Higher resting heart rate (RHR) is associated with increased risk for dementia and accelerated cognitive decline in older adults, independent of the presence of cardiovascular disease (CVD) risk factors, new research shows.

“RHR is easy to measure and might be used to identify older people potentially at high risk of dementia and cognitive decline for early interventions,” Yume Imahori, MD, PhD, with the Aging Research Center, Karolinska Institutet, Stockholm, said in an interview.

“Health care professionals should be aware of potential cognitive consequences associated with elevated RHR in older people and may advise older people with high RHR to have a follow-up assessment of cognitive function,” Dr. Imahori said.

The study was published online Dec. 3, 2021, in Alzheimer’s & Dementia.
 

Heart-brain connection

The findings are based on 2,147 adults (62% women) aged 60 years and older (mean age, 70.6 years) from the population-based Swedish National Aging and Care in Kungsholmen (SNAC-K) study. All were free of dementia at baseline and were followed regularly from 2001-2004 to 2013-2016.

The average RHR at baseline was 65.7 bpm. Individuals in higher RHR groups were older, less educated, and were more likely to be smokers and sedentary and to have hypertension. There were no differences among RHR groups in the prevalence of CVD at baseline.

During a median follow-up of 11.4 years, 289 participants were diagnosed with dementia.

In the fully adjusted model, participants with RHR of 80 bpm or higher had a 55% increased risk of developing dementia, compared with peers with lower RHR of 60 to 69 bpm (hazard ratio, 1.55; 95% CI, 1.06-2.27).

“This association was not due to underlying cardiovascular diseases such as atrial fibrillation and heart failure, which is important because elevated RHR is often related to heart disease,” Dr. Imahori said in an interview.

Regarding cognitive function, Mini-Mental State Examination scores declined over time during the follow-up period in all RHR groups, but participants with RHR 70-79 and 80+ bpm had a greater decline, compared with those with lower RHR of 60-69 bpm.

Dr. Imahori said these findings are in line with data from the U.S. Atherosclerosis Risk in Communities study linking elevated RHR of 80+ bpm in midlife to dementia and cognitive decline in late life.
 

Public health implications

Reached for comment, Claire Sexton, DPhil, Alzheimer’s Association director of scientific programs and outreach, said this study adds to the “growing body of research showing the health of the heart and brain are closely connected. However, this study only shows a correlation between resting heart rate and cognition, not causation. More research is needed.

“Evidence shows that other risk factors for cardiovascular disease and stroke – obesity, high blood pressure, and diabetes – negatively impact your cognitive health,” Dr. Sexton said in an interview.

“The Alzheimer’s Association believes the conversation about heart health management is something everyone should be having with their doctor,” she said.

“There are things you can do today to lower your risk for cardiovascular disease, including regular exercise and maintaining a healthy diet. Improving your heart health is an important step to maintaining your brain health as you age,” Dr. Sexton added.

SNAC-K is supported by the Swedish Ministry of Health and Social Affairs and the participating county councils and municipalities and in part by additional grants from the Swedish Research Council and the Swedish Research Council for Health, Working Life and Welfare. Dr. Imahori and Dr. Sexton disclosed no relevant financial relationships.

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

Higher resting heart rate (RHR) is associated with increased risk for dementia and accelerated cognitive decline in older adults, independent of the presence of cardiovascular disease (CVD) risk factors, new research shows.

“RHR is easy to measure and might be used to identify older people potentially at high risk of dementia and cognitive decline for early interventions,” Yume Imahori, MD, PhD, with the Aging Research Center, Karolinska Institutet, Stockholm, said in an interview.

“Health care professionals should be aware of potential cognitive consequences associated with elevated RHR in older people and may advise older people with high RHR to have a follow-up assessment of cognitive function,” Dr. Imahori said.

The study was published online Dec. 3, 2021, in Alzheimer’s & Dementia.
 

Heart-brain connection

The findings are based on 2,147 adults (62% women) aged 60 years and older (mean age, 70.6 years) from the population-based Swedish National Aging and Care in Kungsholmen (SNAC-K) study. All were free of dementia at baseline and were followed regularly from 2001-2004 to 2013-2016.

The average RHR at baseline was 65.7 bpm. Individuals in higher RHR groups were older, less educated, and were more likely to be smokers and sedentary and to have hypertension. There were no differences among RHR groups in the prevalence of CVD at baseline.

During a median follow-up of 11.4 years, 289 participants were diagnosed with dementia.

In the fully adjusted model, participants with RHR of 80 bpm or higher had a 55% increased risk of developing dementia, compared with peers with lower RHR of 60 to 69 bpm (hazard ratio, 1.55; 95% CI, 1.06-2.27).

“This association was not due to underlying cardiovascular diseases such as atrial fibrillation and heart failure, which is important because elevated RHR is often related to heart disease,” Dr. Imahori said in an interview.

Regarding cognitive function, Mini-Mental State Examination scores declined over time during the follow-up period in all RHR groups, but participants with RHR 70-79 and 80+ bpm had a greater decline, compared with those with lower RHR of 60-69 bpm.

Dr. Imahori said these findings are in line with data from the U.S. Atherosclerosis Risk in Communities study linking elevated RHR of 80+ bpm in midlife to dementia and cognitive decline in late life.
 

Public health implications

Reached for comment, Claire Sexton, DPhil, Alzheimer’s Association director of scientific programs and outreach, said this study adds to the “growing body of research showing the health of the heart and brain are closely connected. However, this study only shows a correlation between resting heart rate and cognition, not causation. More research is needed.

“Evidence shows that other risk factors for cardiovascular disease and stroke – obesity, high blood pressure, and diabetes – negatively impact your cognitive health,” Dr. Sexton said in an interview.

“The Alzheimer’s Association believes the conversation about heart health management is something everyone should be having with their doctor,” she said.

“There are things you can do today to lower your risk for cardiovascular disease, including regular exercise and maintaining a healthy diet. Improving your heart health is an important step to maintaining your brain health as you age,” Dr. Sexton added.

SNAC-K is supported by the Swedish Ministry of Health and Social Affairs and the participating county councils and municipalities and in part by additional grants from the Swedish Research Council and the Swedish Research Council for Health, Working Life and Welfare. Dr. Imahori and Dr. Sexton disclosed no relevant financial relationships.

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

Higher resting heart rate (RHR) is associated with increased risk for dementia and accelerated cognitive decline in older adults, independent of the presence of cardiovascular disease (CVD) risk factors, new research shows.

“RHR is easy to measure and might be used to identify older people potentially at high risk of dementia and cognitive decline for early interventions,” Yume Imahori, MD, PhD, with the Aging Research Center, Karolinska Institutet, Stockholm, said in an interview.

“Health care professionals should be aware of potential cognitive consequences associated with elevated RHR in older people and may advise older people with high RHR to have a follow-up assessment of cognitive function,” Dr. Imahori said.

The study was published online Dec. 3, 2021, in Alzheimer’s & Dementia.
 

Heart-brain connection

The findings are based on 2,147 adults (62% women) aged 60 years and older (mean age, 70.6 years) from the population-based Swedish National Aging and Care in Kungsholmen (SNAC-K) study. All were free of dementia at baseline and were followed regularly from 2001-2004 to 2013-2016.

The average RHR at baseline was 65.7 bpm. Individuals in higher RHR groups were older, less educated, and were more likely to be smokers and sedentary and to have hypertension. There were no differences among RHR groups in the prevalence of CVD at baseline.

During a median follow-up of 11.4 years, 289 participants were diagnosed with dementia.

In the fully adjusted model, participants with RHR of 80 bpm or higher had a 55% increased risk of developing dementia, compared with peers with lower RHR of 60 to 69 bpm (hazard ratio, 1.55; 95% CI, 1.06-2.27).

“This association was not due to underlying cardiovascular diseases such as atrial fibrillation and heart failure, which is important because elevated RHR is often related to heart disease,” Dr. Imahori said in an interview.

Regarding cognitive function, Mini-Mental State Examination scores declined over time during the follow-up period in all RHR groups, but participants with RHR 70-79 and 80+ bpm had a greater decline, compared with those with lower RHR of 60-69 bpm.

Dr. Imahori said these findings are in line with data from the U.S. Atherosclerosis Risk in Communities study linking elevated RHR of 80+ bpm in midlife to dementia and cognitive decline in late life.
 

Public health implications

Reached for comment, Claire Sexton, DPhil, Alzheimer’s Association director of scientific programs and outreach, said this study adds to the “growing body of research showing the health of the heart and brain are closely connected. However, this study only shows a correlation between resting heart rate and cognition, not causation. More research is needed.

“Evidence shows that other risk factors for cardiovascular disease and stroke – obesity, high blood pressure, and diabetes – negatively impact your cognitive health,” Dr. Sexton said in an interview.

“The Alzheimer’s Association believes the conversation about heart health management is something everyone should be having with their doctor,” she said.

“There are things you can do today to lower your risk for cardiovascular disease, including regular exercise and maintaining a healthy diet. Improving your heart health is an important step to maintaining your brain health as you age,” Dr. Sexton added.

SNAC-K is supported by the Swedish Ministry of Health and Social Affairs and the participating county councils and municipalities and in part by additional grants from the Swedish Research Council and the Swedish Research Council for Health, Working Life and Welfare. Dr. Imahori and Dr. Sexton disclosed no relevant financial relationships.

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

Younger patients with two genetic subtypes of diffuse large B cell lymphoma (DLBCL) – specifically MCD and N1 – show substantial improvements in survival with the addition of ibrutinib to standard R-CHOP chemotherapy, compared with R-CHOP alone, new research shows.

The findings, published Nov. 4, 2021, in Cancer Cell, come from a subanalysis of the phase 3 Phoenix trial. They show that patients with DLBCL aged 60 and younger with either the MCD or N1 genetic subtype had 3-year event-free survival rates as high as 100% when treated with ibrutinib plus R-CHOP, whereas with R-CHOP chemotherapy alone, the survival rates were approximately half of that rate.

“A 100% 3-year event-free survival is almost unheard-of in DLBCL and speaks to the intense dependency of these subtypes to constitutive B cell receptor signaling and their vulnerability to ibrutinib,” first author Louis M. Staudt, MD, of the Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Md., said in an interview.

“By contrast, in ABC DLBCL, the addition of ibrutinib to R-CHOP increased event-free survival by 12.4% to 76.9% in younger patients,” Dr. Staudt said.

ABC, along with GCB and unclassified, are among three key genetic classifications of DLBCL, which is the most common type of lymphoma. While previous studies have shown the Bruton kinase (BTK) inhibitor ibrutinib to induce very low responses among those with the GCB type, favorable responses are seen with the ABC type, of which MCD and N1 are genetic subtypes.

For the Phoenix trial, 838 previously untreated DLBCL patients of the ABC subtype were randomized to ibrutinib (560 mg per day, orally) or placebo plus R-CHOP, in a 21-day cycle for 6 or 8 cycles.

In the overall population, the study failed to achieve its primary survival endpoint of improved survival with ibrutinib. However, a subset analysis stratifying patients by age revealed significant event-free, progression-free, and overall survival benefits with ibrutinib among patients aged 60 and under, with manageable safety. Unexpectedly, this treatment was associated with a worsening of survival outcomes among patients over 60, due to toxicities.

In the new subanalysis, focusing on patients aged 60 and under, Dr. Staudt and his colleagues found that those with the MCD subtype of ABC DLBCL (n = 31) who were treated with ibrutinib had 3-year event-free survival and overall survival rates as high as 100% each, while these rates were significantly lower with R-CHOP alone (48%; P = .01, and 69.6%; P = .032, respectively).

Likewise, among younger patients with the N1 subtype (n = 13), the addition of ibrutinib was associated 3-year event-free and overall survival of 100%, while the R-CHOP alone patients had a significantly lower event-free- (50%; P = .0161) and overall survival (50%; P = .0134).

In the study in general, younger patients who were neither MCD nor N1 also showed better responses with ibrutinib versus placebo; however, the effects were not as strong as those with the MCD and N1 genetic subtypes.

Older patients over 60 showed no benefit from ibrutinib, regardless of their genetic subtype. And benefits were not observed in younger patients with BN2 DLBCL (n = 21), another ABC subtype.

The results are important – despite being secondary endpoints, Dr. Staudt emphasized.

“The automatic assumption regarding secondary endpoints is that any positive findings might have occurred by chance. In the present study, we show that this is not the case.”

“Rather, two previously defined genetic subtypes of DLBCL had an exceptional benefit from ibrutinib,” he said.

“Our study provides strong biological support for the view that the original Phoenix trial should be viewed as a positive trial for younger patients (under 60) with non-GCB DLBCL,” Dr. Staudt said.

