas men did not, for which “we do not have a clear biological explanation,” Germani added.

Confining the analysis to so-called “hyperselected” patients, who not only were RAS and BRAF wild type but also had no pathogenic mutations associated with anti-EGFR resistance, did not reveal any significant overall survival differences between the treatment groups.

However, Ducreux took issue with the way in which hyperselection, which is turning up more and more regularly in trials, is defined, as the choice of which mutations to include varies widely. He suggested that a consensus group be assembled to resolve this issue.

Looking more broadly, the researchers were able to show that, in this updated analysis, anti-EGFR re-treatment was superior to regorafenib regardless of the treatment sequence in terms of PFS, at 4.2 months vs 2.4 months (P = .103) when given first in the trial, and 3.9 months vs 2.7 months (P = .019) when given second in the trial, as well as in terms of objective response and disease control rates.

 

Adverse Events

In terms of safety, the results showed that, as expected, acneiform rash, fatigue, and hypomagnesemia were the most common adverse events associated with panitumumb, while those with regorafenib were fatigue, hand-foot skin reactions, and hypertension.

There were no notable differences in the number of patients receiving a post-study treatment nor in the post-study therapeutic choices, between the study arms.

The study was sponsored by GONO Foundation and partially supported by Amgen and Bayer. Germani declared having relationships with MSD and Amgen. Ducreux declared having relationships with Amgen, Bayer, BeiGene, Incyte, Jazz, Merck KGaA, Merck Serono, Merck Sharp & Dohme, Pierre Fabre, Roche, Servier, Keocyt, AbbVie, Abcely, Arcus, Bayer, BMS, Boehringer, GlaxoSmithKline, Sanofi, Scandion, and Zymeworks.

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

BERLIN — Re-treatment with an antiepidermal growth factor receptor (EGFR) agent is effective in patients with chemorefractory metastatic colorectal cancer (mCRC) with RAS and BRAF wild-type tumors confirmed on circulating tumor DNA (ctDNA), although the sequencing of therapy does not seem to matter, suggest overall survival results from the crossover trial PARERE.

The findings nevertheless indicate that anti-EGFR rechallenge with panitumumab may prolong progression-free survival (PFS) over the multiple kinase inhibitor regorafenib. This suggests that “the most pragmatic choice” would be to give the anti-EGFR before regorafenib, said study presenter Marco Maria Germani, MD, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.

The caveat, however, is in patients who have an anti-EGFR interval since previously receiving the drugs of < 6 months. Those patients appeared to do better if they had regorafenib first and then anti-EGFR rechallenge.

Overall, Germani said that “since [trifluridine/tipiracil] plus bevacizumab is today the third-line standard of care” in this patient population, “anti-EGFR re-treatment might be considered after progression” on that combination.

Germani presented the research on October 18 at the European Society for Medical Oncology (ESMO) Annual Meeting 2025, which was simultaneously published in the Annals of Oncology.

Michel P. Ducreux, MD, PhD, head of the Digestive Cancer Committee at Gustave Roussy, Villejuif, France, and invited discussant for the results, said, despite the study being negative, it is “very important to continue to perform this kind of trial to evaluate the [ideal] sequence in the treatment of our patients.”

He continued that the secondary endpoints in the trial of PFS and objective response and disease control rates were “fairly in favor of the use of rechallenge before regorafenib, and in my opinion, this is really quite convincing.”

Ducreux, who was not involved in PARERE trail, also pointed to the sex difference seen in the study, which suggested that women responded much better to having anti-EGFR retreatment before regorafenib than did men.

Similar findings have been reported in a number of other trials, and previous work has suggested that there are sex differences in the pharmacokinetics of several anticancer drugs. However, while this is “very important,” he said that “we never consider it, because we are not able to really explain [it].”

Overall, he concluded that, on the basis of these results, he would agree with the notion that it is better to propose a rechallenge with anti-EGFR treatment as the fourth-line therapy in this patient population, before administering regorafenib.

Ducreux explained that, after a partial response, tumors acquire resistance to EGFR inhibitors through alterations and mutations that occur during treatment, via nongenetic mechanisms, and through treatment-induced selection for preexisting mutations.

Previous work has shown that mutations, such as in the RAS gene, are detectable early during EGFR inhibitor therapy, but that they then decay exponentially once the drugs are stopped, with the potential that tumors regain their sensitivity to them.

Germani said that this means that ctDNA-guided retreatment with anti-EGFR therapies is a “promising approach” in pretreated patients with RAS and BRAF wild-type mCRC, and that the sequencing of the drugs may be important. Indeed, the REVERCE trial showed that giving regorafenib followed by the anti-EGFR drug cetuzximab was associated with longer overall survival than the other way around in anti-EGFR medication-naive patients.

 

Methods and Results

For PARERE, the researchers enrolled patients aged at least 18 years with RAS and BRAF wild-type mCRC who were previously treated with a first-line anti-EGFR-containing regimen and had at least a partial response or stable disease for at least 6 months.

The patients were also required to have had at least one intervening anti-EGFR-free line of therapy, and to have previously received treatment with fluoropyrimidine, oxaliplatin, irinotecan, and anti-angiogenics. At least 4 months were required to have passed between the end of anti-EGFR administration and screening for the study.

In all, 428 patients were screened between December 2020 and December 2024, with 213 patients with RAS and BRAF wild-type mCRC, as detected on ctDNA, enrolled. They were randomized to panitumumab or regorafenib until first progression, followed by regorafenib, if they started on panitumumab, or panitumumab, if they started on regorafenib, until second progression.

The median age of the patients was 61 years among those who started on panitumumab and 64 years among those initially given regorafenib in the trial, and 63% and 57%, respectively, were male. The median number of prior lines of therapy was two in both groups, and 65% and 69%, respectively, had received pantitumumab as their first-line anti-EGFR.

Initial findings from the study presented at the 2025 ASCO Annual Meeting indicated that, after a median follow-up of 23.5 months, there was no significant difference in the median first PFS between the two treatment arms.

However, patients who started with panitumumab had a significant improvement in both the objective response and disease control rates (P < .001), as well as a signal for a potentially longer median second PFS, than those who started with regorafenib, particularly on the per-protocol analysis.

Presenting the overall survival results, Germani said that there was no significant difference between the groups on the intention-to-treat analysis, at a stratified hazard ratio of 1.13 (P = .440), or on the per-protocol analysis, at a hazard ratio of 1.07 (P = .730).

“We then ran a subgroup analysis,” he continued, “and we found out that an anti-EGFR-free interval before liquid biopsy shorter than 6 months was associated with less benefit from a panitumumab [first] sequence, which is biologically sound.”

It was also observed that women did significantly better when having panitumumab first, whereas men did not, for which “we do not have a clear biological explanation,” Germani added.

Confining the analysis to so-called “hyperselected” patients, who not only were RAS and BRAF wild type but also had no pathogenic mutations associated with anti-EGFR resistance, did not reveal any significant overall survival differences between the treatment groups.

However, Ducreux took issue with the way in which hyperselection, which is turning up more and more regularly in trials, is defined, as the choice of which mutations to include varies widely. He suggested that a consensus group be assembled to resolve this issue.

Looking more broadly, the researchers were able to show that, in this updated analysis, anti-EGFR re-treatment was superior to regorafenib regardless of the treatment sequence in terms of PFS, at 4.2 months vs 2.4 months (P = .103) when given first in the trial, and 3.9 months vs 2.7 months (P = .019) when given second in the trial, as well as in terms of objective response and disease control rates.

 

Adverse Events

In terms of safety, the results showed that, as expected, acneiform rash, fatigue, and hypomagnesemia were the most common adverse events associated with panitumumb, while those with regorafenib were fatigue, hand-foot skin reactions, and hypertension.

There were no notable differences in the number of patients receiving a post-study treatment nor in the post-study therapeutic choices, between the study arms.

The study was sponsored by GONO Foundation and partially supported by Amgen and Bayer. Germani declared having relationships with MSD and Amgen. Ducreux declared having relationships with Amgen, Bayer, BeiGene, Incyte, Jazz, Merck KGaA, Merck Serono, Merck Sharp & Dohme, Pierre Fabre, Roche, Servier, Keocyt, AbbVie, Abcely, Arcus, Bayer, BMS, Boehringer, GlaxoSmithKline, Sanofi, Scandion, and Zymeworks.

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

BERLIN — Re-treatment with an antiepidermal growth factor receptor (EGFR) agent is effective in patients with chemorefractory metastatic colorectal cancer (mCRC) with RAS and BRAF wild-type tumors confirmed on circulating tumor DNA (ctDNA), although the sequencing of therapy does not seem to matter, suggest overall survival results from the crossover trial PARERE.

The findings nevertheless indicate that anti-EGFR rechallenge with panitumumab may prolong progression-free survival (PFS) over the multiple kinase inhibitor regorafenib. This suggests that “the most pragmatic choice” would be to give the anti-EGFR before regorafenib, said study presenter Marco Maria Germani, MD, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.

The caveat, however, is in patients who have an anti-EGFR interval since previously receiving the drugs of < 6 months. Those patients appeared to do better if they had regorafenib first and then anti-EGFR rechallenge.

Overall, Germani said that “since [trifluridine/tipiracil] plus bevacizumab is today the third-line standard of care” in this patient population, “anti-EGFR re-treatment might be considered after progression” on that combination.

Germani presented the research on October 18 at the European Society for Medical Oncology (ESMO) Annual Meeting 2025, which was simultaneously published in the Annals of Oncology.

Michel P. Ducreux, MD, PhD, head of the Digestive Cancer Committee at Gustave Roussy, Villejuif, France, and invited discussant for the results, said, despite the study being negative, it is “very important to continue to perform this kind of trial to evaluate the [ideal] sequence in the treatment of our patients.”

He continued that the secondary endpoints in the trial of PFS and objective response and disease control rates were “fairly in favor of the use of rechallenge before regorafenib, and in my opinion, this is really quite convincing.”

Ducreux, who was not involved in PARERE trail, also pointed to the sex difference seen in the study, which suggested that women responded much better to having anti-EGFR retreatment before regorafenib than did men.

Similar findings have been reported in a number of other trials, and previous work has suggested that there are sex differences in the pharmacokinetics of several anticancer drugs. However, while this is “very important,” he said that “we never consider it, because we are not able to really explain [it].”

Overall, he concluded that, on the basis of these results, he would agree with the notion that it is better to propose a rechallenge with anti-EGFR treatment as the fourth-line therapy in this patient population, before administering regorafenib.

Ducreux explained that, after a partial response, tumors acquire resistance to EGFR inhibitors through alterations and mutations that occur during treatment, via nongenetic mechanisms, and through treatment-induced selection for preexisting mutations.

Previous work has shown that mutations, such as in the RAS gene, are detectable early during EGFR inhibitor therapy, but that they then decay exponentially once the drugs are stopped, with the potential that tumors regain their sensitivity to them.

Germani said that this means that ctDNA-guided retreatment with anti-EGFR therapies is a “promising approach” in pretreated patients with RAS and BRAF wild-type mCRC, and that the sequencing of the drugs may be important. Indeed, the REVERCE trial showed that giving regorafenib followed by the anti-EGFR drug cetuzximab was associated with longer overall survival than the other way around in anti-EGFR medication-naive patients.

 

Methods and Results

For PARERE, the researchers enrolled patients aged at least 18 years with RAS and BRAF wild-type mCRC who were previously treated with a first-line anti-EGFR-containing regimen and had at least a partial response or stable disease for at least 6 months.

The patients were also required to have had at least one intervening anti-EGFR-free line of therapy, and to have previously received treatment with fluoropyrimidine, oxaliplatin, irinotecan, and anti-angiogenics. At least 4 months were required to have passed between the end of anti-EGFR administration and screening for the study.

In all, 428 patients were screened between December 2020 and December 2024, with 213 patients with RAS and BRAF wild-type mCRC, as detected on ctDNA, enrolled. They were randomized to panitumumab or regorafenib until first progression, followed by regorafenib, if they started on panitumumab, or panitumumab, if they started on regorafenib, until second progression.

The median age of the patients was 61 years among those who started on panitumumab and 64 years among those initially given regorafenib in the trial, and 63% and 57%, respectively, were male. The median number of prior lines of therapy was two in both groups, and 65% and 69%, respectively, had received pantitumumab as their first-line anti-EGFR.

Initial findings from the study presented at the 2025 ASCO Annual Meeting indicated that, after a median follow-up of 23.5 months, there was no significant difference in the median first PFS between the two treatment arms.

However, patients who started with panitumumab had a significant improvement in both the objective response and disease control rates (P < .001), as well as a signal for a potentially longer median second PFS, than those who started with regorafenib, particularly on the per-protocol analysis.

