The first large population study to investigate the association between different COVID-19 vaccines types and cardiac effects and adverse events shows a small increase in the risk for acute myocarditis with both the mRNA-based vaccines and – in what may a first in the literature – an adenovirus-vector vaccine.

Ivan Pantic/Getty Images

The excess risk was seen following the first dose of the ChAdOc1 (AstraZeneca/Oxford), the adenovirus-based vaccine, and the mRNA-based BNT162b2 (Pfizer/BioNTech). It was observed after first and second doses of the mRNA-1273 (Moderna) vaccine.

The incidence rate ratios for myocarditis 1-7 days after the first AstraZeneca, Pfizer, and Moderna injections were 1.76, 1.45, and 8.38, respectively, and 23.1 after the second dose of the Moderna vaccine.

“There’s a bit more uncertainty and worry about mRNA vaccines because it’s quite a new vector for vaccination and, therefore, there’s been more focus on the potential side effects,” said Nicholas Mills, MD.

“But it doesn’t surprise me the signal is present for all types of vaccines because they’re designed to generate a systemic immune response and that is, unfortunately, where you can cause small risks for immune-mediated illnesses like myocarditis,” Dr. Mills, from the University of Edinburgh, told this news organization. Dr. Mills is a coauthor on the study, published Dec. 14 in Nature Medicine.

To put the risks in context, the group estimated between 1 and 10 additional myocarditis hospitalizations or deaths per 1 million people vaccinated, but 40 excess myocarditis events per million following a positive SARS-CoV-2 test result.

As reported, rates of excess myocarditis events associated with a first dose were 2 per million injections of the AstraZeneca vaccine, 1 per million for the Pfizer vaccine, and 6 per million with the Moderna vaccine.

Following a second dose, there were 10 additional myocarditis events per million people receiving the Moderna vaccine and none among recipients of the AstraZeneca or Pfizer vaccines.

“It was particularly seen within the first 7 days of the first dose, which is very consistent with what we see in people who have viral myocarditis,” Dr. Mills said. “So it looks like a real signal but it’s very small.”

The results are in line with previous studies of the Pfizer vaccine in Israel and studies of the Moderna vaccine in the United States, Biykem Bozkurt, MD, PhD, professor of medicine at Baylor College of Medicine, Houston, told this news organization.

“What this paper does is confirm that cardiovascular complications – and they are only looking at a small component of those cardiovascular complications – are markedly higher with the COVID-19 infection than with the vaccines,” she said.

It also adds a new twist to the search for the mechanisms of myocarditis, which has focused on the immunogenicity of the RNA in the Pfizer and Moderna vaccines but also hypothesized that molecular mimicry between the SARS-CoV-2 spike glycoprotein and cell antigens, antibody production against cardiac proteins, and testosterone may play a role.

“But now it doesn’t look like the risk is solely confined to the mRNA vaccine platform because it’s also happening with the adenovirus,” Dr. Bozkurt said. “The mechanisms require future experimental and clinical research and we’ll need more granular data with cohorts that are closely followed up as well as subclinical follow-up.”

James de Lemos, MD, professor of medicine at the University of Texas Southwestern Medical Center, Dallas, and cochair of the American Heart Association’s COVID-19 CVD Registry, said he was also not surprised by a myocarditis signal with AstraZeneca’s adenovirus vaccine.

“Looking at relative risks has biological implications, but the clinical and public health implications are that the absolute risk with the adenovirus is trivial. And you see that with their estimations of absolute risk where it’s literally sort of a needle in the haystack of 1 or 2 per million,” he said in an interview.
 

Large-scale data

The investigators examined the rates of hospital admission or death from myocarditis, pericarditis, and cardiac arrhythmia in the 28 days following SARS-CoV-2 vaccination or infection by linking the English National Immunisation Database of COVID-19 vaccination with a national patient-level health care database of 38.6 million people, aged 16 years or older, vaccinated from Dec.1, 2020, to Aug. 24, 2021.

The number of people admitted to the hospital or who died during the study period was 1,615 for myocarditis, 1,574 for pericarditis, and 385,508 for cardiac arrhythmia.

There was no evidence of an increased risk for pericarditis or cardiac arrhythmia following vaccination, except for arrhythmia in the 28 days following a second dose of the Moderna vaccine (IRR, 1.46).

In contrast, the risk was increased for pericarditis (IRR, 2.79) and cardiac arrhythmia (IRR, 5.35) in the 28 days following a positive SARS-CoV-2 test result.

Although the scale of the analysis allows for more precise estimates than what’s been possible in smaller data sets, there is the challenge of diagnosing COVID-19 from billing codes and the potential for ascertainment bias, noted Dr. de Lemos.  

“Having said that, I think it’s a really important study, because it’s the first study to put the incidence in context in the same general population the risks of myocarditis with various vaccines and with COVID-19,” he said.

“That’s really important and provides a lot of reassurance for those who are trying to balance the risks and benefits of vaccination.”
 

Analyses by sex and age

A subgroup analysis by age showed increased risks for myocarditis with the mRNA vaccines only in those younger than 40, whereas no association was found with the Oxford adenovirus vaccine.

“We’re not seeing any signal here that would make us change the recommendation for vaccination in children as a consequence of this risk,” Dr. Mills said during a press briefing.

Dr. Bozkurt pointed out, however, that the estimated excess in myocarditis events following a second dose of the Moderna vaccine in these younger adults reportedly exceeded that for SARS-CoV-2 infection (15 per million vs. 10 per million).

“For that age group, it’s concerning and needs further clarification. This hasn’t been seen before,” she said.

The average age was 39 years for those receiving two doses of the Moderna vaccine and 55 for recipients of the Pfizer and Oxford vaccines. The Moderna vaccine wasn’t rolled out until April 2021 in the United Kingdom, the authors noted, so the number of patients who received this vaccine is lower.

Although reports have suggested young males are at greater risk for myocarditis after vaccination, an analysis by sex found that women had an increased risk for myocarditis after a first dose of the AstraZeneca (IRR, 1.40) and Pfizer (IRR, 1.54) vaccines and following a positive COVID-19 test result (IRR, 11.00).

“Women being at increased risk is rather a new message,” Dr. Bozkurt said. “But the incidence rate ratios are being compared against the unvaccinated, so when you see the increase in women, it doesn’t mean it’s increased against men. It would be helpful for sex-specific incidence rate ratios to be reported for younger age subgroups, such as ages 16-20 and 20-30, to determine whether there’s an increased risk for males compared to females at younger ages.”

Age and sex differences are huge questions, but “I think we’ll learn a lot about myocarditis in general from what is going to be an explosion of research into the vaccine-associated causes,” Dr. de Lemos said.

“That will help us understand myocarditis more broadly and prepare us for the next generation of vaccines, which inevitably will be mRNA based.”

Dr. Mills reported having no relevant disclosures. Dr. Bozkurt reported consulting for Bayer and scPharmaceuticals and serving on a clinical-events committee for a trial supported by Abbott Pharmaceuticals and on a data and safety monitoring board for a trial supported by Liva Nova Pharmaceuticals. Dr. De Lemos reported having no relevant conflicts of interest.

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

The first large population study to investigate the association between different COVID-19 vaccines types and cardiac effects and adverse events shows a small increase in the risk for acute myocarditis with both the mRNA-based vaccines and – in what may a first in the literature – an adenovirus-vector vaccine.

Ivan Pantic/Getty Images

The excess risk was seen following the first dose of the ChAdOc1 (AstraZeneca/Oxford), the adenovirus-based vaccine, and the mRNA-based BNT162b2 (Pfizer/BioNTech). It was observed after first and second doses of the mRNA-1273 (Moderna) vaccine.