While the responses to ibrutinib among younger ABC patients in general were not as robust as with the MCD and N1 subtypes, those improvements nevertheless suggest important benefit with the added treatment, he noted.

“Overall, MCD and N1 constitute roughly 10% of DLBCLs; however, our conclusion is that ibrutinib should be considered in younger patients with non-GCB DLBCL, which constitutes roughly 43% of all DLBCLs,” he said.

Dr. Staudt and other authors are inventors on NIH patent applications covering the LymphGen algorithm (a genetic predictor tool) and covering the use of BTK inhibitors in genetic subtypes of DLBCL. The Phoenix trial received support from Janssen Global Services.

Younger patients with two genetic subtypes of diffuse large B cell lymphoma (DLBCL) – specifically MCD and N1 – show substantial improvements in survival with the addition of ibrutinib to standard R-CHOP chemotherapy, compared with R-CHOP alone, new research shows.

The findings, published Nov. 4, 2021, in Cancer Cell, come from a subanalysis of the phase 3 Phoenix trial. They show that patients with DLBCL aged 60 and younger with either the MCD or N1 genetic subtype had 3-year event-free survival rates as high as 100% when treated with ibrutinib plus R-CHOP, whereas with R-CHOP chemotherapy alone, the survival rates were approximately half of that rate.

“A 100% 3-year event-free survival is almost unheard-of in DLBCL and speaks to the intense dependency of these subtypes to constitutive B cell receptor signaling and their vulnerability to ibrutinib,” first author Louis M. Staudt, MD, of the Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Md., said in an interview.

“By contrast, in ABC DLBCL, the addition of ibrutinib to R-CHOP increased event-free survival by 12.4% to 76.9% in younger patients,” Dr. Staudt said.

ABC, along with GCB and unclassified, are among three key genetic classifications of DLBCL, which is the most common type of lymphoma. While previous studies have shown the Bruton kinase (BTK) inhibitor ibrutinib to induce very low responses among those with the GCB type, favorable responses are seen with the ABC type, of which MCD and N1 are genetic subtypes.

For the Phoenix trial, 838 previously untreated DLBCL patients of the ABC subtype were randomized to ibrutinib (560 mg per day, orally) or placebo plus R-CHOP, in a 21-day cycle for 6 or 8 cycles.

In the overall population, the study failed to achieve its primary survival endpoint of improved survival with ibrutinib. However, a subset analysis stratifying patients by age revealed significant event-free, progression-free, and overall survival benefits with ibrutinib among patients aged 60 and under, with manageable safety. Unexpectedly, this treatment was associated with a worsening of survival outcomes among patients over 60, due to toxicities.

In the new subanalysis, focusing on patients aged 60 and under, Dr. Staudt and his colleagues found that those with the MCD subtype of ABC DLBCL (n = 31) who were treated with ibrutinib had 3-year event-free survival and overall survival rates as high as 100% each, while these rates were significantly lower with R-CHOP alone (48%; P = .01, and 69.6%; P = .032, respectively).

Likewise, among younger patients with the N1 subtype (n = 13), the addition of ibrutinib was associated 3-year event-free and overall survival of 100%, while the R-CHOP alone patients had a significantly lower event-free- (50%; P = .0161) and overall survival (50%; P = .0134).

In the study in general, younger patients who were neither MCD nor N1 also showed better responses with ibrutinib versus placebo; however, the effects were not as strong as those with the MCD and N1 genetic subtypes.

Older patients over 60 showed no benefit from ibrutinib, regardless of their genetic subtype. And benefits were not observed in younger patients with BN2 DLBCL (n = 21), another ABC subtype.

The results are important – despite being secondary endpoints, Dr. Staudt emphasized.

“The automatic assumption regarding secondary endpoints is that any positive findings might have occurred by chance. In the present study, we show that this is not the case.”

“Rather, two previously defined genetic subtypes of DLBCL had an exceptional benefit from ibrutinib,” he said.

“Our study provides strong biological support for the view that the original Phoenix trial should be viewed as a positive trial for younger patients (under 60) with non-GCB DLBCL,” Dr. Staudt said.

While the responses to ibrutinib among younger ABC patients in general were not as robust as with the MCD and N1 subtypes, those improvements nevertheless suggest important benefit with the added treatment, he noted.

“Overall, MCD and N1 constitute roughly 10% of DLBCLs; however, our conclusion is that ibrutinib should be considered in younger patients with non-GCB DLBCL, which constitutes roughly 43% of all DLBCLs,” he said.

Dr. Staudt and other authors are inventors on NIH patent applications covering the LymphGen algorithm (a genetic predictor tool) and covering the use of BTK inhibitors in genetic subtypes of DLBCL. The Phoenix trial received support from Janssen Global Services.

Younger patients with two genetic subtypes of diffuse large B cell lymphoma (DLBCL) – specifically MCD and N1 – show substantial improvements in survival with the addition of ibrutinib to standard R-CHOP chemotherapy, compared with R-CHOP alone, new research shows.

The findings, published Nov. 4, 2021, in Cancer Cell, come from a subanalysis of the phase 3 Phoenix trial. They show that patients with DLBCL aged 60 and younger with either the MCD or N1 genetic subtype had 3-year event-free survival rates as high as 100% when treated with ibrutinib plus R-CHOP, whereas with R-CHOP chemotherapy alone, the survival rates were approximately half of that rate.

“A 100% 3-year event-free survival is almost unheard-of in DLBCL and speaks to the intense dependency of these subtypes to constitutive B cell receptor signaling and their vulnerability to ibrutinib,” first author Louis M. Staudt, MD, of the Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Md., said in an interview.

“By contrast, in ABC DLBCL, the addition of ibrutinib to R-CHOP increased event-free survival by 12.4% to 76.9% in younger patients,” Dr. Staudt said.

ABC, along with GCB and unclassified, are among three key genetic classifications of DLBCL, which is the most common type of lymphoma. While previous studies have shown the Bruton kinase (BTK) inhibitor ibrutinib to induce very low responses among those with the GCB type, favorable responses are seen with the ABC type, of which MCD and N1 are genetic subtypes.

For the Phoenix trial, 838 previously untreated DLBCL patients of the ABC subtype were randomized to ibrutinib (560 mg per day, orally) or placebo plus R-CHOP, in a 21-day cycle for 6 or 8 cycles.

In the overall population, the study failed to achieve its primary survival endpoint of improved survival with ibrutinib. However, a subset analysis stratifying patients by age revealed significant event-free, progression-free, and overall survival benefits with ibrutinib among patients aged 60 and under, with manageable safety. Unexpectedly, this treatment was associated with a worsening of survival outcomes among patients over 60, due to toxicities.

In the new subanalysis, focusing on patients aged 60 and under, Dr. Staudt and his colleagues found that those with the MCD subtype of ABC DLBCL (n = 31) who were treated with ibrutinib had 3-year event-free survival and overall survival rates as high as 100% each, while these rates were significantly lower with R-CHOP alone (48%; P = .01, and 69.6%; P = .032, respectively).

Likewise, among younger patients with the N1 subtype (n = 13), the addition of ibrutinib was associated 3-year event-free and overall survival of 100%, while the R-CHOP alone patients had a significantly lower event-free- (50%; P = .0161) and overall survival (50%; P = .0134).

In the study in general, younger patients who were neither MCD nor N1 also showed better responses with ibrutinib versus placebo; however, the effects were not as strong as those with the MCD and N1 genetic subtypes.

Older patients over 60 showed no benefit from ibrutinib, regardless of their genetic subtype. And benefits were not observed in younger patients with BN2 DLBCL (n = 21), another ABC subtype.

The results are important – despite being secondary endpoints, Dr. Staudt emphasized.

“The automatic assumption regarding secondary endpoints is that any positive findings might have occurred by chance. In the present study, we show that this is not the case.”

“Rather, two previously defined genetic subtypes of DLBCL had an exceptional benefit from ibrutinib,” he said.

“Our study provides strong biological support for the view that the original Phoenix trial should be viewed as a positive trial for younger patients (under 60) with non-GCB DLBCL,” Dr. Staudt said.

While the responses to ibrutinib among younger ABC patients in general were not as robust as with the MCD and N1 subtypes, those improvements nevertheless suggest important benefit with the added treatment, he noted.

“Overall, MCD and N1 constitute roughly 10% of DLBCLs; however, our conclusion is that ibrutinib should be considered in younger patients with non-GCB DLBCL, which constitutes roughly 43% of all DLBCLs,” he said.

Dr. Staudt and other authors are inventors on NIH patent applications covering the LymphGen algorithm (a genetic predictor tool) and covering the use of BTK inhibitors in genetic subtypes of DLBCL. The Phoenix trial received support from Janssen Global Services.

Microneedling is a safe and effective adjuvant to topical therapies for melasma, with optimal results typically seen at 12 weeks, results from a combined systematic review and meta-analysis suggest.

“Microneedling has a similar efficacy to other drug delivery methods, such as CO₂ laser or intradermal microinjections, for the treatment of melasma,” presenting author Marcus G. Tan, MD, said during a virtual abstract session at the annual meeting of the American Society for Dermatologic Surgery. “When used in combination with topical depigmenting therapies, microneedling also demonstrated superior efficacy and a more favorable safety profile compared to oral tranexamic acid.”

For the study, Dr. Tan, a 5-year dermatology resident at the University of Ottawa, and colleagues searched MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials using the keywords “melasma” and “microneedling.” They limited their analysis to prospective, comparative studies incorporating the use of microneedling in the treatment of melasma and excluded those involving radiofrequency. The primary outcome was improvement in melasma severity, evaluated through the Melasma Area and Severity Index (MASI). The secondary outcomes were improvement in patient satisfaction, quality of life, and any reported adverse events.

Twelve studies involving 459 patients from seven countries were included in the final analysis. Of these, seven were randomized controlled studies and five were nonrandomized split-face studies. Topical treatments used in the studies included tranexamic acid (TXA), vitamin C, platelet-rich plasma, and hydroquinone-based depigmenting serums such as rucinol, sophora-alpha, and N-acetyl glucosamine. Of the 12 studies, 4 used mechanical microneedling and 8 used electric repeating microneedling. The most common needle length used was 1.5 mm, with a range from 0.1 to 1.5 mm, depending on the anatomic site treated. Topical anesthesia was applied 30-60 minutes prior to treatment. Treatment intervals were 2-4 weeks apart.

Their analysis found that microneedling alone resulted in a 23%-29% improvement in MASI. “Across all studies, adding topical therapies resulted in greater improvements in melasma severity, with a moderate effect at 8 weeks and a large effect at 12-16 weeks,” Dr. Tan said. “This also translated to higher patient satisfaction scores and improved patient-reported quality of life.”

A split-face study in the analysis, which compared topical TXA with microneedling to topical TXA with fractional CO₂ laser, found that both approaches had similar efficacy and rates of adverse events. Another split-face study that evaluated recalcitrant melasma found that adding vitamin C with microneedling to a nonablative Q-switched Nd:YAG laser resulted in a further 38.3% greater improvement in MASI and a 12.5% lower recurrence rate at 6 months.

In two other studies, researchers compared microneedling to intradermal microinjections to deliver platelet-rich plasma or topical TXA. Both modalities were found to have similar efficacy. “However, microneedling was found to be better tolerated and had higher patient satisfaction as a result,” Dr. Tan said.

A separate analysis found that Tri-Luma (fluocinolone acetonide, hydroquinone, and tretinoin) cream with microneedling outperformed Tri-Luma plus oral TXA in terms of efficacy, patient satisfaction, and tolerability. “Interestingly, adding oral TXA to Tri-Luma with microneedling did not lead to further improvements,” Dr. Tan said.

The researchers found that microneedling was well tolerated in all 12 studies. Overall, no scarring or serious adverse events were reported. Mild-transient dyspigmentation occurred in 5%-12% of cases and herpes simplex virus reactivation was seen in a minority of patients.

Dr. Tan commented on three proposed mechanisms of action, which support the efficacy of microneedling for the treatment of melasma. “First, microneedling assists in the transcutaneous delivery of topical agents through the micropores,” he said. “Second, microneedling also assists in the transcutaneous elimination of melanin and other skin debris through the micropores. Third, the microinjuries stimulate the wound healing response, resulting in neocollagenesis, neoelastogenesis, and epidermal thickening.”

In an interview, Dr. Tan acknowledged certain limitations of the study, including the pooling of randomized and nonrandomized studies in the final meta-analysis, the heterogeneity in the treatment protocols and devices used, as well as the inclusion of studies with a moderate risk of bias. “Nonetheless, these limitations do not affect the conclusion that microneedling is a useful and safe adjuvant to topical therapies for melasma,” he said.

