Background: Midline catheters have gained popularity in inpatient medical settings as a convenient alternative to PICC lines. This is primarily because of the ability to avoid central line–associated bloodstream infections (CLABSI) since these catheters terminate in the peripheral veins and cannot be reported as such. Additionally, they are potentially able to dwell longer than are traditional peripheral intravenous catheters. However, insufficient data exist to accurately describe the rate of complications in these catheters, as prior studies are based on single-center experiences.

The article does not provide guidance on when and how midline catheters should be used in order to minimize risk; nor does it include a comparison with traditional peripheral intravenous catheters or with PICC lines. Further studies are needed to guide indications and practices for catheter placement in order to minimize risk. Providers should continue to carefully consider the risks and benefits of midline catheter placement in individual cases.

Bottom line: Midline catheter placement more commonly leads to minor rather than major complications, though patterns of use and outcomes vary substantially across sites.

Citation: Chopra V et al. Variation in use and outcomes related to midline catheters: results from a multicentre pilot study. BMJ Qual Saf. 2019 Mar 18. doi: 10.1136/bmjqs-2018-008554.

Dr. Marcantonio is a Med-Peds hospitalist at Duke University Health System.

Background: Midline catheters have gained popularity in inpatient medical settings as a convenient alternative to PICC lines. This is primarily because of the ability to avoid central line–associated bloodstream infections (CLABSI) since these catheters terminate in the peripheral veins and cannot be reported as such. Additionally, they are potentially able to dwell longer than are traditional peripheral intravenous catheters. However, insufficient data exist to accurately describe the rate of complications in these catheters, as prior studies are based on single-center experiences.

The article does not provide guidance on when and how midline catheters should be used in order to minimize risk; nor does it include a comparison with traditional peripheral intravenous catheters or with PICC lines. Further studies are needed to guide indications and practices for catheter placement in order to minimize risk. Providers should continue to carefully consider the risks and benefits of midline catheter placement in individual cases.

Bottom line: Midline catheter placement more commonly leads to minor rather than major complications, though patterns of use and outcomes vary substantially across sites.

Citation: Chopra V et al. Variation in use and outcomes related to midline catheters: results from a multicentre pilot study. BMJ Qual Saf. 2019 Mar 18. doi: 10.1136/bmjqs-2018-008554.

Dr. Marcantonio is a Med-Peds hospitalist at Duke University Health System.

Background: Midline catheters have gained popularity in inpatient medical settings as a convenient alternative to PICC lines. This is primarily because of the ability to avoid central line–associated bloodstream infections (CLABSI) since these catheters terminate in the peripheral veins and cannot be reported as such. Additionally, they are potentially able to dwell longer than are traditional peripheral intravenous catheters. However, insufficient data exist to accurately describe the rate of complications in these catheters, as prior studies are based on single-center experiences.

The article does not provide guidance on when and how midline catheters should be used in order to minimize risk; nor does it include a comparison with traditional peripheral intravenous catheters or with PICC lines. Further studies are needed to guide indications and practices for catheter placement in order to minimize risk. Providers should continue to carefully consider the risks and benefits of midline catheter placement in individual cases.

Bottom line: Midline catheter placement more commonly leads to minor rather than major complications, though patterns of use and outcomes vary substantially across sites.

Citation: Chopra V et al. Variation in use and outcomes related to midline catheters: results from a multicentre pilot study. BMJ Qual Saf. 2019 Mar 18. doi: 10.1136/bmjqs-2018-008554.

Dr. Marcantonio is a Med-Peds hospitalist at Duke University Health System.

The BEACON study tested both a doublet and a triplet of drugs for patients with previously treated BRAF V600E–mutated metastatic colorectal cancer (CRC).

New results from that trial, with an updated survival analysis, show that the doublet is sufficient and that patients can safely be treated with a combination of the BRAF inhibitor encorafenib (Braftovi, Array BioPharma) and the EGFR inhibitor monoclonal antibody cetuximab (Erbitux, Eli Lilly).

This means that the increased toxicity from the addition of the MEK inhibitor binimetinib (Mektovi, Array BioPharma) can be avoided and that good outcomes can be maintained.

The new results were presented as part of the virtual scientific program of the 2020 American Society of Clinical Oncology annual meeting.

Study discussant Michael S. Lee, MD, from the University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, said he “would consider encorafenib and cetuximab now the standard of care in the second line and beyond in BRAF-mutant colorectal cancer.