The incidence rate ratios for myocarditis 1-7 days after the first AstraZeneca, Pfizer, and Moderna injections were 1.76, 1.45, and 8.38, respectively, and 23.1 after the second dose of the Moderna vaccine.

“There’s a bit more uncertainty and worry about mRNA vaccines because it’s quite a new vector for vaccination and, therefore, there’s been more focus on the potential side effects,” said Nicholas Mills, MD.

“But it doesn’t surprise me the signal is present for all types of vaccines because they’re designed to generate a systemic immune response and that is, unfortunately, where you can cause small risks for immune-mediated illnesses like myocarditis,” Dr. Mills, from the University of Edinburgh, told this news organization. Dr. Mills is a coauthor on the study, published Dec. 14 in Nature Medicine.

To put the risks in context, the group estimated between 1 and 10 additional myocarditis hospitalizations or deaths per 1 million people vaccinated, but 40 excess myocarditis events per million following a positive SARS-CoV-2 test result.

As reported, rates of excess myocarditis events associated with a first dose were 2 per million injections of the AstraZeneca vaccine, 1 per million for the Pfizer vaccine, and 6 per million with the Moderna vaccine.

Following a second dose, there were 10 additional myocarditis events per million people receiving the Moderna vaccine and none among recipients of the AstraZeneca or Pfizer vaccines.

“It was particularly seen within the first 7 days of the first dose, which is very consistent with what we see in people who have viral myocarditis,” Dr. Mills said. “So it looks like a real signal but it’s very small.”

The results are in line with previous studies of the Pfizer vaccine in Israel and studies of the Moderna vaccine in the United States, Biykem Bozkurt, MD, PhD, professor of medicine at Baylor College of Medicine, Houston, told this news organization.

“What this paper does is confirm that cardiovascular complications – and they are only looking at a small component of those cardiovascular complications – are markedly higher with the COVID-19 infection than with the vaccines,” she said.

It also adds a new twist to the search for the mechanisms of myocarditis, which has focused on the immunogenicity of the RNA in the Pfizer and Moderna vaccines but also hypothesized that molecular mimicry between the SARS-CoV-2 spike glycoprotein and cell antigens, antibody production against cardiac proteins, and testosterone may play a role.

“But now it doesn’t look like the risk is solely confined to the mRNA vaccine platform because it’s also happening with the adenovirus,” Dr. Bozkurt said. “The mechanisms require future experimental and clinical research and we’ll need more granular data with cohorts that are closely followed up as well as subclinical follow-up.”

James de Lemos, MD, professor of medicine at the University of Texas Southwestern Medical Center, Dallas, and cochair of the American Heart Association’s COVID-19 CVD Registry, said he was also not surprised by a myocarditis signal with AstraZeneca’s adenovirus vaccine.

“Looking at relative risks has biological implications, but the clinical and public health implications are that the absolute risk with the adenovirus is trivial. And you see that with their estimations of absolute risk where it’s literally sort of a needle in the haystack of 1 or 2 per million,” he said in an interview.
 

Large-scale data

The investigators examined the rates of hospital admission or death from myocarditis, pericarditis, and cardiac arrhythmia in the 28 days following SARS-CoV-2 vaccination or infection by linking the English National Immunisation Database of COVID-19 vaccination with a national patient-level health care database of 38.6 million people, aged 16 years or older, vaccinated from Dec.1, 2020, to Aug. 24, 2021.

The number of people admitted to the hospital or who died during the study period was 1,615 for myocarditis, 1,574 for pericarditis, and 385,508 for cardiac arrhythmia.

There was no evidence of an increased risk for pericarditis or cardiac arrhythmia following vaccination, except for arrhythmia in the 28 days following a second dose of the Moderna vaccine (IRR, 1.46).

In contrast, the risk was increased for pericarditis (IRR, 2.79) and cardiac arrhythmia (IRR, 5.35) in the 28 days following a positive SARS-CoV-2 test result.

Although the scale of the analysis allows for more precise estimates than what’s been possible in smaller data sets, there is the challenge of diagnosing COVID-19 from billing codes and the potential for ascertainment bias, noted Dr. de Lemos.  

“Having said that, I think it’s a really important study, because it’s the first study to put the incidence in context in the same general population the risks of myocarditis with various vaccines and with COVID-19,” he said.

“That’s really important and provides a lot of reassurance for those who are trying to balance the risks and benefits of vaccination.”
 

Analyses by sex and age

A subgroup analysis by age showed increased risks for myocarditis with the mRNA vaccines only in those younger than 40, whereas no association was found with the Oxford adenovirus vaccine.

“We’re not seeing any signal here that would make us change the recommendation for vaccination in children as a consequence of this risk,” Dr. Mills said during a press briefing.

Dr. Bozkurt pointed out, however, that the estimated excess in myocarditis events following a second dose of the Moderna vaccine in these younger adults reportedly exceeded that for SARS-CoV-2 infection (15 per million vs. 10 per million).

“For that age group, it’s concerning and needs further clarification. This hasn’t been seen before,” she said.

The average age was 39 years for those receiving two doses of the Moderna vaccine and 55 for recipients of the Pfizer and Oxford vaccines. The Moderna vaccine wasn’t rolled out until April 2021 in the United Kingdom, the authors noted, so the number of patients who received this vaccine is lower.

Although reports have suggested young males are at greater risk for myocarditis after vaccination, an analysis by sex found that women had an increased risk for myocarditis after a first dose of the AstraZeneca (IRR, 1.40) and Pfizer (IRR, 1.54) vaccines and following a positive COVID-19 test result (IRR, 11.00).

“Women being at increased risk is rather a new message,” Dr. Bozkurt said. “But the incidence rate ratios are being compared against the unvaccinated, so when you see the increase in women, it doesn’t mean it’s increased against men. It would be helpful for sex-specific incidence rate ratios to be reported for younger age subgroups, such as ages 16-20 and 20-30, to determine whether there’s an increased risk for males compared to females at younger ages.”

Age and sex differences are huge questions, but “I think we’ll learn a lot about myocarditis in general from what is going to be an explosion of research into the vaccine-associated causes,” Dr. de Lemos said.

“That will help us understand myocarditis more broadly and prepare us for the next generation of vaccines, which inevitably will be mRNA based.”

Dr. Mills reported having no relevant disclosures. Dr. Bozkurt reported consulting for Bayer and scPharmaceuticals and serving on a clinical-events committee for a trial supported by Abbott Pharmaceuticals and on a data and safety monitoring board for a trial supported by Liva Nova Pharmaceuticals. Dr. De Lemos reported having no relevant conflicts of interest.

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

The first large population study to investigate the association between different COVID-19 vaccines types and cardiac effects and adverse events shows a small increase in the risk for acute myocarditis with both the mRNA-based vaccines and – in what may a first in the literature – an adenovirus-vector vaccine.

Ivan Pantic/Getty Images

The excess risk was seen following the first dose of the ChAdOc1 (AstraZeneca/Oxford), the adenovirus-based vaccine, and the mRNA-based BNT162b2 (Pfizer/BioNTech). It was observed after first and second doses of the mRNA-1273 (Moderna) vaccine.

The incidence rate ratios for myocarditis 1-7 days after the first AstraZeneca, Pfizer, and Moderna injections were 1.76, 1.45, and 8.38, respectively, and 23.1 after the second dose of the Moderna vaccine.

“There’s a bit more uncertainty and worry about mRNA vaccines because it’s quite a new vector for vaccination and, therefore, there’s been more focus on the potential side effects,” said Nicholas Mills, MD.