Catherine M. DiGiorgio, MD, who was asked to comment on the study, noted that melasma is a notoriously difficult condition to treat. “Many energy-based device treatments as well as other therapies have been proposed for treatment over the years. However, none have shown reliable, reproducible, and most importantly long-lasting results,” said Dr. DiGiorgio, a laser and cosmetic dermatologist at The Boston Center for Facial Rejuvenation. “Caution should be employed regarding the true efficacy of treatments for other than, at best, temporary results.”

The review included numerous studies without a clear definition of the strengths or methodologies of the studies, she added, noting that randomized controlled split-face studies with long-term follow up are the best way to assess the efficacy of treatments. “Further, regarding drug delivery, microneedling is the least effective method of delivery of drugs to the skin and laser-assisted drug delivery using ablative fractional lasers is the most effective. As with all melasma treatments, healthy skepticism is never a bad approach.”

Dr. Tan reported having no financial disclosures. Dr. DiGiorgio disclosed that she conducts research for Quthero Inc., and holds stock in the company.

[email protected]

Microneedling is a safe and effective adjuvant to topical therapies for melasma, with optimal results typically seen at 12 weeks, results from a combined systematic review and meta-analysis suggest.

“Microneedling has a similar efficacy to other drug delivery methods, such as CO₂ laser or intradermal microinjections, for the treatment of melasma,” presenting author Marcus G. Tan, MD, said during a virtual abstract session at the annual meeting of the American Society for Dermatologic Surgery. “When used in combination with topical depigmenting therapies, microneedling also demonstrated superior efficacy and a more favorable safety profile compared to oral tranexamic acid.”

For the study, Dr. Tan, a 5-year dermatology resident at the University of Ottawa, and colleagues searched MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials using the keywords “melasma” and “microneedling.” They limited their analysis to prospective, comparative studies incorporating the use of microneedling in the treatment of melasma and excluded those involving radiofrequency. The primary outcome was improvement in melasma severity, evaluated through the Melasma Area and Severity Index (MASI). The secondary outcomes were improvement in patient satisfaction, quality of life, and any reported adverse events.

Twelve studies involving 459 patients from seven countries were included in the final analysis. Of these, seven were randomized controlled studies and five were nonrandomized split-face studies. Topical treatments used in the studies included tranexamic acid (TXA), vitamin C, platelet-rich plasma, and hydroquinone-based depigmenting serums such as rucinol, sophora-alpha, and N-acetyl glucosamine. Of the 12 studies, 4 used mechanical microneedling and 8 used electric repeating microneedling. The most common needle length used was 1.5 mm, with a range from 0.1 to 1.5 mm, depending on the anatomic site treated. Topical anesthesia was applied 30-60 minutes prior to treatment. Treatment intervals were 2-4 weeks apart.

Their analysis found that microneedling alone resulted in a 23%-29% improvement in MASI. “Across all studies, adding topical therapies resulted in greater improvements in melasma severity, with a moderate effect at 8 weeks and a large effect at 12-16 weeks,” Dr. Tan said. “This also translated to higher patient satisfaction scores and improved patient-reported quality of life.”

A split-face study in the analysis, which compared topical TXA with microneedling to topical TXA with fractional CO₂ laser, found that both approaches had similar efficacy and rates of adverse events. Another split-face study that evaluated recalcitrant melasma found that adding vitamin C with microneedling to a nonablative Q-switched Nd:YAG laser resulted in a further 38.3% greater improvement in MASI and a 12.5% lower recurrence rate at 6 months.

In two other studies, researchers compared microneedling to intradermal microinjections to deliver platelet-rich plasma or topical TXA. Both modalities were found to have similar efficacy. “However, microneedling was found to be better tolerated and had higher patient satisfaction as a result,” Dr. Tan said.

A separate analysis found that Tri-Luma (fluocinolone acetonide, hydroquinone, and tretinoin) cream with microneedling outperformed Tri-Luma plus oral TXA in terms of efficacy, patient satisfaction, and tolerability. “Interestingly, adding oral TXA to Tri-Luma with microneedling did not lead to further improvements,” Dr. Tan said.

The researchers found that microneedling was well tolerated in all 12 studies. Overall, no scarring or serious adverse events were reported. Mild-transient dyspigmentation occurred in 5%-12% of cases and herpes simplex virus reactivation was seen in a minority of patients.

Dr. Tan commented on three proposed mechanisms of action, which support the efficacy of microneedling for the treatment of melasma. “First, microneedling assists in the transcutaneous delivery of topical agents through the micropores,” he said. “Second, microneedling also assists in the transcutaneous elimination of melanin and other skin debris through the micropores. Third, the microinjuries stimulate the wound healing response, resulting in neocollagenesis, neoelastogenesis, and epidermal thickening.”

In an interview, Dr. Tan acknowledged certain limitations of the study, including the pooling of randomized and nonrandomized studies in the final meta-analysis, the heterogeneity in the treatment protocols and devices used, as well as the inclusion of studies with a moderate risk of bias. “Nonetheless, these limitations do not affect the conclusion that microneedling is a useful and safe adjuvant to topical therapies for melasma,” he said.

Catherine M. DiGiorgio, MD, who was asked to comment on the study, noted that melasma is a notoriously difficult condition to treat. “Many energy-based device treatments as well as other therapies have been proposed for treatment over the years. However, none have shown reliable, reproducible, and most importantly long-lasting results,” said Dr. DiGiorgio, a laser and cosmetic dermatologist at The Boston Center for Facial Rejuvenation. “Caution should be employed regarding the true efficacy of treatments for other than, at best, temporary results.”

The review included numerous studies without a clear definition of the strengths or methodologies of the studies, she added, noting that randomized controlled split-face studies with long-term follow up are the best way to assess the efficacy of treatments. “Further, regarding drug delivery, microneedling is the least effective method of delivery of drugs to the skin and laser-assisted drug delivery using ablative fractional lasers is the most effective. As with all melasma treatments, healthy skepticism is never a bad approach.”

Dr. Tan reported having no financial disclosures. Dr. DiGiorgio disclosed that she conducts research for Quthero Inc., and holds stock in the company.

[email protected]

Microneedling is a safe and effective adjuvant to topical therapies for melasma, with optimal results typically seen at 12 weeks, results from a combined systematic review and meta-analysis suggest.

“Microneedling has a similar efficacy to other drug delivery methods, such as CO₂ laser or intradermal microinjections, for the treatment of melasma,” presenting author Marcus G. Tan, MD, said during a virtual abstract session at the annual meeting of the American Society for Dermatologic Surgery. “When used in combination with topical depigmenting therapies, microneedling also demonstrated superior efficacy and a more favorable safety profile compared to oral tranexamic acid.”

For the study, Dr. Tan, a 5-year dermatology resident at the University of Ottawa, and colleagues searched MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials using the keywords “melasma” and “microneedling.” They limited their analysis to prospective, comparative studies incorporating the use of microneedling in the treatment of melasma and excluded those involving radiofrequency. The primary outcome was improvement in melasma severity, evaluated through the Melasma Area and Severity Index (MASI). The secondary outcomes were improvement in patient satisfaction, quality of life, and any reported adverse events.

Twelve studies involving 459 patients from seven countries were included in the final analysis. Of these, seven were randomized controlled studies and five were nonrandomized split-face studies. Topical treatments used in the studies included tranexamic acid (TXA), vitamin C, platelet-rich plasma, and hydroquinone-based depigmenting serums such as rucinol, sophora-alpha, and N-acetyl glucosamine. Of the 12 studies, 4 used mechanical microneedling and 8 used electric repeating microneedling. The most common needle length used was 1.5 mm, with a range from 0.1 to 1.5 mm, depending on the anatomic site treated. Topical anesthesia was applied 30-60 minutes prior to treatment. Treatment intervals were 2-4 weeks apart.

Their analysis found that microneedling alone resulted in a 23%-29% improvement in MASI. “Across all studies, adding topical therapies resulted in greater improvements in melasma severity, with a moderate effect at 8 weeks and a large effect at 12-16 weeks,” Dr. Tan said. “This also translated to higher patient satisfaction scores and improved patient-reported quality of life.”

A split-face study in the analysis, which compared topical TXA with microneedling to topical TXA with fractional CO₂ laser, found that both approaches had similar efficacy and rates of adverse events. Another split-face study that evaluated recalcitrant melasma found that adding vitamin C with microneedling to a nonablative Q-switched Nd:YAG laser resulted in a further 38.3% greater improvement in MASI and a 12.5% lower recurrence rate at 6 months.

In two other studies, researchers compared microneedling to intradermal microinjections to deliver platelet-rich plasma or topical TXA. Both modalities were found to have similar efficacy. “However, microneedling was found to be better tolerated and had higher patient satisfaction as a result,” Dr. Tan said.

A separate analysis found that Tri-Luma (fluocinolone acetonide, hydroquinone, and tretinoin) cream with microneedling outperformed Tri-Luma plus oral TXA in terms of efficacy, patient satisfaction, and tolerability. “Interestingly, adding oral TXA to Tri-Luma with microneedling did not lead to further improvements,” Dr. Tan said.

The researchers found that microneedling was well tolerated in all 12 studies. Overall, no scarring or serious adverse events were reported. Mild-transient dyspigmentation occurred in 5%-12% of cases and herpes simplex virus reactivation was seen in a minority of patients.

Dr. Tan commented on three proposed mechanisms of action, which support the efficacy of microneedling for the treatment of melasma. “First, microneedling assists in the transcutaneous delivery of topical agents through the micropores,” he said. “Second, microneedling also assists in the transcutaneous elimination of melanin and other skin debris through the micropores. Third, the microinjuries stimulate the wound healing response, resulting in neocollagenesis, neoelastogenesis, and epidermal thickening.”

In an interview, Dr. Tan acknowledged certain limitations of the study, including the pooling of randomized and nonrandomized studies in the final meta-analysis, the heterogeneity in the treatment protocols and devices used, as well as the inclusion of studies with a moderate risk of bias. “Nonetheless, these limitations do not affect the conclusion that microneedling is a useful and safe adjuvant to topical therapies for melasma,” he said.

Catherine M. DiGiorgio, MD, who was asked to comment on the study, noted that melasma is a notoriously difficult condition to treat. “Many energy-based device treatments as well as other therapies have been proposed for treatment over the years. However, none have shown reliable, reproducible, and most importantly long-lasting results,” said Dr. DiGiorgio, a laser and cosmetic dermatologist at The Boston Center for Facial Rejuvenation. “Caution should be employed regarding the true efficacy of treatments for other than, at best, temporary results.”

The review included numerous studies without a clear definition of the strengths or methodologies of the studies, she added, noting that randomized controlled split-face studies with long-term follow up are the best way to assess the efficacy of treatments. “Further, regarding drug delivery, microneedling is the least effective method of delivery of drugs to the skin and laser-assisted drug delivery using ablative fractional lasers is the most effective. As with all melasma treatments, healthy skepticism is never a bad approach.”

Dr. Tan reported having no financial disclosures. Dr. DiGiorgio disclosed that she conducts research for Quthero Inc., and holds stock in the company.

[email protected]

What are the major manifestations of congenital rubella syndrome?

Continue to the answer...

Rubella is one of the most highly teratogenic of all the viral infections, particularly when maternal infection occurs in the first trimester. Manifestations of congenital rubella include hearing deficits, cataracts, glaucoma, microcephaly, mental retardation, cardiac malformations such as patent ductus arteriosus and pulmonic stenosis, and growth restriction.

What are the major manifestations of congenital rubella syndrome?

Continue to the answer...

Rubella is one of the most highly teratogenic of all the viral infections, particularly when maternal infection occurs in the first trimester. Manifestations of congenital rubella include hearing deficits, cataracts, glaucoma, microcephaly, mental retardation, cardiac malformations such as patent ductus arteriosus and pulmonic stenosis, and growth restriction.

What are the major manifestations of congenital rubella syndrome?

Continue to the answer...

Rubella is one of the most highly teratogenic of all the viral infections, particularly when maternal infection occurs in the first trimester. Manifestations of congenital rubella include hearing deficits, cataracts, glaucoma, microcephaly, mental retardation, cardiac malformations such as patent ductus arteriosus and pulmonic stenosis, and growth restriction.

Pinker or redder actinic keratoses (AKs) indicate greater inflammation, according to a retrospective study that analyzed images and histopathology slides of 49 actinic keratosis lesions.

Data suggest that up to 65% of squamous cell carcinomas (SCCs) were at some point diagnosed as AKs, wrote Jessica G. Labadie, MD, of the department of dermatology at Northwestern University, Chicago, and colleagues. Early identification of AKs is important to prevent progression to SCCs; previous studies have used histology or morphology, but not color, to characterize AK lesions, they said. In the study published in Dermatologic Surgery, the researchers analyzed images and histopathology slides to characterize AKs by color and to examine associations with inflammation and vasculature. They identified AKs from patients diagnosed between January 2018 and October 2019. The lesions were classified as white (4), brown (9), red (15), or pink (21).