“I would give the doublet rather than the triplet because of the comparable survival and better side effect profile,” he said.

“This is immediately practice changing, given the FDA approval of encorafenib and cetuximab,” commented Autumn J. McRee, MD, UNC Lineberger Comprehensive Cancer Center.

This is a “clinically relevant” trial, and it demonstrates that the “poorest prognostic group in colorectal cancer now has viable options,” she said at a Highlights of the Day session.

“We will await the results of the ANCHOR-CRC trial to see if we should be using this targeted approach in earlier lines of therapy,” she added.
 

New survival data

The primary analysis of BEACON CRC, presented at the 2019 World Conference on Gastrointestinal Cancer, showed that use of the triplet therapy was associated with a 48% improvement in overall survival in comparison with standard chemotherapy.

Although that was also linked to improved quality of life, questions have been raised as to whether the benefits are worth the cost, and one commentator singled the study out for harsh criticism.

Scott Kopetz, MD, PhD, from the University of Texas MD Anderson Cancer Center, Houston, presented the updated survival results from BEACON CRC, which included data from an additional 6 months of follow-up.

“We know that the V600E mutation in BRAF occurs in about 10%-15% of patients and is associated with a poor prognosis,” Dr. Kopetz commented.

“BRAF inhibitors alone are not effective,” he noted. He said preclinical models point toward an approach that targets multiple pathways, including BRAF, MEK, and EGFR.

The BEACON study had three arms, each with 205 patients, as follows:

• Encorafenib plus binimetinib plus cetuximab
• Encorafenib plus cetixumab
• A control arm of FOLFIRI plus cetuximab or irinotecan plus cetuximab.

The three arms of the trial were relatively well balanced with respect to patient characteristics, Dr. Kopetz commented. The median age of the patients ranged from 60 to 62 years, and 48%-57% of the patients were women.

Of note, between 5% and 10% of the cases were characterized by high microsatellite instability, and 34%-35% of patients had received more than one prior line of therapy.

The data now presented at ASCO represent a post hoc updated analysis that includes 6 months of additional follow-up since the primary analysis was presented, Dr. Kopetz explained.

After a median follow-up of 12.8 months, 13% of triplet therapy patients, 14% of those who received doublet therapy, and 3% of control patients were still on treatment.

The updated analysis shows that median overall survival with the doublet therapy was 9.3 months versus 5.9 months for the control group (hazard ratio, 0.61). The benefit was seen across all subgroups, including those based on the number of prior regimens.

Dr. Kopetz pointed out that overall survival was numerically superior to that seen in the primary analysis, which was 8.4 months.

The updated survival analysis for the triplet therapy indicated that the median overall survival was 9.3 months versus 5.9 months in the control arm (HR, 0.60). Again, this was consistent across subgroups.

In the primary analysis, the median overall survival with the triplet therapy was 9.0 months.

The team also compared the triplet and doublet therapies, finding that, “in contrast to what was seen in the primary analysis ... we see numerically identical median overall survival with the two arms.” The result was sustained across subgroups.

However, there were indications that there may be survival benefits with the triplet in certain patient subgroups, including those with Eastern Cooperative Oncology Group performance status 1, those in whom three or more organs are involved, those with higher baseline levels of C-reactive protein, and those with partially resected or unresected disease.

Progression-free survival was comparable between the two treatment groups, at 4.5 months with the triplet therapy and 4.3 months with the doublet, compared with just 1.5 months in the control arm.

The updated analysis also showed that the objective response rate was 27% with triplet therapy versus 20% with the doublet and 2% in the control arm. In both the doublet and triplet arms, the majority of responses were partial.

With regard to safety, Dr. Kopetz said that the updated data regarding adverse events were in general “consistent with the previously reported safety profile.”

He added it is “notable” that the triplet therapy “had slightly higher rates of GI toxicity and anemia,” which was not seen with the doublet, something that is “again associated with the known safety profile of a MEK inhibitor.”

The study was funded by Pfizer. Dr. Kopetz has stock and other ownership interests with numerous pharmaceutical companies. Other authors, as well as Dr. Lee and Dr. McRee, have also reported relevant financial relationships.

This article first appeared on Medscape.com.

The BEACON study tested both a doublet and a triplet of drugs for patients with previously treated BRAF V600E–mutated metastatic colorectal cancer (CRC).