Presenting the overall survival results, Germani said that there was no significant difference between the groups on the intention-to-treat analysis, at a stratified hazard ratio of 1.13 (P = .440), or on the per-protocol analysis, at a hazard ratio of 1.07 (P = .730).

“We then ran a subgroup analysis,” he continued, “and we found out that an anti-EGFR-free interval before liquid biopsy shorter than 6 months was associated with less benefit from a panitumumab [first] sequence, which is biologically sound.”

It was also observed that women did significantly better when having panitumumab first, whereas men did not, for which “we do not have a clear biological explanation,” Germani added.

Confining the analysis to so-called “hyperselected” patients, who not only were RAS and BRAF wild type but also had no pathogenic mutations associated with anti-EGFR resistance, did not reveal any significant overall survival differences between the treatment groups.

However, Ducreux took issue with the way in which hyperselection, which is turning up more and more regularly in trials, is defined, as the choice of which mutations to include varies widely. He suggested that a consensus group be assembled to resolve this issue.

Looking more broadly, the researchers were able to show that, in this updated analysis, anti-EGFR re-treatment was superior to regorafenib regardless of the treatment sequence in terms of PFS, at 4.2 months vs 2.4 months (P = .103) when given first in the trial, and 3.9 months vs 2.7 months (P = .019) when given second in the trial, as well as in terms of objective response and disease control rates.

 

Adverse Events

In terms of safety, the results showed that, as expected, acneiform rash, fatigue, and hypomagnesemia were the most common adverse events associated with panitumumb, while those with regorafenib were fatigue, hand-foot skin reactions, and hypertension.

There were no notable differences in the number of patients receiving a post-study treatment nor in the post-study therapeutic choices, between the study arms.

The study was sponsored by GONO Foundation and partially supported by Amgen and Bayer. Germani declared having relationships with MSD and Amgen. Ducreux declared having relationships with Amgen, Bayer, BeiGene, Incyte, Jazz, Merck KGaA, Merck Serono, Merck Sharp & Dohme, Pierre Fabre, Roche, Servier, Keocyt, AbbVie, Abcely, Arcus, Bayer, BMS, Boehringer, GlaxoSmithKline, Sanofi, Scandion, and Zymeworks.

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

A faster, oral alternative to docetaxel is set to reach NHS clinics after the National Institute for Health and Care Excellence (NICE) recommended darolutamide (Nubeqa, Bayer) in combination with androgen deprivation therapy (ADT) for men with metastatic hormone-sensitive prostate cancer who are unable to receive or tolerate chemotherapy.

Detailed in NICE’s final draft guidance, the decision will make darolutamide available through the NHS in England and Wales to approximately 6000 patients, offering a new oral therapy for those who with limited alternatives to docetaxel or other androgen-receptor inhibitors.

 

New Option for Chemo-Ineligible Patients

Darolutamide functions by blocking hormones that fuel cancer growth, specifically depriving prostate cancer cells of testosterone required for multiplication and spread. Patients take two tablets twice daily alongside standard ADT. 

Peter Johnson, national clinical director for cancer at NHS England, welcomed the decision and expects this approval to give clinicians and their patients “more flexibility to choose the approach best suited to individual circumstances and clinical needs.”

The guidance was finalised 5 weeks ahead of the standard review timeline, underscoring NICE’s commitment to accelerating access to effective prostate cancer treatments.

 

Clinical Trial Evidence

The NICE’s decision was supported by evidence from the phase 3 ARASENS trial (N = 1306). 

The results showed that adding darolutamide to ADT and docetaxel significantly improved overall survival in metastatic hormone-sensitive prostate cancer, reducing the risk for death by 32% compared with ADT and docetaxel alone. Progression-free outcomes, measured by time to castration-resistant disease or death, also favoured darolutamide. 

A NICE network meta-analysis of the TITAN, ARCHES, LATITUDE, and STAMPEDE trials suggested that combining ADT with androgen-receptor pathway inhibitors such as apalutamide, enzalutamide, and abiraterone provides comparable survival benefits in this disease setting.

 

Cost and Implementation

NICE determined that darolutamide plus ADT delivers similar or lower overall costs to the NHS compared with apalutamide plus ADT. The list price is £4040.00 for a 28-day supply (112 × 300-mg tablets), though Bayer has agreed to a confidential commercial discount.

The guidance requires healthcare providers to use the least expensive suitable treatment option, considering administration costs, dosages, price per dose, and commercial arrangements when choosing between darolutamide plus ADT and apalutamide plus ADT. 

NHS England and integrated care boards must provide funding within 30 days of final publication, with routine commissioning beginning after this interim period.

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

A faster, oral alternative to docetaxel is set to reach NHS clinics after the National Institute for Health and Care Excellence (NICE) recommended darolutamide (Nubeqa, Bayer) in combination with androgen deprivation therapy (ADT) for men with metastatic hormone-sensitive prostate cancer who are unable to receive or tolerate chemotherapy.

Detailed in NICE’s final draft guidance, the decision will make darolutamide available through the NHS in England and Wales to approximately 6000 patients, offering a new oral therapy for those who with limited alternatives to docetaxel or other androgen-receptor inhibitors.

 

New Option for Chemo-Ineligible Patients

Darolutamide functions by blocking hormones that fuel cancer growth, specifically depriving prostate cancer cells of testosterone required for multiplication and spread. Patients take two tablets twice daily alongside standard ADT. 

Peter Johnson, national clinical director for cancer at NHS England, welcomed the decision and expects this approval to give clinicians and their patients “more flexibility to choose the approach best suited to individual circumstances and clinical needs.”

The guidance was finalised 5 weeks ahead of the standard review timeline, underscoring NICE’s commitment to accelerating access to effective prostate cancer treatments.

 

Clinical Trial Evidence

The NICE’s decision was supported by evidence from the phase 3 ARASENS trial (N = 1306). 

The results showed that adding darolutamide to ADT and docetaxel significantly improved overall survival in metastatic hormone-sensitive prostate cancer, reducing the risk for death by 32% compared with ADT and docetaxel alone. Progression-free outcomes, measured by time to castration-resistant disease or death, also favoured darolutamide. 

A NICE network meta-analysis of the TITAN, ARCHES, LATITUDE, and STAMPEDE trials suggested that combining ADT with androgen-receptor pathway inhibitors such as apalutamide, enzalutamide, and abiraterone provides comparable survival benefits in this disease setting.

 

Cost and Implementation

NICE determined that darolutamide plus ADT delivers similar or lower overall costs to the NHS compared with apalutamide plus ADT. The list price is £4040.00 for a 28-day supply (112 × 300-mg tablets), though Bayer has agreed to a confidential commercial discount.

The guidance requires healthcare providers to use the least expensive suitable treatment option, considering administration costs, dosages, price per dose, and commercial arrangements when choosing between darolutamide plus ADT and apalutamide plus ADT. 

NHS England and integrated care boards must provide funding within 30 days of final publication, with routine commissioning beginning after this interim period.

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

A faster, oral alternative to docetaxel is set to reach NHS clinics after the National Institute for Health and Care Excellence (NICE) recommended darolutamide (Nubeqa, Bayer) in combination with androgen deprivation therapy (ADT) for men with metastatic hormone-sensitive prostate cancer who are unable to receive or tolerate chemotherapy.

Detailed in NICE’s final draft guidance, the decision will make darolutamide available through the NHS in England and Wales to approximately 6000 patients, offering a new oral therapy for those who with limited alternatives to docetaxel or other androgen-receptor inhibitors.

 

New Option for Chemo-Ineligible Patients

Darolutamide functions by blocking hormones that fuel cancer growth, specifically depriving prostate cancer cells of testosterone required for multiplication and spread. Patients take two tablets twice daily alongside standard ADT. 

Peter Johnson, national clinical director for cancer at NHS England, welcomed the decision and expects this approval to give clinicians and their patients “more flexibility to choose the approach best suited to individual circumstances and clinical needs.”

The guidance was finalised 5 weeks ahead of the standard review timeline, underscoring NICE’s commitment to accelerating access to effective prostate cancer treatments.

 

Clinical Trial Evidence

The NICE’s decision was supported by evidence from the phase 3 ARASENS trial (N = 1306). 

The results showed that adding darolutamide to ADT and docetaxel significantly improved overall survival in metastatic hormone-sensitive prostate cancer, reducing the risk for death by 32% compared with ADT and docetaxel alone. Progression-free outcomes, measured by time to castration-resistant disease or death, also favoured darolutamide. 

A NICE network meta-analysis of the TITAN, ARCHES, LATITUDE, and STAMPEDE trials suggested that combining ADT with androgen-receptor pathway inhibitors such as apalutamide, enzalutamide, and abiraterone provides comparable survival benefits in this disease setting.

 

Cost and Implementation

NICE determined that darolutamide plus ADT delivers similar or lower overall costs to the NHS compared with apalutamide plus ADT. The list price is £4040.00 for a 28-day supply (112 × 300-mg tablets), though Bayer has agreed to a confidential commercial discount.

The guidance requires healthcare providers to use the least expensive suitable treatment option, considering administration costs, dosages, price per dose, and commercial arrangements when choosing between darolutamide plus ADT and apalutamide plus ADT. 

NHS England and integrated care boards must provide funding within 30 days of final publication, with routine commissioning beginning after this interim period.

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

BERLIN — Patients with previously untreated locally recurrent inoperable or metastatic triple negative breast cancer (TNBC) who are not candidates for immunotherapy may experience improved survival outcomes with TROP2-directed antibody-drug conjugates (ADCs), suggested two trials presented at European Society for Medical Oncology (ESMO) Annual Meeting 2025 on October 19.

ASCENT-03 compared sacituzumab govitecan with standard of care chemotherapy, finding that the drug was associated with a 38% improvement in progression-free survival (PFS) in this patient population that has, traditionally, a poor prognosis. Overall survival data remain immature.

TROPION-Breast02 studied datopotamab deruxtecan (Dato-DXd) against investigator’s choice of chemotherapy. The PFS improvement with the ADC was 43%, while patients also experienced a 21% improvement in overall survival. In both cases, the safety profile of the experimental drugs was deemed to be manageable.

Discussant Ana C. Garrido-Castro, MD, director, Triple-Negative Breast Cancer Research, Dana-Farber Cancer Institute, Boston, who was not involved in either study, said that both sacituzumab govitecan and Dato-DXd showed a PFS benefit. The choice between them, leaving aside overall survival until the data are mature, will be largely based on factors such as the safety profile and the patient preference, she continued.

Sacituzumab govitecan is associated with an increase in neutropenia, nausea, and diarrhea, she pointed out, while Dato-DXd has increased rates of ocular surface toxicity, oral mucositis/stomatitis, and requires monitoring for interstitial lung disease.

Dato-DXd has a higher objective response rate than chemotherapy, unlike sacituzumab govitecan, but, crucially, requires one infusion vs 2 for sacituzumab govitecan per 21-day cycle, and has a shorter total infusion time.

There are nevertheless a number of unanswered questions about the drugs, including how the ADCs affect quality of life, and how common patient adherence to the recommended prophylaxis is. Patients with early relapse of < 12 months remain an “urgent unmet need,” Garrido-Castro said, and the role of immunotherapy rechallenge remains to be explored.

ADCs are also being tested in the neo-adjuvant TNBC setting, and the potential impact of that on the use of the drugs in the metastatic setting is currently unclear. In addition, there are questions around access to therapy.

“Ultimately, it will be very important to have a better understanding of the biomarkers of response and resistance and toxicity to these agents, and whether we should be sequencing antibody drug conjugates,” Garrido-Castro said. “All of this will help shape the next wave of treatment strategies for this patient population.”

She concluded: “Today, marks a paradigm shift of metastatic TNBC, in my opinion. ASCENT-03 and TROPION-Breast02 support TROP2 ADC therapy as the new preferred first-line regimen for this patient population.”

 

Method and Results of ASCENT-03

ASCENT-03 study presenter Javier C. Cortés, MD, PhD, International Breast Cancer Center, Pangaea Oncology, Quiron Group, Barcelona, Spain, said there is currently an unmet clinical need in the approximately 60% of patients with previously untreated metastatic TNBC who are not candidates for immune checkpoint inhibitors.

Median PFS in previous first-line studies was < 6 months with chemotherapy — the current standard of care — and Cortés said that around half of the patients who receive that in the first-line do not receive second-line therapy because of clinical deterioration or death.

“The sobering truth is that across studies in the US and Europe, approximately 25% to 30% of patients diagnosed with metastatic TNBC are no longer alive at 6 months from their metastatic diagnosis,” said Garrido-Castro. “So if there is a new drug that is able to significantly improve PFS with an acceptable toxicity profile, this should be sufficient to change the current standard of care in the first-line setting.”