Overall, white AKs had an absence of erythema and were significantly less likely to show inflammation on histopathology, compared with other colors. Brown AKs showed no significant increase in vascularity, but were significantly associated with pigment incontinence, basilar pigment presence, and absence of inflammation.

Notably, dermoscopy of red AKs revealed a distinctive polymorphous vessel pattern in most samples, as well as erythema in all. Similarly, all pink AKs showed erythema, and all showed inflammatory infiltrate on histology, although most did not show increased vascularity.

For all colors of AKs, there was a significant association between the presence of erythema on dermoscopy and the presence of inflammation on histology, while the absence of erythema on dermoscopy corresponded to a significant absence of inflammation on histology, the researchers noted.

“This report adds to the armamentarium of a dermatologist by proposing a novel way to characterize AK lesions,” the researchers wrote.

The study findings were limited by several factors including the inability to confirm which AKs would transform into SCCs based on color, and the inclusion of a study population with advanced AKs that may not generalize to typical AKs, the researchers noted. More research is needed to explore the impact of AK color on SCC development, they emphasized.

However, the results represent a novel way to characterize AK lesions, and triage them in a way that may spare some patients from unneeded biopsies, they concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.

Pinker or redder actinic keratoses (AKs) indicate greater inflammation, according to a retrospective study that analyzed images and histopathology slides of 49 actinic keratosis lesions.

Data suggest that up to 65% of squamous cell carcinomas (SCCs) were at some point diagnosed as AKs, wrote Jessica G. Labadie, MD, of the department of dermatology at Northwestern University, Chicago, and colleagues. Early identification of AKs is important to prevent progression to SCCs; previous studies have used histology or morphology, but not color, to characterize AK lesions, they said. In the study published in Dermatologic Surgery, the researchers analyzed images and histopathology slides to characterize AKs by color and to examine associations with inflammation and vasculature. They identified AKs from patients diagnosed between January 2018 and October 2019. The lesions were classified as white (4), brown (9), red (15), or pink (21).

Overall, white AKs had an absence of erythema and were significantly less likely to show inflammation on histopathology, compared with other colors. Brown AKs showed no significant increase in vascularity, but were significantly associated with pigment incontinence, basilar pigment presence, and absence of inflammation.

Notably, dermoscopy of red AKs revealed a distinctive polymorphous vessel pattern in most samples, as well as erythema in all. Similarly, all pink AKs showed erythema, and all showed inflammatory infiltrate on histology, although most did not show increased vascularity.

For all colors of AKs, there was a significant association between the presence of erythema on dermoscopy and the presence of inflammation on histology, while the absence of erythema on dermoscopy corresponded to a significant absence of inflammation on histology, the researchers noted.

“This report adds to the armamentarium of a dermatologist by proposing a novel way to characterize AK lesions,” the researchers wrote.

The study findings were limited by several factors including the inability to confirm which AKs would transform into SCCs based on color, and the inclusion of a study population with advanced AKs that may not generalize to typical AKs, the researchers noted. More research is needed to explore the impact of AK color on SCC development, they emphasized.

However, the results represent a novel way to characterize AK lesions, and triage them in a way that may spare some patients from unneeded biopsies, they concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.

Pinker or redder actinic keratoses (AKs) indicate greater inflammation, according to a retrospective study that analyzed images and histopathology slides of 49 actinic keratosis lesions.

Data suggest that up to 65% of squamous cell carcinomas (SCCs) were at some point diagnosed as AKs, wrote Jessica G. Labadie, MD, of the department of dermatology at Northwestern University, Chicago, and colleagues. Early identification of AKs is important to prevent progression to SCCs; previous studies have used histology or morphology, but not color, to characterize AK lesions, they said. In the study published in Dermatologic Surgery, the researchers analyzed images and histopathology slides to characterize AKs by color and to examine associations with inflammation and vasculature. They identified AKs from patients diagnosed between January 2018 and October 2019. The lesions were classified as white (4), brown (9), red (15), or pink (21).

Overall, white AKs had an absence of erythema and were significantly less likely to show inflammation on histopathology, compared with other colors. Brown AKs showed no significant increase in vascularity, but were significantly associated with pigment incontinence, basilar pigment presence, and absence of inflammation.

Notably, dermoscopy of red AKs revealed a distinctive polymorphous vessel pattern in most samples, as well as erythema in all. Similarly, all pink AKs showed erythema, and all showed inflammatory infiltrate on histology, although most did not show increased vascularity.

For all colors of AKs, there was a significant association between the presence of erythema on dermoscopy and the presence of inflammation on histology, while the absence of erythema on dermoscopy corresponded to a significant absence of inflammation on histology, the researchers noted.

“This report adds to the armamentarium of a dermatologist by proposing a novel way to characterize AK lesions,” the researchers wrote.

The study findings were limited by several factors including the inability to confirm which AKs would transform into SCCs based on color, and the inclusion of a study population with advanced AKs that may not generalize to typical AKs, the researchers noted. More research is needed to explore the impact of AK color on SCC development, they emphasized.

However, the results represent a novel way to characterize AK lesions, and triage them in a way that may spare some patients from unneeded biopsies, they concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.

Genomic profiling improves outcomes for patients with metastatic breast cancer as long as the alteration-drug match has good clinical trial evidence supporting its use, a new pooled analysis suggests.

“The message is very simple,” lead study author Fabrice Andre, MD, PhD, research director, Gustave Roussy Cancer Campus, Villejuif, France, told this news organization during a virtual press briefing. “If a genomic alteration is validated, it is useful to give targeted therapy, but if the genomic alteration is not validated, we should not give a targeted therapy.”

The study, which pooled results from phase 2 randomized trials SAFIR02-BREAST and SAFIR-P13K, was presented Dec. 7 in a virtual press briefing at the San Antonio Breast Cancer Symposium (SABCS) 2021.

The new analysis explored two key questions: Is genomic testing of a cancer effective? And how should oncologists interpret a genomic report?

A total of 1,462 patients with metastatic HER2-negative breast cancer underwent next-generation sequencing. After receiving six to eight cycles of chemotherapy, 238 patients (16%) were randomized to one of nine targeted therapies matched to the genomic alteration identified on testing or to maintenance chemotherapy.

Genomic alterations in the patients’ tumors were classified using the ESMO Scale of Actionability of Molecular Targets (ESCAT). A tier I ranking indicates that the alteration-drug match is associated with improved outcomes in clinical trials, while a tier II ranking means that the alteration-drug match is associated with antitumor activity but the magnitude of benefit remains unknown.

In an analysis of the overall trial population, Dr. Andre and colleagues found an improvement in progression-free survival in the targeted therapy group (median of 5.5 months) in comparison with the maintenance chemotherapy group (2.9 months), but the difference was not significant (P = .109).

In a subgroup of 115 patients presenting with I- or II-tier genomic alterations, median progression-free survival was 59% longer, at 9.1 months, among patients receiving targeted therapy, compared with 2.8 months in the maintenance chemotherapy group (hazard ratio, 0.41; P < .001).

In addition, the team carried out single-nucleotide polymorphism (SNP) array analyses on 926 patients. They identified 21 genes that were altered more frequently in the metastases compared with the primary tumors, and they observed that a high homologous recombination deficiency score in patients with BCRA 1 or 2 mutations was associated with a longer progression-free survival in patients treated with olaparib.

“We also identified a subset of patients who are resistant to CDK4/6 inhibitors who presented with CDK4 amplification, and this amplification is associated with overexpression,” Dr. Andre explained.

When asked whether most oncologists were using genomic profiling to tailor treatment for breast cancer patients, Dr. Andre said that multigene sequencing is now widely used.

“The issue is not so much whether we should use or not use genomics; the issue here is to force everyone to put the genomic alteration in the right context in terms of its level of evidence,” Dr. Andre told this news organization.

Oncologists may overinterpret the genomic activation identified and give a targeted therapy that is not validated, but “oncologists should not use genomic information when the target has not been previously validated in a therapeutic trial,” he added.

Virginia Kaklamani, MD, professor of medicine at the University of Texas Health Sciences Center in San Antonio, said in an interview that approximately 5 years ago, Dr. Andre was part of the first debate at the SABCS discussing whether oncologists should be conducting next-generation sequencing for their patients with breast cancer.

“At the time, [Dr.] Andre’s comment was that we should not be doing it,” recalled Dr. Kaklamani, who is also leader of the breast cancer program at the Mays Cancer Center at the University of Texas Health San Antonio MD Anderson. “At that point, I think it was clear that we did not have the data we needed to be able to use next-generation sequencing to change our clinical management.”

However, the evidence has evolved. “Based on this clinical trial, I think we now do have the data,” she said. “I think that [next-generation sequencing] is something we will be using more and more in practice and treating our patients based on [validated] genomic alterations.”

Dr. Andre has received grants or advisory board/speaker honoraria from Daiichi Sankyo, Roche, Pfizer, AstraZeneca, Lily, and Novartis. Dr. Kaklamani has served as a consultant for Puma, AstraZeneca, Athenex, and Immunomedics, has received research funding from Eisai, and has served as a speaker for Pfizer, Celgene, Genentech, and Genomic Health, among other companies.

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

Genomic profiling improves outcomes for patients with metastatic breast cancer as long as the alteration-drug match has good clinical trial evidence supporting its use, a new pooled analysis suggests.

“The message is very simple,” lead study author Fabrice Andre, MD, PhD, research director, Gustave Roussy Cancer Campus, Villejuif, France, told this news organization during a virtual press briefing. “If a genomic alteration is validated, it is useful to give targeted therapy, but if the genomic alteration is not validated, we should not give a targeted therapy.”

The study, which pooled results from phase 2 randomized trials SAFIR02-BREAST and SAFIR-P13K, was presented Dec. 7 in a virtual press briefing at the San Antonio Breast Cancer Symposium (SABCS) 2021.

The new analysis explored two key questions: Is genomic testing of a cancer effective? And how should oncologists interpret a genomic report?

A total of 1,462 patients with metastatic HER2-negative breast cancer underwent next-generation sequencing. After receiving six to eight cycles of chemotherapy, 238 patients (16%) were randomized to one of nine targeted therapies matched to the genomic alteration identified on testing or to maintenance chemotherapy.

Genomic alterations in the patients’ tumors were classified using the ESMO Scale of Actionability of Molecular Targets (ESCAT). A tier I ranking indicates that the alteration-drug match is associated with improved outcomes in clinical trials, while a tier II ranking means that the alteration-drug match is associated with antitumor activity but the magnitude of benefit remains unknown.

In an analysis of the overall trial population, Dr. Andre and colleagues found an improvement in progression-free survival in the targeted therapy group (median of 5.5 months) in comparison with the maintenance chemotherapy group (2.9 months), but the difference was not significant (P = .109).

In a subgroup of 115 patients presenting with I- or II-tier genomic alterations, median progression-free survival was 59% longer, at 9.1 months, among patients receiving targeted therapy, compared with 2.8 months in the maintenance chemotherapy group (hazard ratio, 0.41; P < .001).

In addition, the team carried out single-nucleotide polymorphism (SNP) array analyses on 926 patients. They identified 21 genes that were altered more frequently in the metastases compared with the primary tumors, and they observed that a high homologous recombination deficiency score in patients with BCRA 1 or 2 mutations was associated with a longer progression-free survival in patients treated with olaparib.

“We also identified a subset of patients who are resistant to CDK4/6 inhibitors who presented with CDK4 amplification, and this amplification is associated with overexpression,” Dr. Andre explained.

When asked whether most oncologists were using genomic profiling to tailor treatment for breast cancer patients, Dr. Andre said that multigene sequencing is now widely used.

“The issue is not so much whether we should use or not use genomics; the issue here is to force everyone to put the genomic alteration in the right context in terms of its level of evidence,” Dr. Andre told this news organization.

Oncologists may overinterpret the genomic activation identified and give a targeted therapy that is not validated, but “oncologists should not use genomic information when the target has not been previously validated in a therapeutic trial,” he added.

Virginia Kaklamani, MD, professor of medicine at the University of Texas Health Sciences Center in San Antonio, said in an interview that approximately 5 years ago, Dr. Andre was part of the first debate at the SABCS discussing whether oncologists should be conducting next-generation sequencing for their patients with breast cancer.

“At the time, [Dr.] Andre’s comment was that we should not be doing it,” recalled Dr. Kaklamani, who is also leader of the breast cancer program at the Mays Cancer Center at the University of Texas Health San Antonio MD Anderson. “At that point, I think it was clear that we did not have the data we needed to be able to use next-generation sequencing to change our clinical management.”

