Conference Coverage

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.

dbrunk@mdedge.com

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.

dbrunk@mdedge.com

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.

dbrunk@mdedge.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.

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.

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.

Black women who undergo axillary lymph node dissection (ALND) as part of their treatment for breast cancer are at much higher risk of developing lymphedema than comparably treated White women, according to a prospective cohort screening study.

“Axillary lymph node dissection remains the main risk factor for the development of lymphedema,” Andrea Barrio, MD, associate attending physician, Memorial Sloan Kettering Cancer Center, New York, said at a virtual press briefing at the San Antonio Breast Cancer Symposium (SABCS) 2021.

“We observed a higher incidence of lymphedema in Black women treated with ALND and RT [radiotherapy] after adjustment for other variables,” Dr. Barrio added. “While the etiology for this increased incidence is largely unknown, future studies should address the biologic mechanisms behind racial disparities in lymphedema development.”

Dr. Barrio and colleagues included 276 patients in the analysis – 60% were White, 20% Black, 11% Asian, and 6% Hispanic. The remaining 3% did not report race or ethnicity. Patients’ median age at baseline was 48 years, and the median body mass index was 26.4 kg/m2. Slightly over-two thirds of participants had hormone receptor (HR)–positive/HER2-negative breast cancer.

All patients underwent unilateral ALND. About 70% received neoadjuvant chemotherapy (NAC), and the remainder had upfront surgery followed by adjuvant chemotherapy. Ninety-five percent of patients received radiotherapy, and almost all underwent nodal radiotherapy as well.

The median number of lymph nodes removed was 18, and the median number of positive lymph nodes was two. Using a perometer, arm volume was measured at baseline, postoperatively, and every 6 months for a total of 2 years. Lymphedema was defined as a relative increase in arm volume of greater than or equal to 10% from baseline.

At 24 months, almost 25% of the group had lymphedema, but the incidence differed significantly by race and ethnicity. The highest incidence was observed among Black women, at 39.4%, compared to 27.7% of Hispanic women, 23.4% of Asian women, and 20.5% of White women in the study.

The incidence of lymphedema also varied significantly by treatment group. The incidence was twofold greater among women treated with NAC in comparison with those who underwent upfront surgery (30.9% vs. 11.1%), Dr. Barrio noted.

On multivariate analysis, Black race was the strongest predictor of lymphedema. Compared to White women, Black women had a 3.5-fold greater risk of lymphedema. Hispanic women also had a threefold increased risk compared to White women, but Dr. Barrio cautioned that there were only 16 Hispanic patients in the study.

Older age and increasing time from surgery were also both modestly associated with an increased risk of lymphedema. Among women who ultimately developed lymphedema, “severity did not vary across race or ethnicity with similar relative volume changes observed,” Dr. Barrio said.

Given that the study found that NAC was an independent predictor of lymphedema, should alternatives to NAC be favored?

Although oncologists provide NAC for a variety of reasons, women with HR-positive/HER2-negative disease – which represent the majority of patients in the current analysis – are most likely to have residual disease after NAC, Dr. Barrio noted. This suggests that oncologists need to start looking at surgical de-escalation trials in this group of patients to help them avoid ALND.

Asked whether oncologists still underestimate the impact that lymphedema has on patients’ quality of life, Virginia Kaklamani, MD, professor of medicine, UT Health San Antonio MD Anderson Cancer Center, Texas, said the oncology community has come a long way.

“Any surgeon or medical oncologist will tell you that in the 1960s and 70s, women were having much higher rates of lymphedema than they are now, so this is something that we do recognize and we are a lot more careful about,” she told this news organization.

Surgical techniques are also better now, and the number of lymph nodes that are being removed is much reduced. Nevertheless, when physicians add ALND and radiation to the axilla, “rates of lymphedema go up,” Dr. Kaklamani acknowledged. “We need these women to have physical therapy before they develop lymphedema.”

Dr. Barrio agreed, adding that if oncologists could identify earlier thresholds for lymphedema, before patients develop arm swelling, “we may be able to intervene and see a reduction in its development.”

In the meantime, Dr. Barrio and colleagues are testing the protective value of offering immediate lymphatic reconstruction following ALND versus no reconstruction. In addition, they will be studying banked tissue from Black women to better understand any racial differences in inflammatory responses, the risk of fibrosis, and the reaction to radiotherapy.

“I think we see that inflammation is a key driver of lymphedema development, and so maybe Black women are predisposed to a different inflammatory reaction to treatment or perhaps have higher levels of inflammation at baseline,” Dr. Barrio speculated.

“I think it’s also important to stratify a woman’s risk for lymphedema, and once we can tailor that risk, we can start to identify which patients might benefit from preventative strategies,” she added.

Dr. Barrio has disclosed no relevant financial relationships. Dr. Kaklamani has served as a consultant for Puma, AstraZeneca, Athenex, and Immunomedics and as a speaker for Pfizer, Celgene, Genentech, Genomic Health, Puma, Eisai, Novartis, AstraZeneca, Daiichi Sankyo, and Seattle Genetics. She has also received research funding from Eisai.

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

Black women who undergo axillary lymph node dissection (ALND) as part of their treatment for breast cancer are at much higher risk of developing lymphedema than comparably treated White women, according to a prospective cohort screening study.

“Axillary lymph node dissection remains the main risk factor for the development of lymphedema,” Andrea Barrio, MD, associate attending physician, Memorial Sloan Kettering Cancer Center, New York, said at a virtual press briefing at the San Antonio Breast Cancer Symposium (SABCS) 2021.

“We observed a higher incidence of lymphedema in Black women treated with ALND and RT [radiotherapy] after adjustment for other variables,” Dr. Barrio added. “While the etiology for this increased incidence is largely unknown, future studies should address the biologic mechanisms behind racial disparities in lymphedema development.”

Dr. Barrio and colleagues included 276 patients in the analysis – 60% were White, 20% Black, 11% Asian, and 6% Hispanic. The remaining 3% did not report race or ethnicity. Patients’ median age at baseline was 48 years, and the median body mass index was 26.4 kg/m2. Slightly over-two thirds of participants had hormone receptor (HR)–positive/HER2-negative breast cancer.

All patients underwent unilateral ALND. About 70% received neoadjuvant chemotherapy (NAC), and the remainder had upfront surgery followed by adjuvant chemotherapy. Ninety-five percent of patients received radiotherapy, and almost all underwent nodal radiotherapy as well.

The median number of lymph nodes removed was 18, and the median number of positive lymph nodes was two. Using a perometer, arm volume was measured at baseline, postoperatively, and every 6 months for a total of 2 years. Lymphedema was defined as a relative increase in arm volume of greater than or equal to 10% from baseline.

At 24 months, almost 25% of the group had lymphedema, but the incidence differed significantly by race and ethnicity. The highest incidence was observed among Black women, at 39.4%, compared to 27.7% of Hispanic women, 23.4% of Asian women, and 20.5% of White women in the study.

The incidence of lymphedema also varied significantly by treatment group. The incidence was twofold greater among women treated with NAC in comparison with those who underwent upfront surgery (30.9% vs. 11.1%), Dr. Barrio noted.

On multivariate analysis, Black race was the strongest predictor of lymphedema. Compared to White women, Black women had a 3.5-fold greater risk of lymphedema. Hispanic women also had a threefold increased risk compared to White women, but Dr. Barrio cautioned that there were only 16 Hispanic patients in the study.

Older age and increasing time from surgery were also both modestly associated with an increased risk of lymphedema. Among women who ultimately developed lymphedema, “severity did not vary across race or ethnicity with similar relative volume changes observed,” Dr. Barrio said.

Given that the study found that NAC was an independent predictor of lymphedema, should alternatives to NAC be favored?

Although oncologists provide NAC for a variety of reasons, women with HR-positive/HER2-negative disease – which represent the majority of patients in the current analysis – are most likely to have residual disease after NAC, Dr. Barrio noted. This suggests that oncologists need to start looking at surgical de-escalation trials in this group of patients to help them avoid ALND.

Asked whether oncologists still underestimate the impact that lymphedema has on patients’ quality of life, Virginia Kaklamani, MD, professor of medicine, UT Health San Antonio MD Anderson Cancer Center, Texas, said the oncology community has come a long way.

“Any surgeon or medical oncologist will tell you that in the 1960s and 70s, women were having much higher rates of lymphedema than they are now, so this is something that we do recognize and we are a lot more careful about,” she told this news organization.

Surgical techniques are also better now, and the number of lymph nodes that are being removed is much reduced. Nevertheless, when physicians add ALND and radiation to the axilla, “rates of lymphedema go up,” Dr. Kaklamani acknowledged. “We need these women to have physical therapy before they develop lymphedema.”

Dr. Barrio agreed, adding that if oncologists could identify earlier thresholds for lymphedema, before patients develop arm swelling, “we may be able to intervene and see a reduction in its development.”

In the meantime, Dr. Barrio and colleagues are testing the protective value of offering immediate lymphatic reconstruction following ALND versus no reconstruction. In addition, they will be studying banked tissue from Black women to better understand any racial differences in inflammatory responses, the risk of fibrosis, and the reaction to radiotherapy.

“I think we see that inflammation is a key driver of lymphedema development, and so maybe Black women are predisposed to a different inflammatory reaction to treatment or perhaps have higher levels of inflammation at baseline,” Dr. Barrio speculated.

“I think it’s also important to stratify a woman’s risk for lymphedema, and once we can tailor that risk, we can start to identify which patients might benefit from preventative strategies,” she added.

Dr. Barrio has disclosed no relevant financial relationships. Dr. Kaklamani has served as a consultant for Puma, AstraZeneca, Athenex, and Immunomedics and as a speaker for Pfizer, Celgene, Genentech, Genomic Health, Puma, Eisai, Novartis, AstraZeneca, Daiichi Sankyo, and Seattle Genetics. She has also received research funding from Eisai.

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

Black women who undergo axillary lymph node dissection (ALND) as part of their treatment for breast cancer are at much higher risk of developing lymphedema than comparably treated White women, according to a prospective cohort screening study.

“Axillary lymph node dissection remains the main risk factor for the development of lymphedema,” Andrea Barrio, MD, associate attending physician, Memorial Sloan Kettering Cancer Center, New York, said at a virtual press briefing at the San Antonio Breast Cancer Symposium (SABCS) 2021.

“We observed a higher incidence of lymphedema in Black women treated with ALND and RT [radiotherapy] after adjustment for other variables,” Dr. Barrio added. “While the etiology for this increased incidence is largely unknown, future studies should address the biologic mechanisms behind racial disparities in lymphedema development.”

Dr. Barrio and colleagues included 276 patients in the analysis – 60% were White, 20% Black, 11% Asian, and 6% Hispanic. The remaining 3% did not report race or ethnicity. Patients’ median age at baseline was 48 years, and the median body mass index was 26.4 kg/m2. Slightly over-two thirds of participants had hormone receptor (HR)–positive/HER2-negative breast cancer.

All patients underwent unilateral ALND. About 70% received neoadjuvant chemotherapy (NAC), and the remainder had upfront surgery followed by adjuvant chemotherapy. Ninety-five percent of patients received radiotherapy, and almost all underwent nodal radiotherapy as well.

The median number of lymph nodes removed was 18, and the median number of positive lymph nodes was two. Using a perometer, arm volume was measured at baseline, postoperatively, and every 6 months for a total of 2 years. Lymphedema was defined as a relative increase in arm volume of greater than or equal to 10% from baseline.

At 24 months, almost 25% of the group had lymphedema, but the incidence differed significantly by race and ethnicity. The highest incidence was observed among Black women, at 39.4%, compared to 27.7% of Hispanic women, 23.4% of Asian women, and 20.5% of White women in the study.

The incidence of lymphedema also varied significantly by treatment group. The incidence was twofold greater among women treated with NAC in comparison with those who underwent upfront surgery (30.9% vs. 11.1%), Dr. Barrio noted.

On multivariate analysis, Black race was the strongest predictor of lymphedema. Compared to White women, Black women had a 3.5-fold greater risk of lymphedema. Hispanic women also had a threefold increased risk compared to White women, but Dr. Barrio cautioned that there were only 16 Hispanic patients in the study.

Older age and increasing time from surgery were also both modestly associated with an increased risk of lymphedema. Among women who ultimately developed lymphedema, “severity did not vary across race or ethnicity with similar relative volume changes observed,” Dr. Barrio said.

Given that the study found that NAC was an independent predictor of lymphedema, should alternatives to NAC be favored?

Although oncologists provide NAC for a variety of reasons, women with HR-positive/HER2-negative disease – which represent the majority of patients in the current analysis – are most likely to have residual disease after NAC, Dr. Barrio noted. This suggests that oncologists need to start looking at surgical de-escalation trials in this group of patients to help them avoid ALND.

Asked whether oncologists still underestimate the impact that lymphedema has on patients’ quality of life, Virginia Kaklamani, MD, professor of medicine, UT Health San Antonio MD Anderson Cancer Center, Texas, said the oncology community has come a long way.