As sacituzumab govitecan is already approved for second-line metastatic TNBC and for pretreated hormone receptor positive/HER2- metastatic breast cancer, the ASCENT-03 researchers studied the drug in patients with previously untreated locally advanced inoperable, or metastatic TNBC.

The patients were deemed not to be candidates for PD-L1 inhibitors through having PD-L1-negative tumors, by having PD-L1-positive tumors that had previously been treated with PD-L1 inhibitors in the curative setting, or by having a comorbidity that precluded PD-L1 inhibitor use.

The patients were required to have finished any prior treatment in the curative setting at least 6 months previously. Previously treated, stable central nervous system metastases were allowed.

They were randomized to sacituzumab govitecan or chemotherapy, comprising paclitaxel or nab-paclitaxel, or gemcitabine plus carboplatin, until progression, as verified by blinded independent central review (BICR), or unacceptable toxicity. Patients who progressed on chemotherapy were offered crossover to second-line sacituzumab govitecan.

In all, 558 patients were randomized. The median age was 56 years in the sacituzumab govitecan group vs 54 years in the chemotherapy group. The majority (64% in both groups) of patients were White individuals. The most common metastatic site was the lung (59% vs 61%), and 58% of patients in both groups had previously received a taxane.

Cortés reported that sacituzumab govitecan was associated with a “statistically significant and clinically meaningful” improvement in PFS by BICR, at a median of 9.7 months vs 6.9 months, or a hazard ratio (HR) of 0.62 (P < .0001). This benefit was seen across prespecified subgroups.

The objective response rate was almost identical between the two treatment groups, at 48% with sacituzumab govitecan vs 46% with chemotherapy, although the median duration of response was longer with the ADC, at 12.2 months vs 7.2 months.

Cortés showed the latest results on overall survival. This showed no significant difference between the two treatments, although he underlined that the data are not yet mature.

He also reported that the rates of grade ≥ 3 treatment-emergent adverse events (TEAEs) were similar in the two groups, at 66% with sacituzumab govitecan vs 62% with chemotherapy. However, the rates of TEAEs leading to treatment discontinuation (4% vs 12%) or dose reduction (37% vs 45%) were lower with the ADC.

Cortés concluded that the results suggest that sacituzumab govitecan “is a good option for patients with triple negative breast cancer when they develop metastasis and are unable to receive immune checkpoint inhibitors.”

 

TROPION-Breast02 Methods and Results

Presenting TROPION-Breast02, Rebecca A. Dent, MD, MSc, National Cancer Center Singapore and Duke-NUS Medical School, Singapore, explained that the trial looked at a patient population similar to that of ASCENT-03, here focusing instead on Dato-DXd.

Patients were included if they had histologically or cytologically documented locally recurrent inoperable or metastatic TNBC, no prior chemotherapy or targeted systemic therapy in this setting, and in whom immunotherapy was not an option.

They were randomized to Dato-DXd or the investigator’s choice of chemotherapy, with treatment continued until investigator-assessed progressive disease on RECIST v1.1, unacceptable toxicity, or another criterion for discontinuation was met.

In total, 642 patients were enrolled. The median age was 56 years for those in the Dato-DXd group and 57 years for those in chemotherapy group, and less than half (41% in the Dato-DXd group and 48% in the chemotherapy group) were White individuals. The number of metastatic sites was less than three in 64% and 67% of patients, respectively.

Dent showed that Dato-DXd was associated with a statistically significant and clinically meaningful improvement in BICR-assessed PFS, at a median of 10.8 months vs 5.6 months with chemotherapy, at a HR of 0.57 (P < .0001). The findings were replicated across the prespecified subgroups.

There was a marked overall survival benefit with Dato-DXd, at a median of 23.7 months vs 18.7 months, at a HR of 0.79 (P = .0291). Dent reported that, at 18 months, 61.2% of patients in the Dato-DXd group were still alive vs 51.3% in the chemotherapy group. Again, the benefit was seen across subgroups.

The confirmed objective response rate with Dato-DXd was far higher than that with chemotherapy, at 62.5% vs 29.3%, or an odds ratio of 4.24. The duration of response was also longer, at 12.3 months vs 7.1 months.

Rates of grade ≥ 3 adverse events were comparable, at 33% with Dato-DXd vs 29% with chemotherapy, although there were more events associated with dose reduction (27% vs 18%) and dose interruption (24% vs 19%) with the ADC.

“These results support Dato-DXd as the first new first-line standard of care for patients with locally recurrent inoperable or metastatic TNBC for whom immunotherapy is not an option,” Dent said.

“What’s important is the patients enrolled into this trial are clearly representative of real world patients that we are treating in our clinics every day. These patients are often excluded from our current clinical trials,” she said.

ASCENT-03 was funded by Gilead Sciences.

TROPION-Breast02 was funded by AstraZeneca.Cortés declared relationships with Roche, AstraZeneca, Seattle Genetics, Daiichi Sankyo, Lilly, Merck Sharpe & Dohme, Leuko, Bioasis, Clovis oncology, Boehringer Ingelheim, Ellipses, HiberCell, BioInvent, GEMoaB, Gilead, Menarini, Zymeworks, Reveal Genomics, Expres2ion Biotechnologies, Jazz Pharmaceuticals, AbbVie, Scorpion Therapeutics, Bridgebio, Biocon, Biontech, Circle Pharma, Delcath Systems, Hexagon Bio, Novartis, Eisai, Pfizer, Stemline Therapeutics, MAJ3 Capital, Leuko, Ariad Pharmaceuticals, Baxalta GmbH/Servier Affaires, Bayer healthcare, Guardant Health, and PIQUR Therapeutics.

Dent declared relationships with AstraZeneca, MSD, Pfizer, Eisai, Novartis, Daiichi Sankyo/AstraZeneca, Roche, and Gilead Sciences.

Garrido-Castro declared relationships with AstraZeneca, MSD, Pfizer, Eisai, Novartis, Daiichi Sankyo/AstraZeneca, Roche, Gilead Sciences, Pfizer, TD Cowen, and Roche/Genentech.

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

BERLIN — Patients with previously untreated locally recurrent inoperable or metastatic triple negative breast cancer (TNBC) who are not candidates for immunotherapy may experience improved survival outcomes with TROP2-directed antibody-drug conjugates (ADCs), suggested two trials presented at European Society for Medical Oncology (ESMO) Annual Meeting 2025 on October 19.

ASCENT-03 compared sacituzumab govitecan with standard of care chemotherapy, finding that the drug was associated with a 38% improvement in progression-free survival (PFS) in this patient population that has, traditionally, a poor prognosis. Overall survival data remain immature.

TROPION-Breast02 studied datopotamab deruxtecan (Dato-DXd) against investigator’s choice of chemotherapy. The PFS improvement with the ADC was 43%, while patients also experienced a 21% improvement in overall survival. In both cases, the safety profile of the experimental drugs was deemed to be manageable.

Discussant Ana C. Garrido-Castro, MD, director, Triple-Negative Breast Cancer Research, Dana-Farber Cancer Institute, Boston, who was not involved in either study, said that both sacituzumab govitecan and Dato-DXd showed a PFS benefit. The choice between them, leaving aside overall survival until the data are mature, will be largely based on factors such as the safety profile and the patient preference, she continued.

Sacituzumab govitecan is associated with an increase in neutropenia, nausea, and diarrhea, she pointed out, while Dato-DXd has increased rates of ocular surface toxicity, oral mucositis/stomatitis, and requires monitoring for interstitial lung disease.

Dato-DXd has a higher objective response rate than chemotherapy, unlike sacituzumab govitecan, but, crucially, requires one infusion vs 2 for sacituzumab govitecan per 21-day cycle, and has a shorter total infusion time.

There are nevertheless a number of unanswered questions about the drugs, including how the ADCs affect quality of life, and how common patient adherence to the recommended prophylaxis is. Patients with early relapse of < 12 months remain an “urgent unmet need,” Garrido-Castro said, and the role of immunotherapy rechallenge remains to be explored.

ADCs are also being tested in the neo-adjuvant TNBC setting, and the potential impact of that on the use of the drugs in the metastatic setting is currently unclear. In addition, there are questions around access to therapy.

“Ultimately, it will be very important to have a better understanding of the biomarkers of response and resistance and toxicity to these agents, and whether we should be sequencing antibody drug conjugates,” Garrido-Castro said. “All of this will help shape the next wave of treatment strategies for this patient population.”

She concluded: “Today, marks a paradigm shift of metastatic TNBC, in my opinion. ASCENT-03 and TROPION-Breast02 support TROP2 ADC therapy as the new preferred first-line regimen for this patient population.”

 

Method and Results of ASCENT-03

ASCENT-03 study presenter Javier C. Cortés, MD, PhD, International Breast Cancer Center, Pangaea Oncology, Quiron Group, Barcelona, Spain, said there is currently an unmet clinical need in the approximately 60% of patients with previously untreated metastatic TNBC who are not candidates for immune checkpoint inhibitors.

Median PFS in previous first-line studies was < 6 months with chemotherapy — the current standard of care — and Cortés said that around half of the patients who receive that in the first-line do not receive second-line therapy because of clinical deterioration or death.

“The sobering truth is that across studies in the US and Europe, approximately 25% to 30% of patients diagnosed with metastatic TNBC are no longer alive at 6 months from their metastatic diagnosis,” said Garrido-Castro. “So if there is a new drug that is able to significantly improve PFS with an acceptable toxicity profile, this should be sufficient to change the current standard of care in the first-line setting.”

As sacituzumab govitecan is already approved for second-line metastatic TNBC and for pretreated hormone receptor positive/HER2- metastatic breast cancer, the ASCENT-03 researchers studied the drug in patients with previously untreated locally advanced inoperable, or metastatic TNBC.

The patients were deemed not to be candidates for PD-L1 inhibitors through having PD-L1-negative tumors, by having PD-L1-positive tumors that had previously been treated with PD-L1 inhibitors in the curative setting, or by having a comorbidity that precluded PD-L1 inhibitor use.

The patients were required to have finished any prior treatment in the curative setting at least 6 months previously. Previously treated, stable central nervous system metastases were allowed.

They were randomized to sacituzumab govitecan or chemotherapy, comprising paclitaxel or nab-paclitaxel, or gemcitabine plus carboplatin, until progression, as verified by blinded independent central review (BICR), or unacceptable toxicity. Patients who progressed on chemotherapy were offered crossover to second-line sacituzumab govitecan.

In all, 558 patients were randomized. The median age was 56 years in the sacituzumab govitecan group vs 54 years in the chemotherapy group. The majority (64% in both groups) of patients were White individuals. The most common metastatic site was the lung (59% vs 61%), and 58% of patients in both groups had previously received a taxane.

Cortés reported that sacituzumab govitecan was associated with a “statistically significant and clinically meaningful” improvement in PFS by BICR, at a median of 9.7 months vs 6.9 months, or a hazard ratio (HR) of 0.62 (P < .0001). This benefit was seen across prespecified subgroups.

The objective response rate was almost identical between the two treatment groups, at 48% with sacituzumab govitecan vs 46% with chemotherapy, although the median duration of response was longer with the ADC, at 12.2 months vs 7.2 months.

Cortés showed the latest results on overall survival. This showed no significant difference between the two treatments, although he underlined that the data are not yet mature.

He also reported that the rates of grade ≥ 3 treatment-emergent adverse events (TEAEs) were similar in the two groups, at 66% with sacituzumab govitecan vs 62% with chemotherapy. However, the rates of TEAEs leading to treatment discontinuation (4% vs 12%) or dose reduction (37% vs 45%) were lower with the ADC.

Cortés concluded that the results suggest that sacituzumab govitecan “is a good option for patients with triple negative breast cancer when they develop metastasis and are unable to receive immune checkpoint inhibitors.”

 

TROPION-Breast02 Methods and Results

Presenting TROPION-Breast02, Rebecca A. Dent, MD, MSc, National Cancer Center Singapore and Duke-NUS Medical School, Singapore, explained that the trial looked at a patient population similar to that of ASCENT-03, here focusing instead on Dato-DXd.

Patients were included if they had histologically or cytologically documented locally recurrent inoperable or metastatic TNBC, no prior chemotherapy or targeted systemic therapy in this setting, and in whom immunotherapy was not an option.

They were randomized to Dato-DXd or the investigator’s choice of chemotherapy, with treatment continued until investigator-assessed progressive disease on RECIST v1.1, unacceptable toxicity, or another criterion for discontinuation was met.

In total, 642 patients were enrolled. The median age was 56 years for those in the Dato-DXd group and 57 years for those in chemotherapy group, and less than half (41% in the Dato-DXd group and 48% in the chemotherapy group) were White individuals. The number of metastatic sites was less than three in 64% and 67% of patients, respectively.