However, the evidence has evolved. “Based on this clinical trial, I think we now do have the data,” she said. “I think that [next-generation sequencing] is something we will be using more and more in practice and treating our patients based on [validated] genomic alterations.”

Dr. Andre has received grants or advisory board/speaker honoraria from Daiichi Sankyo, Roche, Pfizer, AstraZeneca, Lily, and Novartis. Dr. Kaklamani has served as a consultant for Puma, AstraZeneca, Athenex, and Immunomedics, has received research funding from Eisai, and has served as a speaker for Pfizer, Celgene, Genentech, and Genomic Health, among other companies.

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

Genomic profiling improves outcomes for patients with metastatic breast cancer as long as the alteration-drug match has good clinical trial evidence supporting its use, a new pooled analysis suggests.

“The message is very simple,” lead study author Fabrice Andre, MD, PhD, research director, Gustave Roussy Cancer Campus, Villejuif, France, told this news organization during a virtual press briefing. “If a genomic alteration is validated, it is useful to give targeted therapy, but if the genomic alteration is not validated, we should not give a targeted therapy.”

The study, which pooled results from phase 2 randomized trials SAFIR02-BREAST and SAFIR-P13K, was presented Dec. 7 in a virtual press briefing at the San Antonio Breast Cancer Symposium (SABCS) 2021.

The new analysis explored two key questions: Is genomic testing of a cancer effective? And how should oncologists interpret a genomic report?

A total of 1,462 patients with metastatic HER2-negative breast cancer underwent next-generation sequencing. After receiving six to eight cycles of chemotherapy, 238 patients (16%) were randomized to one of nine targeted therapies matched to the genomic alteration identified on testing or to maintenance chemotherapy.

Genomic alterations in the patients’ tumors were classified using the ESMO Scale of Actionability of Molecular Targets (ESCAT). A tier I ranking indicates that the alteration-drug match is associated with improved outcomes in clinical trials, while a tier II ranking means that the alteration-drug match is associated with antitumor activity but the magnitude of benefit remains unknown.

In an analysis of the overall trial population, Dr. Andre and colleagues found an improvement in progression-free survival in the targeted therapy group (median of 5.5 months) in comparison with the maintenance chemotherapy group (2.9 months), but the difference was not significant (P = .109).

In a subgroup of 115 patients presenting with I- or II-tier genomic alterations, median progression-free survival was 59% longer, at 9.1 months, among patients receiving targeted therapy, compared with 2.8 months in the maintenance chemotherapy group (hazard ratio, 0.41; P < .001).

In addition, the team carried out single-nucleotide polymorphism (SNP) array analyses on 926 patients. They identified 21 genes that were altered more frequently in the metastases compared with the primary tumors, and they observed that a high homologous recombination deficiency score in patients with BCRA 1 or 2 mutations was associated with a longer progression-free survival in patients treated with olaparib.

“We also identified a subset of patients who are resistant to CDK4/6 inhibitors who presented with CDK4 amplification, and this amplification is associated with overexpression,” Dr. Andre explained.

When asked whether most oncologists were using genomic profiling to tailor treatment for breast cancer patients, Dr. Andre said that multigene sequencing is now widely used.

“The issue is not so much whether we should use or not use genomics; the issue here is to force everyone to put the genomic alteration in the right context in terms of its level of evidence,” Dr. Andre told this news organization.

Oncologists may overinterpret the genomic activation identified and give a targeted therapy that is not validated, but “oncologists should not use genomic information when the target has not been previously validated in a therapeutic trial,” he added.

Virginia Kaklamani, MD, professor of medicine at the University of Texas Health Sciences Center in San Antonio, said in an interview that approximately 5 years ago, Dr. Andre was part of the first debate at the SABCS discussing whether oncologists should be conducting next-generation sequencing for their patients with breast cancer.

“At the time, [Dr.] Andre’s comment was that we should not be doing it,” recalled Dr. Kaklamani, who is also leader of the breast cancer program at the Mays Cancer Center at the University of Texas Health San Antonio MD Anderson. “At that point, I think it was clear that we did not have the data we needed to be able to use next-generation sequencing to change our clinical management.”

However, the evidence has evolved. “Based on this clinical trial, I think we now do have the data,” she said. “I think that [next-generation sequencing] is something we will be using more and more in practice and treating our patients based on [validated] genomic alterations.”

Dr. Andre has received grants or advisory board/speaker honoraria from Daiichi Sankyo, Roche, Pfizer, AstraZeneca, Lily, and Novartis. Dr. Kaklamani has served as a consultant for Puma, AstraZeneca, Athenex, and Immunomedics, has received research funding from Eisai, and has served as a speaker for Pfizer, Celgene, Genentech, and Genomic Health, among other companies.

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

People with thyroid cancer treated with thyroidectomy have as much as a 40% increased risk of developing type 2 diabetes, regardless of their age, with the elevated risk observed with low as well as high doses of postoperative levothyroxine, new research shows.

“This is the first population-based study to demonstrate an elevated risk of type 2 diabetes in postthyroidectomy patients with thyroid cancer, compared with that in matched controls,” wrote the authors of the research, published recently in the Journal of Clinical Endocrinology & Metabolism.

“Notably, there was a U-shaped relationship between postoperative levothyroxine dosage, a surrogate marker of TSH suppression, and the risk of type 2 diabetes,” said Hye Jin Yoo, MD, of the division of endocrinology and metabolism, Korea University College of Medicine, Seoul, and colleagues.

While other studies have linked thyroidectomy for thyroid cancer with an elevated risk for other metabolic conditions, including coronary heart disease and ischemic stroke, the relatively high diabetes risk is unexpected, said Tyler Drake, MD, an endocrinologist with the Minneapolis VA Health Care System.

“A 40% increased risk of diabetes is a big surprise,” he said in an interview.

“Diabetes is very common, with about one in 10 U.S. adults having type 2 diabetes, but a 40% increased risk in thyroid cancer patients is higher than I see in my clinical practice. [However], it is important to note that the [highest] risk was predominantly among the groups on the lowest and highest doses of levothyroxine,” said Dr. Drake, assistant professor of medicine at the University of Minnesota, Minneapolis.
 

U-shaped relationship between levothyroxine dose and diabetes risk

The findings are from a study of 36,377 patients with thyroid cancer in the National Health Insurance Service (NHIS) database in Korea who had undergone a thyroidectomy between 2004 and 2013.

The patients were matched 1:1 with controls who had nonthyroid cancers. Their mean age was 46.6 years, about 30% were male, and their mean body mass index was 23.8 kg/m².

Over a mean follow-up of 6.6 years, the patients with thyroid cancer had a significantly higher risk of developing type 2 diabetes, at a rate of 47.5% (10,812) compared with 36.9% (9414; HR, 1.43; P < .001) in the control group, after adjustment for factors such as age, sex, BMI, smoking, drinking, systolic blood pressure, and fasting glucose.

The risk of type 2 diabetes among those with thyroid cancer was higher among the 83.2% of patients who underwent a total thyroidectomy compared with the 16.8% who had a unilateral lobectomy (HR, 1.06; P < .001).

In addition, those with thyroid cancer who received the lowest as well as highest dosages of levothyroxine had significantly higher risks of type 2 diabetes compared with controls (HR, 1.50 and 1.39, respectively; both P < .001).

A closer look at quartiles of levothyroxine dosing showed the first (lowest) quartile (defined as a mean levothyroxine dosage of < 101 mcg/day) was associated with an increased risk of type 2 diabetes compared with the second quartile group (101-127 mcg/day; HR, 1.45), as was the fourth quartile (≥ 150 mcg/day; HR, 1.37), while a decreased risk of type 2 diabetes was observed in the third quartile group (128-149 mcg/day versus the second quartile group; HR, 0.91).

“This result suggests a U-shaped relationship between the mean levothyroxine dosage and risk of type 2 diabetes in postthyroidectomy patients with thyroid cancer,” the authors said.

However, “consistent with previous studies, the present study showed that the highest risk of type 2 diabetes was observed in patients with thyroid cancer who were treated with the lowest mean dosage of levothyroxine,” they noted.

“This result suggests that inadequate supplementation of thyroid hormones may worsen glucose metabolism and should therefore be avoided.”
 

Potential mechanisms

Abnormal thyroid function, including hypo- and hyperthyroidism, following thyroidectomy and subsequent treatment with levothyroxine, is known to have potentially detrimental effects on glucose regulation among patients with thyroid cancer.

The potential mechanisms linking hypothyroidism with diabetes specifically include the possibility that insulin becomes unable to promote the utilization of glucose by muscles and adipose tissue. However, thyroid hormone replacement has been associated with a normalization of insulin sensitivity, the authors noted.

Meanwhile, glucose intolerance is common among patients with hyperthyroidism, largely due to an increase in hepatic glucose production, and likewise, the normalization of thyroid levels among those treated with methimazole has been linked to normalization of glucose and lipid metabolism alterations.

Dr. Drake noted that an important study limitation is that patients were analyzed based on their levothyroxine dose and not their TSH values, which the authors explain was due to the unavailability of the TSH values. 

“By looking at levothyroxine doses, and not TSH values, it is possible some patients were being improperly treated with either too much or too little levothyroxine,” Dr. Drake noted.
 

Control group should have had hypothyroidism

The findings nevertheless shed light on the risk of diabetes following thyroidectomy for thyroid cancer, Anupam Kotwal, MD, commented on the study.

“This study is significant because it addresses an important topic exploring the link between thyroid dysfunction and metabolic disease, in this case ... hypothyroidism, due to surgery for thyroid cancer and type 2 diabetes,” Dr. Kotwal, assistant professor of medicine in the division of diabetes, endocrinology & metabolism at the University of Nebraska Medical Center, Omaha, said in an interview.

In terms of other limitations, Dr. Kotwal noted that the controls did not have hypothyroidism; therefore, “from this study, it is impossible to confirm whether hypothyroidism from any cause would be associated with higher incidence of diabetes or if it is specific to thyroid surgery for thyroid cancer.

“It would have been useful to have a control group of autoimmune primary hypothyroidism to evaluate the rate of diabetes during a similar follow-up duration,” Dr. Kotwal said.

“Hence, cohort studies with more granular data such as degree of TSH suppression and having a control group of hypothyroid patients due to autoimmune thyroid disease are needed to better understand this risk.”

Dr. Kotwal and Dr. Drake have reported no relevant financial relationships.

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

People with thyroid cancer treated with thyroidectomy have as much as a 40% increased risk of developing type 2 diabetes, regardless of their age, with the elevated risk observed with low as well as high doses of postoperative levothyroxine, new research shows.

“This is the first population-based study to demonstrate an elevated risk of type 2 diabetes in postthyroidectomy patients with thyroid cancer, compared with that in matched controls,” wrote the authors of the research, published recently in the Journal of Clinical Endocrinology & Metabolism.

“Notably, there was a U-shaped relationship between postoperative levothyroxine dosage, a surrogate marker of TSH suppression, and the risk of type 2 diabetes,” said Hye Jin Yoo, MD, of the division of endocrinology and metabolism, Korea University College of Medicine, Seoul, and colleagues.

While other studies have linked thyroidectomy for thyroid cancer with an elevated risk for other metabolic conditions, including coronary heart disease and ischemic stroke, the relatively high diabetes risk is unexpected, said Tyler Drake, MD, an endocrinologist with the Minneapolis VA Health Care System.

“A 40% increased risk of diabetes is a big surprise,” he said in an interview.

“Diabetes is very common, with about one in 10 U.S. adults having type 2 diabetes, but a 40% increased risk in thyroid cancer patients is higher than I see in my clinical practice. [However], it is important to note that the [highest] risk was predominantly among the groups on the lowest and highest doses of levothyroxine,” said Dr. Drake, assistant professor of medicine at the University of Minnesota, Minneapolis.
 

U-shaped relationship between levothyroxine dose and diabetes risk

The findings are from a study of 36,377 patients with thyroid cancer in the National Health Insurance Service (NHIS) database in Korea who had undergone a thyroidectomy between 2004 and 2013.

The patients were matched 1:1 with controls who had nonthyroid cancers. Their mean age was 46.6 years, about 30% were male, and their mean body mass index was 23.8 kg/m².

Over a mean follow-up of 6.6 years, the patients with thyroid cancer had a significantly higher risk of developing type 2 diabetes, at a rate of 47.5% (10,812) compared with 36.9% (9414; HR, 1.43; P < .001) in the control group, after adjustment for factors such as age, sex, BMI, smoking, drinking, systolic blood pressure, and fasting glucose.

The risk of type 2 diabetes among those with thyroid cancer was higher among the 83.2% of patients who underwent a total thyroidectomy compared with the 16.8% who had a unilateral lobectomy (HR, 1.06; P < .001).