“Any surgeon or medical oncologist will tell you that in the 1960s and 70s, women were having much higher rates of lymphedema than they are now, so this is something that we do recognize and we are a lot more careful about,” she told this news organization.

Surgical techniques are also better now, and the number of lymph nodes that are being removed is much reduced. Nevertheless, when physicians add ALND and radiation to the axilla, “rates of lymphedema go up,” Dr. Kaklamani acknowledged. “We need these women to have physical therapy before they develop lymphedema.”

Dr. Barrio agreed, adding that if oncologists could identify earlier thresholds for lymphedema, before patients develop arm swelling, “we may be able to intervene and see a reduction in its development.”

In the meantime, Dr. Barrio and colleagues are testing the protective value of offering immediate lymphatic reconstruction following ALND versus no reconstruction. In addition, they will be studying banked tissue from Black women to better understand any racial differences in inflammatory responses, the risk of fibrosis, and the reaction to radiotherapy.

“I think we see that inflammation is a key driver of lymphedema development, and so maybe Black women are predisposed to a different inflammatory reaction to treatment or perhaps have higher levels of inflammation at baseline,” Dr. Barrio speculated.

“I think it’s also important to stratify a woman’s risk for lymphedema, and once we can tailor that risk, we can start to identify which patients might benefit from preventative strategies,” she added.

Dr. Barrio has disclosed no relevant financial relationships. Dr. Kaklamani has served as a consultant for Puma, AstraZeneca, Athenex, and Immunomedics and as a speaker for Pfizer, Celgene, Genentech, Genomic Health, Puma, Eisai, Novartis, AstraZeneca, Daiichi Sankyo, and Seattle Genetics. She has also received research funding from Eisai.

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

The surgical resection rates of the primary tumor in metastatic breast cancer has declined in recent years, possibly reflecting changes in practice following randomized, controlled trials that have not consistently shown a survival benefit.

Retrospective studies have suggested a possible benefit to resection, according to Sasha Douglas, MD, who presented the study (abstract PD7-06) at the 2021 San Antonio Breast Cancer Symposium. “Intuitively, you would think that you would want to get the primary tumor out even if it’s metastasized, so that it couldn’t metastasize more,” said Dr. Douglas, who is a surgical resident at the University of California, San Diego.

However, clinical trials have yielded mixed results, and the picture is complicated by the various molecular subtypes of breast cancer, metastatic sites, and other factors. “Different studies, whether it’s retrospective, and a really large database that has lots of numbers of patients, can give you a different answer than a smaller prospective randomized, controlled study in a different cohort of patients. So, we just thought it would be really interesting to look at all the trends over time at Commission on Cancer–accredited hospitals. Do they seem to be following what the latest literature is showing?” Dr. Douglas said in an interview.

The researchers used data from 87,331 cases from the National Cancer Database (NCDB) and examined rates of primary surgery as well as palliative care in women with metastatic breast cancer who had responded well to systemic therapy.

Between 2004 and 2009, the frequency of primary tumor resection remained near 35% (with a peak of 37% in 2009), then began a steady descent to 18% by 2017. The researchers found similar trends in estrogen receptor–positive/progesterone receptor–positive, HER2-negative (ER/PR+HERer2–); HER2-positive; and triple-negative subtypes.

In 2004, 48% of patients received only systemic therapy, while 37% received some combination of surgery and radiation to the primary tumor. By 2019, 69% received only systemic therapy and 20% received locoregional therapy (P < .001). “It seems that surgeons and providers and medical oncologists are becoming more selective about who they’re going to offer surgery to, and I think that’s very appropriate,” said Dr. Douglas.

But another finding suggests room for improvement: Just 21% of patients received palliative care. “I think that everybody with a major systemic illness like this would benefit from palliative care, just on a supportive basis. The palliative care team can really help people with quality of life, but I think it still has that stigma, and I think that’s what we’ve seen from our study,” said Dr. Douglas.

“We’re just postulating, [but] a lot of that could be from the stigma of thinking that palliative care means giving up. It doesn’t necessarily mean that. It means you’re dealing with a difficult chronic illness, and [palliative care] can be very, very helpful for patients,” said Dr. Douglas.

The study is limited by its retrospective nature, and palliative care might be underreported in the NCDB.

The study was funded by the National Cancer Institute and the University of California, San Diego. Dr. Douglas has no financial disclosures.

The surgical resection rates of the primary tumor in metastatic breast cancer has declined in recent years, possibly reflecting changes in practice following randomized, controlled trials that have not consistently shown a survival benefit.

Retrospective studies have suggested a possible benefit to resection, according to Sasha Douglas, MD, who presented the study (abstract PD7-06) at the 2021 San Antonio Breast Cancer Symposium. “Intuitively, you would think that you would want to get the primary tumor out even if it’s metastasized, so that it couldn’t metastasize more,” said Dr. Douglas, who is a surgical resident at the University of California, San Diego.

However, clinical trials have yielded mixed results, and the picture is complicated by the various molecular subtypes of breast cancer, metastatic sites, and other factors. “Different studies, whether it’s retrospective, and a really large database that has lots of numbers of patients, can give you a different answer than a smaller prospective randomized, controlled study in a different cohort of patients. So, we just thought it would be really interesting to look at all the trends over time at Commission on Cancer–accredited hospitals. Do they seem to be following what the latest literature is showing?” Dr. Douglas said in an interview.

The researchers used data from 87,331 cases from the National Cancer Database (NCDB) and examined rates of primary surgery as well as palliative care in women with metastatic breast cancer who had responded well to systemic therapy.

Between 2004 and 2009, the frequency of primary tumor resection remained near 35% (with a peak of 37% in 2009), then began a steady descent to 18% by 2017. The researchers found similar trends in estrogen receptor–positive/progesterone receptor–positive, HER2-negative (ER/PR+HERer2–); HER2-positive; and triple-negative subtypes.

In 2004, 48% of patients received only systemic therapy, while 37% received some combination of surgery and radiation to the primary tumor. By 2019, 69% received only systemic therapy and 20% received locoregional therapy (P < .001). “It seems that surgeons and providers and medical oncologists are becoming more selective about who they’re going to offer surgery to, and I think that’s very appropriate,” said Dr. Douglas.

But another finding suggests room for improvement: Just 21% of patients received palliative care. “I think that everybody with a major systemic illness like this would benefit from palliative care, just on a supportive basis. The palliative care team can really help people with quality of life, but I think it still has that stigma, and I think that’s what we’ve seen from our study,” said Dr. Douglas.

“We’re just postulating, [but] a lot of that could be from the stigma of thinking that palliative care means giving up. It doesn’t necessarily mean that. It means you’re dealing with a difficult chronic illness, and [palliative care] can be very, very helpful for patients,” said Dr. Douglas.

The study is limited by its retrospective nature, and palliative care might be underreported in the NCDB.

The study was funded by the National Cancer Institute and the University of California, San Diego. Dr. Douglas has no financial disclosures.

The surgical resection rates of the primary tumor in metastatic breast cancer has declined in recent years, possibly reflecting changes in practice following randomized, controlled trials that have not consistently shown a survival benefit.

Retrospective studies have suggested a possible benefit to resection, according to Sasha Douglas, MD, who presented the study (abstract PD7-06) at the 2021 San Antonio Breast Cancer Symposium. “Intuitively, you would think that you would want to get the primary tumor out even if it’s metastasized, so that it couldn’t metastasize more,” said Dr. Douglas, who is a surgical resident at the University of California, San Diego.

However, clinical trials have yielded mixed results, and the picture is complicated by the various molecular subtypes of breast cancer, metastatic sites, and other factors. “Different studies, whether it’s retrospective, and a really large database that has lots of numbers of patients, can give you a different answer than a smaller prospective randomized, controlled study in a different cohort of patients. So, we just thought it would be really interesting to look at all the trends over time at Commission on Cancer–accredited hospitals. Do they seem to be following what the latest literature is showing?” Dr. Douglas said in an interview.

The researchers used data from 87,331 cases from the National Cancer Database (NCDB) and examined rates of primary surgery as well as palliative care in women with metastatic breast cancer who had responded well to systemic therapy.

Between 2004 and 2009, the frequency of primary tumor resection remained near 35% (with a peak of 37% in 2009), then began a steady descent to 18% by 2017. The researchers found similar trends in estrogen receptor–positive/progesterone receptor–positive, HER2-negative (ER/PR+HERer2–); HER2-positive; and triple-negative subtypes.

In 2004, 48% of patients received only systemic therapy, while 37% received some combination of surgery and radiation to the primary tumor. By 2019, 69% received only systemic therapy and 20% received locoregional therapy (P < .001). “It seems that surgeons and providers and medical oncologists are becoming more selective about who they’re going to offer surgery to, and I think that’s very appropriate,” said Dr. Douglas.

But another finding suggests room for improvement: Just 21% of patients received palliative care. “I think that everybody with a major systemic illness like this would benefit from palliative care, just on a supportive basis. The palliative care team can really help people with quality of life, but I think it still has that stigma, and I think that’s what we’ve seen from our study,” said Dr. Douglas.

“We’re just postulating, [but] a lot of that could be from the stigma of thinking that palliative care means giving up. It doesn’t necessarily mean that. It means you’re dealing with a difficult chronic illness, and [palliative care] can be very, very helpful for patients,” said Dr. Douglas.

The study is limited by its retrospective nature, and palliative care might be underreported in the NCDB.

The study was funded by the National Cancer Institute and the University of California, San Diego. Dr. Douglas has no financial disclosures.

A pair of updated scoring models for estimating a patient’s risk for contrast-associated acute kidney injury during and immediately after percutaneous coronary intervention worked better than a widely used prior version in initial validation testing using data collected at a single U.S. tertiary-care hospital.

Mount Sinai Medical Center

While the two new risk scores looked promising, they need further, external validation with additional, diverse patient cohorts, Roxana Mehran, MD, cautioned at the American Heart Association scientific sessions.

“Don’t change anything until we externally validate this,” urged Dr. Mehran, professor and director of the Center for Interventional Cardiovascular Research and Clinical Trials at Icahn School of Medicine at Mount Sinai in New York. External validation of the two new risk scores is in progress with planned reporting of the results in 2022, she said in an interview.

One of the two new algorithms, which both predict a patient’s risk for developing acute kidney injury (AKI) as a result of receiving iodinated contrast media within 48 hours of a percutaneous coronary intervention (PCI), relies on eight easily available variables taken from a patient’s medical record just prior to undergoing PCI: age, type of coronary disease (ranging from asymptomatic or stable angina to ST-segment elevation MI), estimated glomerular filtration rate, left ventricular ejection fraction, diabetes, hemoglobin, basal glucose, and heart failure.

This risk score accounted for 72% (a C-statistic of 0.72) of the observed AKI episodes during the derivation phase, which used data from 14,616 consecutive Mount Sinai patients who underwent PCI during January 2012–December 2017.

Internal validation using data from 5,606 consecutive Mount Sinai patients who underwent PCI during January 2018–December 2020 showed that the eight-item formula accounted for 84% of all incident AKI events occurring during or within 48 hours of a PCI procedure.
 

Accounting for periprocedural variables

A second risk score included the eight preprocedural variables plus four additional periprocedural variables: complex PCI anatomy, contrast volume during the procedure, development of a periprocedural bleed, and having slow or no reflow into affected coronaries (less than TIMI grade 3 flow) immediately after the procedure. The second model produced a C-statistic of 0.74 during derivation and accounted for 86% of incident AKI events in the validation analysis.

The data Dr. Mehran reported appeared in The Lancet .

She and her coauthors designed these two new algorithms to replace a “widely used” and externally validated risk score that Dr. Mehran and associates introduced in 2004. Despite its merits, the 17-year-old scoring formula has limitations including “low discrimination” with a C-statistic of 0.67, derivation from data that’s now 20 years old, and exclusion of patients with ST-elevation MIs, the authors said in the new report.

Dr. Mehran encouraged interventional cardiologists to use both new risk scores (once externally validated) when possible.

The eight-item preprocedural model “gives clinicians an idea about a patient’s risk [for incident AKI] before they go into the catheterization laboratory,” and then they can further refine the risk assessment during the procedure based on the four periprocedural risk factors, she explained. The goal is to target “tailored preventive strategies” to patients identified by the scoring algorithms as being at high risk for AKI.
 

A role for preventive measures

Preventive strategies to consider for higher-risk patients include limiting the administered volume of iodinated contrast media, increasing hydration, and avoiding nephrotoxic agents, Dr. Mehran said. The two new risk-assessment tools will “allow for better evaluation of PCI patients” when testing “innovative strategies and treatments” designed to help avoid contrast-associated AKI.

“The focus to date has been on measures to protect renal function from contrast media, based on indirect data,” Estelle C. Nijssen, MSc, and Joachim E. Wildberger, MD, wrote in an editorial that accompanied the published report. “The effect of prophylactic measures on longer-term averse outcomes is still unclear,” they noted. “Perhaps our focus should shift from contrast and renal function to the heart, the role of which has probably been undervalued in this setting,” wrote Ms. Nijssen, a researcher at Maastricht (The Netherlands) University, and Dr. Wildberger, professor and chairman of the department of radiology at Maastricht University.