“But it doesn’t surprise me the signal is present for all types of vaccines because they’re designed to generate a systemic immune response and that is, unfortunately, where you can cause small risks for immune-mediated illnesses like myocarditis,” Dr. Mills, from the University of Edinburgh, told this news organization. Dr. Mills is a coauthor on the study, published Dec. 14 in Nature Medicine.

To put the risks in context, the group estimated between 1 and 10 additional myocarditis hospitalizations or deaths per 1 million people vaccinated, but 40 excess myocarditis events per million following a positive SARS-CoV-2 test result.

As reported, rates of excess myocarditis events associated with a first dose were 2 per million injections of the AstraZeneca vaccine, 1 per million for the Pfizer vaccine, and 6 per million with the Moderna vaccine.

Following a second dose, there were 10 additional myocarditis events per million people receiving the Moderna vaccine and none among recipients of the AstraZeneca or Pfizer vaccines.

“It was particularly seen within the first 7 days of the first dose, which is very consistent with what we see in people who have viral myocarditis,” Dr. Mills said. “So it looks like a real signal but it’s very small.”

The results are in line with previous studies of the Pfizer vaccine in Israel and studies of the Moderna vaccine in the United States, Biykem Bozkurt, MD, PhD, professor of medicine at Baylor College of Medicine, Houston, told this news organization.

“What this paper does is confirm that cardiovascular complications – and they are only looking at a small component of those cardiovascular complications – are markedly higher with the COVID-19 infection than with the vaccines,” she said.

It also adds a new twist to the search for the mechanisms of myocarditis, which has focused on the immunogenicity of the RNA in the Pfizer and Moderna vaccines but also hypothesized that molecular mimicry between the SARS-CoV-2 spike glycoprotein and cell antigens, antibody production against cardiac proteins, and testosterone may play a role.

“But now it doesn’t look like the risk is solely confined to the mRNA vaccine platform because it’s also happening with the adenovirus,” Dr. Bozkurt said. “The mechanisms require future experimental and clinical research and we’ll need more granular data with cohorts that are closely followed up as well as subclinical follow-up.”

James de Lemos, MD, professor of medicine at the University of Texas Southwestern Medical Center, Dallas, and cochair of the American Heart Association’s COVID-19 CVD Registry, said he was also not surprised by a myocarditis signal with AstraZeneca’s adenovirus vaccine.

“Looking at relative risks has biological implications, but the clinical and public health implications are that the absolute risk with the adenovirus is trivial. And you see that with their estimations of absolute risk where it’s literally sort of a needle in the haystack of 1 or 2 per million,” he said in an interview.
 

Large-scale data

The investigators examined the rates of hospital admission or death from myocarditis, pericarditis, and cardiac arrhythmia in the 28 days following SARS-CoV-2 vaccination or infection by linking the English National Immunisation Database of COVID-19 vaccination with a national patient-level health care database of 38.6 million people, aged 16 years or older, vaccinated from Dec.1, 2020, to Aug. 24, 2021.

The number of people admitted to the hospital or who died during the study period was 1,615 for myocarditis, 1,574 for pericarditis, and 385,508 for cardiac arrhythmia.

There was no evidence of an increased risk for pericarditis or cardiac arrhythmia following vaccination, except for arrhythmia in the 28 days following a second dose of the Moderna vaccine (IRR, 1.46).

In contrast, the risk was increased for pericarditis (IRR, 2.79) and cardiac arrhythmia (IRR, 5.35) in the 28 days following a positive SARS-CoV-2 test result.

Although the scale of the analysis allows for more precise estimates than what’s been possible in smaller data sets, there is the challenge of diagnosing COVID-19 from billing codes and the potential for ascertainment bias, noted Dr. de Lemos.  

“Having said that, I think it’s a really important study, because it’s the first study to put the incidence in context in the same general population the risks of myocarditis with various vaccines and with COVID-19,” he said.

“That’s really important and provides a lot of reassurance for those who are trying to balance the risks and benefits of vaccination.”
 

Analyses by sex and age

A subgroup analysis by age showed increased risks for myocarditis with the mRNA vaccines only in those younger than 40, whereas no association was found with the Oxford adenovirus vaccine.

“We’re not seeing any signal here that would make us change the recommendation for vaccination in children as a consequence of this risk,” Dr. Mills said during a press briefing.

Dr. Bozkurt pointed out, however, that the estimated excess in myocarditis events following a second dose of the Moderna vaccine in these younger adults reportedly exceeded that for SARS-CoV-2 infection (15 per million vs. 10 per million).

“For that age group, it’s concerning and needs further clarification. This hasn’t been seen before,” she said.

The average age was 39 years for those receiving two doses of the Moderna vaccine and 55 for recipients of the Pfizer and Oxford vaccines. The Moderna vaccine wasn’t rolled out until April 2021 in the United Kingdom, the authors noted, so the number of patients who received this vaccine is lower.

Although reports have suggested young males are at greater risk for myocarditis after vaccination, an analysis by sex found that women had an increased risk for myocarditis after a first dose of the AstraZeneca (IRR, 1.40) and Pfizer (IRR, 1.54) vaccines and following a positive COVID-19 test result (IRR, 11.00).

“Women being at increased risk is rather a new message,” Dr. Bozkurt said. “But the incidence rate ratios are being compared against the unvaccinated, so when you see the increase in women, it doesn’t mean it’s increased against men. It would be helpful for sex-specific incidence rate ratios to be reported for younger age subgroups, such as ages 16-20 and 20-30, to determine whether there’s an increased risk for males compared to females at younger ages.”

Age and sex differences are huge questions, but “I think we’ll learn a lot about myocarditis in general from what is going to be an explosion of research into the vaccine-associated causes,” Dr. de Lemos said.

“That will help us understand myocarditis more broadly and prepare us for the next generation of vaccines, which inevitably will be mRNA based.”

Dr. Mills reported having no relevant disclosures. Dr. Bozkurt reported consulting for Bayer and scPharmaceuticals and serving on a clinical-events committee for a trial supported by Abbott Pharmaceuticals and on a data and safety monitoring board for a trial supported by Liva Nova Pharmaceuticals. Dr. De Lemos reported having no relevant conflicts of interest.

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

A cluster analysis of circulating plasma biomarkers in prurigo nodularis (PN) has identified two disease endotypes with inflammatory and noninflammatory biomarker profiles.

The findings confirm clinical observations of disease heterogeneity, and highlight that PN “involves a spectrum of neuroimmune dysfunction, where patients can be at either end of the spectrum [toward either immune or neural dysregulation],” said senior author Shawn G. Kwatra, MD, of the department of dermatology at Johns Hopkins University, Baltimore. “This is the beginning of personalized medicine in prurigo nodularis.”

He and others have long observed significant clinical heterogeneity both in the presentation of PN – with the nodules in African American patients, for instance, appearing larger, thicker, and more fibrotic – and in patients’ response to immunomodulating and neuromodulating therapies.

To avoid the introduction of bias, the researchers used an unsupervised machine-learning approach to analyze the levels of 12 inflammatory biomarkers in 20 patients with PN and in matched healthy controls. The biomarkers were chosen based on their demonstrated dysregulation in PN and other inflammatory dermatoses.

The researchers then conducted a population-level analysis using multicenter electronic medical record data to explore inflammatory markers and verify findings from the cluster analysis. The study was published online Oct. 27, 2021, in the Journal of Investigative Dermatology.

One cluster of the 20 patients had higher levels of nine inflammatory biomarkers representing multiple immune axes: Higher interleukin-1 alpha, IL-4, IL-5, IL-6, IL-10, IL-17A, IL-22, and IL-25. This cluster had a higher percentage of Black patients, a higher severity of itch, and lower quality of life scores, the authors report in the preprint.