In addition, those with thyroid cancer who received the lowest as well as highest dosages of levothyroxine had significantly higher risks of type 2 diabetes compared with controls (HR, 1.50 and 1.39, respectively; both P < .001).

A closer look at quartiles of levothyroxine dosing showed the first (lowest) quartile (defined as a mean levothyroxine dosage of < 101 mcg/day) was associated with an increased risk of type 2 diabetes compared with the second quartile group (101-127 mcg/day; HR, 1.45), as was the fourth quartile (≥ 150 mcg/day; HR, 1.37), while a decreased risk of type 2 diabetes was observed in the third quartile group (128-149 mcg/day versus the second quartile group; HR, 0.91).

“This result suggests a U-shaped relationship between the mean levothyroxine dosage and risk of type 2 diabetes in postthyroidectomy patients with thyroid cancer,” the authors said.

However, “consistent with previous studies, the present study showed that the highest risk of type 2 diabetes was observed in patients with thyroid cancer who were treated with the lowest mean dosage of levothyroxine,” they noted.

“This result suggests that inadequate supplementation of thyroid hormones may worsen glucose metabolism and should therefore be avoided.”
 

Potential mechanisms

Abnormal thyroid function, including hypo- and hyperthyroidism, following thyroidectomy and subsequent treatment with levothyroxine, is known to have potentially detrimental effects on glucose regulation among patients with thyroid cancer.

The potential mechanisms linking hypothyroidism with diabetes specifically include the possibility that insulin becomes unable to promote the utilization of glucose by muscles and adipose tissue. However, thyroid hormone replacement has been associated with a normalization of insulin sensitivity, the authors noted.

Meanwhile, glucose intolerance is common among patients with hyperthyroidism, largely due to an increase in hepatic glucose production, and likewise, the normalization of thyroid levels among those treated with methimazole has been linked to normalization of glucose and lipid metabolism alterations.

Dr. Drake noted that an important study limitation is that patients were analyzed based on their levothyroxine dose and not their TSH values, which the authors explain was due to the unavailability of the TSH values. 

“By looking at levothyroxine doses, and not TSH values, it is possible some patients were being improperly treated with either too much or too little levothyroxine,” Dr. Drake noted.
 

Control group should have had hypothyroidism

The findings nevertheless shed light on the risk of diabetes following thyroidectomy for thyroid cancer, Anupam Kotwal, MD, commented on the study.

“This study is significant because it addresses an important topic exploring the link between thyroid dysfunction and metabolic disease, in this case ... hypothyroidism, due to surgery for thyroid cancer and type 2 diabetes,” Dr. Kotwal, assistant professor of medicine in the division of diabetes, endocrinology & metabolism at the University of Nebraska Medical Center, Omaha, said in an interview.

In terms of other limitations, Dr. Kotwal noted that the controls did not have hypothyroidism; therefore, “from this study, it is impossible to confirm whether hypothyroidism from any cause would be associated with higher incidence of diabetes or if it is specific to thyroid surgery for thyroid cancer.

“It would have been useful to have a control group of autoimmune primary hypothyroidism to evaluate the rate of diabetes during a similar follow-up duration,” Dr. Kotwal said.

“Hence, cohort studies with more granular data such as degree of TSH suppression and having a control group of hypothyroid patients due to autoimmune thyroid disease are needed to better understand this risk.”

Dr. Kotwal and Dr. Drake have reported no relevant financial relationships.

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

People with thyroid cancer treated with thyroidectomy have as much as a 40% increased risk of developing type 2 diabetes, regardless of their age, with the elevated risk observed with low as well as high doses of postoperative levothyroxine, new research shows.

“This is the first population-based study to demonstrate an elevated risk of type 2 diabetes in postthyroidectomy patients with thyroid cancer, compared with that in matched controls,” wrote the authors of the research, published recently in the Journal of Clinical Endocrinology & Metabolism.

“Notably, there was a U-shaped relationship between postoperative levothyroxine dosage, a surrogate marker of TSH suppression, and the risk of type 2 diabetes,” said Hye Jin Yoo, MD, of the division of endocrinology and metabolism, Korea University College of Medicine, Seoul, and colleagues.

While other studies have linked thyroidectomy for thyroid cancer with an elevated risk for other metabolic conditions, including coronary heart disease and ischemic stroke, the relatively high diabetes risk is unexpected, said Tyler Drake, MD, an endocrinologist with the Minneapolis VA Health Care System.

“A 40% increased risk of diabetes is a big surprise,” he said in an interview.

“Diabetes is very common, with about one in 10 U.S. adults having type 2 diabetes, but a 40% increased risk in thyroid cancer patients is higher than I see in my clinical practice. [However], it is important to note that the [highest] risk was predominantly among the groups on the lowest and highest doses of levothyroxine,” said Dr. Drake, assistant professor of medicine at the University of Minnesota, Minneapolis.
 

U-shaped relationship between levothyroxine dose and diabetes risk

The findings are from a study of 36,377 patients with thyroid cancer in the National Health Insurance Service (NHIS) database in Korea who had undergone a thyroidectomy between 2004 and 2013.

The patients were matched 1:1 with controls who had nonthyroid cancers. Their mean age was 46.6 years, about 30% were male, and their mean body mass index was 23.8 kg/m².

Over a mean follow-up of 6.6 years, the patients with thyroid cancer had a significantly higher risk of developing type 2 diabetes, at a rate of 47.5% (10,812) compared with 36.9% (9414; HR, 1.43; P < .001) in the control group, after adjustment for factors such as age, sex, BMI, smoking, drinking, systolic blood pressure, and fasting glucose.

The risk of type 2 diabetes among those with thyroid cancer was higher among the 83.2% of patients who underwent a total thyroidectomy compared with the 16.8% who had a unilateral lobectomy (HR, 1.06; P < .001).

In addition, those with thyroid cancer who received the lowest as well as highest dosages of levothyroxine had significantly higher risks of type 2 diabetes compared with controls (HR, 1.50 and 1.39, respectively; both P < .001).

A closer look at quartiles of levothyroxine dosing showed the first (lowest) quartile (defined as a mean levothyroxine dosage of < 101 mcg/day) was associated with an increased risk of type 2 diabetes compared with the second quartile group (101-127 mcg/day; HR, 1.45), as was the fourth quartile (≥ 150 mcg/day; HR, 1.37), while a decreased risk of type 2 diabetes was observed in the third quartile group (128-149 mcg/day versus the second quartile group; HR, 0.91).

“This result suggests a U-shaped relationship between the mean levothyroxine dosage and risk of type 2 diabetes in postthyroidectomy patients with thyroid cancer,” the authors said.

However, “consistent with previous studies, the present study showed that the highest risk of type 2 diabetes was observed in patients with thyroid cancer who were treated with the lowest mean dosage of levothyroxine,” they noted.

“This result suggests that inadequate supplementation of thyroid hormones may worsen glucose metabolism and should therefore be avoided.”
 

Potential mechanisms

Abnormal thyroid function, including hypo- and hyperthyroidism, following thyroidectomy and subsequent treatment with levothyroxine, is known to have potentially detrimental effects on glucose regulation among patients with thyroid cancer.

The potential mechanisms linking hypothyroidism with diabetes specifically include the possibility that insulin becomes unable to promote the utilization of glucose by muscles and adipose tissue. However, thyroid hormone replacement has been associated with a normalization of insulin sensitivity, the authors noted.

Meanwhile, glucose intolerance is common among patients with hyperthyroidism, largely due to an increase in hepatic glucose production, and likewise, the normalization of thyroid levels among those treated with methimazole has been linked to normalization of glucose and lipid metabolism alterations.

Dr. Drake noted that an important study limitation is that patients were analyzed based on their levothyroxine dose and not their TSH values, which the authors explain was due to the unavailability of the TSH values. 

“By looking at levothyroxine doses, and not TSH values, it is possible some patients were being improperly treated with either too much or too little levothyroxine,” Dr. Drake noted.
 

Control group should have had hypothyroidism

The findings nevertheless shed light on the risk of diabetes following thyroidectomy for thyroid cancer, Anupam Kotwal, MD, commented on the study.

“This study is significant because it addresses an important topic exploring the link between thyroid dysfunction and metabolic disease, in this case ... hypothyroidism, due to surgery for thyroid cancer and type 2 diabetes,” Dr. Kotwal, assistant professor of medicine in the division of diabetes, endocrinology & metabolism at the University of Nebraska Medical Center, Omaha, said in an interview.

In terms of other limitations, Dr. Kotwal noted that the controls did not have hypothyroidism; therefore, “from this study, it is impossible to confirm whether hypothyroidism from any cause would be associated with higher incidence of diabetes or if it is specific to thyroid surgery for thyroid cancer.

“It would have been useful to have a control group of autoimmune primary hypothyroidism to evaluate the rate of diabetes during a similar follow-up duration,” Dr. Kotwal said.

“Hence, cohort studies with more granular data such as degree of TSH suppression and having a control group of hypothyroid patients due to autoimmune thyroid disease are needed to better understand this risk.”

Dr. Kotwal and Dr. Drake have reported no relevant financial relationships.

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

Interruption of 4-6 cyclin D-dependent kinase inhibitors (CDK4/6i) was associated with a high rate of progression among women with metastatic breast cancer, particularly those with liver metastases. The treatment interruptions occurred during the COVID-19 pandemic, out of concern that myelosuppression from the drugs might make patients more vulnerable to COVID-19 infection, and that other side effects might be confused with symptoms of COVID-19 infection.

The finding comes from a multicenter study presented by Sophie Martin, PhD, at the San Antonio Breast Cancer Symposium. Dr. Martin is a researcher at ICANS Institut de cancérologie Strasbourg Europe. The patient population had a complete or partial response, or stable disease complete for at least 6 months.

Although CDK4/6i combined with endocrine therapy has led to significant improvements in outcomes among metastatic HR-positive, HER-2-negative patients, the treatment can lead to chronic toxicities that may affect quality of life.

In its 2020 guidance on management of cancer patients during the COVID-19 pandemic, the European Society for Medical Oncology noted that cancer patients are at higher risk of severe symptoms and worse outcomes. However, it points out that there is no direct evidence that neutropenia caused CDK4/6i or poly-adenosine diphosphate ribose polymer inhibitors leads to an increase risk of COVID-19 infection.

The American Society for Clinical Oncology guidance for managing treatment of cancer patients in the context of COVID-19 also says there is little direct evidence to guide practice regarding therapies that may lead to immunosuppression. Therefore, the society recommends against changing or withholding those drugs. “The balance of potential harms that may result from delaying or interrupting treatment versus the potential benefits of possibly preventing or delaying COVID-19 infection is very uncertain,” the authors wrote.

There were 60 patients in the study, and the median age was 64 years. The average interruption period was 8 weeks. Twenty-two patients (37%) experienced radiological and/or clinical disease progression. Sixteen of the 22 (73%) restarted on CDK4/6I, while the remaining 4 patients initiated chemotherapy or targeted therapy. Two patients died during CDK4/6i treatment interruption. A univariate analysis found that the presence of liver metastases was associated with increased risk of progression during CDK4/6I withdrawal (odds ratio, 5.50; 95% confidence interval, 1.14-26.41).

There was also a trend toward greater likelihood of disease progression when the withdrawal period was 2 or more months (OR, 2.38), but the finding was not statistically significant. Although the study looked at treatment interruption due to the COVID-19 pandemic, the authors noted that the findings likely apply to other reasons for interruption, such as analgesic radiotherapy or programmed surgery.

Although the study authors advise against stopping CDK4/6i inhibitors, another small study conducted at a single German center suggested that treatment interruption might be an option in patients with stable disease. The authors examined elective CDK4/6i discontinuation among 22 patients with advanced, hormone receptor–positive, HER-2-negative breast cancer who had stable disease for at least 6 months with treatment regimens of CDK4/6i plus aromatase inhibitors or fulvestrant. After discontinuation of CDK4/6i but maintenance of endocrine therapy, 13 patients had stable disease, 8 had a partial response, and 1 had a complete response. After withdrawal, 5 patients had a local relapse and 1 experienced systemic progression. The patients restabilized with chemotherapy or retreatment with CDK4/6i.

“Discontinuation of CDK4/6 inhibitors seems to be safe in selected patients with metastatic HR-positive HER-2-negative breast cancer and prolonged disease control,” the authors wrote, although they noted that the results need to be backed up with prospective clinical trials.

Both studies had small sample sizes and were retrospective in nature.

One author on the COVID-19 study has received consulting fees from Lilly, Novartis, Pfizer, Daïchi, Seagen, and AstraZeneca. Authors of the German study have received honoraria from Iomedico, Novartis, Roche, AstraZeneca, Boehringer Ingelheim, Merck, Sanofi, and BMS.