The editorial’s authors noted that the two new risk scores have the advantage of relying on variables that are “readily available in clinical practice.” But they also noted several limitations, such as the model’s development from largely low-risk patients who had a low, roughly 30% prevalence of chronic kidney disease. During 9 full years studied, 2012-2020, the annual incidence of AKI showed a downward trend, with an incidence of just over 3% in 2020.

Dr. Mehran attributed this decline in AKI to “great work identifying high-risk patients” and using the prophylactic measures she cited. But even when occurring at relatively low incidence, “AKI is still an important complication that is associated with mortality post PCI,” she stressed.

Establishing a safe contrast dose

“The study is great, and helps reinforce the risk factors that are most important to consider when risk stratifying patients prior to PCI,” said Neal Yuan, MD, a cardiologist at the University of California, San Francisco, who has studied contrast-associated AKI in patients who undergo PCI. The report from Dr. Mehran also “confirms in a large cohort the association between contrast-associated AKI and death,” and describes “an easy method for calculating risk,” he said in an interview.

Dr. Yuan agreed on the need for external validation, and once adequately validated he called for incorporation of the risk score into EHRs. Another important issue for future study is “how much [AKI] risk is too much risk,” he said.

The risk factors identified in Dr. Mehran’s report “are some of the same ones identified in previous studies. Even though this was a more contemporary dataset, there is not a ton of new [findings]; it mainly strengthens findings from prior studies.”

Results published by Dr. Yuan and his associates in 2020 used data from more than 20,000 U.S. patients who underwent PCI to try to identify a generally safe upper limit for the dose of iodinated contrast.

The main purpose for performing AKI risk stratification on PCI patients is to “identify high-risk patients and use preventive strategies when treating these patients.” Current AKI preventive strategies “mainly fall into intravascular volume expansion, and reduced contrast.” What’s less clear is “how to operationalize reduced contrast,” he said.

The report by Dr. Yuan showed that “about 10% of PCI patients were at very high risk” for contrast-associated AKI “no matter what is done.” In contrast, about two-thirds of PCI patients “could receive lots of contrast and still be very unlikely to develop AKI,” Dr. Yuan said.

He voiced some skepticism about the willingness of many clinicians to routinely use a formal risk score to assess their patients scheduled for PCI.

Most operators “approximate AKI risk based on variables such as age and creatinine level, but few take time to put the variables into a calculator to get an exact risk number.” In a “small survey” he ran, he found that these rough approximations often ignore important risk factors like hemoglobin level. This inertia by clinicians against routinely using a risk score could be addressed, at least in part, by integrating the risk score into an EHR for automatic calculation, Dr. Yuan suggested.

Dr. Mehran noted that the risk score that she introduced in 2004 is used “in many EHRs to identify high-risk patients.”

The current study received no commercial or external funding. Dr. Mehran has been a consultant to Boston Scientific, Cine-Med Research, CIRM, and Janssen, and she holds equity in Applied Therapeutics, Elixir Medical, and STEL. Dr. Wildberger had no relevant disclosures. Ms. Nijssen and Dr. Yuan had no disclosures.

mzoler@mdedge.com

A pair of updated scoring models for estimating a patient’s risk for contrast-associated acute kidney injury during and immediately after percutaneous coronary intervention worked better than a widely used prior version in initial validation testing using data collected at a single U.S. tertiary-care hospital.

Mount Sinai Medical Center

While the two new risk scores looked promising, they need further, external validation with additional, diverse patient cohorts, Roxana Mehran, MD, cautioned at the American Heart Association scientific sessions.

“Don’t change anything until we externally validate this,” urged Dr. Mehran, professor and director of the Center for Interventional Cardiovascular Research and Clinical Trials at Icahn School of Medicine at Mount Sinai in New York. External validation of the two new risk scores is in progress with planned reporting of the results in 2022, she said in an interview.

One of the two new algorithms, which both predict a patient’s risk for developing acute kidney injury (AKI) as a result of receiving iodinated contrast media within 48 hours of a percutaneous coronary intervention (PCI), relies on eight easily available variables taken from a patient’s medical record just prior to undergoing PCI: age, type of coronary disease (ranging from asymptomatic or stable angina to ST-segment elevation MI), estimated glomerular filtration rate, left ventricular ejection fraction, diabetes, hemoglobin, basal glucose, and heart failure.

This risk score accounted for 72% (a C-statistic of 0.72) of the observed AKI episodes during the derivation phase, which used data from 14,616 consecutive Mount Sinai patients who underwent PCI during January 2012–December 2017.

Internal validation using data from 5,606 consecutive Mount Sinai patients who underwent PCI during January 2018–December 2020 showed that the eight-item formula accounted for 84% of all incident AKI events occurring during or within 48 hours of a PCI procedure.
 

Accounting for periprocedural variables

A second risk score included the eight preprocedural variables plus four additional periprocedural variables: complex PCI anatomy, contrast volume during the procedure, development of a periprocedural bleed, and having slow or no reflow into affected coronaries (less than TIMI grade 3 flow) immediately after the procedure. The second model produced a C-statistic of 0.74 during derivation and accounted for 86% of incident AKI events in the validation analysis.

The data Dr. Mehran reported appeared in The Lancet .

She and her coauthors designed these two new algorithms to replace a “widely used” and externally validated risk score that Dr. Mehran and associates introduced in 2004. Despite its merits, the 17-year-old scoring formula has limitations including “low discrimination” with a C-statistic of 0.67, derivation from data that’s now 20 years old, and exclusion of patients with ST-elevation MIs, the authors said in the new report.

Dr. Mehran encouraged interventional cardiologists to use both new risk scores (once externally validated) when possible.

The eight-item preprocedural model “gives clinicians an idea about a patient’s risk [for incident AKI] before they go into the catheterization laboratory,” and then they can further refine the risk assessment during the procedure based on the four periprocedural risk factors, she explained. The goal is to target “tailored preventive strategies” to patients identified by the scoring algorithms as being at high risk for AKI.
 

A role for preventive measures

Preventive strategies to consider for higher-risk patients include limiting the administered volume of iodinated contrast media, increasing hydration, and avoiding nephrotoxic agents, Dr. Mehran said. The two new risk-assessment tools will “allow for better evaluation of PCI patients” when testing “innovative strategies and treatments” designed to help avoid contrast-associated AKI.

“The focus to date has been on measures to protect renal function from contrast media, based on indirect data,” Estelle C. Nijssen, MSc, and Joachim E. Wildberger, MD, wrote in an editorial that accompanied the published report. “The effect of prophylactic measures on longer-term averse outcomes is still unclear,” they noted. “Perhaps our focus should shift from contrast and renal function to the heart, the role of which has probably been undervalued in this setting,” wrote Ms. Nijssen, a researcher at Maastricht (The Netherlands) University, and Dr. Wildberger, professor and chairman of the department of radiology at Maastricht University.

The editorial’s authors noted that the two new risk scores have the advantage of relying on variables that are “readily available in clinical practice.” But they also noted several limitations, such as the model’s development from largely low-risk patients who had a low, roughly 30% prevalence of chronic kidney disease. During 9 full years studied, 2012-2020, the annual incidence of AKI showed a downward trend, with an incidence of just over 3% in 2020.

Dr. Mehran attributed this decline in AKI to “great work identifying high-risk patients” and using the prophylactic measures she cited. But even when occurring at relatively low incidence, “AKI is still an important complication that is associated with mortality post PCI,” she stressed.

Establishing a safe contrast dose

“The study is great, and helps reinforce the risk factors that are most important to consider when risk stratifying patients prior to PCI,” said Neal Yuan, MD, a cardiologist at the University of California, San Francisco, who has studied contrast-associated AKI in patients who undergo PCI. The report from Dr. Mehran also “confirms in a large cohort the association between contrast-associated AKI and death,” and describes “an easy method for calculating risk,” he said in an interview.

Dr. Yuan agreed on the need for external validation, and once adequately validated he called for incorporation of the risk score into EHRs. Another important issue for future study is “how much [AKI] risk is too much risk,” he said.

The risk factors identified in Dr. Mehran’s report “are some of the same ones identified in previous studies. Even though this was a more contemporary dataset, there is not a ton of new [findings]; it mainly strengthens findings from prior studies.”

Results published by Dr. Yuan and his associates in 2020 used data from more than 20,000 U.S. patients who underwent PCI to try to identify a generally safe upper limit for the dose of iodinated contrast.

The main purpose for performing AKI risk stratification on PCI patients is to “identify high-risk patients and use preventive strategies when treating these patients.” Current AKI preventive strategies “mainly fall into intravascular volume expansion, and reduced contrast.” What’s less clear is “how to operationalize reduced contrast,” he said.

The report by Dr. Yuan showed that “about 10% of PCI patients were at very high risk” for contrast-associated AKI “no matter what is done.” In contrast, about two-thirds of PCI patients “could receive lots of contrast and still be very unlikely to develop AKI,” Dr. Yuan said.

He voiced some skepticism about the willingness of many clinicians to routinely use a formal risk score to assess their patients scheduled for PCI.

Most operators “approximate AKI risk based on variables such as age and creatinine level, but few take time to put the variables into a calculator to get an exact risk number.” In a “small survey” he ran, he found that these rough approximations often ignore important risk factors like hemoglobin level. This inertia by clinicians against routinely using a risk score could be addressed, at least in part, by integrating the risk score into an EHR for automatic calculation, Dr. Yuan suggested.

Dr. Mehran noted that the risk score that she introduced in 2004 is used “in many EHRs to identify high-risk patients.”

The current study received no commercial or external funding. Dr. Mehran has been a consultant to Boston Scientific, Cine-Med Research, CIRM, and Janssen, and she holds equity in Applied Therapeutics, Elixir Medical, and STEL. Dr. Wildberger had no relevant disclosures. Ms. Nijssen and Dr. Yuan had no disclosures.

mzoler@mdedge.com

A pair of updated scoring models for estimating a patient’s risk for contrast-associated acute kidney injury during and immediately after percutaneous coronary intervention worked better than a widely used prior version in initial validation testing using data collected at a single U.S. tertiary-care hospital.

Mount Sinai Medical Center

While the two new risk scores looked promising, they need further, external validation with additional, diverse patient cohorts, Roxana Mehran, MD, cautioned at the American Heart Association scientific sessions.

“Don’t change anything until we externally validate this,” urged Dr. Mehran, professor and director of the Center for Interventional Cardiovascular Research and Clinical Trials at Icahn School of Medicine at Mount Sinai in New York. External validation of the two new risk scores is in progress with planned reporting of the results in 2022, she said in an interview.

One of the two new algorithms, which both predict a patient’s risk for developing acute kidney injury (AKI) as a result of receiving iodinated contrast media within 48 hours of a percutaneous coronary intervention (PCI), relies on eight easily available variables taken from a patient’s medical record just prior to undergoing PCI: age, type of coronary disease (ranging from asymptomatic or stable angina to ST-segment elevation MI), estimated glomerular filtration rate, left ventricular ejection fraction, diabetes, hemoglobin, basal glucose, and heart failure.

This risk score accounted for 72% (a C-statistic of 0.72) of the observed AKI episodes during the derivation phase, which used data from 14,616 consecutive Mount Sinai patients who underwent PCI during January 2012–December 2017.

Internal validation using data from 5,606 consecutive Mount Sinai patients who underwent PCI during January 2018–December 2020 showed that the eight-item formula accounted for 84% of all incident AKI events occurring during or within 48 hours of a PCI procedure.
 

Accounting for periprocedural variables

A second risk score included the eight preprocedural variables plus four additional periprocedural variables: complex PCI anatomy, contrast volume during the procedure, development of a periprocedural bleed, and having slow or no reflow into affected coronaries (less than TIMI grade 3 flow) immediately after the procedure. The second model produced a C-statistic of 0.74 during derivation and accounted for 86% of incident AKI events in the validation analysis.

The data Dr. Mehran reported appeared in The Lancet .

She and her coauthors designed these two new algorithms to replace a “widely used” and externally validated risk score that Dr. Mehran and associates introduced in 2004. Despite its merits, the 17-year-old scoring formula has limitations including “low discrimination” with a C-statistic of 0.67, derivation from data that’s now 20 years old, and exclusion of patients with ST-elevation MIs, the authors said in the new report.

Dr. Mehran encouraged interventional cardiologists to use both new risk scores (once externally validated) when possible.

The eight-item preprocedural model “gives clinicians an idea about a patient’s risk [for incident AKI] before they go into the catheterization laboratory,” and then they can further refine the risk assessment during the procedure based on the four periprocedural risk factors, she explained. The goal is to target “tailored preventive strategies” to patients identified by the scoring algorithms as being at high risk for AKI.
 

A role for preventive measures

Preventive strategies to consider for higher-risk patients include limiting the administered volume of iodinated contrast media, increasing hydration, and avoiding nephrotoxic agents, Dr. Mehran said. The two new risk-assessment tools will “allow for better evaluation of PCI patients” when testing “innovative strategies and treatments” designed to help avoid contrast-associated AKI.