The other cluster – without such an inflammatory profile – had fewer Black patients and a higher percentage of patients with myelopathy (e.g. spinal stenosis, spinal trauma, degenerative disc disease). The rates of inflammatory comorbidities and of immune- and neuromodulating treatments at the time of blood draw were relatively equivalent between the two clusters.

In the subsequent population-level analysis, using data from a global health research network of EMRs from almost 50 health care organizations, Black patients with PN were found to have higher erythrocyte sedimentation rate, C-reactive protein, ferritin, and eosinophils, and lower transferrin, than White patients with PN. (The analysis included only Black and White patients.)

There are no Food and Drug Administration–approved therapies for PN, and “clinicians need to be really creative in managing these patients,” Dr. Kwatra said.

“There may be suggestions at the bedside that patients have more immune dysregulation, or maybe I’ll see increased circulating blood eosinophils,” he said. “And there are those who don’t seem to have any immune dysregulation and have more features of neurosensitization ... who may have a history of neck pain or back injury.”

The existence of endotypes in PN suggests that patients may benefit from personalized therapies with either immunomodulating or neuromodulating treatments, he and his colleagues wrote. “Further neuroimmune phenotyping studies of PN may pave the way for a future precision medicine management approach.”

Studies of PN conducted in Europe have been almost exclusively in White patients, Dr. Kwatra noted, even though PN has been shown to disproportionately affect Black and other racial/ethnic-minority patients.

Black patients with PN were found to have the highest all-cause mortality over 20 years post diagnosis in a separate analysis of over 22,000 patients with PN. Using data from the same health research network, Dr. Kwatra and coinvestigators stratified patients by race/ethnicity and compared each subgroup with a corresponding subgroup of similar race/ethnicity to control for inherent differences in mortality.

Overall, patients with PN had higher all-cause mortality than controls (hazard ratio, 1.70), likely because of a high comorbidity burden, they wrote in their research letter. Black patients with PN had the highest mortality (HR, 2.07), followed by White (HR, 1.74) and Hispanic (HR, 1.62) patients.

PN may exacerbate existing racial disparities in the social determinants of health, and Black patients may suffer from greater systemic inflammation, Dr. Kwatra and coauthors wrote. Certainly, he said, these findings, as well as the finding of a distinct inflammatory signature in Black patients with PN, support “that the disease burden is much higher” in these patients.

Dr Kwatra disclosed that he is an advisory board member/consultant for Celldex Therapeutics, Galderma, Incyte, Pfizer, Regeneron, and Kiniksa Pharmaceuticals and has received grant funding from several companies. His research is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Grants from the Dermatology Foundation and the Skin of Color Society also helped fund the cluster analysis.

A cluster analysis of circulating plasma biomarkers in prurigo nodularis (PN) has identified two disease endotypes with inflammatory and noninflammatory biomarker profiles.

The findings confirm clinical observations of disease heterogeneity, and highlight that PN “involves a spectrum of neuroimmune dysfunction, where patients can be at either end of the spectrum [toward either immune or neural dysregulation],” said senior author Shawn G. Kwatra, MD, of the department of dermatology at Johns Hopkins University, Baltimore. “This is the beginning of personalized medicine in prurigo nodularis.”

He and others have long observed significant clinical heterogeneity both in the presentation of PN – with the nodules in African American patients, for instance, appearing larger, thicker, and more fibrotic – and in patients’ response to immunomodulating and neuromodulating therapies.

To avoid the introduction of bias, the researchers used an unsupervised machine-learning approach to analyze the levels of 12 inflammatory biomarkers in 20 patients with PN and in matched healthy controls. The biomarkers were chosen based on their demonstrated dysregulation in PN and other inflammatory dermatoses.

The researchers then conducted a population-level analysis using multicenter electronic medical record data to explore inflammatory markers and verify findings from the cluster analysis. The study was published online Oct. 27, 2021, in the Journal of Investigative Dermatology.

One cluster of the 20 patients had higher levels of nine inflammatory biomarkers representing multiple immune axes: Higher interleukin-1 alpha, IL-4, IL-5, IL-6, IL-10, IL-17A, IL-22, and IL-25. This cluster had a higher percentage of Black patients, a higher severity of itch, and lower quality of life scores, the authors report in the preprint.

The other cluster – without such an inflammatory profile – had fewer Black patients and a higher percentage of patients with myelopathy (e.g. spinal stenosis, spinal trauma, degenerative disc disease). The rates of inflammatory comorbidities and of immune- and neuromodulating treatments at the time of blood draw were relatively equivalent between the two clusters.

In the subsequent population-level analysis, using data from a global health research network of EMRs from almost 50 health care organizations, Black patients with PN were found to have higher erythrocyte sedimentation rate, C-reactive protein, ferritin, and eosinophils, and lower transferrin, than White patients with PN. (The analysis included only Black and White patients.)

There are no Food and Drug Administration–approved therapies for PN, and “clinicians need to be really creative in managing these patients,” Dr. Kwatra said.

“There may be suggestions at the bedside that patients have more immune dysregulation, or maybe I’ll see increased circulating blood eosinophils,” he said. “And there are those who don’t seem to have any immune dysregulation and have more features of neurosensitization ... who may have a history of neck pain or back injury.”

The existence of endotypes in PN suggests that patients may benefit from personalized therapies with either immunomodulating or neuromodulating treatments, he and his colleagues wrote. “Further neuroimmune phenotyping studies of PN may pave the way for a future precision medicine management approach.”

Studies of PN conducted in Europe have been almost exclusively in White patients, Dr. Kwatra noted, even though PN has been shown to disproportionately affect Black and other racial/ethnic-minority patients.

Black patients with PN were found to have the highest all-cause mortality over 20 years post diagnosis in a separate analysis of over 22,000 patients with PN. Using data from the same health research network, Dr. Kwatra and coinvestigators stratified patients by race/ethnicity and compared each subgroup with a corresponding subgroup of similar race/ethnicity to control for inherent differences in mortality.

Overall, patients with PN had higher all-cause mortality than controls (hazard ratio, 1.70), likely because of a high comorbidity burden, they wrote in their research letter. Black patients with PN had the highest mortality (HR, 2.07), followed by White (HR, 1.74) and Hispanic (HR, 1.62) patients.

PN may exacerbate existing racial disparities in the social determinants of health, and Black patients may suffer from greater systemic inflammation, Dr. Kwatra and coauthors wrote. Certainly, he said, these findings, as well as the finding of a distinct inflammatory signature in Black patients with PN, support “that the disease burden is much higher” in these patients.

Dr Kwatra disclosed that he is an advisory board member/consultant for Celldex Therapeutics, Galderma, Incyte, Pfizer, Regeneron, and Kiniksa Pharmaceuticals and has received grant funding from several companies. His research is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Grants from the Dermatology Foundation and the Skin of Color Society also helped fund the cluster analysis.

A cluster analysis of circulating plasma biomarkers in prurigo nodularis (PN) has identified two disease endotypes with inflammatory and noninflammatory biomarker profiles.

The findings confirm clinical observations of disease heterogeneity, and highlight that PN “involves a spectrum of neuroimmune dysfunction, where patients can be at either end of the spectrum [toward either immune or neural dysregulation],” said senior author Shawn G. Kwatra, MD, of the department of dermatology at Johns Hopkins University, Baltimore. “This is the beginning of personalized medicine in prurigo nodularis.”

He and others have long observed significant clinical heterogeneity both in the presentation of PN – with the nodules in African American patients, for instance, appearing larger, thicker, and more fibrotic – and in patients’ response to immunomodulating and neuromodulating therapies.

To avoid the introduction of bias, the researchers used an unsupervised machine-learning approach to analyze the levels of 12 inflammatory biomarkers in 20 patients with PN and in matched healthy controls. The biomarkers were chosen based on their demonstrated dysregulation in PN and other inflammatory dermatoses.