Interruption of 4-6 cyclin D-dependent kinase inhibitors (CDK4/6i) was associated with a high rate of progression among women with metastatic breast cancer, particularly those with liver metastases. The treatment interruptions occurred during the COVID-19 pandemic, out of concern that myelosuppression from the drugs might make patients more vulnerable to COVID-19 infection, and that other side effects might be confused with symptoms of COVID-19 infection.

The finding comes from a multicenter study presented by Sophie Martin, PhD, at the San Antonio Breast Cancer Symposium. Dr. Martin is a researcher at ICANS Institut de cancérologie Strasbourg Europe. The patient population had a complete or partial response, or stable disease complete for at least 6 months.

Although CDK4/6i combined with endocrine therapy has led to significant improvements in outcomes among metastatic HR-positive, HER-2-negative patients, the treatment can lead to chronic toxicities that may affect quality of life.

In its 2020 guidance on management of cancer patients during the COVID-19 pandemic, the European Society for Medical Oncology noted that cancer patients are at higher risk of severe symptoms and worse outcomes. However, it points out that there is no direct evidence that neutropenia caused CDK4/6i or poly-adenosine diphosphate ribose polymer inhibitors leads to an increase risk of COVID-19 infection.

The American Society for Clinical Oncology guidance for managing treatment of cancer patients in the context of COVID-19 also says there is little direct evidence to guide practice regarding therapies that may lead to immunosuppression. Therefore, the society recommends against changing or withholding those drugs. “The balance of potential harms that may result from delaying or interrupting treatment versus the potential benefits of possibly preventing or delaying COVID-19 infection is very uncertain,” the authors wrote.

There were 60 patients in the study, and the median age was 64 years. The average interruption period was 8 weeks. Twenty-two patients (37%) experienced radiological and/or clinical disease progression. Sixteen of the 22 (73%) restarted on CDK4/6I, while the remaining 4 patients initiated chemotherapy or targeted therapy. Two patients died during CDK4/6i treatment interruption. A univariate analysis found that the presence of liver metastases was associated with increased risk of progression during CDK4/6I withdrawal (odds ratio, 5.50; 95% confidence interval, 1.14-26.41).

There was also a trend toward greater likelihood of disease progression when the withdrawal period was 2 or more months (OR, 2.38), but the finding was not statistically significant. Although the study looked at treatment interruption due to the COVID-19 pandemic, the authors noted that the findings likely apply to other reasons for interruption, such as analgesic radiotherapy or programmed surgery.

Although the study authors advise against stopping CDK4/6i inhibitors, another small study conducted at a single German center suggested that treatment interruption might be an option in patients with stable disease. The authors examined elective CDK4/6i discontinuation among 22 patients with advanced, hormone receptor–positive, HER-2-negative breast cancer who had stable disease for at least 6 months with treatment regimens of CDK4/6i plus aromatase inhibitors or fulvestrant. After discontinuation of CDK4/6i but maintenance of endocrine therapy, 13 patients had stable disease, 8 had a partial response, and 1 had a complete response. After withdrawal, 5 patients had a local relapse and 1 experienced systemic progression. The patients restabilized with chemotherapy or retreatment with CDK4/6i.

“Discontinuation of CDK4/6 inhibitors seems to be safe in selected patients with metastatic HR-positive HER-2-negative breast cancer and prolonged disease control,” the authors wrote, although they noted that the results need to be backed up with prospective clinical trials.

Both studies had small sample sizes and were retrospective in nature.

One author on the COVID-19 study has received consulting fees from Lilly, Novartis, Pfizer, Daïchi, Seagen, and AstraZeneca. Authors of the German study have received honoraria from Iomedico, Novartis, Roche, AstraZeneca, Boehringer Ingelheim, Merck, Sanofi, and BMS.

Interruption of 4-6 cyclin D-dependent kinase inhibitors (CDK4/6i) was associated with a high rate of progression among women with metastatic breast cancer, particularly those with liver metastases. The treatment interruptions occurred during the COVID-19 pandemic, out of concern that myelosuppression from the drugs might make patients more vulnerable to COVID-19 infection, and that other side effects might be confused with symptoms of COVID-19 infection.

The finding comes from a multicenter study presented by Sophie Martin, PhD, at the San Antonio Breast Cancer Symposium. Dr. Martin is a researcher at ICANS Institut de cancérologie Strasbourg Europe. The patient population had a complete or partial response, or stable disease complete for at least 6 months.

Although CDK4/6i combined with endocrine therapy has led to significant improvements in outcomes among metastatic HR-positive, HER-2-negative patients, the treatment can lead to chronic toxicities that may affect quality of life.

In its 2020 guidance on management of cancer patients during the COVID-19 pandemic, the European Society for Medical Oncology noted that cancer patients are at higher risk of severe symptoms and worse outcomes. However, it points out that there is no direct evidence that neutropenia caused CDK4/6i or poly-adenosine diphosphate ribose polymer inhibitors leads to an increase risk of COVID-19 infection.

The American Society for Clinical Oncology guidance for managing treatment of cancer patients in the context of COVID-19 also says there is little direct evidence to guide practice regarding therapies that may lead to immunosuppression. Therefore, the society recommends against changing or withholding those drugs. “The balance of potential harms that may result from delaying or interrupting treatment versus the potential benefits of possibly preventing or delaying COVID-19 infection is very uncertain,” the authors wrote.

There were 60 patients in the study, and the median age was 64 years. The average interruption period was 8 weeks. Twenty-two patients (37%) experienced radiological and/or clinical disease progression. Sixteen of the 22 (73%) restarted on CDK4/6I, while the remaining 4 patients initiated chemotherapy or targeted therapy. Two patients died during CDK4/6i treatment interruption. A univariate analysis found that the presence of liver metastases was associated with increased risk of progression during CDK4/6I withdrawal (odds ratio, 5.50; 95% confidence interval, 1.14-26.41).

There was also a trend toward greater likelihood of disease progression when the withdrawal period was 2 or more months (OR, 2.38), but the finding was not statistically significant. Although the study looked at treatment interruption due to the COVID-19 pandemic, the authors noted that the findings likely apply to other reasons for interruption, such as analgesic radiotherapy or programmed surgery.

Although the study authors advise against stopping CDK4/6i inhibitors, another small study conducted at a single German center suggested that treatment interruption might be an option in patients with stable disease. The authors examined elective CDK4/6i discontinuation among 22 patients with advanced, hormone receptor–positive, HER-2-negative breast cancer who had stable disease for at least 6 months with treatment regimens of CDK4/6i plus aromatase inhibitors or fulvestrant. After discontinuation of CDK4/6i but maintenance of endocrine therapy, 13 patients had stable disease, 8 had a partial response, and 1 had a complete response. After withdrawal, 5 patients had a local relapse and 1 experienced systemic progression. The patients restabilized with chemotherapy or retreatment with CDK4/6i.

“Discontinuation of CDK4/6 inhibitors seems to be safe in selected patients with metastatic HR-positive HER-2-negative breast cancer and prolonged disease control,” the authors wrote, although they noted that the results need to be backed up with prospective clinical trials.

Both studies had small sample sizes and were retrospective in nature.

One author on the COVID-19 study has received consulting fees from Lilly, Novartis, Pfizer, Daïchi, Seagen, and AstraZeneca. Authors of the German study have received honoraria from Iomedico, Novartis, Roche, AstraZeneca, Boehringer Ingelheim, Merck, Sanofi, and BMS.

As compared with standard of care, an investigational oral selective estrogen receptor degrader (SERD) demonstrated a 30% lower risk of death or disease progression in women with estrogen receptor (ER)–positive/HER2-negative metastatic breast cancer.

Findings from the phase 3 EMERALD trial, presented at the San Antonio Breast Cancer Symposium, revealed that the effects of elacestrant (Menarini and Radius Health) were even more pronounced in women with ESR1 mutations. Women in the elacestrant arm had a 45% reduced risk of death or disease progression in comparison with those who received standard of care.

This new agent is the “first oral SERD to demonstrate a statistically significant and clinically meaningful improvement of progression-free survival in patients with ER-positive/HER2-negative metastatic breast cancer in the second- and third-line settings,” said lead author Aditya Bardia, MD, MPH, director of the breast cancer research program at Mass General Cancer Center and associate professor at Harvard Medical School, both in Boston. “Clinically, elacestrant has the potential to become the new standard of care in the study population.”

Endocrine therapy and CDK4/6 inhibitors remain the mainstay for the management of ER-positive/HER2 metastatic breast cancer. However, most patients will eventually develop resistance to these agents, often caused by the development of ESR1 mutations.

At the current time, fulvestrant is the only SERD available on the U.S. market, which means there is an urgent unmet need for new, effective SERDs in this setting, especially for patients harboring ESR1 mutations, Dr. Bardia explained.

In an early phase 1 trial, Dr. Bardia and his team evaluated elacestrant for safety and antitumor activity and found it had an acceptable safety profile and demonstrated single-agent activity with confirmed partial responses in heavily pretreated patients with ER-positive metastatic breast cancer.

This trial provided the rationale for investigating elacestrant in a phase 3 setting, Dr. Bardia said.

The multicenter, randomized, controlled phase 3 EMERALD trial included 477 postmenopausal women with ER-positive/HER2-negative metastatic breast cancer who had received one or two prior lines of endocrine therapy and no more than one line of chemotherapy in the metastatic setting. Patients had also progressed on prior treatment with a CDK4/6 inhibitor.

Patients were randomized to elacestrant 400 mg orally daily (n = 239) or standard of care (investigator’s choice of fulvestrant or an aromatase inhibitor, n = 238). The cohorts were further stratified by ESR1 mutation status, prior fulvestrant exposure, and presence of visceral disease.

The coprimary endpoints were progression-free survival in patients with tumors harboring ESR1 mutations and in the entire cohort. Secondary endpoints included overall survival, safety, tolerability, and quality of life.

“This was a positive study as it met both primary endpoints,” said Dr. Bardia.

The team found a 30% reduction in the risk of progression or death in the elacestrant arm for all patients (hazard ratio, 0.697; P = .0018) and a 45% (HR, 0.546; P =.0005) reduction in the risk of progression or death among those with ESR1 mutations.

At 12 months, the progression-free survival rate was 22.32% with elacestrant versus 9.42% for those receiving the standard of care. Among the ESR1 mutation group, those rates were slightly more pronounced: 26.76% with elacestrant versus 8.19% with standard of care.

Overall survival data were not yet mature but trended in favor of elacestrant in all patients (HR, 0.751; P = .0821) as well as those with ESR1 mutations (HR, 0.592; P = .0325). The final overall survival analysis is expected next year, Dr. Bardia said.

Common treatment-related adverse events with elacestrant versus standard of care included mostly grade 1 or 2 nausea (25.3% vs. 8.7%), vomiting (11% vs. 2.6%), and fatigue (11% vs. 7.9%). The rate of grade 3 or higher adverse events was 7.2% in the elacestrant arm versus 3.1% in the standard of care group and was mainly driven by nausea. Treatment-emergent adverse events leading to discontinuation of elacestrant or standard of care were infrequent in both arms (6.3% and 4.4%, respectively). No treatment-related deaths occurred in either group.

Dr. Bardia added that further studies are planned and assess the efficacy of elacestrant during earlier lines of treatment and in combination with other therapies, such as CDK4/6 inhibitors.

Weighing in on the recent findings, Carlos Arteaga, MD, who was not involved in the research, said this represents an important study evaluating a therapeutic priority.

“The data suggest that [elacestrant] may be a new option, not only as monotherapy but in combination with other therapies,” Dr. Arteaga, director of Simmons Comprehensive Cancer Center at the University of Texas Southwestern Medical Center, Dallas, and cochair of SABCS, said in an interview.

Coral Omene, MD, PhD, a medical oncologist at Rutgers Cancer Institute of New Jersey and assistant professor of medicine at Robert Wood Johnson Medical School, both in New Brunswick, also commented on the importance of the EMERALD results.

“I would think that this is practice changing,” said Dr. Omene, who was also not involved in the research. The new oral SERD “demonstrates a significant advantage in progression-free survival over either fulvestrant or an aromatase inhibitor.”

An oral drug could also potentially save patients from painful injections that can occasionally result in injection-site abscesses from long-term administration, she explained. “It’s also more convenient to take oral pills at home. It saves on transportation and omits waiting in treatment rooms for administrations.”

Although the overall survival data are not yet mature and the rate of adverse events was higher with elacestrant, “progression-free survival is a surrogate endpoint widely used for overall survival and is reasonable to consider a treatment regimen based on this while awaiting mature survival data,” Dr. Omene added. “The increase in nausea and vomiting seen in oral SERD arm is likely manageable, as there were no significant differences in discontinuation in both arms of treatment.”