New results from that trial, with an updated survival analysis, show that the doublet is sufficient and that patients can safely be treated with a combination of the BRAF inhibitor encorafenib (Braftovi, Array BioPharma) and the EGFR inhibitor monoclonal antibody cetuximab (Erbitux, Eli Lilly).

This means that the increased toxicity from the addition of the MEK inhibitor binimetinib (Mektovi, Array BioPharma) can be avoided and that good outcomes can be maintained.

The new results were presented as part of the virtual scientific program of the 2020 American Society of Clinical Oncology annual meeting.

Study discussant Michael S. Lee, MD, from the University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, said he “would consider encorafenib and cetuximab now the standard of care in the second line and beyond in BRAF-mutant colorectal cancer.

“I would give the doublet rather than the triplet because of the comparable survival and better side effect profile,” he said.

“This is immediately practice changing, given the FDA approval of encorafenib and cetuximab,” commented Autumn J. McRee, MD, UNC Lineberger Comprehensive Cancer Center.

This is a “clinically relevant” trial, and it demonstrates that the “poorest prognostic group in colorectal cancer now has viable options,” she said at a Highlights of the Day session.

“We will await the results of the ANCHOR-CRC trial to see if we should be using this targeted approach in earlier lines of therapy,” she added.
 

New survival data

The primary analysis of BEACON CRC, presented at the 2019 World Conference on Gastrointestinal Cancer, showed that use of the triplet therapy was associated with a 48% improvement in overall survival in comparison with standard chemotherapy.

Although that was also linked to improved quality of life, questions have been raised as to whether the benefits are worth the cost, and one commentator singled the study out for harsh criticism.

Scott Kopetz, MD, PhD, from the University of Texas MD Anderson Cancer Center, Houston, presented the updated survival results from BEACON CRC, which included data from an additional 6 months of follow-up.

“We know that the V600E mutation in BRAF occurs in about 10%-15% of patients and is associated with a poor prognosis,” Dr. Kopetz commented.

“BRAF inhibitors alone are not effective,” he noted. He said preclinical models point toward an approach that targets multiple pathways, including BRAF, MEK, and EGFR.

The BEACON study had three arms, each with 205 patients, as follows:

• Encorafenib plus binimetinib plus cetuximab
• Encorafenib plus cetixumab
• A control arm of FOLFIRI plus cetuximab or irinotecan plus cetuximab.

The three arms of the trial were relatively well balanced with respect to patient characteristics, Dr. Kopetz commented. The median age of the patients ranged from 60 to 62 years, and 48%-57% of the patients were women.

Of note, between 5% and 10% of the cases were characterized by high microsatellite instability, and 34%-35% of patients had received more than one prior line of therapy.

The data now presented at ASCO represent a post hoc updated analysis that includes 6 months of additional follow-up since the primary analysis was presented, Dr. Kopetz explained.

After a median follow-up of 12.8 months, 13% of triplet therapy patients, 14% of those who received doublet therapy, and 3% of control patients were still on treatment.

The updated analysis shows that median overall survival with the doublet therapy was 9.3 months versus 5.9 months for the control group (hazard ratio, 0.61). The benefit was seen across all subgroups, including those based on the number of prior regimens.

Dr. Kopetz pointed out that overall survival was numerically superior to that seen in the primary analysis, which was 8.4 months.

The updated survival analysis for the triplet therapy indicated that the median overall survival was 9.3 months versus 5.9 months in the control arm (HR, 0.60). Again, this was consistent across subgroups.

In the primary analysis, the median overall survival with the triplet therapy was 9.0 months.

The team also compared the triplet and doublet therapies, finding that, “in contrast to what was seen in the primary analysis ... we see numerically identical median overall survival with the two arms.” The result was sustained across subgroups.

However, there were indications that there may be survival benefits with the triplet in certain patient subgroups, including those with Eastern Cooperative Oncology Group performance status 1, those in whom three or more organs are involved, those with higher baseline levels of C-reactive protein, and those with partially resected or unresected disease.

Progression-free survival was comparable between the two treatment groups, at 4.5 months with the triplet therapy and 4.3 months with the doublet, compared with just 1.5 months in the control arm.

The updated analysis also showed that the objective response rate was 27% with triplet therapy versus 20% with the doublet and 2% in the control arm. In both the doublet and triplet arms, the majority of responses were partial.

With regard to safety, Dr. Kopetz said that the updated data regarding adverse events were in general “consistent with the previously reported safety profile.”

He added it is “notable” that the triplet therapy “had slightly higher rates of GI toxicity and anemia,” which was not seen with the doublet, something that is “again associated with the known safety profile of a MEK inhibitor.”