Dent showed that Dato-DXd was associated with a statistically significant and clinically meaningful improvement in BICR-assessed PFS, at a median of 10.8 months vs 5.6 months with chemotherapy, at a HR of 0.57 (P < .0001). The findings were replicated across the prespecified subgroups.

There was a marked overall survival benefit with Dato-DXd, at a median of 23.7 months vs 18.7 months, at a HR of 0.79 (P = .0291). Dent reported that, at 18 months, 61.2% of patients in the Dato-DXd group were still alive vs 51.3% in the chemotherapy group. Again, the benefit was seen across subgroups.

The confirmed objective response rate with Dato-DXd was far higher than that with chemotherapy, at 62.5% vs 29.3%, or an odds ratio of 4.24. The duration of response was also longer, at 12.3 months vs 7.1 months.

Rates of grade ≥ 3 adverse events were comparable, at 33% with Dato-DXd vs 29% with chemotherapy, although there were more events associated with dose reduction (27% vs 18%) and dose interruption (24% vs 19%) with the ADC.

“These results support Dato-DXd as the first new first-line standard of care for patients with locally recurrent inoperable or metastatic TNBC for whom immunotherapy is not an option,” Dent said.

“What’s important is the patients enrolled into this trial are clearly representative of real world patients that we are treating in our clinics every day. These patients are often excluded from our current clinical trials,” she said.

ASCENT-03 was funded by Gilead Sciences.

TROPION-Breast02 was funded by AstraZeneca.Cortés declared relationships with Roche, AstraZeneca, Seattle Genetics, Daiichi Sankyo, Lilly, Merck Sharpe & Dohme, Leuko, Bioasis, Clovis oncology, Boehringer Ingelheim, Ellipses, HiberCell, BioInvent, GEMoaB, Gilead, Menarini, Zymeworks, Reveal Genomics, Expres2ion Biotechnologies, Jazz Pharmaceuticals, AbbVie, Scorpion Therapeutics, Bridgebio, Biocon, Biontech, Circle Pharma, Delcath Systems, Hexagon Bio, Novartis, Eisai, Pfizer, Stemline Therapeutics, MAJ3 Capital, Leuko, Ariad Pharmaceuticals, Baxalta GmbH/Servier Affaires, Bayer healthcare, Guardant Health, and PIQUR Therapeutics.

Dent declared relationships with AstraZeneca, MSD, Pfizer, Eisai, Novartis, Daiichi Sankyo/AstraZeneca, Roche, and Gilead Sciences.

Garrido-Castro declared relationships with AstraZeneca, MSD, Pfizer, Eisai, Novartis, Daiichi Sankyo/AstraZeneca, Roche, Gilead Sciences, Pfizer, TD Cowen, and Roche/Genentech.

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

BERLIN — Patients with previously untreated locally recurrent inoperable or metastatic triple negative breast cancer (TNBC) who are not candidates for immunotherapy may experience improved survival outcomes with TROP2-directed antibody-drug conjugates (ADCs), suggested two trials presented at European Society for Medical Oncology (ESMO) Annual Meeting 2025 on October 19.

ASCENT-03 compared sacituzumab govitecan with standard of care chemotherapy, finding that the drug was associated with a 38% improvement in progression-free survival (PFS) in this patient population that has, traditionally, a poor prognosis. Overall survival data remain immature.

TROPION-Breast02 studied datopotamab deruxtecan (Dato-DXd) against investigator’s choice of chemotherapy. The PFS improvement with the ADC was 43%, while patients also experienced a 21% improvement in overall survival. In both cases, the safety profile of the experimental drugs was deemed to be manageable.

Discussant Ana C. Garrido-Castro, MD, director, Triple-Negative Breast Cancer Research, Dana-Farber Cancer Institute, Boston, who was not involved in either study, said that both sacituzumab govitecan and Dato-DXd showed a PFS benefit. The choice between them, leaving aside overall survival until the data are mature, will be largely based on factors such as the safety profile and the patient preference, she continued.

Sacituzumab govitecan is associated with an increase in neutropenia, nausea, and diarrhea, she pointed out, while Dato-DXd has increased rates of ocular surface toxicity, oral mucositis/stomatitis, and requires monitoring for interstitial lung disease.

Dato-DXd has a higher objective response rate than chemotherapy, unlike sacituzumab govitecan, but, crucially, requires one infusion vs 2 for sacituzumab govitecan per 21-day cycle, and has a shorter total infusion time.

There are nevertheless a number of unanswered questions about the drugs, including how the ADCs affect quality of life, and how common patient adherence to the recommended prophylaxis is. Patients with early relapse of < 12 months remain an “urgent unmet need,” Garrido-Castro said, and the role of immunotherapy rechallenge remains to be explored.

ADCs are also being tested in the neo-adjuvant TNBC setting, and the potential impact of that on the use of the drugs in the metastatic setting is currently unclear. In addition, there are questions around access to therapy.

“Ultimately, it will be very important to have a better understanding of the biomarkers of response and resistance and toxicity to these agents, and whether we should be sequencing antibody drug conjugates,” Garrido-Castro said. “All of this will help shape the next wave of treatment strategies for this patient population.”

She concluded: “Today, marks a paradigm shift of metastatic TNBC, in my opinion. ASCENT-03 and TROPION-Breast02 support TROP2 ADC therapy as the new preferred first-line regimen for this patient population.”

 

Method and Results of ASCENT-03

ASCENT-03 study presenter Javier C. Cortés, MD, PhD, International Breast Cancer Center, Pangaea Oncology, Quiron Group, Barcelona, Spain, said there is currently an unmet clinical need in the approximately 60% of patients with previously untreated metastatic TNBC who are not candidates for immune checkpoint inhibitors.

Median PFS in previous first-line studies was < 6 months with chemotherapy — the current standard of care — and Cortés said that around half of the patients who receive that in the first-line do not receive second-line therapy because of clinical deterioration or death.

“The sobering truth is that across studies in the US and Europe, approximately 25% to 30% of patients diagnosed with metastatic TNBC are no longer alive at 6 months from their metastatic diagnosis,” said Garrido-Castro. “So if there is a new drug that is able to significantly improve PFS with an acceptable toxicity profile, this should be sufficient to change the current standard of care in the first-line setting.”

As sacituzumab govitecan is already approved for second-line metastatic TNBC and for pretreated hormone receptor positive/HER2- metastatic breast cancer, the ASCENT-03 researchers studied the drug in patients with previously untreated locally advanced inoperable, or metastatic TNBC.

The patients were deemed not to be candidates for PD-L1 inhibitors through having PD-L1-negative tumors, by having PD-L1-positive tumors that had previously been treated with PD-L1 inhibitors in the curative setting, or by having a comorbidity that precluded PD-L1 inhibitor use.

The patients were required to have finished any prior treatment in the curative setting at least 6 months previously. Previously treated, stable central nervous system metastases were allowed.

They were randomized to sacituzumab govitecan or chemotherapy, comprising paclitaxel or nab-paclitaxel, or gemcitabine plus carboplatin, until progression, as verified by blinded independent central review (BICR), or unacceptable toxicity. Patients who progressed on chemotherapy were offered crossover to second-line sacituzumab govitecan.

In all, 558 patients were randomized. The median age was 56 years in the sacituzumab govitecan group vs 54 years in the chemotherapy group. The majority (64% in both groups) of patients were White individuals. The most common metastatic site was the lung (59% vs 61%), and 58% of patients in both groups had previously received a taxane.

Cortés reported that sacituzumab govitecan was associated with a “statistically significant and clinically meaningful” improvement in PFS by BICR, at a median of 9.7 months vs 6.9 months, or a hazard ratio (HR) of 0.62 (P < .0001). This benefit was seen across prespecified subgroups.

The objective response rate was almost identical between the two treatment groups, at 48% with sacituzumab govitecan vs 46% with chemotherapy, although the median duration of response was longer with the ADC, at 12.2 months vs 7.2 months.

Cortés showed the latest results on overall survival. This showed no significant difference between the two treatments, although he underlined that the data are not yet mature.

He also reported that the rates of grade ≥ 3 treatment-emergent adverse events (TEAEs) were similar in the two groups, at 66% with sacituzumab govitecan vs 62% with chemotherapy. However, the rates of TEAEs leading to treatment discontinuation (4% vs 12%) or dose reduction (37% vs 45%) were lower with the ADC.

Cortés concluded that the results suggest that sacituzumab govitecan “is a good option for patients with triple negative breast cancer when they develop metastasis and are unable to receive immune checkpoint inhibitors.”

 

TROPION-Breast02 Methods and Results

Presenting TROPION-Breast02, Rebecca A. Dent, MD, MSc, National Cancer Center Singapore and Duke-NUS Medical School, Singapore, explained that the trial looked at a patient population similar to that of ASCENT-03, here focusing instead on Dato-DXd.

Patients were included if they had histologically or cytologically documented locally recurrent inoperable or metastatic TNBC, no prior chemotherapy or targeted systemic therapy in this setting, and in whom immunotherapy was not an option.

They were randomized to Dato-DXd or the investigator’s choice of chemotherapy, with treatment continued until investigator-assessed progressive disease on RECIST v1.1, unacceptable toxicity, or another criterion for discontinuation was met.

In total, 642 patients were enrolled. The median age was 56 years for those in the Dato-DXd group and 57 years for those in chemotherapy group, and less than half (41% in the Dato-DXd group and 48% in the chemotherapy group) were White individuals. The number of metastatic sites was less than three in 64% and 67% of patients, respectively.

Dent showed that Dato-DXd was associated with a statistically significant and clinically meaningful improvement in BICR-assessed PFS, at a median of 10.8 months vs 5.6 months with chemotherapy, at a HR of 0.57 (P < .0001). The findings were replicated across the prespecified subgroups.

There was a marked overall survival benefit with Dato-DXd, at a median of 23.7 months vs 18.7 months, at a HR of 0.79 (P = .0291). Dent reported that, at 18 months, 61.2% of patients in the Dato-DXd group were still alive vs 51.3% in the chemotherapy group. Again, the benefit was seen across subgroups.

The confirmed objective response rate with Dato-DXd was far higher than that with chemotherapy, at 62.5% vs 29.3%, or an odds ratio of 4.24. The duration of response was also longer, at 12.3 months vs 7.1 months.

Rates of grade ≥ 3 adverse events were comparable, at 33% with Dato-DXd vs 29% with chemotherapy, although there were more events associated with dose reduction (27% vs 18%) and dose interruption (24% vs 19%) with the ADC.

“These results support Dato-DXd as the first new first-line standard of care for patients with locally recurrent inoperable or metastatic TNBC for whom immunotherapy is not an option,” Dent said.

“What’s important is the patients enrolled into this trial are clearly representative of real world patients that we are treating in our clinics every day. These patients are often excluded from our current clinical trials,” she said.

ASCENT-03 was funded by Gilead Sciences.

TROPION-Breast02 was funded by AstraZeneca.Cortés declared relationships with Roche, AstraZeneca, Seattle Genetics, Daiichi Sankyo, Lilly, Merck Sharpe & Dohme, Leuko, Bioasis, Clovis oncology, Boehringer Ingelheim, Ellipses, HiberCell, BioInvent, GEMoaB, Gilead, Menarini, Zymeworks, Reveal Genomics, Expres2ion Biotechnologies, Jazz Pharmaceuticals, AbbVie, Scorpion Therapeutics, Bridgebio, Biocon, Biontech, Circle Pharma, Delcath Systems, Hexagon Bio, Novartis, Eisai, Pfizer, Stemline Therapeutics, MAJ3 Capital, Leuko, Ariad Pharmaceuticals, Baxalta GmbH/Servier Affaires, Bayer healthcare, Guardant Health, and PIQUR Therapeutics.

Dent declared relationships with AstraZeneca, MSD, Pfizer, Eisai, Novartis, Daiichi Sankyo/AstraZeneca, Roche, and Gilead Sciences.

Garrido-Castro declared relationships with AstraZeneca, MSD, Pfizer, Eisai, Novartis, Daiichi Sankyo/AstraZeneca, Roche, Gilead Sciences, Pfizer, TD Cowen, and Roche/Genentech.

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

In this Practical AI column, we’ve explored everything from large language models to the nuances of trial matching, but one of the most immediate and impactful applications of AI is unfolding right now in breast imaging. For oncologists, this isn’t an abstract future — with new screening guidelines, dense-breast mandates, and a shrinking radiology workforce, it’s the imaging reports and patient questions landing in your clinic today.

Here is what oncologists need to know, and how to put it to work for their patients.

 

Why AI in Mammography Matters

More than 200 million women undergo breast cancer screening each year. In the US alone, 10% of the 40 million women screened annually require additional diagnostic imaging, and 4%–5% of these women are eventually diagnosed with breast cancer.