The study was supported by Radius Health. Dr. Bardia has served as a consultant or on an advisory board for Radius Health, Pfizer, Novartis, Genentech, Merck, Immunomedics/Gilead, Sanofi, Daiichi Sankyo/AstraZeneca, Phillips, Eli Lilly, and Foundation Medicine. He has conducted contracted research or received grants from Genentech, Novartis, Pfizer, Merck, Sanofi, Radius Health, Immunomedics/Gilead, Daiichi Sankyo/AstraZeneca, Natera, and Eli Lilly.

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

As compared with standard of care, an investigational oral selective estrogen receptor degrader (SERD) demonstrated a 30% lower risk of death or disease progression in women with estrogen receptor (ER)–positive/HER2-negative metastatic breast cancer.

Findings from the phase 3 EMERALD trial, presented at the San Antonio Breast Cancer Symposium, revealed that the effects of elacestrant (Menarini and Radius Health) were even more pronounced in women with ESR1 mutations. Women in the elacestrant arm had a 45% reduced risk of death or disease progression in comparison with those who received standard of care.

This new agent is the “first oral SERD to demonstrate a statistically significant and clinically meaningful improvement of progression-free survival in patients with ER-positive/HER2-negative metastatic breast cancer in the second- and third-line settings,” said lead author Aditya Bardia, MD, MPH, director of the breast cancer research program at Mass General Cancer Center and associate professor at Harvard Medical School, both in Boston. “Clinically, elacestrant has the potential to become the new standard of care in the study population.”

Endocrine therapy and CDK4/6 inhibitors remain the mainstay for the management of ER-positive/HER2 metastatic breast cancer. However, most patients will eventually develop resistance to these agents, often caused by the development of ESR1 mutations.

At the current time, fulvestrant is the only SERD available on the U.S. market, which means there is an urgent unmet need for new, effective SERDs in this setting, especially for patients harboring ESR1 mutations, Dr. Bardia explained.

In an early phase 1 trial, Dr. Bardia and his team evaluated elacestrant for safety and antitumor activity and found it had an acceptable safety profile and demonstrated single-agent activity with confirmed partial responses in heavily pretreated patients with ER-positive metastatic breast cancer.

This trial provided the rationale for investigating elacestrant in a phase 3 setting, Dr. Bardia said.

The multicenter, randomized, controlled phase 3 EMERALD trial included 477 postmenopausal women with ER-positive/HER2-negative metastatic breast cancer who had received one or two prior lines of endocrine therapy and no more than one line of chemotherapy in the metastatic setting. Patients had also progressed on prior treatment with a CDK4/6 inhibitor.

Patients were randomized to elacestrant 400 mg orally daily (n = 239) or standard of care (investigator’s choice of fulvestrant or an aromatase inhibitor, n = 238). The cohorts were further stratified by ESR1 mutation status, prior fulvestrant exposure, and presence of visceral disease.

The coprimary endpoints were progression-free survival in patients with tumors harboring ESR1 mutations and in the entire cohort. Secondary endpoints included overall survival, safety, tolerability, and quality of life.

“This was a positive study as it met both primary endpoints,” said Dr. Bardia.

The team found a 30% reduction in the risk of progression or death in the elacestrant arm for all patients (hazard ratio, 0.697; P = .0018) and a 45% (HR, 0.546; P =.0005) reduction in the risk of progression or death among those with ESR1 mutations.

At 12 months, the progression-free survival rate was 22.32% with elacestrant versus 9.42% for those receiving the standard of care. Among the ESR1 mutation group, those rates were slightly more pronounced: 26.76% with elacestrant versus 8.19% with standard of care.

Overall survival data were not yet mature but trended in favor of elacestrant in all patients (HR, 0.751; P = .0821) as well as those with ESR1 mutations (HR, 0.592; P = .0325). The final overall survival analysis is expected next year, Dr. Bardia said.

Common treatment-related adverse events with elacestrant versus standard of care included mostly grade 1 or 2 nausea (25.3% vs. 8.7%), vomiting (11% vs. 2.6%), and fatigue (11% vs. 7.9%). The rate of grade 3 or higher adverse events was 7.2% in the elacestrant arm versus 3.1% in the standard of care group and was mainly driven by nausea. Treatment-emergent adverse events leading to discontinuation of elacestrant or standard of care were infrequent in both arms (6.3% and 4.4%, respectively). No treatment-related deaths occurred in either group.

Dr. Bardia added that further studies are planned and assess the efficacy of elacestrant during earlier lines of treatment and in combination with other therapies, such as CDK4/6 inhibitors.

Weighing in on the recent findings, Carlos Arteaga, MD, who was not involved in the research, said this represents an important study evaluating a therapeutic priority.

“The data suggest that [elacestrant] may be a new option, not only as monotherapy but in combination with other therapies,” Dr. Arteaga, director of Simmons Comprehensive Cancer Center at the University of Texas Southwestern Medical Center, Dallas, and cochair of SABCS, said in an interview.

Coral Omene, MD, PhD, a medical oncologist at Rutgers Cancer Institute of New Jersey and assistant professor of medicine at Robert Wood Johnson Medical School, both in New Brunswick, also commented on the importance of the EMERALD results.

“I would think that this is practice changing,” said Dr. Omene, who was also not involved in the research. The new oral SERD “demonstrates a significant advantage in progression-free survival over either fulvestrant or an aromatase inhibitor.”

An oral drug could also potentially save patients from painful injections that can occasionally result in injection-site abscesses from long-term administration, she explained. “It’s also more convenient to take oral pills at home. It saves on transportation and omits waiting in treatment rooms for administrations.”

Although the overall survival data are not yet mature and the rate of adverse events was higher with elacestrant, “progression-free survival is a surrogate endpoint widely used for overall survival and is reasonable to consider a treatment regimen based on this while awaiting mature survival data,” Dr. Omene added. “The increase in nausea and vomiting seen in oral SERD arm is likely manageable, as there were no significant differences in discontinuation in both arms of treatment.”

The study was supported by Radius Health. Dr. Bardia has served as a consultant or on an advisory board for Radius Health, Pfizer, Novartis, Genentech, Merck, Immunomedics/Gilead, Sanofi, Daiichi Sankyo/AstraZeneca, Phillips, Eli Lilly, and Foundation Medicine. He has conducted contracted research or received grants from Genentech, Novartis, Pfizer, Merck, Sanofi, Radius Health, Immunomedics/Gilead, Daiichi Sankyo/AstraZeneca, Natera, and Eli Lilly.

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

As compared with standard of care, an investigational oral selective estrogen receptor degrader (SERD) demonstrated a 30% lower risk of death or disease progression in women with estrogen receptor (ER)–positive/HER2-negative metastatic breast cancer.

Findings from the phase 3 EMERALD trial, presented at the San Antonio Breast Cancer Symposium, revealed that the effects of elacestrant (Menarini and Radius Health) were even more pronounced in women with ESR1 mutations. Women in the elacestrant arm had a 45% reduced risk of death or disease progression in comparison with those who received standard of care.

This new agent is the “first oral SERD to demonstrate a statistically significant and clinically meaningful improvement of progression-free survival in patients with ER-positive/HER2-negative metastatic breast cancer in the second- and third-line settings,” said lead author Aditya Bardia, MD, MPH, director of the breast cancer research program at Mass General Cancer Center and associate professor at Harvard Medical School, both in Boston. “Clinically, elacestrant has the potential to become the new standard of care in the study population.”

Endocrine therapy and CDK4/6 inhibitors remain the mainstay for the management of ER-positive/HER2 metastatic breast cancer. However, most patients will eventually develop resistance to these agents, often caused by the development of ESR1 mutations.

At the current time, fulvestrant is the only SERD available on the U.S. market, which means there is an urgent unmet need for new, effective SERDs in this setting, especially for patients harboring ESR1 mutations, Dr. Bardia explained.

In an early phase 1 trial, Dr. Bardia and his team evaluated elacestrant for safety and antitumor activity and found it had an acceptable safety profile and demonstrated single-agent activity with confirmed partial responses in heavily pretreated patients with ER-positive metastatic breast cancer.

This trial provided the rationale for investigating elacestrant in a phase 3 setting, Dr. Bardia said.

The multicenter, randomized, controlled phase 3 EMERALD trial included 477 postmenopausal women with ER-positive/HER2-negative metastatic breast cancer who had received one or two prior lines of endocrine therapy and no more than one line of chemotherapy in the metastatic setting. Patients had also progressed on prior treatment with a CDK4/6 inhibitor.

Patients were randomized to elacestrant 400 mg orally daily (n = 239) or standard of care (investigator’s choice of fulvestrant or an aromatase inhibitor, n = 238). The cohorts were further stratified by ESR1 mutation status, prior fulvestrant exposure, and presence of visceral disease.

The coprimary endpoints were progression-free survival in patients with tumors harboring ESR1 mutations and in the entire cohort. Secondary endpoints included overall survival, safety, tolerability, and quality of life.

“This was a positive study as it met both primary endpoints,” said Dr. Bardia.

The team found a 30% reduction in the risk of progression or death in the elacestrant arm for all patients (hazard ratio, 0.697; P = .0018) and a 45% (HR, 0.546; P =.0005) reduction in the risk of progression or death among those with ESR1 mutations.

At 12 months, the progression-free survival rate was 22.32% with elacestrant versus 9.42% for those receiving the standard of care. Among the ESR1 mutation group, those rates were slightly more pronounced: 26.76% with elacestrant versus 8.19% with standard of care.

Overall survival data were not yet mature but trended in favor of elacestrant in all patients (HR, 0.751; P = .0821) as well as those with ESR1 mutations (HR, 0.592; P = .0325). The final overall survival analysis is expected next year, Dr. Bardia said.

Common treatment-related adverse events with elacestrant versus standard of care included mostly grade 1 or 2 nausea (25.3% vs. 8.7%), vomiting (11% vs. 2.6%), and fatigue (11% vs. 7.9%). The rate of grade 3 or higher adverse events was 7.2% in the elacestrant arm versus 3.1% in the standard of care group and was mainly driven by nausea. Treatment-emergent adverse events leading to discontinuation of elacestrant or standard of care were infrequent in both arms (6.3% and 4.4%, respectively). No treatment-related deaths occurred in either group.

Dr. Bardia added that further studies are planned and assess the efficacy of elacestrant during earlier lines of treatment and in combination with other therapies, such as CDK4/6 inhibitors.

Weighing in on the recent findings, Carlos Arteaga, MD, who was not involved in the research, said this represents an important study evaluating a therapeutic priority.

“The data suggest that [elacestrant] may be a new option, not only as monotherapy but in combination with other therapies,” Dr. Arteaga, director of Simmons Comprehensive Cancer Center at the University of Texas Southwestern Medical Center, Dallas, and cochair of SABCS, said in an interview.

Coral Omene, MD, PhD, a medical oncologist at Rutgers Cancer Institute of New Jersey and assistant professor of medicine at Robert Wood Johnson Medical School, both in New Brunswick, also commented on the importance of the EMERALD results.

“I would think that this is practice changing,” said Dr. Omene, who was also not involved in the research. The new oral SERD “demonstrates a significant advantage in progression-free survival over either fulvestrant or an aromatase inhibitor.”

An oral drug could also potentially save patients from painful injections that can occasionally result in injection-site abscesses from long-term administration, she explained. “It’s also more convenient to take oral pills at home. It saves on transportation and omits waiting in treatment rooms for administrations.”

Although the overall survival data are not yet mature and the rate of adverse events was higher with elacestrant, “progression-free survival is a surrogate endpoint widely used for overall survival and is reasonable to consider a treatment regimen based on this while awaiting mature survival data,” Dr. Omene added. “The increase in nausea and vomiting seen in oral SERD arm is likely manageable, as there were no significant differences in discontinuation in both arms of treatment.”

The study was supported by Radius Health. Dr. Bardia has served as a consultant or on an advisory board for Radius Health, Pfizer, Novartis, Genentech, Merck, Immunomedics/Gilead, Sanofi, Daiichi Sankyo/AstraZeneca, Phillips, Eli Lilly, and Foundation Medicine. He has conducted contracted research or received grants from Genentech, Novartis, Pfizer, Merck, Sanofi, Radius Health, Immunomedics/Gilead, Daiichi Sankyo/AstraZeneca, Natera, and Eli Lilly.

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

Blood pressure control declined in both men and women with the onset of the COVID-19 pandemic in the United States in 2020, especially among women and older adults, according to a new analysis.

Ingram Publishing/ThinkStock

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

Blood pressure control declined in both men and women with the onset of the COVID-19 pandemic in the United States in 2020, especially among women and older adults, according to a new analysis.

Ingram Publishing/ThinkStock

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

Blood pressure control declined in both men and women with the onset of the COVID-19 pandemic in the United States in 2020, especially among women and older adults, according to a new analysis.

Ingram Publishing/ThinkStock

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