The study was funded by Pfizer. Dr. Kopetz has stock and other ownership interests with numerous pharmaceutical companies. Other authors, as well as Dr. Lee and Dr. McRee, have also reported relevant financial relationships.

This article first appeared on Medscape.com.

The BEACON study tested both a doublet and a triplet of drugs for patients with previously treated BRAF V600E–mutated metastatic colorectal cancer (CRC).

New results from that trial, with an updated survival analysis, show that the doublet is sufficient and that patients can safely be treated with a combination of the BRAF inhibitor encorafenib (Braftovi, Array BioPharma) and the EGFR inhibitor monoclonal antibody cetuximab (Erbitux, Eli Lilly).

This means that the increased toxicity from the addition of the MEK inhibitor binimetinib (Mektovi, Array BioPharma) can be avoided and that good outcomes can be maintained.

The new results were presented as part of the virtual scientific program of the 2020 American Society of Clinical Oncology annual meeting.

Study discussant Michael S. Lee, MD, from the University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, said he “would consider encorafenib and cetuximab now the standard of care in the second line and beyond in BRAF-mutant colorectal cancer.

“I would give the doublet rather than the triplet because of the comparable survival and better side effect profile,” he said.

“This is immediately practice changing, given the FDA approval of encorafenib and cetuximab,” commented Autumn J. McRee, MD, UNC Lineberger Comprehensive Cancer Center.

This is a “clinically relevant” trial, and it demonstrates that the “poorest prognostic group in colorectal cancer now has viable options,” she said at a Highlights of the Day session.

“We will await the results of the ANCHOR-CRC trial to see if we should be using this targeted approach in earlier lines of therapy,” she added.
 

New survival data

The primary analysis of BEACON CRC, presented at the 2019 World Conference on Gastrointestinal Cancer, showed that use of the triplet therapy was associated with a 48% improvement in overall survival in comparison with standard chemotherapy.

Although that was also linked to improved quality of life, questions have been raised as to whether the benefits are worth the cost, and one commentator singled the study out for harsh criticism.

Scott Kopetz, MD, PhD, from the University of Texas MD Anderson Cancer Center, Houston, presented the updated survival results from BEACON CRC, which included data from an additional 6 months of follow-up.

“We know that the V600E mutation in BRAF occurs in about 10%-15% of patients and is associated with a poor prognosis,” Dr. Kopetz commented.

“BRAF inhibitors alone are not effective,” he noted. He said preclinical models point toward an approach that targets multiple pathways, including BRAF, MEK, and EGFR.

The BEACON study had three arms, each with 205 patients, as follows:

• Encorafenib plus binimetinib plus cetuximab
• Encorafenib plus cetixumab
• A control arm of FOLFIRI plus cetuximab or irinotecan plus cetuximab.

The three arms of the trial were relatively well balanced with respect to patient characteristics, Dr. Kopetz commented. The median age of the patients ranged from 60 to 62 years, and 48%-57% of the patients were women.

Of note, between 5% and 10% of the cases were characterized by high microsatellite instability, and 34%-35% of patients had received more than one prior line of therapy.

The data now presented at ASCO represent a post hoc updated analysis that includes 6 months of additional follow-up since the primary analysis was presented, Dr. Kopetz explained.

After a median follow-up of 12.8 months, 13% of triplet therapy patients, 14% of those who received doublet therapy, and 3% of control patients were still on treatment.

The updated analysis shows that median overall survival with the doublet therapy was 9.3 months versus 5.9 months for the control group (hazard ratio, 0.61). The benefit was seen across all subgroups, including those based on the number of prior regimens.

Dr. Kopetz pointed out that overall survival was numerically superior to that seen in the primary analysis, which was 8.4 months.

The updated survival analysis for the triplet therapy indicated that the median overall survival was 9.3 months versus 5.9 months in the control arm (HR, 0.60). Again, this was consistent across subgroups.

In the primary analysis, the median overall survival with the triplet therapy was 9.0 months.

The team also compared the triplet and doublet therapies, finding that, “in contrast to what was seen in the primary analysis ... we see numerically identical median overall survival with the two arms.” The result was sustained across subgroups.

However, there were indications that there may be survival benefits with the triplet in certain patient subgroups, including those with Eastern Cooperative Oncology Group performance status 1, those in whom three or more organs are involved, those with higher baseline levels of C-reactive protein, and those with partially resected or unresected disease.