“The focus to date has been on measures to protect renal function from contrast media, based on indirect data,” Estelle C. Nijssen, MSc, and Joachim E. Wildberger, MD, wrote in an editorial that accompanied the published report. “The effect of prophylactic measures on longer-term averse outcomes is still unclear,” they noted. “Perhaps our focus should shift from contrast and renal function to the heart, the role of which has probably been undervalued in this setting,” wrote Ms. Nijssen, a researcher at Maastricht (The Netherlands) University, and Dr. Wildberger, professor and chairman of the department of radiology at Maastricht University.

The editorial’s authors noted that the two new risk scores have the advantage of relying on variables that are “readily available in clinical practice.” But they also noted several limitations, such as the model’s development from largely low-risk patients who had a low, roughly 30% prevalence of chronic kidney disease. During 9 full years studied, 2012-2020, the annual incidence of AKI showed a downward trend, with an incidence of just over 3% in 2020.

Dr. Mehran attributed this decline in AKI to “great work identifying high-risk patients” and using the prophylactic measures she cited. But even when occurring at relatively low incidence, “AKI is still an important complication that is associated with mortality post PCI,” she stressed.

Establishing a safe contrast dose

“The study is great, and helps reinforce the risk factors that are most important to consider when risk stratifying patients prior to PCI,” said Neal Yuan, MD, a cardiologist at the University of California, San Francisco, who has studied contrast-associated AKI in patients who undergo PCI. The report from Dr. Mehran also “confirms in a large cohort the association between contrast-associated AKI and death,” and describes “an easy method for calculating risk,” he said in an interview.

Dr. Yuan agreed on the need for external validation, and once adequately validated he called for incorporation of the risk score into EHRs. Another important issue for future study is “how much [AKI] risk is too much risk,” he said.

The risk factors identified in Dr. Mehran’s report “are some of the same ones identified in previous studies. Even though this was a more contemporary dataset, there is not a ton of new [findings]; it mainly strengthens findings from prior studies.”

Results published by Dr. Yuan and his associates in 2020 used data from more than 20,000 U.S. patients who underwent PCI to try to identify a generally safe upper limit for the dose of iodinated contrast.

The main purpose for performing AKI risk stratification on PCI patients is to “identify high-risk patients and use preventive strategies when treating these patients.” Current AKI preventive strategies “mainly fall into intravascular volume expansion, and reduced contrast.” What’s less clear is “how to operationalize reduced contrast,” he said.

The report by Dr. Yuan showed that “about 10% of PCI patients were at very high risk” for contrast-associated AKI “no matter what is done.” In contrast, about two-thirds of PCI patients “could receive lots of contrast and still be very unlikely to develop AKI,” Dr. Yuan said.

He voiced some skepticism about the willingness of many clinicians to routinely use a formal risk score to assess their patients scheduled for PCI.

Most operators “approximate AKI risk based on variables such as age and creatinine level, but few take time to put the variables into a calculator to get an exact risk number.” In a “small survey” he ran, he found that these rough approximations often ignore important risk factors like hemoglobin level. This inertia by clinicians against routinely using a risk score could be addressed, at least in part, by integrating the risk score into an EHR for automatic calculation, Dr. Yuan suggested.

Dr. Mehran noted that the risk score that she introduced in 2004 is used “in many EHRs to identify high-risk patients.”

The current study received no commercial or external funding. Dr. Mehran has been a consultant to Boston Scientific, Cine-Med Research, CIRM, and Janssen, and she holds equity in Applied Therapeutics, Elixir Medical, and STEL. Dr. Wildberger had no relevant disclosures. Ms. Nijssen and Dr. Yuan had no disclosures.

mzoler@mdedge.com

In 2021, the American Society of Hematology will be hosting its annual meeting in a hybrid format. Content will be presented both live and in person at the Georgia World Congress Center in Atlanta and also online for those who can’t or don’t want to be there in person.

Inevitably during the ongoing pandemic, the meeting will contain key sessions on COVID-19 in hematology, including a plenary presentation outlining a biologic mechanism for the increased coagulopathy with SARS-CoV-2 infections.

In addition, there will be a scientific symposium on COVID-19 vaccination in immunocompromised patients and a special moderated session summarizing nine abstracts on the science of thrombosis in COVID-19, outcomes in patients with hematologic disease, and vaccine responses.

And speaking of COVID, lest anyone forget, annual meeting attendees will be required to be fully vaccinated and masked. Free COVID-19 testing will be available at stations situated throughout the convention center.
 

Diversifying care

A glimpse of some of the most exciting research to be presented at ASH 2021 was given at a premeeting press briefing by Mikkael A. Sekeres, MD, chair of the ASH committee on communications and chief of the division of hematology at the Sylvester Comprehensive Cancer Center at the University of Miami.

For example, investigators at Massachusetts General Hospital in Boston will present new data on code-status transitions among patients with poor-prognosis high-risk acute myeloid leukemia (AML) who are approaching the end of life. Their findings suggest that physician-patient discussions about the goals of care may occur too late in the course of illness for many patients (abstract 109).

“While there have been many advances in the treatment of acute myeloid leukemia, and in fact there has been significant progress even among high-risk patients, addressing end-of-life issues is an often neglected area,” commented briefing participant Martin A. Tallman, MD, from Memorial Sloan Kettering Cancer Center, New York, who is also the current ASH president.

On a more upbeat note, Dr. Tallman also pointed to the results of the phase 3, randomized AGILE trial as an example of progress in AML, especially for patients with newly diagnosed high-risk disease who have mutations in IDH1. This trial investigated a new approach to treatment, with a combination of the combination of the IDH1 inhibitor ivosidenib (Tibsovo) and azacitidine, and compared it with azacitidine alone. The investigators assessed impact on event-free survival, overall survival, and clinical responses (abstract 697).

Dr. Tallman also highlighted abstracts touching on racial, social, and socioeconomic contributors to health care disparities among children with acute lymphoblastic leukemia (ALL; abstract 211) and on clinical trial enrollment characteristics and outcomes for Black and Hispanic adolescents and young adults with ALL (abstract 337).
 

Immunotherapy advances

Some of the most eagerly awaited abstracts will be highlighting advances in immunotherapy for hematologic malignancies, and these were previewed by Cynthia E. Dunbar, MD, ASH secretary and chief of the Translational Stem Cell Biology Branch within the Intramural Research Program of the National Heart, Lung, and Blood Institute in Bethesda, Md.

These abstracts include the primary analysis of the ZUMA-7 trial, a randomized, phase 3 study comparing the chimeric antigen receptor T-cell (CAR T) construct axicabtagene ciloleucel (axi-cel; Yescarta) with standard of care in patients with relapsed or refractory large B-cell lymphomas (LBCLs; abstract 2) and the interim analysis of the randomized, phase 3 Transform Study comparing the CAR T construct lisocabtagene maralecleucl (liso-cel; Breyanzi) with salvage chemotherapy in patients with relapsed/refractory LBCL (abstract 91).

“Over 500 patients were enrolled in the two studies, and both abstracts report significantly longer survival without relapse in the CAR T arm – for instance, fourfold higher in ZUMA-7, compared to standard of care,” Dr. Dunbar said at the briefing.

“These abstracts provide really critical information to patients, their treating physicians, and the payers who are trying to decide whether use of these expensive, complex, and potentially toxic CAR T-cell therapies are justified, compared to standard therapy,” she said.

Dr. Dunbar also highlighted an abstract on the addition of the anti-CD38 monoclonal antibody isatuximab (Sarclisa) to lenalidomide, bortezomib, and dexamethasone as induction therapy for patients with newly diagnosed multiple myeloma who are eligible for stem cell transplantation (abstract 463).

“The authors report that patients on the isatuximab arm had significantly fewer tumor cells following treatment,” Dr. Dunbar said. “We have come a long way beyond treating myeloma with a single drug, with remissions now measured in many years instead of 1 or 2 following initiation of treatment, and this abstract is another demonstration that novel combinations of multiple agents are really making a difference in this very debilitating disease.”

She also cited an abstract (abstract 127) on monotherapy with the novel bispecific T-cell–engaging monoclonal antibody mosunetuzumab for treatment of patients with follicular lymphoma that has relapsed or is refractory to at least two prior lines of therapy.
 

Old disorders, new insights

Other abstracts highlighted at the premeeting press briefing included a study that found a high prevalence of monoclonal gammopathy in persons at risk for multiple myeloma (abstract 152) and another with the surprising finding that clonal hematopoiesis, a risk factor myeloid malignancies, may be protective against Alzheimer’s disease (abstract 5).

In addition, a long-term follow-up study of patients with transfusion-dependent beta-thalassemia treated with gene therapy showed that some patients have become transfusion independent and iron homeostasis was restored (abstract 573).
 

Presentations from CDC and FDA

Dr. Sekeres highlighted other events of interest scheduled for ASH 2021, including a Grassroots Network Lunch featuring a discussion with Rochelle Walensky, MD, MPH, director of the Centers for Disease Control and Prevention in Atlanta, and a joint symposium between ASH and the Food and Drug Administration on newly approved drugs in hematology.

Dr. Sekeres has disclosed consulting/advising for Novartis, Takea/Millennium, and Bristol-Myers Squibb. Dr. Dunbar reported no relevant conflicts of interest. Dr. Tallman disclosed consulting/advising with and research funding from multiple entities.

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

In 2021, the American Society of Hematology will be hosting its annual meeting in a hybrid format. Content will be presented both live and in person at the Georgia World Congress Center in Atlanta and also online for those who can’t or don’t want to be there in person.

Inevitably during the ongoing pandemic, the meeting will contain key sessions on COVID-19 in hematology, including a plenary presentation outlining a biologic mechanism for the increased coagulopathy with SARS-CoV-2 infections.

In addition, there will be a scientific symposium on COVID-19 vaccination in immunocompromised patients and a special moderated session summarizing nine abstracts on the science of thrombosis in COVID-19, outcomes in patients with hematologic disease, and vaccine responses.

And speaking of COVID, lest anyone forget, annual meeting attendees will be required to be fully vaccinated and masked. Free COVID-19 testing will be available at stations situated throughout the convention center.
 

Diversifying care

A glimpse of some of the most exciting research to be presented at ASH 2021 was given at a premeeting press briefing by Mikkael A. Sekeres, MD, chair of the ASH committee on communications and chief of the division of hematology at the Sylvester Comprehensive Cancer Center at the University of Miami.

For example, investigators at Massachusetts General Hospital in Boston will present new data on code-status transitions among patients with poor-prognosis high-risk acute myeloid leukemia (AML) who are approaching the end of life. Their findings suggest that physician-patient discussions about the goals of care may occur too late in the course of illness for many patients (abstract 109).

“While there have been many advances in the treatment of acute myeloid leukemia, and in fact there has been significant progress even among high-risk patients, addressing end-of-life issues is an often neglected area,” commented briefing participant Martin A. Tallman, MD, from Memorial Sloan Kettering Cancer Center, New York, who is also the current ASH president.

On a more upbeat note, Dr. Tallman also pointed to the results of the phase 3, randomized AGILE trial as an example of progress in AML, especially for patients with newly diagnosed high-risk disease who have mutations in IDH1. This trial investigated a new approach to treatment, with a combination of the combination of the IDH1 inhibitor ivosidenib (Tibsovo) and azacitidine, and compared it with azacitidine alone. The investigators assessed impact on event-free survival, overall survival, and clinical responses (abstract 697).

Dr. Tallman also highlighted abstracts touching on racial, social, and socioeconomic contributors to health care disparities among children with acute lymphoblastic leukemia (ALL; abstract 211) and on clinical trial enrollment characteristics and outcomes for Black and Hispanic adolescents and young adults with ALL (abstract 337).
 

Immunotherapy advances

Some of the most eagerly awaited abstracts will be highlighting advances in immunotherapy for hematologic malignancies, and these were previewed by Cynthia E. Dunbar, MD, ASH secretary and chief of the Translational Stem Cell Biology Branch within the Intramural Research Program of the National Heart, Lung, and Blood Institute in Bethesda, Md.

These abstracts include the primary analysis of the ZUMA-7 trial, a randomized, phase 3 study comparing the chimeric antigen receptor T-cell (CAR T) construct axicabtagene ciloleucel (axi-cel; Yescarta) with standard of care in patients with relapsed or refractory large B-cell lymphomas (LBCLs; abstract 2) and the interim analysis of the randomized, phase 3 Transform Study comparing the CAR T construct lisocabtagene maralecleucl (liso-cel; Breyanzi) with salvage chemotherapy in patients with relapsed/refractory LBCL (abstract 91).

“Over 500 patients were enrolled in the two studies, and both abstracts report significantly longer survival without relapse in the CAR T arm – for instance, fourfold higher in ZUMA-7, compared to standard of care,” Dr. Dunbar said at the briefing.

“These abstracts provide really critical information to patients, their treating physicians, and the payers who are trying to decide whether use of these expensive, complex, and potentially toxic CAR T-cell therapies are justified, compared to standard therapy,” she said.