Two major shifts are redefining breast cancer screening in the US: The US Preventive Services Task Force (USPSTF) now recommends biennial screening from age 40 to 74 years, and notifying patients of breast density is a federal requirement as of September 10, 2024. That means more mammograms, more patient questions, and more downstream oncology decisions. Patients will increasingly ask about “dense” breast results and what to do next. Add a national radiologist shortage into the mix, and the pressure on timely callbacks, biopsies, and treatment planning will only grow.

 

Can AI Help Without Compromising Care?

The short answer is yes. With AI, we may be able to transform these rate-limiting steps into opportunities for earlier detection, decentralized screening, and smarter triage and save hundreds of thousands of women from an unnecessary diagnostic procedure, if implemented deliberately.

Don’t Confuse Today’s AI With Yesterday’s CAD 

Think of older computer-aided detection (CAD) like a 1990s chemotherapy drug: It sometimes helped, but it came with significant toxicity and rarely delivered consistent survival benefits. Today’s deep-learning AI is closer to targeted therapy — trained on millions of “trial participants” (mammograms), more precise, and applied in specific contexts where it adds value. If you once dismissed CAD as noise, it’s time to revisit what AI can now offer.

The role of AI is broader than drawing boxes. It provides second readings, worklist triage, risk prediction, density assessment, and decision support. FDA has cleared several AI tools for both 2D and digital breast tomosynthesis (DBT), which include iCAD ProFound (DBT), ScreenPoint Transpara (2D/DBT), and Lunit INSIGHT DBT. 

Some of the strongest evidence for AI in mammography is as a second reader during screening. Large trials show that AI plus one radiologist can match reading from two radiologists, cutting workload by about 40%. For example, the MASAI randomized trial showed that AI-supported screening achieved similar cancer detection but cut human screen-reading workload about 44% vs standard double reading (39,996 vs 40,024 participants). The primary interval cancer outcomes are maturing, but the safety analysis is reassuring.

Reducing second reads and arbitration time are important for clinicians because it frees capacity for callbacks and diagnostic workups. This will be especially key given that screening now starts at age 40. That will mean about 21 to 22 million more women are newly eligible, translating to about 10 to 11 million additional mammograms each year under biennial screening.

Another important area where AI can make its mark in mammography is triage and time to diagnosis. The results from a randomized implementation study showed that AI-prioritized worklists accelerated time to additional imaging and biopsy diagnosis without harming efficiency for others — exactly the kind of outcome patients feel.

Multiple studies have demonstrated improved diagnostic performance and shorter reading times when AI supports DBT interpretation, which is important because DBT can otherwise be time intensive.

We are also seeing rapid advancement in risk-based screening, moving beyond a single dense vs not dense approach. Deep-learning risk models, such as Mirai, predict 1- to 5-year breast cancer risk directly from the mammogram, and these tools are now being assessed prospectively to guide supplemental MRI. Cost-effectiveness modeling supports risk-stratified intervals vs one-size-fits-all schedules.

Finally, automated density tools, such as Transpara Density and Volpara, offer objective, reproducible volumetric measures that map to the Breast Imaging-Reporting and Data System, which is useful for Mammography Quality Standards Act-required reporting and as inputs to risk calculators.

While early evidence suggests AI may help surface future or interval cancers earlier, including more invasive tumors, the definitive impacts on interval cancer rates and mortality require longitudinal follow-up, which is now in progress.

 

Pitfalls to Watch For

Bias is real. Studies show false-positive differences by race, age, and density. AI can even infer racial identity from images, potentially amplifying disparities. Performance can also shift by vendor, demographics, and prevalence.

A Radiology study of 4855 DBT exams showed that an algorithm produced more false-positive case scores in Black patients and older patients (aged 71-80 years) patients and in women with extremely dense breasts. This can happen because AI can infer proxies for race directly from images, even when humans cannot, and this can propagate disparities if not addressed. External validations and reviews emphasize that performance can shift with device manufacturer, demographics, and prevalence, which is why all tools need to undergo local validation and calibration. 

Here’s a pragmatic adoption checklist before going live with an AI tool.

• Confirm FDA clearance: Verify the name and version of the algorithm, imaging modes (2D vs DBT), and operating points. Confirm 510(k) numbers.
• Local validation: Test on your patient mix and vendor stack (Hologic, GE, Siemens, Fuji). Compare this to your baseline recall rate, positive predictive value of recall (PPV1), cancer detection rate, and reading time. Commit to recalibration if drift occurs.
• Equity plan: Monitor false-positive and negative false-rates by age, race/ethnicity, and density; document corrective actions if disparities emerge. (This isn’t optional.)
• Workflow clarity: Is AI a second reader, an additional reader, or a triage tool? Who arbitrates discordance? What’s the escalation path for high-risk or interval cancer-like patterns?
• Regulatory strategy: Confirm whether the vendor has (or will file) a Predetermined Change Control Plan so models can be updated safely without repeated submissions. Also confirm how you’ll be notified about performance-relevant changes.
• Data governance: Audit logs of AI outputs, retention, protected health information handling, and the patient communication policy for AI-assisted reads.

After going live, set up a quarterly dashboard. It should include cancer detection rate per 1000 patients, recall rate, PPV1, interval cancer rate (as it matures), reading time, and turnaround time to diagnostic imaging or biopsy — all stratified by age, race/ethnicity, and density.

Here, I dissect what this discussion means through the lens of Moravec’s paradox (machines excel at what clinicians find hard, and vice versa) and offer a possible playbook for putting these tools to work.

 

What to Tell Patients

When speaking with patients, emphasize that a radiologist still reads their mammogram. AI helps with consistency and efficiency; it doesn’t replace human oversight. Patients with dense breasts should still expect a standard notice; discussion of individualized risk factors, such as family history, genetics, and prior biopsies; and consideration of supplemental imaging if risk warrants. But it’s also important to tell these patients that while dense breasts are common, they do not automatically mean high cancer risk.

As for screening schedules, remind patients that screening is at least biennial from 40 to 74 years of age per the USPSTF guidelines; however, specialty groups may recommend starting on an annual schedule at 40.

 

What You Can Implement Now

There are multiple practical use cases you can introduce now. One is to use AI as a second reader or an additional reader safety net to preserve detection while reducing human workload. This helps your breast center absorb screening expansion to age 40 without diluting quality. Another is to turn on AI triage to shorten the time to callback and biopsy for the few who need it most — patients notice and appreciate faster answers. You can also begin adopting automated density plus risk models to move beyond “dense/not dense.” For selected patients, AI-informed risk can justify MRI or tailored intervals. 

Here’s a quick cheat sheet (for your next leadership or tumor-board meeting).

 

Do:

• Use AI as a second or additional reader or triage tool, not as a black box.
• Track cancer detection rate, recall, PPV1, interval cancers, and reading time, stratified by age, race, and breast density.
• Pair automated density with AI risk to personalize screening and supplemental imaging.
• Enroll patients in future clinical trials, such as PRISM, the first large-scale randomized controlled trial of AI for screening mammography. This US-based, $16 million, seven-site study is funded by the Patient-Centered Outcomes Research Institute.

Don’t:

• Assume “AI = CAD.” The 2015 CAD story is over; modern deep learning systems are different and require different oversight.
• Go live without a local validation and equity plan or without clarity on software updates.
• Forget to remind patients that screening starts at age 40, and dense breast notifications are now universal. Use the visit to discuss risk, supplemental imaging, and why a human still directs their care.

The Bottom Line

AI won’t replace radiologists or read mammograms for us — just as PET scans didn’t replace oncologists and stethoscopes didn’t make cardiologists obsolete. What it will do is catch what the tired human eye might miss, shave days off anxious waiting, and turn breast density into data instead of doubt. For oncologists, that means staging sooner, enrolling smarter, and spending more time talking with patients instead of chasing callbacks.

In short, AI may not take the picture, but it helps us frame the story, making it sharper, faster, and with fewer blind spots. By pairing this powerful technology with rigorous, equity-focused local validation and transparent governance under the FDA’s emerging Predetermined Change Control Plan framework, we can realize the tangible benefits of practical AI for our patients without widening disparities. 

Now, during Breast Cancer Awareness Month, how about we add on AI to that pink ribbon — how cool would that be?

Thoughts? Drop me a line at [email protected]. Let’s keep the conversation — and pink ribbons — going.

Arturo Loaiza-Bonilla, MD, MSEd, is the co-founder and chief medical AI officer at Massive Bio, a company connecting patients to clinical trials using artificial intelligence. His research and professional interests focus on precision medicine, clinical trial design, digital health, entrepreneurship, and patient advocacy. Dr Loaiza-Bonilla serves as Systemwide Chief of Hematology and Oncology at St. Luke’s University Health Network, where he maintains a connection to patient care by attending to patients 2 days a week.

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

In this Practical AI column, we’ve explored everything from large language models to the nuances of trial matching, but one of the most immediate and impactful applications of AI is unfolding right now in breast imaging. For oncologists, this isn’t an abstract future — with new screening guidelines, dense-breast mandates, and a shrinking radiology workforce, it’s the imaging reports and patient questions landing in your clinic today.

Here is what oncologists need to know, and how to put it to work for their patients.

 

Why AI in Mammography Matters

More than 200 million women undergo breast cancer screening each year. In the US alone, 10% of the 40 million women screened annually require additional diagnostic imaging, and 4%–5% of these women are eventually diagnosed with breast cancer.

Two major shifts are redefining breast cancer screening in the US: The US Preventive Services Task Force (USPSTF) now recommends biennial screening from age 40 to 74 years, and notifying patients of breast density is a federal requirement as of September 10, 2024. That means more mammograms, more patient questions, and more downstream oncology decisions. Patients will increasingly ask about “dense” breast results and what to do next. Add a national radiologist shortage into the mix, and the pressure on timely callbacks, biopsies, and treatment planning will only grow.

 

Can AI Help Without Compromising Care?

The short answer is yes. With AI, we may be able to transform these rate-limiting steps into opportunities for earlier detection, decentralized screening, and smarter triage and save hundreds of thousands of women from an unnecessary diagnostic procedure, if implemented deliberately.

Don’t Confuse Today’s AI With Yesterday’s CAD 

Think of older computer-aided detection (CAD) like a 1990s chemotherapy drug: It sometimes helped, but it came with significant toxicity and rarely delivered consistent survival benefits. Today’s deep-learning AI is closer to targeted therapy — trained on millions of “trial participants” (mammograms), more precise, and applied in specific contexts where it adds value. If you once dismissed CAD as noise, it’s time to revisit what AI can now offer.

The role of AI is broader than drawing boxes. It provides second readings, worklist triage, risk prediction, density assessment, and decision support. FDA has cleared several AI tools for both 2D and digital breast tomosynthesis (DBT), which include iCAD ProFound (DBT), ScreenPoint Transpara (2D/DBT), and Lunit INSIGHT DBT. 

Some of the strongest evidence for AI in mammography is as a second reader during screening. Large trials show that AI plus one radiologist can match reading from two radiologists, cutting workload by about 40%. For example, the MASAI randomized trial showed that AI-supported screening achieved similar cancer detection but cut human screen-reading workload about 44% vs standard double reading (39,996 vs 40,024 participants). The primary interval cancer outcomes are maturing, but the safety analysis is reassuring.

Reducing second reads and arbitration time are important for clinicians because it frees capacity for callbacks and diagnostic workups. This will be especially key given that screening now starts at age 40. That will mean about 21 to 22 million more women are newly eligible, translating to about 10 to 11 million additional mammograms each year under biennial screening.

Another important area where AI can make its mark in mammography is triage and time to diagnosis. The results from a randomized implementation study showed that AI-prioritized worklists accelerated time to additional imaging and biopsy diagnosis without harming efficiency for others — exactly the kind of outcome patients feel.

Multiple studies have demonstrated improved diagnostic performance and shorter reading times when AI supports DBT interpretation, which is important because DBT can otherwise be time intensive.

We are also seeing rapid advancement in risk-based screening, moving beyond a single dense vs not dense approach. Deep-learning risk models, such as Mirai, predict 1- to 5-year breast cancer risk directly from the mammogram, and these tools are now being assessed prospectively to guide supplemental MRI. Cost-effectiveness modeling supports risk-stratified intervals vs one-size-fits-all schedules.

Finally, automated density tools, such as Transpara Density and Volpara, offer objective, reproducible volumetric measures that map to the Breast Imaging-Reporting and Data System, which is useful for Mammography Quality Standards Act-required reporting and as inputs to risk calculators.

While early evidence suggests AI may help surface future or interval cancers earlier, including more invasive tumors, the definitive impacts on interval cancer rates and mortality require longitudinal follow-up, which is now in progress.

 

Pitfalls to Watch For

Bias is real. Studies show false-positive differences by race, age, and density. AI can even infer racial identity from images, potentially amplifying disparities. Performance can also shift by vendor, demographics, and prevalence.