The researchers then conducted a population-level analysis using multicenter electronic medical record data to explore inflammatory markers and verify findings from the cluster analysis. The study was published online Oct. 27, 2021, in the Journal of Investigative Dermatology.

One cluster of the 20 patients had higher levels of nine inflammatory biomarkers representing multiple immune axes: Higher interleukin-1 alpha, IL-4, IL-5, IL-6, IL-10, IL-17A, IL-22, and IL-25. This cluster had a higher percentage of Black patients, a higher severity of itch, and lower quality of life scores, the authors report in the preprint.

The other cluster – without such an inflammatory profile – had fewer Black patients and a higher percentage of patients with myelopathy (e.g. spinal stenosis, spinal trauma, degenerative disc disease). The rates of inflammatory comorbidities and of immune- and neuromodulating treatments at the time of blood draw were relatively equivalent between the two clusters.

In the subsequent population-level analysis, using data from a global health research network of EMRs from almost 50 health care organizations, Black patients with PN were found to have higher erythrocyte sedimentation rate, C-reactive protein, ferritin, and eosinophils, and lower transferrin, than White patients with PN. (The analysis included only Black and White patients.)

There are no Food and Drug Administration–approved therapies for PN, and “clinicians need to be really creative in managing these patients,” Dr. Kwatra said.

“There may be suggestions at the bedside that patients have more immune dysregulation, or maybe I’ll see increased circulating blood eosinophils,” he said. “And there are those who don’t seem to have any immune dysregulation and have more features of neurosensitization ... who may have a history of neck pain or back injury.”

The existence of endotypes in PN suggests that patients may benefit from personalized therapies with either immunomodulating or neuromodulating treatments, he and his colleagues wrote. “Further neuroimmune phenotyping studies of PN may pave the way for a future precision medicine management approach.”

Studies of PN conducted in Europe have been almost exclusively in White patients, Dr. Kwatra noted, even though PN has been shown to disproportionately affect Black and other racial/ethnic-minority patients.

Black patients with PN were found to have the highest all-cause mortality over 20 years post diagnosis in a separate analysis of over 22,000 patients with PN. Using data from the same health research network, Dr. Kwatra and coinvestigators stratified patients by race/ethnicity and compared each subgroup with a corresponding subgroup of similar race/ethnicity to control for inherent differences in mortality.

Overall, patients with PN had higher all-cause mortality than controls (hazard ratio, 1.70), likely because of a high comorbidity burden, they wrote in their research letter. Black patients with PN had the highest mortality (HR, 2.07), followed by White (HR, 1.74) and Hispanic (HR, 1.62) patients.

PN may exacerbate existing racial disparities in the social determinants of health, and Black patients may suffer from greater systemic inflammation, Dr. Kwatra and coauthors wrote. Certainly, he said, these findings, as well as the finding of a distinct inflammatory signature in Black patients with PN, support “that the disease burden is much higher” in these patients.

Dr Kwatra disclosed that he is an advisory board member/consultant for Celldex Therapeutics, Galderma, Incyte, Pfizer, Regeneron, and Kiniksa Pharmaceuticals and has received grant funding from several companies. His research is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Grants from the Dermatology Foundation and the Skin of Color Society also helped fund the cluster analysis.

Key clinical point: Palbociclib dose reduction occurs in real-world practice among patients with advanced breast cancer (BC) and has no negative clinical outcomes. It is more common in older patients, with no effect on survival.

Major finding: Overall, palbociclib dose reduction occurred in 33% of patients, with median time-to-next treatment (P < .001) and median overall survival (OS; P = .003) significantly longer in patients with vs without dose reduction. Dose reductions were more common in patients aged ≥70 years vs <70 years (P = .041), with no effect observed on median OS (P = .051).

Study details: This real-world analysis included 598 patients (median age, 64 years) with hormone receptor-positive, human epidermal growth factor receptor 2-negative, advanced BC who were treated with palbociclib combined with either fulvestrant or aromatase inhibitors.

Disclosures: This study was funded by Dutch health insurer VGZ. The authors declared no conflict of interests.

Source: Ismail RK et al. Breast. 2021 Nov 17. doi: 10.1016/j.breast.2021.11.013.

Key clinical point: Palbociclib dose reduction occurs in real-world practice among patients with advanced breast cancer (BC) and has no negative clinical outcomes. It is more common in older patients, with no effect on survival.

Major finding: Overall, palbociclib dose reduction occurred in 33% of patients, with median time-to-next treatment (P < .001) and median overall survival (OS; P = .003) significantly longer in patients with vs without dose reduction. Dose reductions were more common in patients aged ≥70 years vs <70 years (P = .041), with no effect observed on median OS (P = .051).

Study details: This real-world analysis included 598 patients (median age, 64 years) with hormone receptor-positive, human epidermal growth factor receptor 2-negative, advanced BC who were treated with palbociclib combined with either fulvestrant or aromatase inhibitors.

Disclosures: This study was funded by Dutch health insurer VGZ. The authors declared no conflict of interests.

Source: Ismail RK et al. Breast. 2021 Nov 17. doi: 10.1016/j.breast.2021.11.013.

Key clinical point: Palbociclib dose reduction occurs in real-world practice among patients with advanced breast cancer (BC) and has no negative clinical outcomes. It is more common in older patients, with no effect on survival.

Major finding: Overall, palbociclib dose reduction occurred in 33% of patients, with median time-to-next treatment (P < .001) and median overall survival (OS; P = .003) significantly longer in patients with vs without dose reduction. Dose reductions were more common in patients aged ≥70 years vs <70 years (P = .041), with no effect observed on median OS (P = .051).

Study details: This real-world analysis included 598 patients (median age, 64 years) with hormone receptor-positive, human epidermal growth factor receptor 2-negative, advanced BC who were treated with palbociclib combined with either fulvestrant or aromatase inhibitors.

Disclosures: This study was funded by Dutch health insurer VGZ. The authors declared no conflict of interests.

Source: Ismail RK et al. Breast. 2021 Nov 17. doi: 10.1016/j.breast.2021.11.013.

Key clinical point: The possibility of cancer-related or pathologic vertebral fracture should be considered in women with invasive breast cancer who received endocrine therapy, particularly those with, advanced stage cancer history where every 1 in 3 incident vetrtebral fractures was a pathologic fracture.

.Major finding: Overall, 21.2% of vertebral fractures were pathologic with the chances of vertebral fractures being pathologic higher in patients with stage 3-4 vs initial stage 1 and 2 breast cancer (41.2% vs 17.2%; P < .05).

Study details: Findings are from a cohort study including 5010 women with newly-diagnosed invasive breast cancer who received endocrine therapy and were followed up from invasive breast cancer diagnosis to 10 years or until September 30, 2015, for incident bone fracture.

Disclosures: This study was funded by the National Cancer Institute, National Institutes of Health, and the Research Program on Genes, Environment and Health of Kaiser Permanente Northern California. The authors declared no conflicts of interest.

Source: Lo JC et al. JAMA Netw Open. 2021 Nov 17. doi: 10.1001/jamanetworkopen.2021.33861.

Key clinical point: The possibility of cancer-related or pathologic vertebral fracture should be considered in women with invasive breast cancer who received endocrine therapy, particularly those with, advanced stage cancer history where every 1 in 3 incident vetrtebral fractures was a pathologic fracture.

.Major finding: Overall, 21.2% of vertebral fractures were pathologic with the chances of vertebral fractures being pathologic higher in patients with stage 3-4 vs initial stage 1 and 2 breast cancer (41.2% vs 17.2%; P < .05).