Dr. Dunbar also highlighted an abstract on the addition of the anti-CD38 monoclonal antibody isatuximab (Sarclisa) to lenalidomide, bortezomib, and dexamethasone as induction therapy for patients with newly diagnosed multiple myeloma who are eligible for stem cell transplantation (abstract 463).

“The authors report that patients on the isatuximab arm had significantly fewer tumor cells following treatment,” Dr. Dunbar said. “We have come a long way beyond treating myeloma with a single drug, with remissions now measured in many years instead of 1 or 2 following initiation of treatment, and this abstract is another demonstration that novel combinations of multiple agents are really making a difference in this very debilitating disease.”

She also cited an abstract (abstract 127) on monotherapy with the novel bispecific T-cell–engaging monoclonal antibody mosunetuzumab for treatment of patients with follicular lymphoma that has relapsed or is refractory to at least two prior lines of therapy.
 

Old disorders, new insights

Other abstracts highlighted at the premeeting press briefing included a study that found a high prevalence of monoclonal gammopathy in persons at risk for multiple myeloma (abstract 152) and another with the surprising finding that clonal hematopoiesis, a risk factor myeloid malignancies, may be protective against Alzheimer’s disease (abstract 5).

In addition, a long-term follow-up study of patients with transfusion-dependent beta-thalassemia treated with gene therapy showed that some patients have become transfusion independent and iron homeostasis was restored (abstract 573).
 

Presentations from CDC and FDA

Dr. Sekeres highlighted other events of interest scheduled for ASH 2021, including a Grassroots Network Lunch featuring a discussion with Rochelle Walensky, MD, MPH, director of the Centers for Disease Control and Prevention in Atlanta, and a joint symposium between ASH and the Food and Drug Administration on newly approved drugs in hematology.

Dr. Sekeres has disclosed consulting/advising for Novartis, Takea/Millennium, and Bristol-Myers Squibb. Dr. Dunbar reported no relevant conflicts of interest. Dr. Tallman disclosed consulting/advising with and research funding from multiple entities.

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

In 2021, the American Society of Hematology will be hosting its annual meeting in a hybrid format. Content will be presented both live and in person at the Georgia World Congress Center in Atlanta and also online for those who can’t or don’t want to be there in person.

Inevitably during the ongoing pandemic, the meeting will contain key sessions on COVID-19 in hematology, including a plenary presentation outlining a biologic mechanism for the increased coagulopathy with SARS-CoV-2 infections.

In addition, there will be a scientific symposium on COVID-19 vaccination in immunocompromised patients and a special moderated session summarizing nine abstracts on the science of thrombosis in COVID-19, outcomes in patients with hematologic disease, and vaccine responses.

And speaking of COVID, lest anyone forget, annual meeting attendees will be required to be fully vaccinated and masked. Free COVID-19 testing will be available at stations situated throughout the convention center.
 

Diversifying care

A glimpse of some of the most exciting research to be presented at ASH 2021 was given at a premeeting press briefing by Mikkael A. Sekeres, MD, chair of the ASH committee on communications and chief of the division of hematology at the Sylvester Comprehensive Cancer Center at the University of Miami.

For example, investigators at Massachusetts General Hospital in Boston will present new data on code-status transitions among patients with poor-prognosis high-risk acute myeloid leukemia (AML) who are approaching the end of life. Their findings suggest that physician-patient discussions about the goals of care may occur too late in the course of illness for many patients (abstract 109).

“While there have been many advances in the treatment of acute myeloid leukemia, and in fact there has been significant progress even among high-risk patients, addressing end-of-life issues is an often neglected area,” commented briefing participant Martin A. Tallman, MD, from Memorial Sloan Kettering Cancer Center, New York, who is also the current ASH president.

On a more upbeat note, Dr. Tallman also pointed to the results of the phase 3, randomized AGILE trial as an example of progress in AML, especially for patients with newly diagnosed high-risk disease who have mutations in IDH1. This trial investigated a new approach to treatment, with a combination of the combination of the IDH1 inhibitor ivosidenib (Tibsovo) and azacitidine, and compared it with azacitidine alone. The investigators assessed impact on event-free survival, overall survival, and clinical responses (abstract 697).

Dr. Tallman also highlighted abstracts touching on racial, social, and socioeconomic contributors to health care disparities among children with acute lymphoblastic leukemia (ALL; abstract 211) and on clinical trial enrollment characteristics and outcomes for Black and Hispanic adolescents and young adults with ALL (abstract 337).
 

Immunotherapy advances

Some of the most eagerly awaited abstracts will be highlighting advances in immunotherapy for hematologic malignancies, and these were previewed by Cynthia E. Dunbar, MD, ASH secretary and chief of the Translational Stem Cell Biology Branch within the Intramural Research Program of the National Heart, Lung, and Blood Institute in Bethesda, Md.

These abstracts include the primary analysis of the ZUMA-7 trial, a randomized, phase 3 study comparing the chimeric antigen receptor T-cell (CAR T) construct axicabtagene ciloleucel (axi-cel; Yescarta) with standard of care in patients with relapsed or refractory large B-cell lymphomas (LBCLs; abstract 2) and the interim analysis of the randomized, phase 3 Transform Study comparing the CAR T construct lisocabtagene maralecleucl (liso-cel; Breyanzi) with salvage chemotherapy in patients with relapsed/refractory LBCL (abstract 91).

“Over 500 patients were enrolled in the two studies, and both abstracts report significantly longer survival without relapse in the CAR T arm – for instance, fourfold higher in ZUMA-7, compared to standard of care,” Dr. Dunbar said at the briefing.

“These abstracts provide really critical information to patients, their treating physicians, and the payers who are trying to decide whether use of these expensive, complex, and potentially toxic CAR T-cell therapies are justified, compared to standard therapy,” she said.

Dr. Dunbar also highlighted an abstract on the addition of the anti-CD38 monoclonal antibody isatuximab (Sarclisa) to lenalidomide, bortezomib, and dexamethasone as induction therapy for patients with newly diagnosed multiple myeloma who are eligible for stem cell transplantation (abstract 463).

“The authors report that patients on the isatuximab arm had significantly fewer tumor cells following treatment,” Dr. Dunbar said. “We have come a long way beyond treating myeloma with a single drug, with remissions now measured in many years instead of 1 or 2 following initiation of treatment, and this abstract is another demonstration that novel combinations of multiple agents are really making a difference in this very debilitating disease.”

She also cited an abstract (abstract 127) on monotherapy with the novel bispecific T-cell–engaging monoclonal antibody mosunetuzumab for treatment of patients with follicular lymphoma that has relapsed or is refractory to at least two prior lines of therapy.
 

Old disorders, new insights

Other abstracts highlighted at the premeeting press briefing included a study that found a high prevalence of monoclonal gammopathy in persons at risk for multiple myeloma (abstract 152) and another with the surprising finding that clonal hematopoiesis, a risk factor myeloid malignancies, may be protective against Alzheimer’s disease (abstract 5).

In addition, a long-term follow-up study of patients with transfusion-dependent beta-thalassemia treated with gene therapy showed that some patients have become transfusion independent and iron homeostasis was restored (abstract 573).
 

Presentations from CDC and FDA

Dr. Sekeres highlighted other events of interest scheduled for ASH 2021, including a Grassroots Network Lunch featuring a discussion with Rochelle Walensky, MD, MPH, director of the Centers for Disease Control and Prevention in Atlanta, and a joint symposium between ASH and the Food and Drug Administration on newly approved drugs in hematology.

Dr. Sekeres has disclosed consulting/advising for Novartis, Takea/Millennium, and Bristol-Myers Squibb. Dr. Dunbar reported no relevant conflicts of interest. Dr. Tallman disclosed consulting/advising with and research funding from multiple entities.

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

A new lipid-lowering agent in a class that had been written off by many is being developed by a group of academic experts, with new data showing large LDL reductions on top of high-intensity statins.

Obicetrapib is a member of the cholesteryl ester transfer protein (CETP) inhibitor class, which had fallen out of favor after several disappointments with previous drugs in this class.

These agents were initially developed for their ability to raise HDL cholesterol, which was thought to be beneficial. But that approach has now been virtually abandoned after several studies failed to show a link between raising HDL and a reduction in subsequent cardiovascular events.

However, obicetrapib, which is said to be the most potent CETP inhibitor to date, has been shown to produce impressive LDL reductions, and it’s this important data that has caused several lipid experts to want to continue its development.

New data, presented at the recent American Heart Association scientific sessions, show that obicetrapib reduces LDL by 50% when given in addition to high-intensity statins, which could place it as competition for PCSK9 inhibitors or the new agent, inclisiran, but with the advantage of oral dosing.

The drug was in development by Amgen, but the company decided to discontinue its development in 2017 after disappointing results had been seen with several other CETP inhibitors and interest in this class of agent was waning.

But academic experts in the lipid field, led by John Kastelein, MD, PhD, professor of medicine at the Academic Medical Center, University of Amsterdam, and Michael Davidson, MD, clinical professor of medicine at University of Chicago, believed the drug had potential and have acquired obicetrapib from Amgen.

Dr. Kastelein and Dr. Davidson have set up a new company – New Amsterdam Pharma – to further develop obicetrapib, and have raised $200 million from venture capital funding to complete phase 2 and phase 3 studies.

The company has a heavyweight academic advisory board including Stephen Nicholls, MD, Monash University, Clayton, Australia; Kausik Ray, MD, Imperial College London; and Christie Ballantyne, MD, Baylor College of Medicine, Houston.

“We wanted to develop obicetrapib further because of its amazing LDL-lowering properties,” Dr. Kastelein said in an interview.

“No one has paid much attention to CETP inhibitors after the HDL hypothesis was disregarded, as everyone thought these drugs were just about raising HDL. But actually, they can also lower LDL, and this particular agent reduces LDL very effectively,” Dr. Kastelein said.
 

ROSE study

Dr. Nicholls presented the latest data on obicetrapib at the AHA meeting.

“Despite the use of high-intensity statins, two-thirds of patients do not reach their target LDL level, so we have a need for new therapies that lower LDL and can be used in combination with high-intensity statins,” he explained.

He noted that earlier studies with obicetrapib showed a 45% lowering of LDL with monotherapy.

Dr. Nicholls reported that recent evidence has emerged that increases interest in inhibiting CETP to be potentially cardioprotective.

To begin, genetic studies have shown that genetic polymorphisms associated with lower levels of CETP appear to be cardioprotective, and this is associated with lower levels of LDL rather than higher levels of HDL. 

Furthermore, the REVEAL cardiovascular outcomes trial with anacetrapib (also a CETP inhibitor) in 2017 showed a significant 9% reduction in major adverse cardiac events (MACE) after 4 years of follow-up. “This was exactly predicted by the 11 mg/dL drop in absolute LDL cholesterol level. It was not predicted or associated with the increase in HDL level observed with that agent,” Dr. Nicholls said.

The objective of the current ROSE study was to evaluate the lipid-lowering ability, safety, and tolerability of obicetrapib in patients on high-intensity statins.

The study included 120 patients who had been treated on a stable dose of high-intensity statins (atorvastatin at a dose of at least 40 mg daily or rosuvastatin at a dose of 20 mg daily) for at least 8 weeks. All patients were required to have a fasting LDL of at least 70 mg/dL and the median baseline LDL was 90 mg/dL. They were randomly assigned to obicetrapib (5 mg or 10 mg daily) or placebo.

The primary endpoint was the difference between groups in percentage change in LDL from baseline to week 8, with LDL levels measured by two different techniques.

Results showed a “robust” 51% reduction in LDL with the 10-mg dose of obicetrapib, and a 42% reduction with the 5-mg dose, Dr. Nicholls reported.

These effects were comparable regardless of baseline LDL and were similar with both methods of LDL measurement. 

Almost all patients demonstrated some degree of LDL cholesterol lowering, with only three patients on the 5-mg dose and one patient on the 10-mg dose not showing any reduction in LDL.

Other results showed a dose-dependent lowering of Apo B of up to 30%, and a reduction of non-HDL cholesterol of up to 44%.

“Predictably, there were also increases of HDL cholesterol,” Dr. Nicholls said. “At the 10-mg dose, we see a 165% increase in HDL levels. That is associated with a 48% increase in Apo A1 levels. This is very consistent with findings from the previous monotherapy study.”  

There was a 56% reduction in Lp(a) levels, and a modest 11% reduction in triglycerides.

Both doses of obicetrapib were well tolerated, with no increase in the rate of adverse events. Only one patient discontinued the study drug because of an adverse event and that patient was in the placebo group, Dr. Nicholls noted.  

“Blood pressure is an important adverse event to look at in the CETP class given the challenges seen with the first CETP evaluated – torcetrapib,” Dr. Nicholls said. “But in the three clinical trials with obicetrapib conducted to date, reassuringly, we see no increase in either systolic or diastolic blood pressure with either the 5-mg or 10-mg dose.”

He concluded that obicetrapib “could be a valuable addition to high-risk patients with atherosclerotic cardiovascular disease who do not achieve their target LDL level despite use of high-intensity statin therapy.”
 