A Radiology study of 4855 DBT exams showed that an algorithm produced more false-positive case scores in Black patients and older patients (aged 71-80 years) patients and in women with extremely dense breasts. This can happen because AI can infer proxies for race directly from images, even when humans cannot, and this can propagate disparities if not addressed. External validations and reviews emphasize that performance can shift with device manufacturer, demographics, and prevalence, which is why all tools need to undergo local validation and calibration. 

Here’s a pragmatic adoption checklist before going live with an AI tool.

• Confirm FDA clearance: Verify the name and version of the algorithm, imaging modes (2D vs DBT), and operating points. Confirm 510(k) numbers.
• Local validation: Test on your patient mix and vendor stack (Hologic, GE, Siemens, Fuji). Compare this to your baseline recall rate, positive predictive value of recall (PPV1), cancer detection rate, and reading time. Commit to recalibration if drift occurs.
• Equity plan: Monitor false-positive and negative false-rates by age, race/ethnicity, and density; document corrective actions if disparities emerge. (This isn’t optional.)
• Workflow clarity: Is AI a second reader, an additional reader, or a triage tool? Who arbitrates discordance? What’s the escalation path for high-risk or interval cancer-like patterns?
• Regulatory strategy: Confirm whether the vendor has (or will file) a Predetermined Change Control Plan so models can be updated safely without repeated submissions. Also confirm how you’ll be notified about performance-relevant changes.
• Data governance: Audit logs of AI outputs, retention, protected health information handling, and the patient communication policy for AI-assisted reads.

After going live, set up a quarterly dashboard. It should include cancer detection rate per 1000 patients, recall rate, PPV1, interval cancer rate (as it matures), reading time, and turnaround time to diagnostic imaging or biopsy — all stratified by age, race/ethnicity, and density.

Here, I dissect what this discussion means through the lens of Moravec’s paradox (machines excel at what clinicians find hard, and vice versa) and offer a possible playbook for putting these tools to work.

 

What to Tell Patients

When speaking with patients, emphasize that a radiologist still reads their mammogram. AI helps with consistency and efficiency; it doesn’t replace human oversight. Patients with dense breasts should still expect a standard notice; discussion of individualized risk factors, such as family history, genetics, and prior biopsies; and consideration of supplemental imaging if risk warrants. But it’s also important to tell these patients that while dense breasts are common, they do not automatically mean high cancer risk.

As for screening schedules, remind patients that screening is at least biennial from 40 to 74 years of age per the USPSTF guidelines; however, specialty groups may recommend starting on an annual schedule at 40.

 

What You Can Implement Now

There are multiple practical use cases you can introduce now. One is to use AI as a second reader or an additional reader safety net to preserve detection while reducing human workload. This helps your breast center absorb screening expansion to age 40 without diluting quality. Another is to turn on AI triage to shorten the time to callback and biopsy for the few who need it most — patients notice and appreciate faster answers. You can also begin adopting automated density plus risk models to move beyond “dense/not dense.” For selected patients, AI-informed risk can justify MRI or tailored intervals. 

Here’s a quick cheat sheet (for your next leadership or tumor-board meeting).

 

Do:

• Use AI as a second or additional reader or triage tool, not as a black box.
• Track cancer detection rate, recall, PPV1, interval cancers, and reading time, stratified by age, race, and breast density.
• Pair automated density with AI risk to personalize screening and supplemental imaging.
• Enroll patients in future clinical trials, such as PRISM, the first large-scale randomized controlled trial of AI for screening mammography. This US-based, $16 million, seven-site study is funded by the Patient-Centered Outcomes Research Institute.

Don’t:

• Assume “AI = CAD.” The 2015 CAD story is over; modern deep learning systems are different and require different oversight.
• Go live without a local validation and equity plan or without clarity on software updates.
• Forget to remind patients that screening starts at age 40, and dense breast notifications are now universal. Use the visit to discuss risk, supplemental imaging, and why a human still directs their care.

The Bottom Line

AI won’t replace radiologists or read mammograms for us — just as PET scans didn’t replace oncologists and stethoscopes didn’t make cardiologists obsolete. What it will do is catch what the tired human eye might miss, shave days off anxious waiting, and turn breast density into data instead of doubt. For oncologists, that means staging sooner, enrolling smarter, and spending more time talking with patients instead of chasing callbacks.

In short, AI may not take the picture, but it helps us frame the story, making it sharper, faster, and with fewer blind spots. By pairing this powerful technology with rigorous, equity-focused local validation and transparent governance under the FDA’s emerging Predetermined Change Control Plan framework, we can realize the tangible benefits of practical AI for our patients without widening disparities. 

Now, during Breast Cancer Awareness Month, how about we add on AI to that pink ribbon — how cool would that be?

Thoughts? Drop me a line at [email protected]. Let’s keep the conversation — and pink ribbons — going.

Arturo Loaiza-Bonilla, MD, MSEd, is the co-founder and chief medical AI officer at Massive Bio, a company connecting patients to clinical trials using artificial intelligence. His research and professional interests focus on precision medicine, clinical trial design, digital health, entrepreneurship, and patient advocacy. Dr Loaiza-Bonilla serves as Systemwide Chief of Hematology and Oncology at St. Luke’s University Health Network, where he maintains a connection to patient care by attending to patients 2 days a week.

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

In this Practical AI column, we’ve explored everything from large language models to the nuances of trial matching, but one of the most immediate and impactful applications of AI is unfolding right now in breast imaging. For oncologists, this isn’t an abstract future — with new screening guidelines, dense-breast mandates, and a shrinking radiology workforce, it’s the imaging reports and patient questions landing in your clinic today.

Here is what oncologists need to know, and how to put it to work for their patients.

 

Why AI in Mammography Matters

More than 200 million women undergo breast cancer screening each year. In the US alone, 10% of the 40 million women screened annually require additional diagnostic imaging, and 4%–5% of these women are eventually diagnosed with breast cancer.

Two major shifts are redefining breast cancer screening in the US: The US Preventive Services Task Force (USPSTF) now recommends biennial screening from age 40 to 74 years, and notifying patients of breast density is a federal requirement as of September 10, 2024. That means more mammograms, more patient questions, and more downstream oncology decisions. Patients will increasingly ask about “dense” breast results and what to do next. Add a national radiologist shortage into the mix, and the pressure on timely callbacks, biopsies, and treatment planning will only grow.

 

Can AI Help Without Compromising Care?

The short answer is yes. With AI, we may be able to transform these rate-limiting steps into opportunities for earlier detection, decentralized screening, and smarter triage and save hundreds of thousands of women from an unnecessary diagnostic procedure, if implemented deliberately.

Don’t Confuse Today’s AI With Yesterday’s CAD 

Think of older computer-aided detection (CAD) like a 1990s chemotherapy drug: It sometimes helped, but it came with significant toxicity and rarely delivered consistent survival benefits. Today’s deep-learning AI is closer to targeted therapy — trained on millions of “trial participants” (mammograms), more precise, and applied in specific contexts where it adds value. If you once dismissed CAD as noise, it’s time to revisit what AI can now offer.

The role of AI is broader than drawing boxes. It provides second readings, worklist triage, risk prediction, density assessment, and decision support. FDA has cleared several AI tools for both 2D and digital breast tomosynthesis (DBT), which include iCAD ProFound (DBT), ScreenPoint Transpara (2D/DBT), and Lunit INSIGHT DBT. 

Some of the strongest evidence for AI in mammography is as a second reader during screening. Large trials show that AI plus one radiologist can match reading from two radiologists, cutting workload by about 40%. For example, the MASAI randomized trial showed that AI-supported screening achieved similar cancer detection but cut human screen-reading workload about 44% vs standard double reading (39,996 vs 40,024 participants). The primary interval cancer outcomes are maturing, but the safety analysis is reassuring.

Reducing second reads and arbitration time are important for clinicians because it frees capacity for callbacks and diagnostic workups. This will be especially key given that screening now starts at age 40. That will mean about 21 to 22 million more women are newly eligible, translating to about 10 to 11 million additional mammograms each year under biennial screening.

Another important area where AI can make its mark in mammography is triage and time to diagnosis. The results from a randomized implementation study showed that AI-prioritized worklists accelerated time to additional imaging and biopsy diagnosis without harming efficiency for others — exactly the kind of outcome patients feel.

Multiple studies have demonstrated improved diagnostic performance and shorter reading times when AI supports DBT interpretation, which is important because DBT can otherwise be time intensive.

We are also seeing rapid advancement in risk-based screening, moving beyond a single dense vs not dense approach. Deep-learning risk models, such as Mirai, predict 1- to 5-year breast cancer risk directly from the mammogram, and these tools are now being assessed prospectively to guide supplemental MRI. Cost-effectiveness modeling supports risk-stratified intervals vs one-size-fits-all schedules.

Finally, automated density tools, such as Transpara Density and Volpara, offer objective, reproducible volumetric measures that map to the Breast Imaging-Reporting and Data System, which is useful for Mammography Quality Standards Act-required reporting and as inputs to risk calculators.

While early evidence suggests AI may help surface future or interval cancers earlier, including more invasive tumors, the definitive impacts on interval cancer rates and mortality require longitudinal follow-up, which is now in progress.

 

Pitfalls to Watch For

Bias is real. Studies show false-positive differences by race, age, and density. AI can even infer racial identity from images, potentially amplifying disparities. Performance can also shift by vendor, demographics, and prevalence.

A Radiology study of 4855 DBT exams showed that an algorithm produced more false-positive case scores in Black patients and older patients (aged 71-80 years) patients and in women with extremely dense breasts. This can happen because AI can infer proxies for race directly from images, even when humans cannot, and this can propagate disparities if not addressed. External validations and reviews emphasize that performance can shift with device manufacturer, demographics, and prevalence, which is why all tools need to undergo local validation and calibration. 

Here’s a pragmatic adoption checklist before going live with an AI tool.

• Confirm FDA clearance: Verify the name and version of the algorithm, imaging modes (2D vs DBT), and operating points. Confirm 510(k) numbers.
• Local validation: Test on your patient mix and vendor stack (Hologic, GE, Siemens, Fuji). Compare this to your baseline recall rate, positive predictive value of recall (PPV1), cancer detection rate, and reading time. Commit to recalibration if drift occurs.
• Equity plan: Monitor false-positive and negative false-rates by age, race/ethnicity, and density; document corrective actions if disparities emerge. (This isn’t optional.)
• Workflow clarity: Is AI a second reader, an additional reader, or a triage tool? Who arbitrates discordance? What’s the escalation path for high-risk or interval cancer-like patterns?
• Regulatory strategy: Confirm whether the vendor has (or will file) a Predetermined Change Control Plan so models can be updated safely without repeated submissions. Also confirm how you’ll be notified about performance-relevant changes.
• Data governance: Audit logs of AI outputs, retention, protected health information handling, and the patient communication policy for AI-assisted reads.

After going live, set up a quarterly dashboard. It should include cancer detection rate per 1000 patients, recall rate, PPV1, interval cancer rate (as it matures), reading time, and turnaround time to diagnostic imaging or biopsy — all stratified by age, race/ethnicity, and density.

Here, I dissect what this discussion means through the lens of Moravec’s paradox (machines excel at what clinicians find hard, and vice versa) and offer a possible playbook for putting these tools to work.

 

What to Tell Patients

When speaking with patients, emphasize that a radiologist still reads their mammogram. AI helps with consistency and efficiency; it doesn’t replace human oversight. Patients with dense breasts should still expect a standard notice; discussion of individualized risk factors, such as family history, genetics, and prior biopsies; and consideration of supplemental imaging if risk warrants. But it’s also important to tell these patients that while dense breasts are common, they do not automatically mean high cancer risk.

As for screening schedules, remind patients that screening is at least biennial from 40 to 74 years of age per the USPSTF guidelines; however, specialty groups may recommend starting on an annual schedule at 40.

 

What You Can Implement Now

There are multiple practical use cases you can introduce now. One is to use AI as a second reader or an additional reader safety net to preserve detection while reducing human workload. This helps your breast center absorb screening expansion to age 40 without diluting quality. Another is to turn on AI triage to shorten the time to callback and biopsy for the few who need it most — patients notice and appreciate faster answers. You can also begin adopting automated density plus risk models to move beyond “dense/not dense.” For selected patients, AI-informed risk can justify MRI or tailored intervals. 

Here’s a quick cheat sheet (for your next leadership or tumor-board meeting).

 

Do:

• Use AI as a second or additional reader or triage tool, not as a black box.
• Track cancer detection rate, recall, PPV1, interval cancers, and reading time, stratified by age, race, and breast density.
• Pair automated density with AI risk to personalize screening and supplemental imaging.
• Enroll patients in future clinical trials, such as PRISM, the first large-scale randomized controlled trial of AI for screening mammography. This US-based, $16 million, seven-site study is funded by the Patient-Centered Outcomes Research Institute.