Study details: Findings are from a cohort study including 5010 women with newly-diagnosed invasive breast cancer who received endocrine therapy and were followed up from invasive breast cancer diagnosis to 10 years or until September 30, 2015, for incident bone fracture.

Disclosures: This study was funded by the National Cancer Institute, National Institutes of Health, and the Research Program on Genes, Environment and Health of Kaiser Permanente Northern California. The authors declared no conflicts of interest.

Source: Lo JC et al. JAMA Netw Open. 2021 Nov 17. doi: 10.1001/jamanetworkopen.2021.33861.

Key clinical point: The possibility of cancer-related or pathologic vertebral fracture should be considered in women with invasive breast cancer who received endocrine therapy, particularly those with, advanced stage cancer history where every 1 in 3 incident vetrtebral fractures was a pathologic fracture.

.Major finding: Overall, 21.2% of vertebral fractures were pathologic with the chances of vertebral fractures being pathologic higher in patients with stage 3-4 vs initial stage 1 and 2 breast cancer (41.2% vs 17.2%; P < .05).

Study details: Findings are from a cohort study including 5010 women with newly-diagnosed invasive breast cancer who received endocrine therapy and were followed up from invasive breast cancer diagnosis to 10 years or until September 30, 2015, for incident bone fracture.

Disclosures: This study was funded by the National Cancer Institute, National Institutes of Health, and the Research Program on Genes, Environment and Health of Kaiser Permanente Northern California. The authors declared no conflicts of interest.

Source: Lo JC et al. JAMA Netw Open. 2021 Nov 17. doi: 10.1001/jamanetworkopen.2021.33861.

Key clinical point: Rupacarib did not show clinical benefits in the overall cohort of patients with metastatic breast cancer, but a small proportion of patients with high loss of heterozygosity (LOH) scores and no mutations in germline BReast CAncer genes 1 and 2 (BRCA1/2) seemed to benefit.

Major finding: Investigator-assessed clinical benefit rate was 13.5% (95% CI, 4.5%-28.8%) in the overall cohort, which was below the clinically relevant 20% mark. However, 5 patients achieved clinical benefits with rucaparib, with 2 of them with high LOH scores and no somatic BRCA1/2 mutation achieving a complete response of 12 months and 28.5 months, respectively.

Study details: Findings are from a phase 2 RUBY study including 40 adult patients with progressive human epidermal growth factor receptor 2-negative breast cancer with high LOH or nongermline BRCA1/2 mutation, who received at least 1 dose of rucaparib.

Disclosures: This study was funded by Clovis. The authors declared serving as speaker and advisor and/or receiving research grants, travel fees, consulting fees, and personal fees from various pharmaceutical companies.

Source: Patsouris A et al. Eur J Cancer. 2021 Nov 25. doi: 10.1016/j.ejca.2021.09.028.

Key clinical point: Rupacarib did not show clinical benefits in the overall cohort of patients with metastatic breast cancer, but a small proportion of patients with high loss of heterozygosity (LOH) scores and no mutations in germline BReast CAncer genes 1 and 2 (BRCA1/2) seemed to benefit.

Major finding: Investigator-assessed clinical benefit rate was 13.5% (95% CI, 4.5%-28.8%) in the overall cohort, which was below the clinically relevant 20% mark. However, 5 patients achieved clinical benefits with rucaparib, with 2 of them with high LOH scores and no somatic BRCA1/2 mutation achieving a complete response of 12 months and 28.5 months, respectively.

Study details: Findings are from a phase 2 RUBY study including 40 adult patients with progressive human epidermal growth factor receptor 2-negative breast cancer with high LOH or nongermline BRCA1/2 mutation, who received at least 1 dose of rucaparib.

Disclosures: This study was funded by Clovis. The authors declared serving as speaker and advisor and/or receiving research grants, travel fees, consulting fees, and personal fees from various pharmaceutical companies.

Source: Patsouris A et al. Eur J Cancer. 2021 Nov 25. doi: 10.1016/j.ejca.2021.09.028.

Key clinical point: Rupacarib did not show clinical benefits in the overall cohort of patients with metastatic breast cancer, but a small proportion of patients with high loss of heterozygosity (LOH) scores and no mutations in germline BReast CAncer genes 1 and 2 (BRCA1/2) seemed to benefit.

Major finding: Investigator-assessed clinical benefit rate was 13.5% (95% CI, 4.5%-28.8%) in the overall cohort, which was below the clinically relevant 20% mark. However, 5 patients achieved clinical benefits with rucaparib, with 2 of them with high LOH scores and no somatic BRCA1/2 mutation achieving a complete response of 12 months and 28.5 months, respectively.

Study details: Findings are from a phase 2 RUBY study including 40 adult patients with progressive human epidermal growth factor receptor 2-negative breast cancer with high LOH or nongermline BRCA1/2 mutation, who received at least 1 dose of rucaparib.

Disclosures: This study was funded by Clovis. The authors declared serving as speaker and advisor and/or receiving research grants, travel fees, consulting fees, and personal fees from various pharmaceutical companies.

Source: Patsouris A et al. Eur J Cancer. 2021 Nov 25. doi: 10.1016/j.ejca.2021.09.028.

Key clinical point: Including internal mammary node irradiation (IMNI) with regional node irradiation did not improve disease-free survival (DFS) significantly in the overall cohort of patients with node-positive breast cancer but benefited those with mediocentrally located tumors.

Major finding: The 7-year DFS rate was not significantly different between groups treated without vs with IMNI (81.9% vs 85.3%; hazard ratio [HR], 0.80; 95% CI, 0.57-1.14); however, it was significantly higher in patients with mediocentrally located tumor who were treated with vs without IMNI  (91.8% vs 81.6%; HR, 0.42; 95% CI, 0.22-0.82).

Study details: Findings are from phase 3 KROG 08-06 study including 735 patients with histologically confirmed, node-positive breast cancer who underwent breast-conservation surgery or mastectomy and axillary dissection and were randomly assigned to receive regional nodal irradiation with or without IMNI.

Disclosures: This work was supported by the Cancer Control of the Ministry of Health, Welfare, and Family Affairs, Korea. The authors declared no conflict of interests.

Source: Kim YB et al. JAMA Oncol. 2021 Oct 25. doi: 10.1001/jamaoncol.2021.6036.

Key clinical point: Including internal mammary node irradiation (IMNI) with regional node irradiation did not improve disease-free survival (DFS) significantly in the overall cohort of patients with node-positive breast cancer but benefited those with mediocentrally located tumors.

Major finding: The 7-year DFS rate was not significantly different between groups treated without vs with IMNI (81.9% vs 85.3%; hazard ratio [HR], 0.80; 95% CI, 0.57-1.14); however, it was significantly higher in patients with mediocentrally located tumor who were treated with vs without IMNI  (91.8% vs 81.6%; HR, 0.42; 95% CI, 0.22-0.82).

Study details: Findings are from phase 3 KROG 08-06 study including 735 patients with histologically confirmed, node-positive breast cancer who underwent breast-conservation surgery or mastectomy and axillary dissection and were randomly assigned to receive regional nodal irradiation with or without IMNI.

Disclosures: This work was supported by the Cancer Control of the Ministry of Health, Welfare, and Family Affairs, Korea. The authors declared no conflict of interests.

Source: Kim YB et al. JAMA Oncol. 2021 Oct 25. doi: 10.1001/jamaoncol.2021.6036.

Key clinical point: Including internal mammary node irradiation (IMNI) with regional node irradiation did not improve disease-free survival (DFS) significantly in the overall cohort of patients with node-positive breast cancer but benefited those with mediocentrally located tumors.