Differences from other CETP inhibitors

Asked how obicetrapib differs from other agents in the CETP inhibitor class, Dr. Nicholls replied that obicetrapib is much more potent, as shown by the large lipid changes seen with very small quantities of this drug, 5 mg or 10 mg, whereas prior CETP inhibitors showed smaller changes with much higher doses.

“We are giving very small amounts of obicetrapib and seeing very robust effects on both atherogenic and lipid parameters,” he said.  

“The other major point with this class of agent is that the first drug, torcetrapib, had toxicity, which resulted in increased cardiovascular events. But it has now been established that torcetrapib had a number of off-target effects that have not been seen with subsequent agents in this class,” he said.

Studies so far show that obicetrapib does not have torcetrapib-like effects. “That is encouraging. This, and the impressive LDL lowering effects, certainly lay the foundation for larger studies moving forward,” he added.

“This has been an intriguing field to many of us involved from the start. We started with a very disappointing result with torcetrapib. Then a couple of studies looked to be clinically futile, but we were encouraged by the REVEAL study which suggested that there might be benefit,” Dr. Nicholls said.

“If we combined the REVEAL results with the genetic data, it has actually flipped the whole CETP story upside down. We started thinking that inhibiting CETP was all about raising HDL, but it turns out that it is about LDL lowering,” he said. “And that is not only important in terms of the lipid effects but also the trials and the way they are designed.

“I think you’ll find that the future trials in this class and with this agent will have LDL very much in mind and that will very much influence the study design,” he said, adding that a larger cardiovascular outcome trial is now being planned. 

“The regulatory perspective is that LDL is a pretty trusted surrogate ... but I think an outcomes trial will be important to reinforce and reassure on safety and outline cost-effectiveness, which will help us understand where the sweet spot for using this agent in the clinic will be,” Dr. Nicholls noted.  

Dr. Kastelein explained that it has taken some time to realize that CETP inhibitors may be valuable for reducing LDL.   

“The first agent, torcetrapib, had an off-target toxicity that led to increased blood pressure but a specific part of the torcetrapib molecule was subsequently identified that was responsible for that, and subsequent agents in the CETP inhibitor class did not have such adverse effects,” he said.  

“The next agent, dalcetrapib (Roche), raised HDL but didn’t move LDL, and an outcomes trial with evacetrapib (Lilly) was stopped after 2 years because of futility, but we now believe that lipid lowering trials need longer term follow-up – up to 5 years – to see a benefit,” he noted.  

Dr. Kastelein reports that anacetrapib (Merck) has been the most powerful CETP inhibitor until now, giving an LDL reduction of about 20%, which was associated with a 10% reduction in cardiovascular events in first 4 years of follow-up. 

“Oxford academic researchers decided to continue follow-up in this trial without Merck and showed a 20% reduction in cardiovascular events by 6 years. This has been the strongest rationale for our investors,” Dr. Kastelein said.   

He pointed out that obicetrapib is much more potent than anacetrapib. “Obicetrapib reduces LDL by 50% at just a 10-mg dose, whereas anacetrapib was used at a dose of 100 mg to give a 17%-20% LDL reduction.”
 

Could HDL increase be beneficial after all?

Although increasing HDL is currently not thought to bring about a direct reduction in cardiovascular events, there is new evidence emerging that increasing HDL may confer some benefit in protecting against the development of type 2 diabetes, Dr. Kastelein noted.

“We know that statins can increase risk of developing type 2 diabetes, and post hoc analyses of previous trials with CETP inhibitors suggest that these drugs have the opposite effect,” he said. “We will investigate this protectively in our phase 3 outcomes trial. If this is a true effect, it should eventually translate into a reduction in cardiovascular outcomes, but this could take a longer time to see than the benefits of lowering LDL.”

Commenting on the current data, Steven Nissen, MD, of Cleveland Clinic, said: “The results are truly impressive – a nearly 50% LDL reduction on a background of statins with a once-daily oral agent. While PCSK9 inhibitors can achieve similar results, they are injectable and costly.

“Since anacetrapib, a much weaker CETP inhibitor, was successful at reducing major adverse cardiac events, the likelihood that obicetrapib would reduce MACE even more substantially is very high,” he added.

Dr. Nissen said he has been aware of this drug for some time and has advised the company about development options and regulatory strategy. “I have encouraged this company to develop this very promising drug,” he said.

The current study was funded by New Amsterdam Pharma. Dr. Nicholls reports grants from AstraZeneca, Amgen, Anthera, Eli Lilly, Esperion, Novartis, Cerenis, The Medicines Company, Resverlogix, Infraredx, Roche, Sanofi-Regeneron and LipoScience, and honoraria from New Amsterdam Pharma, AstraZeneca, Akcea, Eli Lilly, Anthera, Omthera, Merck, Takeda, Resverlogix, Sanofi-Regeneron, CSL Behring, Esperion, and Boehringer Ingelheim. Dr. Kastelein is chief scientific officer of New Amsterdam Pharma.  

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

A new lipid-lowering agent in a class that had been written off by many is being developed by a group of academic experts, with new data showing large LDL reductions on top of high-intensity statins.

Obicetrapib is a member of the cholesteryl ester transfer protein (CETP) inhibitor class, which had fallen out of favor after several disappointments with previous drugs in this class.

These agents were initially developed for their ability to raise HDL cholesterol, which was thought to be beneficial. But that approach has now been virtually abandoned after several studies failed to show a link between raising HDL and a reduction in subsequent cardiovascular events.

However, obicetrapib, which is said to be the most potent CETP inhibitor to date, has been shown to produce impressive LDL reductions, and it’s this important data that has caused several lipid experts to want to continue its development.

New data, presented at the recent American Heart Association scientific sessions, show that obicetrapib reduces LDL by 50% when given in addition to high-intensity statins, which could place it as competition for PCSK9 inhibitors or the new agent, inclisiran, but with the advantage of oral dosing.

The drug was in development by Amgen, but the company decided to discontinue its development in 2017 after disappointing results had been seen with several other CETP inhibitors and interest in this class of agent was waning.

But academic experts in the lipid field, led by John Kastelein, MD, PhD, professor of medicine at the Academic Medical Center, University of Amsterdam, and Michael Davidson, MD, clinical professor of medicine at University of Chicago, believed the drug had potential and have acquired obicetrapib from Amgen.

Dr. Kastelein and Dr. Davidson have set up a new company – New Amsterdam Pharma – to further develop obicetrapib, and have raised $200 million from venture capital funding to complete phase 2 and phase 3 studies.

The company has a heavyweight academic advisory board including Stephen Nicholls, MD, Monash University, Clayton, Australia; Kausik Ray, MD, Imperial College London; and Christie Ballantyne, MD, Baylor College of Medicine, Houston.

“We wanted to develop obicetrapib further because of its amazing LDL-lowering properties,” Dr. Kastelein said in an interview.

“No one has paid much attention to CETP inhibitors after the HDL hypothesis was disregarded, as everyone thought these drugs were just about raising HDL. But actually, they can also lower LDL, and this particular agent reduces LDL very effectively,” Dr. Kastelein said.
 

ROSE study

Dr. Nicholls presented the latest data on obicetrapib at the AHA meeting.

“Despite the use of high-intensity statins, two-thirds of patients do not reach their target LDL level, so we have a need for new therapies that lower LDL and can be used in combination with high-intensity statins,” he explained.

He noted that earlier studies with obicetrapib showed a 45% lowering of LDL with monotherapy.

Dr. Nicholls reported that recent evidence has emerged that increases interest in inhibiting CETP to be potentially cardioprotective.

To begin, genetic studies have shown that genetic polymorphisms associated with lower levels of CETP appear to be cardioprotective, and this is associated with lower levels of LDL rather than higher levels of HDL. 

Furthermore, the REVEAL cardiovascular outcomes trial with anacetrapib (also a CETP inhibitor) in 2017 showed a significant 9% reduction in major adverse cardiac events (MACE) after 4 years of follow-up. “This was exactly predicted by the 11 mg/dL drop in absolute LDL cholesterol level. It was not predicted or associated with the increase in HDL level observed with that agent,” Dr. Nicholls said.

The objective of the current ROSE study was to evaluate the lipid-lowering ability, safety, and tolerability of obicetrapib in patients on high-intensity statins.

The study included 120 patients who had been treated on a stable dose of high-intensity statins (atorvastatin at a dose of at least 40 mg daily or rosuvastatin at a dose of 20 mg daily) for at least 8 weeks. All patients were required to have a fasting LDL of at least 70 mg/dL and the median baseline LDL was 90 mg/dL. They were randomly assigned to obicetrapib (5 mg or 10 mg daily) or placebo.

The primary endpoint was the difference between groups in percentage change in LDL from baseline to week 8, with LDL levels measured by two different techniques.

Results showed a “robust” 51% reduction in LDL with the 10-mg dose of obicetrapib, and a 42% reduction with the 5-mg dose, Dr. Nicholls reported.

These effects were comparable regardless of baseline LDL and were similar with both methods of LDL measurement. 

Almost all patients demonstrated some degree of LDL cholesterol lowering, with only three patients on the 5-mg dose and one patient on the 10-mg dose not showing any reduction in LDL.

Other results showed a dose-dependent lowering of Apo B of up to 30%, and a reduction of non-HDL cholesterol of up to 44%.

“Predictably, there were also increases of HDL cholesterol,” Dr. Nicholls said. “At the 10-mg dose, we see a 165% increase in HDL levels. That is associated with a 48% increase in Apo A1 levels. This is very consistent with findings from the previous monotherapy study.”  

There was a 56% reduction in Lp(a) levels, and a modest 11% reduction in triglycerides.

Both doses of obicetrapib were well tolerated, with no increase in the rate of adverse events. Only one patient discontinued the study drug because of an adverse event and that patient was in the placebo group, Dr. Nicholls noted.  

“Blood pressure is an important adverse event to look at in the CETP class given the challenges seen with the first CETP evaluated – torcetrapib,” Dr. Nicholls said. “But in the three clinical trials with obicetrapib conducted to date, reassuringly, we see no increase in either systolic or diastolic blood pressure with either the 5-mg or 10-mg dose.”

He concluded that obicetrapib “could be a valuable addition to high-risk patients with atherosclerotic cardiovascular disease who do not achieve their target LDL level despite use of high-intensity statin therapy.”
 

Differences from other CETP inhibitors

Asked how obicetrapib differs from other agents in the CETP inhibitor class, Dr. Nicholls replied that obicetrapib is much more potent, as shown by the large lipid changes seen with very small quantities of this drug, 5 mg or 10 mg, whereas prior CETP inhibitors showed smaller changes with much higher doses.

“We are giving very small amounts of obicetrapib and seeing very robust effects on both atherogenic and lipid parameters,” he said.  

“The other major point with this class of agent is that the first drug, torcetrapib, had toxicity, which resulted in increased cardiovascular events. But it has now been established that torcetrapib had a number of off-target effects that have not been seen with subsequent agents in this class,” he said.

Studies so far show that obicetrapib does not have torcetrapib-like effects. “That is encouraging. This, and the impressive LDL lowering effects, certainly lay the foundation for larger studies moving forward,” he added.

“This has been an intriguing field to many of us involved from the start. We started with a very disappointing result with torcetrapib. Then a couple of studies looked to be clinically futile, but we were encouraged by the REVEAL study which suggested that there might be benefit,” Dr. Nicholls said.

“If we combined the REVEAL results with the genetic data, it has actually flipped the whole CETP story upside down. We started thinking that inhibiting CETP was all about raising HDL, but it turns out that it is about LDL lowering,” he said. “And that is not only important in terms of the lipid effects but also the trials and the way they are designed.

“I think you’ll find that the future trials in this class and with this agent will have LDL very much in mind and that will very much influence the study design,” he said, adding that a larger cardiovascular outcome trial is now being planned. 

“The regulatory perspective is that LDL is a pretty trusted surrogate ... but I think an outcomes trial will be important to reinforce and reassure on safety and outline cost-effectiveness, which will help us understand where the sweet spot for using this agent in the clinic will be,” Dr. Nicholls noted.  

Dr. Kastelein explained that it has taken some time to realize that CETP inhibitors may be valuable for reducing LDL.   

“The first agent, torcetrapib, had an off-target toxicity that led to increased blood pressure but a specific part of the torcetrapib molecule was subsequently identified that was responsible for that, and subsequent agents in the CETP inhibitor class did not have such adverse effects,” he said.  

“The next agent, dalcetrapib (Roche), raised HDL but didn’t move LDL, and an outcomes trial with evacetrapib (Lilly) was stopped after 2 years because of futility, but we now believe that lipid lowering trials need longer term follow-up – up to 5 years – to see a benefit,” he noted.  

Dr. Kastelein reports that anacetrapib (Merck) has been the most powerful CETP inhibitor until now, giving an LDL reduction of about 20%, which was associated with a 10% reduction in cardiovascular events in first 4 years of follow-up. 