Don’t:

• Assume “AI = CAD.” The 2015 CAD story is over; modern deep learning systems are different and require different oversight.
• Go live without a local validation and equity plan or without clarity on software updates.
• Forget to remind patients that screening starts at age 40, and dense breast notifications are now universal. Use the visit to discuss risk, supplemental imaging, and why a human still directs their care.

The Bottom Line

AI won’t replace radiologists or read mammograms for us — just as PET scans didn’t replace oncologists and stethoscopes didn’t make cardiologists obsolete. What it will do is catch what the tired human eye might miss, shave days off anxious waiting, and turn breast density into data instead of doubt. For oncologists, that means staging sooner, enrolling smarter, and spending more time talking with patients instead of chasing callbacks.

In short, AI may not take the picture, but it helps us frame the story, making it sharper, faster, and with fewer blind spots. By pairing this powerful technology with rigorous, equity-focused local validation and transparent governance under the FDA’s emerging Predetermined Change Control Plan framework, we can realize the tangible benefits of practical AI for our patients without widening disparities. 

Now, during Breast Cancer Awareness Month, how about we add on AI to that pink ribbon — how cool would that be?

Thoughts? Drop me a line at [email protected]. Let’s keep the conversation — and pink ribbons — going.

Arturo Loaiza-Bonilla, MD, MSEd, is the co-founder and chief medical AI officer at Massive Bio, a company connecting patients to clinical trials using artificial intelligence. His research and professional interests focus on precision medicine, clinical trial design, digital health, entrepreneurship, and patient advocacy. Dr Loaiza-Bonilla serves as Systemwide Chief of Hematology and Oncology at St. Luke’s University Health Network, where he maintains a connection to patient care by attending to patients 2 days a week.

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

The ongoing US government partial shutdown has unintended consequences for seniors and their doctors as most telehealth appointments are now no longer being covered by Medicare.

That's because without a budget deal, federal lawmakers did not renew some pandemic-era telehealth flexibilities allowing Medicare beneficiaries to have medical appointments with doctors over audio or video at home.

This policy was first put into place under the first Trump Administration in 2020 during the COVID-19 pandemic. Previously, Medicare covered very limited telehealth services for rural patients.

For the past 5 years, lawmakers have always managed to renew the telehealth flexibilities in every government funding bill before the expiration date. This year, however, they expired for the first time on October 1.

Federal lawmakers remain at odds on the 2026 federal funding bill, meaning the shutdown could last into more days and even weeks.

But with Congress in a standoff, clinicians and patients outside Washington, DC, are already grappling with the consequences of the funding impasse.

Clinicians, Patients Already Feeling Effects

For the South Dakota-based Sanford Health System, which is the largest rural health system in the country, the past week without the Medicare telehealth waivers being in place has caused a lot of anxiety and uncertainty for both patients and clinicians.

Dave Newman, an endocrinologist and chief medical officer of virtual care at Sanford, said the health system decided to keep providing Medicare telehealth appointments to patients for now.

"We're maintaining telehealth access because we know that's the best thing for our patients. We've got full confidence that reimbursement will follow, but patients can't wait for Congress to act at this point," Newman told Medscape Medical News. "They still need access to their specialists. They still need access to their primary care providers, and this is one of the only ways that a lot of our patients get access. For them, it's either virtual care or no care at all."

Newman said as the shutdown continues, Sanford may reconsidered whether it can keep providing these appointments without reimbursement.

Some health systems have stopped providing an Medicare telehealth appointments, said Alexis Apple, director of federal affairs at the American Telemedicine Association. That means patients must appear in person for their doctor's appointment or cancel.

NYU Langone Health system's website currently has a banner that reads: "Due to the federal government shutdown, Medicare and Medicaid patients are unable to schedule new telehealth/video visits. If you already have a visit scheduled, it will continue as planned. If not, contact your doctor's office to schedule an in-person appointment.

"It's creating lots of confusion in the industry from patients, providers, hospital systems. You know, what do we do next? How do we grapple with this shutdown?" said Apple. "Patients have been able to receive care within their homes over the past 5 years, and now, all of a sudden, they've been stripped of that access."

Medicare patients who continue telehealth after October 1 may find out they're on the hook for the bill, if Congress doesn't act, said Apple.

Some physicians worry that commercial insurance payers may follow suit and no longer cover virtual appointments. Medicare, which is the largest health care payer in the country, is often seen as the standard for what services should be covered.

Patients and doctors have come to rely on telehealth as an integral part of health care, said Richard Chou, an anesthesiologist at the US Department of Veterans Affairs (VA) in Sacramento, California.

"You're seeing that postpandemic, telehealth is kind of a new way of doing things. It's part of the day for us as doctors," said Chou. He said tha tmany of his VA patients do their preliminary surgery appointments via telehealth before coming into the facility.

"Telehealth is that bridge to making sure patients get the care they need, and when these patients don't get that preliminary care they need, this builds up and builds up," said Chou. "And next thing you know, you have people flooding the emergency rooms, and we can't have that."

Will Telehealth Reimbursement See a Permanent Fix?

With Congressional budget negotiations at an impasse, it remains unclear when the shutdown will end.

Health care spending disagreements weigh heavily in negotiations. Democrats are currently unwilling to give the votes to pass the 60-vote threshold in the Senate unless Republicans agree to extend Affordable Care Act subsidies that expire at the end of the year. Democrats also want to reverse the Medicaid cuts that were part of the large Republican domestic tax and spending bill passed by Congress earlier this year.

When lawmakers do reach an agreement and reopen the government, it's likely telehealth flexibilities will be included in any package but for how long remains in question.

A newly introduced bipartisan bill would permanently allow Medicare patients to access telehealth appointments in their homes. But the legislation has been estimated to be very costly.

Federal data does show that telehealth appointments have been popular with Medicare recipients and increased over time since telehealth became more accessible.

"I used to say that virtual care was the future of medicine, and now it's just kind of the present of medicine. It used to be like a cool technology that we used to advertise, now it's just the standard of care," said Newman. "We think that permanent coverage would mean stability for both patients and providers."

Victoria Knight is a freelance reporter based in Washington, DC.

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

The ongoing US government partial shutdown has unintended consequences for seniors and their doctors as most telehealth appointments are now no longer being covered by Medicare.

That's because without a budget deal, federal lawmakers did not renew some pandemic-era telehealth flexibilities allowing Medicare beneficiaries to have medical appointments with doctors over audio or video at home.

This policy was first put into place under the first Trump Administration in 2020 during the COVID-19 pandemic. Previously, Medicare covered very limited telehealth services for rural patients.

For the past 5 years, lawmakers have always managed to renew the telehealth flexibilities in every government funding bill before the expiration date. This year, however, they expired for the first time on October 1.

Federal lawmakers remain at odds on the 2026 federal funding bill, meaning the shutdown could last into more days and even weeks.

But with Congress in a standoff, clinicians and patients outside Washington, DC, are already grappling with the consequences of the funding impasse.

Clinicians, Patients Already Feeling Effects

For the South Dakota-based Sanford Health System, which is the largest rural health system in the country, the past week without the Medicare telehealth waivers being in place has caused a lot of anxiety and uncertainty for both patients and clinicians.

Dave Newman, an endocrinologist and chief medical officer of virtual care at Sanford, said the health system decided to keep providing Medicare telehealth appointments to patients for now.

"We're maintaining telehealth access because we know that's the best thing for our patients. We've got full confidence that reimbursement will follow, but patients can't wait for Congress to act at this point," Newman told Medscape Medical News. "They still need access to their specialists. They still need access to their primary care providers, and this is one of the only ways that a lot of our patients get access. For them, it's either virtual care or no care at all."

Newman said as the shutdown continues, Sanford may reconsidered whether it can keep providing these appointments without reimbursement.

Some health systems have stopped providing an Medicare telehealth appointments, said Alexis Apple, director of federal affairs at the American Telemedicine Association. That means patients must appear in person for their doctor's appointment or cancel.

NYU Langone Health system's website currently has a banner that reads: "Due to the federal government shutdown, Medicare and Medicaid patients are unable to schedule new telehealth/video visits. If you already have a visit scheduled, it will continue as planned. If not, contact your doctor's office to schedule an in-person appointment.

"It's creating lots of confusion in the industry from patients, providers, hospital systems. You know, what do we do next? How do we grapple with this shutdown?" said Apple. "Patients have been able to receive care within their homes over the past 5 years, and now, all of a sudden, they've been stripped of that access."

Medicare patients who continue telehealth after October 1 may find out they're on the hook for the bill, if Congress doesn't act, said Apple.

Some physicians worry that commercial insurance payers may follow suit and no longer cover virtual appointments. Medicare, which is the largest health care payer in the country, is often seen as the standard for what services should be covered.

Patients and doctors have come to rely on telehealth as an integral part of health care, said Richard Chou, an anesthesiologist at the US Department of Veterans Affairs (VA) in Sacramento, California.

"You're seeing that postpandemic, telehealth is kind of a new way of doing things. It's part of the day for us as doctors," said Chou. He said tha tmany of his VA patients do their preliminary surgery appointments via telehealth before coming into the facility.

"Telehealth is that bridge to making sure patients get the care they need, and when these patients don't get that preliminary care they need, this builds up and builds up," said Chou. "And next thing you know, you have people flooding the emergency rooms, and we can't have that."

Will Telehealth Reimbursement See a Permanent Fix?

With Congressional budget negotiations at an impasse, it remains unclear when the shutdown will end.

Health care spending disagreements weigh heavily in negotiations. Democrats are currently unwilling to give the votes to pass the 60-vote threshold in the Senate unless Republicans agree to extend Affordable Care Act subsidies that expire at the end of the year. Democrats also want to reverse the Medicaid cuts that were part of the large Republican domestic tax and spending bill passed by Congress earlier this year.

When lawmakers do reach an agreement and reopen the government, it's likely telehealth flexibilities will be included in any package but for how long remains in question.

A newly introduced bipartisan bill would permanently allow Medicare patients to access telehealth appointments in their homes. But the legislation has been estimated to be very costly.

Federal data does show that telehealth appointments have been popular with Medicare recipients and increased over time since telehealth became more accessible.

"I used to say that virtual care was the future of medicine, and now it's just kind of the present of medicine. It used to be like a cool technology that we used to advertise, now it's just the standard of care," said Newman. "We think that permanent coverage would mean stability for both patients and providers."

Victoria Knight is a freelance reporter based in Washington, DC.

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

The ongoing US government partial shutdown has unintended consequences for seniors and their doctors as most telehealth appointments are now no longer being covered by Medicare.

That's because without a budget deal, federal lawmakers did not renew some pandemic-era telehealth flexibilities allowing Medicare beneficiaries to have medical appointments with doctors over audio or video at home.

This policy was first put into place under the first Trump Administration in 2020 during the COVID-19 pandemic. Previously, Medicare covered very limited telehealth services for rural patients.

For the past 5 years, lawmakers have always managed to renew the telehealth flexibilities in every government funding bill before the expiration date. This year, however, they expired for the first time on October 1.

Federal lawmakers remain at odds on the 2026 federal funding bill, meaning the shutdown could last into more days and even weeks.

But with Congress in a standoff, clinicians and patients outside Washington, DC, are already grappling with the consequences of the funding impasse.

Clinicians, Patients Already Feeling Effects

For the South Dakota-based Sanford Health System, which is the largest rural health system in the country, the past week without the Medicare telehealth waivers being in place has caused a lot of anxiety and uncertainty for both patients and clinicians.

Dave Newman, an endocrinologist and chief medical officer of virtual care at Sanford, said the health system decided to keep providing Medicare telehealth appointments to patients for now.

"We're maintaining telehealth access because we know that's the best thing for our patients. We've got full confidence that reimbursement will follow, but patients can't wait for Congress to act at this point," Newman told Medscape Medical News. "They still need access to their specialists. They still need access to their primary care providers, and this is one of the only ways that a lot of our patients get access. For them, it's either virtual care or no care at all."

Newman said as the shutdown continues, Sanford may reconsidered whether it can keep providing these appointments without reimbursement.

Some health systems have stopped providing an Medicare telehealth appointments, said Alexis Apple, director of federal affairs at the American Telemedicine Association. That means patients must appear in person for their doctor's appointment or cancel.

NYU Langone Health system's website currently has a banner that reads: "Due to the federal government shutdown, Medicare and Medicaid patients are unable to schedule new telehealth/video visits. If you already have a visit scheduled, it will continue as planned. If not, contact your doctor's office to schedule an in-person appointment.