Major finding: The 7-year DFS rate was not significantly different between groups treated without vs with IMNI (81.9% vs 85.3%; hazard ratio [HR], 0.80; 95% CI, 0.57-1.14); however, it was significantly higher in patients with mediocentrally located tumor who were treated with vs without IMNI  (91.8% vs 81.6%; HR, 0.42; 95% CI, 0.22-0.82).

Study details: Findings are from phase 3 KROG 08-06 study including 735 patients with histologically confirmed, node-positive breast cancer who underwent breast-conservation surgery or mastectomy and axillary dissection and were randomly assigned to receive regional nodal irradiation with or without IMNI.

Disclosures: This work was supported by the Cancer Control of the Ministry of Health, Welfare, and Family Affairs, Korea. The authors declared no conflict of interests.

Source: Kim YB et al. JAMA Oncol. 2021 Oct 25. doi: 10.1001/jamaoncol.2021.6036.

Key clinical point: COVID-19 pandemic has changed breast cancer (BC) management strategies, with the use of neoadjuvant endocrine therapy (NET) increasing significantly during the pandemic; however, no effect was observed on BC stage at diagnosis.

Major finding: The use of NET increased significantly during COVID-19 pandemic period (P = .002), particularly in patients with stage I hormone receptor-positive, human epidermal growth factor receptor 2-negative BC where the use of NET increased from 10% pre-COVID-19 to 23% during COVID-19 pandemic (P = .001). The pandemic had no effect on clinical prognostic stage (P = 0.39) and proportion of patients with clinical nodal status+ BC (P = 0.38).

Study details: This was a retrospective chart review including patients with newly diagnosed BC who presented at Mayo Clinic, Rochester during (March-August 2020; n=197) or before (March-August 2019; n=376) the COVID-19 pandemic.

Disclosures: Dr. Boughey declared receiving research funding from Lilly and was on a data and safety monitoring board for Cairns Surgical.

Source: Tonneson JE et al. Ann Surg Oncol. 2021 Nov 23. doi: 10.1245/s10434-021-11088-6.

Key clinical point: COVID-19 pandemic has changed breast cancer (BC) management strategies, with the use of neoadjuvant endocrine therapy (NET) increasing significantly during the pandemic; however, no effect was observed on BC stage at diagnosis.

Major finding: The use of NET increased significantly during COVID-19 pandemic period (P = .002), particularly in patients with stage I hormone receptor-positive, human epidermal growth factor receptor 2-negative BC where the use of NET increased from 10% pre-COVID-19 to 23% during COVID-19 pandemic (P = .001). The pandemic had no effect on clinical prognostic stage (P = 0.39) and proportion of patients with clinical nodal status+ BC (P = 0.38).

Study details: This was a retrospective chart review including patients with newly diagnosed BC who presented at Mayo Clinic, Rochester during (March-August 2020; n=197) or before (March-August 2019; n=376) the COVID-19 pandemic.

Disclosures: Dr. Boughey declared receiving research funding from Lilly and was on a data and safety monitoring board for Cairns Surgical.

Source: Tonneson JE et al. Ann Surg Oncol. 2021 Nov 23. doi: 10.1245/s10434-021-11088-6.

Key clinical point: COVID-19 pandemic has changed breast cancer (BC) management strategies, with the use of neoadjuvant endocrine therapy (NET) increasing significantly during the pandemic; however, no effect was observed on BC stage at diagnosis.

Major finding: The use of NET increased significantly during COVID-19 pandemic period (P = .002), particularly in patients with stage I hormone receptor-positive, human epidermal growth factor receptor 2-negative BC where the use of NET increased from 10% pre-COVID-19 to 23% during COVID-19 pandemic (P = .001). The pandemic had no effect on clinical prognostic stage (P = 0.39) and proportion of patients with clinical nodal status+ BC (P = 0.38).

Study details: This was a retrospective chart review including patients with newly diagnosed BC who presented at Mayo Clinic, Rochester during (March-August 2020; n=197) or before (March-August 2019; n=376) the COVID-19 pandemic.

Disclosures: Dr. Boughey declared receiving research funding from Lilly and was on a data and safety monitoring board for Cairns Surgical.

Source: Tonneson JE et al. Ann Surg Oncol. 2021 Nov 23. doi: 10.1245/s10434-021-11088-6.

Key clinical point: Patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC) significantly benefitted from neoadjuvant chemotherapy with intense dose-dense epirubicin, paclitaxel and cyclophosphamide (iddPEC) vs paclitaxel plus non-pegylated liposomal doxorubicin (PM) plus carboplatin ([Cb], triple-negative BC only).

Major finding: Although the 4-year invasive disease-free survival (iDFS; P log-rank = .334) and overall survival (OS, P log-rank = .637) was not significantly different between iddEPC vs PM(Cb) arms in the entire cohort, the subgroup of patients with HR+/HER-2-, BC, showed significantly improved iDFS (hazard ratio [HR], 2.11; P log-rank = .025) and OS (HR,  3.26; P log-rank = .029).with iddEPC.

Study details: Findings are from phase 3 GeparOcto trial including 961 patients with high-risk early BC, who were randomly assigned 1:1 to receive iddEPC or PM(Cb), of which 706 patients completed treatment.

Disclosures: This study was funded by Roche, Amgen, TEVA, and Vifor. The authors reported receiving research grants, personal fees, consulting fees, honoraria and/ or travel support from the above companies and other sources.

Source: Schneeweiss A et al. Eur J Cancer. 2021 Nov 17. doi: 10.1016/j.ejca.2021.10.011.

Key clinical point: Patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC) significantly benefitted from neoadjuvant chemotherapy with intense dose-dense epirubicin, paclitaxel and cyclophosphamide (iddPEC) vs paclitaxel plus non-pegylated liposomal doxorubicin (PM) plus carboplatin ([Cb], triple-negative BC only).

Major finding: Although the 4-year invasive disease-free survival (iDFS; P log-rank = .334) and overall survival (OS, P log-rank = .637) was not significantly different between iddEPC vs PM(Cb) arms in the entire cohort, the subgroup of patients with HR+/HER-2-, BC, showed significantly improved iDFS (hazard ratio [HR], 2.11; P log-rank = .025) and OS (HR,  3.26; P log-rank = .029).with iddEPC.

Study details: Findings are from phase 3 GeparOcto trial including 961 patients with high-risk early BC, who were randomly assigned 1:1 to receive iddEPC or PM(Cb), of which 706 patients completed treatment.

Disclosures: This study was funded by Roche, Amgen, TEVA, and Vifor. The authors reported receiving research grants, personal fees, consulting fees, honoraria and/ or travel support from the above companies and other sources.

Source: Schneeweiss A et al. Eur J Cancer. 2021 Nov 17. doi: 10.1016/j.ejca.2021.10.011.

Key clinical point: Patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC) significantly benefitted from neoadjuvant chemotherapy with intense dose-dense epirubicin, paclitaxel and cyclophosphamide (iddPEC) vs paclitaxel plus non-pegylated liposomal doxorubicin (PM) plus carboplatin ([Cb], triple-negative BC only).

Major finding: Although the 4-year invasive disease-free survival (iDFS; P log-rank = .334) and overall survival (OS, P log-rank = .637) was not significantly different between iddEPC vs PM(Cb) arms in the entire cohort, the subgroup of patients with HR+/HER-2-, BC, showed significantly improved iDFS (hazard ratio [HR], 2.11; P log-rank = .025) and OS (HR,  3.26; P log-rank = .029).with iddEPC.

Study details: Findings are from phase 3 GeparOcto trial including 961 patients with high-risk early BC, who were randomly assigned 1:1 to receive iddEPC or PM(Cb), of which 706 patients completed treatment.

Disclosures: This study was funded by Roche, Amgen, TEVA, and Vifor. The authors reported receiving research grants, personal fees, consulting fees, honoraria and/ or travel support from the above companies and other sources.