“Oxford academic researchers decided to continue follow-up in this trial without Merck and showed a 20% reduction in cardiovascular events by 6 years. This has been the strongest rationale for our investors,” Dr. Kastelein said.   

He pointed out that obicetrapib is much more potent than anacetrapib. “Obicetrapib reduces LDL by 50% at just a 10-mg dose, whereas anacetrapib was used at a dose of 100 mg to give a 17%-20% LDL reduction.”
 

Could HDL increase be beneficial after all?

Although increasing HDL is currently not thought to bring about a direct reduction in cardiovascular events, there is new evidence emerging that increasing HDL may confer some benefit in protecting against the development of type 2 diabetes, Dr. Kastelein noted.

“We know that statins can increase risk of developing type 2 diabetes, and post hoc analyses of previous trials with CETP inhibitors suggest that these drugs have the opposite effect,” he said. “We will investigate this protectively in our phase 3 outcomes trial. If this is a true effect, it should eventually translate into a reduction in cardiovascular outcomes, but this could take a longer time to see than the benefits of lowering LDL.”

Commenting on the current data, Steven Nissen, MD, of Cleveland Clinic, said: “The results are truly impressive – a nearly 50% LDL reduction on a background of statins with a once-daily oral agent. While PCSK9 inhibitors can achieve similar results, they are injectable and costly.

“Since anacetrapib, a much weaker CETP inhibitor, was successful at reducing major adverse cardiac events, the likelihood that obicetrapib would reduce MACE even more substantially is very high,” he added.

Dr. Nissen said he has been aware of this drug for some time and has advised the company about development options and regulatory strategy. “I have encouraged this company to develop this very promising drug,” he said.

The current study was funded by New Amsterdam Pharma. Dr. Nicholls reports grants from AstraZeneca, Amgen, Anthera, Eli Lilly, Esperion, Novartis, Cerenis, The Medicines Company, Resverlogix, Infraredx, Roche, Sanofi-Regeneron and LipoScience, and honoraria from New Amsterdam Pharma, AstraZeneca, Akcea, Eli Lilly, Anthera, Omthera, Merck, Takeda, Resverlogix, Sanofi-Regeneron, CSL Behring, Esperion, and Boehringer Ingelheim. Dr. Kastelein is chief scientific officer of New Amsterdam Pharma.  

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

A new lipid-lowering agent in a class that had been written off by many is being developed by a group of academic experts, with new data showing large LDL reductions on top of high-intensity statins.

Obicetrapib is a member of the cholesteryl ester transfer protein (CETP) inhibitor class, which had fallen out of favor after several disappointments with previous drugs in this class.

These agents were initially developed for their ability to raise HDL cholesterol, which was thought to be beneficial. But that approach has now been virtually abandoned after several studies failed to show a link between raising HDL and a reduction in subsequent cardiovascular events.

However, obicetrapib, which is said to be the most potent CETP inhibitor to date, has been shown to produce impressive LDL reductions, and it’s this important data that has caused several lipid experts to want to continue its development.

New data, presented at the recent American Heart Association scientific sessions, show that obicetrapib reduces LDL by 50% when given in addition to high-intensity statins, which could place it as competition for PCSK9 inhibitors or the new agent, inclisiran, but with the advantage of oral dosing.

The drug was in development by Amgen, but the company decided to discontinue its development in 2017 after disappointing results had been seen with several other CETP inhibitors and interest in this class of agent was waning.

But academic experts in the lipid field, led by John Kastelein, MD, PhD, professor of medicine at the Academic Medical Center, University of Amsterdam, and Michael Davidson, MD, clinical professor of medicine at University of Chicago, believed the drug had potential and have acquired obicetrapib from Amgen.

Dr. Kastelein and Dr. Davidson have set up a new company – New Amsterdam Pharma – to further develop obicetrapib, and have raised $200 million from venture capital funding to complete phase 2 and phase 3 studies.

The company has a heavyweight academic advisory board including Stephen Nicholls, MD, Monash University, Clayton, Australia; Kausik Ray, MD, Imperial College London; and Christie Ballantyne, MD, Baylor College of Medicine, Houston.

“We wanted to develop obicetrapib further because of its amazing LDL-lowering properties,” Dr. Kastelein said in an interview.

“No one has paid much attention to CETP inhibitors after the HDL hypothesis was disregarded, as everyone thought these drugs were just about raising HDL. But actually, they can also lower LDL, and this particular agent reduces LDL very effectively,” Dr. Kastelein said.
 

ROSE study

Dr. Nicholls presented the latest data on obicetrapib at the AHA meeting.

“Despite the use of high-intensity statins, two-thirds of patients do not reach their target LDL level, so we have a need for new therapies that lower LDL and can be used in combination with high-intensity statins,” he explained.

He noted that earlier studies with obicetrapib showed a 45% lowering of LDL with monotherapy.

Dr. Nicholls reported that recent evidence has emerged that increases interest in inhibiting CETP to be potentially cardioprotective.

To begin, genetic studies have shown that genetic polymorphisms associated with lower levels of CETP appear to be cardioprotective, and this is associated with lower levels of LDL rather than higher levels of HDL. 

Furthermore, the REVEAL cardiovascular outcomes trial with anacetrapib (also a CETP inhibitor) in 2017 showed a significant 9% reduction in major adverse cardiac events (MACE) after 4 years of follow-up. “This was exactly predicted by the 11 mg/dL drop in absolute LDL cholesterol level. It was not predicted or associated with the increase in HDL level observed with that agent,” Dr. Nicholls said.

The objective of the current ROSE study was to evaluate the lipid-lowering ability, safety, and tolerability of obicetrapib in patients on high-intensity statins.

The study included 120 patients who had been treated on a stable dose of high-intensity statins (atorvastatin at a dose of at least 40 mg daily or rosuvastatin at a dose of 20 mg daily) for at least 8 weeks. All patients were required to have a fasting LDL of at least 70 mg/dL and the median baseline LDL was 90 mg/dL. They were randomly assigned to obicetrapib (5 mg or 10 mg daily) or placebo.

The primary endpoint was the difference between groups in percentage change in LDL from baseline to week 8, with LDL levels measured by two different techniques.

Results showed a “robust” 51% reduction in LDL with the 10-mg dose of obicetrapib, and a 42% reduction with the 5-mg dose, Dr. Nicholls reported.

These effects were comparable regardless of baseline LDL and were similar with both methods of LDL measurement. 

Almost all patients demonstrated some degree of LDL cholesterol lowering, with only three patients on the 5-mg dose and one patient on the 10-mg dose not showing any reduction in LDL.

Other results showed a dose-dependent lowering of Apo B of up to 30%, and a reduction of non-HDL cholesterol of up to 44%.

“Predictably, there were also increases of HDL cholesterol,” Dr. Nicholls said. “At the 10-mg dose, we see a 165% increase in HDL levels. That is associated with a 48% increase in Apo A1 levels. This is very consistent with findings from the previous monotherapy study.”  

There was a 56% reduction in Lp(a) levels, and a modest 11% reduction in triglycerides.

Both doses of obicetrapib were well tolerated, with no increase in the rate of adverse events. Only one patient discontinued the study drug because of an adverse event and that patient was in the placebo group, Dr. Nicholls noted.  

“Blood pressure is an important adverse event to look at in the CETP class given the challenges seen with the first CETP evaluated – torcetrapib,” Dr. Nicholls said. “But in the three clinical trials with obicetrapib conducted to date, reassuringly, we see no increase in either systolic or diastolic blood pressure with either the 5-mg or 10-mg dose.”

He concluded that obicetrapib “could be a valuable addition to high-risk patients with atherosclerotic cardiovascular disease who do not achieve their target LDL level despite use of high-intensity statin therapy.”
 

Differences from other CETP inhibitors

Asked how obicetrapib differs from other agents in the CETP inhibitor class, Dr. Nicholls replied that obicetrapib is much more potent, as shown by the large lipid changes seen with very small quantities of this drug, 5 mg or 10 mg, whereas prior CETP inhibitors showed smaller changes with much higher doses.

“We are giving very small amounts of obicetrapib and seeing very robust effects on both atherogenic and lipid parameters,” he said.  

“The other major point with this class of agent is that the first drug, torcetrapib, had toxicity, which resulted in increased cardiovascular events. But it has now been established that torcetrapib had a number of off-target effects that have not been seen with subsequent agents in this class,” he said.

Studies so far show that obicetrapib does not have torcetrapib-like effects. “That is encouraging. This, and the impressive LDL lowering effects, certainly lay the foundation for larger studies moving forward,” he added.

“This has been an intriguing field to many of us involved from the start. We started with a very disappointing result with torcetrapib. Then a couple of studies looked to be clinically futile, but we were encouraged by the REVEAL study which suggested that there might be benefit,” Dr. Nicholls said.

“If we combined the REVEAL results with the genetic data, it has actually flipped the whole CETP story upside down. We started thinking that inhibiting CETP was all about raising HDL, but it turns out that it is about LDL lowering,” he said. “And that is not only important in terms of the lipid effects but also the trials and the way they are designed.

“I think you’ll find that the future trials in this class and with this agent will have LDL very much in mind and that will very much influence the study design,” he said, adding that a larger cardiovascular outcome trial is now being planned. 

“The regulatory perspective is that LDL is a pretty trusted surrogate ... but I think an outcomes trial will be important to reinforce and reassure on safety and outline cost-effectiveness, which will help us understand where the sweet spot for using this agent in the clinic will be,” Dr. Nicholls noted.  

Dr. Kastelein explained that it has taken some time to realize that CETP inhibitors may be valuable for reducing LDL.   

“The first agent, torcetrapib, had an off-target toxicity that led to increased blood pressure but a specific part of the torcetrapib molecule was subsequently identified that was responsible for that, and subsequent agents in the CETP inhibitor class did not have such adverse effects,” he said.  

“The next agent, dalcetrapib (Roche), raised HDL but didn’t move LDL, and an outcomes trial with evacetrapib (Lilly) was stopped after 2 years because of futility, but we now believe that lipid lowering trials need longer term follow-up – up to 5 years – to see a benefit,” he noted.  

Dr. Kastelein reports that anacetrapib (Merck) has been the most powerful CETP inhibitor until now, giving an LDL reduction of about 20%, which was associated with a 10% reduction in cardiovascular events in first 4 years of follow-up. 

“Oxford academic researchers decided to continue follow-up in this trial without Merck and showed a 20% reduction in cardiovascular events by 6 years. This has been the strongest rationale for our investors,” Dr. Kastelein said.   

He pointed out that obicetrapib is much more potent than anacetrapib. “Obicetrapib reduces LDL by 50% at just a 10-mg dose, whereas anacetrapib was used at a dose of 100 mg to give a 17%-20% LDL reduction.”
 

Could HDL increase be beneficial after all?

Although increasing HDL is currently not thought to bring about a direct reduction in cardiovascular events, there is new evidence emerging that increasing HDL may confer some benefit in protecting against the development of type 2 diabetes, Dr. Kastelein noted.

“We know that statins can increase risk of developing type 2 diabetes, and post hoc analyses of previous trials with CETP inhibitors suggest that these drugs have the opposite effect,” he said. “We will investigate this protectively in our phase 3 outcomes trial. If this is a true effect, it should eventually translate into a reduction in cardiovascular outcomes, but this could take a longer time to see than the benefits of lowering LDL.”

Commenting on the current data, Steven Nissen, MD, of Cleveland Clinic, said: “The results are truly impressive – a nearly 50% LDL reduction on a background of statins with a once-daily oral agent. While PCSK9 inhibitors can achieve similar results, they are injectable and costly.

“Since anacetrapib, a much weaker CETP inhibitor, was successful at reducing major adverse cardiac events, the likelihood that obicetrapib would reduce MACE even more substantially is very high,” he added.

Dr. Nissen said he has been aware of this drug for some time and has advised the company about development options and regulatory strategy. “I have encouraged this company to develop this very promising drug,” he said.

The current study was funded by New Amsterdam Pharma. Dr. Nicholls reports grants from AstraZeneca, Amgen, Anthera, Eli Lilly, Esperion, Novartis, Cerenis, The Medicines Company, Resverlogix, Infraredx, Roche, Sanofi-Regeneron and LipoScience, and honoraria from New Amsterdam Pharma, AstraZeneca, Akcea, Eli Lilly, Anthera, Omthera, Merck, Takeda, Resverlogix, Sanofi-Regeneron, CSL Behring, Esperion, and Boehringer Ingelheim. Dr. Kastelein is chief scientific officer of New Amsterdam Pharma.  

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

A single dose of human papillomavirus (HPV) vaccine was highly effective at preventing oncogenic infection, rivaling the protection offered by multidose regimens, according to results from the KEN SHE trial, based in Kenya.

The findings, published on the preprint server Research Square and presented Nov. 17 at the 34th International Papillomavirus Conference in Toronto, bring “renewed energy to the push to make cervical cancer the first cancer to be wiped out globally,” according to co–principal investigator Ruanne V. Barnabas, PhD, a professor of global health at the University of Washington, Seattle.