"It's creating lots of confusion in the industry from patients, providers, hospital systems. You know, what do we do next? How do we grapple with this shutdown?" said Apple. "Patients have been able to receive care within their homes over the past 5 years, and now, all of a sudden, they've been stripped of that access."

Medicare patients who continue telehealth after October 1 may find out they're on the hook for the bill, if Congress doesn't act, said Apple.

Some physicians worry that commercial insurance payers may follow suit and no longer cover virtual appointments. Medicare, which is the largest health care payer in the country, is often seen as the standard for what services should be covered.

Patients and doctors have come to rely on telehealth as an integral part of health care, said Richard Chou, an anesthesiologist at the US Department of Veterans Affairs (VA) in Sacramento, California.

"You're seeing that postpandemic, telehealth is kind of a new way of doing things. It's part of the day for us as doctors," said Chou. He said tha tmany of his VA patients do their preliminary surgery appointments via telehealth before coming into the facility.

"Telehealth is that bridge to making sure patients get the care they need, and when these patients don't get that preliminary care they need, this builds up and builds up," said Chou. "And next thing you know, you have people flooding the emergency rooms, and we can't have that."

Will Telehealth Reimbursement See a Permanent Fix?

With Congressional budget negotiations at an impasse, it remains unclear when the shutdown will end.

Health care spending disagreements weigh heavily in negotiations. Democrats are currently unwilling to give the votes to pass the 60-vote threshold in the Senate unless Republicans agree to extend Affordable Care Act subsidies that expire at the end of the year. Democrats also want to reverse the Medicaid cuts that were part of the large Republican domestic tax and spending bill passed by Congress earlier this year.

When lawmakers do reach an agreement and reopen the government, it's likely telehealth flexibilities will be included in any package but for how long remains in question.

A newly introduced bipartisan bill would permanently allow Medicare patients to access telehealth appointments in their homes. But the legislation has been estimated to be very costly.

Federal data does show that telehealth appointments have been popular with Medicare recipients and increased over time since telehealth became more accessible.

"I used to say that virtual care was the future of medicine, and now it's just kind of the present of medicine. It used to be like a cool technology that we used to advertise, now it's just the standard of care," said Newman. "We think that permanent coverage would mean stability for both patients and providers."

Victoria Knight is a freelance reporter based in Washington, DC.

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

PHOENIX – Medications used in oncology clinical trials pose unique challenges in areas such as labeling, packaging, and administration, a US Department of Veterans Affairs (VA) pharmacist cautioned colleagues, and placebos have special needs too.

Even basic safety protections can be lacking when a drug is investigational, said Emily Hennes, PharmD, BCOP, clinical pharmacy specialist for research at William S. Middleton Memorial Veterans Hospital in Shorewood Hills, Wisconsin, in a presentation at the annual meeting of the Association of VA Hematology/Oncology.

“All of the safety features that we have come to know and love in dispensing commercial drugs are absent. There’s no Tall Man lettering, there's no color differentiation, and there's no barcoding, because these are not registered drugs," she said.

A 2017 report found that 81% of pharmacists surveyed indicated some level of concern regarding the safety risk in using  investigational drugs. At the same time, Hennes noted, the Joint Commission has mandated that pharmacists must control the storage, dispensing, labeling, and distribution of investigational medications.

Here are things to know about the use of investigational cancer drugs:

Drug Interactions Are Common

Hennes highlighted a 2023 study of medication reconciliation of 501 patients in 79 clinical trials that found alarming levels of drug interactions: 

• 360 clinically relevant drug-drug interactions were identified among 189 patients, including 158 therapies that were prohibited by protocols. Of these, 57.7% involved cytochrome P450 enzymes, which are involved in metabolism. 

• Reconciliation revealed that 35.2% of medications were not otherwise known or documented.

• A median of 2 previously unknown therapies per patient was discovered in 74% of patients.

• Alternative medicine products such as supplements and over-the-counter drugs were implicated in 60% of identified drug interactions.

• Only 41% of oncologists discussed alternative medicine use with patients, which Hennes attributed to “lack of familiarity with many alternative medicine products or insufficient training.”

To make things more complicated, “We sometimes don’t know the full pharmacokinetic and pharmacodynamic profile of an investigational agent,” she said. 

Naming and Labeling May Not Be Standard

Investigational products may not have genetic names and instead have an alphanumeric identifier such as INV54826 that can be quite similar to other products, she said. Investigational drugs may even go through name changes, forcing pharmacists to be alerted to protect patients. 

In addition, labeling may not be standardized. Drugs may arrive unlabeled, with the wrong volume and size, and lack of barcoding. In some cases, pharmacists choose to put new, patient-friendly labels on these products, Hennes said. 

Information Distribution is Key

“Something that comes up in our practice quite a bit is that there’s no standard drug reference regarding investigational drugs,” Hennes said. “Finding ways to get key information to staff at the point of care is really critical to make sure we’re able to safely treat our patients.”

Precautions May Be Needed to Maintain Blinding Protocols 

Hennes explained that pharmacists must use opaque brown bag covers to maintain blinding when parenteral products have distinctive colors. Lines may have to be covered too, which can create challenges during administration. 

“Pumps aren’t meant to run lines that are covered,” she said, which can lead to jams. “If you don’t do education with your point of care staff, it can cause a lot of confusion.” 

It’s also important for blinding purposes to keep an eye on how long it takes to prepare a treatment, she said. A study’s integrity, for example, could be violated if a complex investigational product takes an hour to equilibrate to room temperature and 20-30 minutes to prepare, while a placebo only requires “drawing a few mils of saline out of a bag and labeling it.”

Education for Patients Can Be Useful 

Hennes urged colleagues to remind patients to save investigational medication at the end of each cycle and return it to the clinic site for accountability.

She also suggested creating treatment calendars/reminders for patients and discussing adherence strategies with them. 

Hennes reported no disclosures. 

PHOENIX – Medications used in oncology clinical trials pose unique challenges in areas such as labeling, packaging, and administration, a US Department of Veterans Affairs (VA) pharmacist cautioned colleagues, and placebos have special needs too.

Even basic safety protections can be lacking when a drug is investigational, said Emily Hennes, PharmD, BCOP, clinical pharmacy specialist for research at William S. Middleton Memorial Veterans Hospital in Shorewood Hills, Wisconsin, in a presentation at the annual meeting of the Association of VA Hematology/Oncology.

“All of the safety features that we have come to know and love in dispensing commercial drugs are absent. There’s no Tall Man lettering, there's no color differentiation, and there's no barcoding, because these are not registered drugs," she said.

A 2017 report found that 81% of pharmacists surveyed indicated some level of concern regarding the safety risk in using  investigational drugs. At the same time, Hennes noted, the Joint Commission has mandated that pharmacists must control the storage, dispensing, labeling, and distribution of investigational medications.

Here are things to know about the use of investigational cancer drugs:

Drug Interactions Are Common

Hennes highlighted a 2023 study of medication reconciliation of 501 patients in 79 clinical trials that found alarming levels of drug interactions: 

• 360 clinically relevant drug-drug interactions were identified among 189 patients, including 158 therapies that were prohibited by protocols. Of these, 57.7% involved cytochrome P450 enzymes, which are involved in metabolism. 

• Reconciliation revealed that 35.2% of medications were not otherwise known or documented.

• A median of 2 previously unknown therapies per patient was discovered in 74% of patients.

• Alternative medicine products such as supplements and over-the-counter drugs were implicated in 60% of identified drug interactions.

• Only 41% of oncologists discussed alternative medicine use with patients, which Hennes attributed to “lack of familiarity with many alternative medicine products or insufficient training.”

To make things more complicated, “We sometimes don’t know the full pharmacokinetic and pharmacodynamic profile of an investigational agent,” she said. 

Naming and Labeling May Not Be Standard

Investigational products may not have genetic names and instead have an alphanumeric identifier such as INV54826 that can be quite similar to other products, she said. Investigational drugs may even go through name changes, forcing pharmacists to be alerted to protect patients. 

In addition, labeling may not be standardized. Drugs may arrive unlabeled, with the wrong volume and size, and lack of barcoding. In some cases, pharmacists choose to put new, patient-friendly labels on these products, Hennes said. 

Information Distribution is Key

“Something that comes up in our practice quite a bit is that there’s no standard drug reference regarding investigational drugs,” Hennes said. “Finding ways to get key information to staff at the point of care is really critical to make sure we’re able to safely treat our patients.”

Precautions May Be Needed to Maintain Blinding Protocols 

Hennes explained that pharmacists must use opaque brown bag covers to maintain blinding when parenteral products have distinctive colors. Lines may have to be covered too, which can create challenges during administration. 

“Pumps aren’t meant to run lines that are covered,” she said, which can lead to jams. “If you don’t do education with your point of care staff, it can cause a lot of confusion.” 

It’s also important for blinding purposes to keep an eye on how long it takes to prepare a treatment, she said. A study’s integrity, for example, could be violated if a complex investigational product takes an hour to equilibrate to room temperature and 20-30 minutes to prepare, while a placebo only requires “drawing a few mils of saline out of a bag and labeling it.”

Education for Patients Can Be Useful 

Hennes urged colleagues to remind patients to save investigational medication at the end of each cycle and return it to the clinic site for accountability.

She also suggested creating treatment calendars/reminders for patients and discussing adherence strategies with them. 

Hennes reported no disclosures. 

PHOENIX – Medications used in oncology clinical trials pose unique challenges in areas such as labeling, packaging, and administration, a US Department of Veterans Affairs (VA) pharmacist cautioned colleagues, and placebos have special needs too.

Even basic safety protections can be lacking when a drug is investigational, said Emily Hennes, PharmD, BCOP, clinical pharmacy specialist for research at William S. Middleton Memorial Veterans Hospital in Shorewood Hills, Wisconsin, in a presentation at the annual meeting of the Association of VA Hematology/Oncology.

“All of the safety features that we have come to know and love in dispensing commercial drugs are absent. There’s no Tall Man lettering, there's no color differentiation, and there's no barcoding, because these are not registered drugs," she said.

A 2017 report found that 81% of pharmacists surveyed indicated some level of concern regarding the safety risk in using  investigational drugs. At the same time, Hennes noted, the Joint Commission has mandated that pharmacists must control the storage, dispensing, labeling, and distribution of investigational medications.

Here are things to know about the use of investigational cancer drugs:

Drug Interactions Are Common

Hennes highlighted a 2023 study of medication reconciliation of 501 patients in 79 clinical trials that found alarming levels of drug interactions: 

• 360 clinically relevant drug-drug interactions were identified among 189 patients, including 158 therapies that were prohibited by protocols. Of these, 57.7% involved cytochrome P450 enzymes, which are involved in metabolism. 

• Reconciliation revealed that 35.2% of medications were not otherwise known or documented.

• A median of 2 previously unknown therapies per patient was discovered in 74% of patients.

• Alternative medicine products such as supplements and over-the-counter drugs were implicated in 60% of identified drug interactions.

• Only 41% of oncologists discussed alternative medicine use with patients, which Hennes attributed to “lack of familiarity with many alternative medicine products or insufficient training.”

To make things more complicated, “We sometimes don’t know the full pharmacokinetic and pharmacodynamic profile of an investigational agent,” she said. 

Naming and Labeling May Not Be Standard

Investigational products may not have genetic names and instead have an alphanumeric identifier such as INV54826 that can be quite similar to other products, she said. Investigational drugs may even go through name changes, forcing pharmacists to be alerted to protect patients. 

In addition, labeling may not be standardized. Drugs may arrive unlabeled, with the wrong volume and size, and lack of barcoding. In some cases, pharmacists choose to put new, patient-friendly labels on these products, Hennes said. 

Information Distribution is Key

“Something that comes up in our practice quite a bit is that there’s no standard drug reference regarding investigational drugs,” Hennes said. “Finding ways to get key information to staff at the point of care is really critical to make sure we’re able to safely treat our patients.”

Precautions May Be Needed to Maintain Blinding Protocols 

Hennes explained that pharmacists must use opaque brown bag covers to maintain blinding when parenteral products have distinctive colors. Lines may have to be covered too, which can create challenges during administration. 

“Pumps aren’t meant to run lines that are covered,” she said, which can lead to jams. “If you don’t do education with your point of care staff, it can cause a lot of confusion.” 

It’s also important for blinding purposes to keep an eye on how long it takes to prepare a treatment, she said. A study’s integrity, for example, could be violated if a complex investigational product takes an hour to equilibrate to room temperature and 20-30 minutes to prepare, while a placebo only requires “drawing a few mils of saline out of a bag and labeling it.”

Education for Patients Can Be Useful 

Hennes urged colleagues to remind patients to save investigational medication at the end of each cycle and return it to the clinic site for accountability.

She also suggested creating treatment calendars/reminders for patients and discussing adherence strategies with them. 

Hennes reported no disclosures.