Source: Schneeweiss A et al. Eur J Cancer. 2021 Nov 17. doi: 10.1016/j.ejca.2021.10.011.

Key clinical point: Preliminary evidence indicated feasibility of LY2780301, a dual inhibitor of p70 ribosomal protein S6 kinase and protein kinase B (AKT) and paclitaxel combination in patients with hormone-resistant2 (HER2)-negative advanced breast cancer (BC).

Major finding: The recommended phase 2 dose was LY2780301 500 mg once daily + weekly paclitaxel 80 mg/m². The 6-month objective response rate for phase 2 was 63.9% (90% CI, 48.8-76.8) in the overall population and 55% (90% CI, 35.0-73.7) in phosphatidylinositol-3-kinase/AKT positive patients. The common drug-related adverse events were neuropathy, asthenia, ungual toxicity and pneumonitis.

Study details: Findings are from a prospective, multi-centred, phase 1b/2 TAKTIC trial including 48 patients with HER2-negative advanced BC with (phase 1B; n=12) or without (phase 2; n=36) previous cytotoxic treatment for advanced disease who were administered oral LY2780301 + intravenous paclitaxel.

Disclosures: This study was funded by the French National Cancer Institute, the Caritative Foundation and the Ligue Nationale Contre le Cancer. Three authors declared serving as advisory board member and/or receiving research grants and non-financial support from various pharmaceutical companies.

Source: Vicier C et al. Eur J Cancer. 2021 Nov 12. doi: 10.1016/j.ejca.2021.09.040.

Key clinical point: Preliminary evidence indicated feasibility of LY2780301, a dual inhibitor of p70 ribosomal protein S6 kinase and protein kinase B (AKT) and paclitaxel combination in patients with hormone-resistant2 (HER2)-negative advanced breast cancer (BC).

Major finding: The recommended phase 2 dose was LY2780301 500 mg once daily + weekly paclitaxel 80 mg/m². The 6-month objective response rate for phase 2 was 63.9% (90% CI, 48.8-76.8) in the overall population and 55% (90% CI, 35.0-73.7) in phosphatidylinositol-3-kinase/AKT positive patients. The common drug-related adverse events were neuropathy, asthenia, ungual toxicity and pneumonitis.

Study details: Findings are from a prospective, multi-centred, phase 1b/2 TAKTIC trial including 48 patients with HER2-negative advanced BC with (phase 1B; n=12) or without (phase 2; n=36) previous cytotoxic treatment for advanced disease who were administered oral LY2780301 + intravenous paclitaxel.

Disclosures: This study was funded by the French National Cancer Institute, the Caritative Foundation and the Ligue Nationale Contre le Cancer. Three authors declared serving as advisory board member and/or receiving research grants and non-financial support from various pharmaceutical companies.

Source: Vicier C et al. Eur J Cancer. 2021 Nov 12. doi: 10.1016/j.ejca.2021.09.040.

Key clinical point: Preliminary evidence indicated feasibility of LY2780301, a dual inhibitor of p70 ribosomal protein S6 kinase and protein kinase B (AKT) and paclitaxel combination in patients with hormone-resistant2 (HER2)-negative advanced breast cancer (BC).

Major finding: The recommended phase 2 dose was LY2780301 500 mg once daily + weekly paclitaxel 80 mg/m². The 6-month objective response rate for phase 2 was 63.9% (90% CI, 48.8-76.8) in the overall population and 55% (90% CI, 35.0-73.7) in phosphatidylinositol-3-kinase/AKT positive patients. The common drug-related adverse events were neuropathy, asthenia, ungual toxicity and pneumonitis.

Study details: Findings are from a prospective, multi-centred, phase 1b/2 TAKTIC trial including 48 patients with HER2-negative advanced BC with (phase 1B; n=12) or without (phase 2; n=36) previous cytotoxic treatment for advanced disease who were administered oral LY2780301 + intravenous paclitaxel.

Disclosures: This study was funded by the French National Cancer Institute, the Caritative Foundation and the Ligue Nationale Contre le Cancer. Three authors declared serving as advisory board member and/or receiving research grants and non-financial support from various pharmaceutical companies.

Source: Vicier C et al. Eur J Cancer. 2021 Nov 12. doi: 10.1016/j.ejca.2021.09.040.

Key clinical point: Dalpiciclib plus fulvestrant prolonged progression-free survival (PFS) compared with placebo+fulvestrant in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer who progressed during or after endocrine therapy.

Major finding: Patients receiving dalpiciclib+fulvestrant showed significantly prolonged investigator-assessed progression-free survival than those who received placebo+fulvestrant (median, 15.7 months vs 7.2 months; hazard ratio, 0.42; P < .0001). Serious adverse events were reported by 5.8% vs 6.7% of patients recieving dalpiciclib+fulvestrant vs placebo+fulvestrant.

Study details: Findings are interim results from phase 3 DAWNA-1 trial, including 361 patients with HR-positive, HER2-negative locally advanced breast cancer who progressed on endocrine therapy and were randomly assigned to dalpiciclib+fulvestrant or placebo+fulvestrant.

Disclosures: This study was funded by Jiangsu Hengrui Pharmaceuticals. The authors reported receiving research grants, advisory fees from Hengrui and other sources. Four authors declared being employees of Hengrui.

Source: Xu B et al. Nat Med. 2021 Nov 4. doi: 10.1038/s41591-021-01562-9.

Key clinical point: Dalpiciclib plus fulvestrant prolonged progression-free survival (PFS) compared with placebo+fulvestrant in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer who progressed during or after endocrine therapy.

Major finding: Patients receiving dalpiciclib+fulvestrant showed significantly prolonged investigator-assessed progression-free survival than those who received placebo+fulvestrant (median, 15.7 months vs 7.2 months; hazard ratio, 0.42; P < .0001). Serious adverse events were reported by 5.8% vs 6.7% of patients recieving dalpiciclib+fulvestrant vs placebo+fulvestrant.

Study details: Findings are interim results from phase 3 DAWNA-1 trial, including 361 patients with HR-positive, HER2-negative locally advanced breast cancer who progressed on endocrine therapy and were randomly assigned to dalpiciclib+fulvestrant or placebo+fulvestrant.

Disclosures: This study was funded by Jiangsu Hengrui Pharmaceuticals. The authors reported receiving research grants, advisory fees from Hengrui and other sources. Four authors declared being employees of Hengrui.

Source: Xu B et al. Nat Med. 2021 Nov 4. doi: 10.1038/s41591-021-01562-9.

Key clinical point: Dalpiciclib plus fulvestrant prolonged progression-free survival (PFS) compared with placebo+fulvestrant in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer who progressed during or after endocrine therapy.

Major finding: Patients receiving dalpiciclib+fulvestrant showed significantly prolonged investigator-assessed progression-free survival than those who received placebo+fulvestrant (median, 15.7 months vs 7.2 months; hazard ratio, 0.42; P < .0001). Serious adverse events were reported by 5.8% vs 6.7% of patients recieving dalpiciclib+fulvestrant vs placebo+fulvestrant.

Study details: Findings are interim results from phase 3 DAWNA-1 trial, including 361 patients with HR-positive, HER2-negative locally advanced breast cancer who progressed on endocrine therapy and were randomly assigned to dalpiciclib+fulvestrant or placebo+fulvestrant.

Disclosures: This study was funded by Jiangsu Hengrui Pharmaceuticals. The authors reported receiving research grants, advisory fees from Hengrui and other sources. Four authors declared being employees of Hengrui.

Source: Xu B et al. Nat Med. 2021 Nov 4. doi: 10.1038/s41591-021-01562-9.