Decision-makers will consider these findings, which have not yet been peer-reviewed, along with other evidence to determine if dosing-schedule changes are warranted, she told this news organization.

In a press release, Samuel Kariuki, PhD, acting director general, Kenya Medical Research Institute, who was not involved in the research, called the findings a “game changer” that could “substantially reduce the incidence of HPV-attributable cervical cancer.”

Between 2018 and 2019, Dr. Barnabas and her colleagues enrolled 2,275 sexually active, HPV-vaccine–naive women in Kenya in their study. The women, 15-20 years of age, were randomly assigned to receive a bivalent vaccine (HPV 16/18), a nonavalent vaccine (HPV 16/18/31/33/45/52/58/6/11), or a vaccine against meningococcal meningitis.

Most participants (57%) were between 15 and 17 years of age, and 61% reported one lifetime sexual partner. The women underwent genital and cervical swabs at enrollment to test for HPV DNA and had blood drawn to test for antibodies. During 18 months of follow-up, they had cervical swabs every 6 months and a vaginal swab at 3 months to test for HPV DNA.

The researchers detected 38 persistent HPV 16/18 infections in women who had tested negative for HPV 16/18 antibodies at enrollment and for HPV 16/18 DNA at enrollment and month 3 – one in each of the HPV-vaccine groups and 36 in the meningococcal group. This infection rate corresponded to a vaccine efficacy of 97.5% (P < .001) against HPV 16/18 for both the bivalent and nonavalent vaccines, which is “comparable to that seen in multidose vaccine trials,” the researchers write.

Among women negative for HPV 16/18/31/33/45/52/58 at the beginning of the trial, 33 had persistent infections: four in the nonavalent vaccine group and 29 in the meningococcal group, demonstrating an efficacy of 89% (P < .001) against all seven oncogenic strains contained in the vaccine.

Even if women tested positive for one strain of HPV, the vaccine protected them from other strains of the virus, the investigators noted.

Serious adverse events occurred in 4.5%-5.2% of participants across the study arms.

The KEN SHE trial comes 15 years after the U.S. Food and Drug Administration approved the first HPV vaccine – Merck’s Gardasil. Two others, Cervarix and Gardasil-9, have since been approved, but cost and supply issues have inhibited coverage, particularly in areas where the cervical cancer burden is high, the researchers noted.

Recent data indicate that just 15% of girls globally are vaccinated against HPV, but a single-dose vaccine would “simplify logistics and decrease costs,” thereby improving the chances of reaching the World Health Organization goal of vaccinating 90% of 15-year-old girls against HPV by 2030, Dr. Barnabas said in a press release about the trial.

Co–principal investigator Nelly Mugo, MBChB, MPH, senior principal clinical research scientist with the Center for Clinical Research at the Kenya Medical Research Institute in Nairobi, further emphasized the importance of the findings, noting in the press release that the “trial brings new energy to the elimination of cervical cancer. It brings great hope to the women living in countries like Kenya, who have a high burden of the disease.”

Dr. Mugo is also an associate research professor of global health at the University of Washington, Seattle.

Dr. Barnabas said women have been given multiple doses of the HPV vaccine because of “gaps in evidence for the effectiveness of a single-dose vaccine and concerns about clinically meaningful differences in efficacy.

“Observational data suggested that the single-dose HPV vaccine could have good efficacy, but because the data were not from randomized trials, that could have been from chance,” she explained, noting, however, that “sufficient evidence supported the decrease in doses from three to two doses for girls 15 years of age and younger.”

Going forward, the researchers will conduct immunobridging studies to other populations and will continue follow-up to assess the durability of single-dose efficacy, Dr. Barnabas said.

“The results from the KEN SHE trial support the use of single-dose HPV vaccination to increase access and coverage,” she concluded.

The KEN SHE trial was funded by the Bill & Melinda Gates Foundation (BMGF). Dr. Barnabas reports grants from BMGF and grants from King K. Holmes Professorship in STDs and AIDS during the conduct of the study, and grants from BMGF, National Institutes of Health, and manuscript and abstract writing support from Regeneron Pharmaceuticals outside the submitted work.

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

A single dose of human papillomavirus (HPV) vaccine was highly effective at preventing oncogenic infection, rivaling the protection offered by multidose regimens, according to results from the KEN SHE trial, based in Kenya.

The findings, published on the preprint server Research Square and presented Nov. 17 at the 34th International Papillomavirus Conference in Toronto, bring “renewed energy to the push to make cervical cancer the first cancer to be wiped out globally,” according to co–principal investigator Ruanne V. Barnabas, PhD, a professor of global health at the University of Washington, Seattle.

Decision-makers will consider these findings, which have not yet been peer-reviewed, along with other evidence to determine if dosing-schedule changes are warranted, she told this news organization.

In a press release, Samuel Kariuki, PhD, acting director general, Kenya Medical Research Institute, who was not involved in the research, called the findings a “game changer” that could “substantially reduce the incidence of HPV-attributable cervical cancer.”

Between 2018 and 2019, Dr. Barnabas and her colleagues enrolled 2,275 sexually active, HPV-vaccine–naive women in Kenya in their study. The women, 15-20 years of age, were randomly assigned to receive a bivalent vaccine (HPV 16/18), a nonavalent vaccine (HPV 16/18/31/33/45/52/58/6/11), or a vaccine against meningococcal meningitis.

Most participants (57%) were between 15 and 17 years of age, and 61% reported one lifetime sexual partner. The women underwent genital and cervical swabs at enrollment to test for HPV DNA and had blood drawn to test for antibodies. During 18 months of follow-up, they had cervical swabs every 6 months and a vaginal swab at 3 months to test for HPV DNA.

The researchers detected 38 persistent HPV 16/18 infections in women who had tested negative for HPV 16/18 antibodies at enrollment and for HPV 16/18 DNA at enrollment and month 3 – one in each of the HPV-vaccine groups and 36 in the meningococcal group. This infection rate corresponded to a vaccine efficacy of 97.5% (P < .001) against HPV 16/18 for both the bivalent and nonavalent vaccines, which is “comparable to that seen in multidose vaccine trials,” the researchers write.

Among women negative for HPV 16/18/31/33/45/52/58 at the beginning of the trial, 33 had persistent infections: four in the nonavalent vaccine group and 29 in the meningococcal group, demonstrating an efficacy of 89% (P < .001) against all seven oncogenic strains contained in the vaccine.

Even if women tested positive for one strain of HPV, the vaccine protected them from other strains of the virus, the investigators noted.

Serious adverse events occurred in 4.5%-5.2% of participants across the study arms.

The KEN SHE trial comes 15 years after the U.S. Food and Drug Administration approved the first HPV vaccine – Merck’s Gardasil. Two others, Cervarix and Gardasil-9, have since been approved, but cost and supply issues have inhibited coverage, particularly in areas where the cervical cancer burden is high, the researchers noted.

Recent data indicate that just 15% of girls globally are vaccinated against HPV, but a single-dose vaccine would “simplify logistics and decrease costs,” thereby improving the chances of reaching the World Health Organization goal of vaccinating 90% of 15-year-old girls against HPV by 2030, Dr. Barnabas said in a press release about the trial.

Co–principal investigator Nelly Mugo, MBChB, MPH, senior principal clinical research scientist with the Center for Clinical Research at the Kenya Medical Research Institute in Nairobi, further emphasized the importance of the findings, noting in the press release that the “trial brings new energy to the elimination of cervical cancer. It brings great hope to the women living in countries like Kenya, who have a high burden of the disease.”

Dr. Mugo is also an associate research professor of global health at the University of Washington, Seattle.

Dr. Barnabas said women have been given multiple doses of the HPV vaccine because of “gaps in evidence for the effectiveness of a single-dose vaccine and concerns about clinically meaningful differences in efficacy.

“Observational data suggested that the single-dose HPV vaccine could have good efficacy, but because the data were not from randomized trials, that could have been from chance,” she explained, noting, however, that “sufficient evidence supported the decrease in doses from three to two doses for girls 15 years of age and younger.”

Going forward, the researchers will conduct immunobridging studies to other populations and will continue follow-up to assess the durability of single-dose efficacy, Dr. Barnabas said.

“The results from the KEN SHE trial support the use of single-dose HPV vaccination to increase access and coverage,” she concluded.

The KEN SHE trial was funded by the Bill & Melinda Gates Foundation (BMGF). Dr. Barnabas reports grants from BMGF and grants from King K. Holmes Professorship in STDs and AIDS during the conduct of the study, and grants from BMGF, National Institutes of Health, and manuscript and abstract writing support from Regeneron Pharmaceuticals outside the submitted work.

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

A single dose of human papillomavirus (HPV) vaccine was highly effective at preventing oncogenic infection, rivaling the protection offered by multidose regimens, according to results from the KEN SHE trial, based in Kenya.

The findings, published on the preprint server Research Square and presented Nov. 17 at the 34th International Papillomavirus Conference in Toronto, bring “renewed energy to the push to make cervical cancer the first cancer to be wiped out globally,” according to co–principal investigator Ruanne V. Barnabas, PhD, a professor of global health at the University of Washington, Seattle.

Decision-makers will consider these findings, which have not yet been peer-reviewed, along with other evidence to determine if dosing-schedule changes are warranted, she told this news organization.

In a press release, Samuel Kariuki, PhD, acting director general, Kenya Medical Research Institute, who was not involved in the research, called the findings a “game changer” that could “substantially reduce the incidence of HPV-attributable cervical cancer.”

Between 2018 and 2019, Dr. Barnabas and her colleagues enrolled 2,275 sexually active, HPV-vaccine–naive women in Kenya in their study. The women, 15-20 years of age, were randomly assigned to receive a bivalent vaccine (HPV 16/18), a nonavalent vaccine (HPV 16/18/31/33/45/52/58/6/11), or a vaccine against meningococcal meningitis.

Most participants (57%) were between 15 and 17 years of age, and 61% reported one lifetime sexual partner. The women underwent genital and cervical swabs at enrollment to test for HPV DNA and had blood drawn to test for antibodies. During 18 months of follow-up, they had cervical swabs every 6 months and a vaginal swab at 3 months to test for HPV DNA.

The researchers detected 38 persistent HPV 16/18 infections in women who had tested negative for HPV 16/18 antibodies at enrollment and for HPV 16/18 DNA at enrollment and month 3 – one in each of the HPV-vaccine groups and 36 in the meningococcal group. This infection rate corresponded to a vaccine efficacy of 97.5% (P < .001) against HPV 16/18 for both the bivalent and nonavalent vaccines, which is “comparable to that seen in multidose vaccine trials,” the researchers write.

Among women negative for HPV 16/18/31/33/45/52/58 at the beginning of the trial, 33 had persistent infections: four in the nonavalent vaccine group and 29 in the meningococcal group, demonstrating an efficacy of 89% (P < .001) against all seven oncogenic strains contained in the vaccine.

Even if women tested positive for one strain of HPV, the vaccine protected them from other strains of the virus, the investigators noted.

Serious adverse events occurred in 4.5%-5.2% of participants across the study arms.

The KEN SHE trial comes 15 years after the U.S. Food and Drug Administration approved the first HPV vaccine – Merck’s Gardasil. Two others, Cervarix and Gardasil-9, have since been approved, but cost and supply issues have inhibited coverage, particularly in areas where the cervical cancer burden is high, the researchers noted.

Recent data indicate that just 15% of girls globally are vaccinated against HPV, but a single-dose vaccine would “simplify logistics and decrease costs,” thereby improving the chances of reaching the World Health Organization goal of vaccinating 90% of 15-year-old girls against HPV by 2030, Dr. Barnabas said in a press release about the trial.

Co–principal investigator Nelly Mugo, MBChB, MPH, senior principal clinical research scientist with the Center for Clinical Research at the Kenya Medical Research Institute in Nairobi, further emphasized the importance of the findings, noting in the press release that the “trial brings new energy to the elimination of cervical cancer. It brings great hope to the women living in countries like Kenya, who have a high burden of the disease.”

Dr. Mugo is also an associate research professor of global health at the University of Washington, Seattle.

Dr. Barnabas said women have been given multiple doses of the HPV vaccine because of “gaps in evidence for the effectiveness of a single-dose vaccine and concerns about clinically meaningful differences in efficacy.

“Observational data suggested that the single-dose HPV vaccine could have good efficacy, but because the data were not from randomized trials, that could have been from chance,” she explained, noting, however, that “sufficient evidence supported the decrease in doses from three to two doses for girls 15 years of age and younger.”

Going forward, the researchers will conduct immunobridging studies to other populations and will continue follow-up to assess the durability of single-dose efficacy, Dr. Barnabas said.

“The results from the KEN SHE trial support the use of single-dose HPV vaccination to increase access and coverage,” she concluded.

The KEN SHE trial was funded by the Bill & Melinda Gates Foundation (BMGF). Dr. Barnabas reports grants from BMGF and grants from King K. Holmes Professorship in STDs and AIDS during the conduct of the study, and grants from BMGF, National Institutes of Health, and manuscript and abstract writing support from Regeneron Pharmaceuticals outside the submitted work.

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