Progression-free survival was comparable between the two treatment groups, at 4.5 months with the triplet therapy and 4.3 months with the doublet, compared with just 1.5 months in the control arm.

The updated analysis also showed that the objective response rate was 27% with triplet therapy versus 20% with the doublet and 2% in the control arm. In both the doublet and triplet arms, the majority of responses were partial.

With regard to safety, Dr. Kopetz said that the updated data regarding adverse events were in general “consistent with the previously reported safety profile.”

He added it is “notable” that the triplet therapy “had slightly higher rates of GI toxicity and anemia,” which was not seen with the doublet, something that is “again associated with the known safety profile of a MEK inhibitor.”

The study was funded by Pfizer. Dr. Kopetz has stock and other ownership interests with numerous pharmaceutical companies. Other authors, as well as Dr. Lee and Dr. McRee, have also reported relevant financial relationships.

This article first appeared on Medscape.com.

From 7% to nearly 9% of patients with advanced cancer were found to harbor a germline variant with targeted therapeutic actionability in the first study of its kind.

The study involved 11,974 patients with various tumor types. All the patients underwent germline genetic testing from 2015 to 2019 at the Memorial Sloan Kettering Cancer Center (MSKCC) in New York, using the next-generation sequencing panel MSK-IMPACT.

This testing showed that 17.1% of patients had variants in cancer predisposition genes, and 7.1%-8.6% had variants that could potentially be targeted.

“Of course, these numbers are not static,” commented lead author Zsofia K. Stadler, MD, a medical oncologist at MSKCC. “And with the emergence of novel targeted treatments with new FDA indications, the therapeutic actionability of germline variants is likely to increase over time.

“Our study demonstrates the first comprehensive assessment of the clinical utility of germline alterations for therapeutic actionability in a population of patients with advanced cancer,” she added.

Dr. Stadler presented the study results during a virtual scientific program of the American Society of Clinical Oncology 2020.

Testing for somatic mutations is evolving as the standard of care in many cancer types, and somatic genomic testing is rapidly becoming an integral part of the regimen for patients with advanced disease. Some studies suggest that 9%-11% of patients harbor actionable genetic alterations, as determined on the basis of tumor profiling.

“The take-home message from this is that now, more than ever before, germline testing is indicated for the selection of cancer treatment,” said Erin Wysong Hofstatter, MD, from Yale University, New Haven, Conn., in a Highlights of the Day session.

An emerging indication for germline testing is the selection of treatment in the advanced setting, she noted. “And it is important to know your test. Remember that tumor sequencing is not a substitute for comprehensive germline testing.”
 

Implications in cancer treatment

For their study, Dr. Stadler and colleagues reviewed the medical records of patients with likely pathogenic/pathogenic germline (LP/P) alterations in genes that had known therapeutic targets so as to identify germline-targeted treatment either in a clinical or research setting.

“Since 2015, patients undergoing MSK-IMPACT may also choose to provide additional consent for secondary germline genetic analysis, wherein up to 88 genes known to be associated with cancer predisposition are analyzed,” she said. “Likely pathogenic and pathogenic germline alterations identified are disclosed to the patient and treating physician via the Clinical Genetic Service.”

A total of 2043 (17.1%) patients who harbored LP/P variants in a cancer predisposition gene were identified. Of these, 11% of patients harbored pathogenic alterations in high or moderate penetrance cancer predisposition genes. When the analysis was limited to genes with targeted therapeutic actionability, or what the authors defined as tier 1 and tier 2 genes, 7.1% of patients (n = 849) harbored a targetable pathogenic germline alteration.

BRCA alterations accounted for half (52%) of the findings, and 20% were associated with Lynch syndrome.

The tier 2 genes, which included PALB2, ATM, RAD51C, and RAD51D, accounted for about a quarter of the findings. Dr. Hofstatter noted that, using strict criteria, 7.1% of patients (n = 849) were found to harbor a pathogenic alteration and a targetable gene. Using less stringent criteria, additional tier 3 genes and additional genes associated with DNA homologous recombination repair brought the number up to 8.6% (n = 1,003).

Therapeutic action

For determining therapeutic actionability, the strict criteria were used; 593 patients (4.95%) with recurrent or metastatic disease were identified. For these patients, consideration of a targeted therapy, either as part of standard care or as part of an investigation or research protocol, was important.

Of this group, 44% received therapy targeting the germline alteration. Regarding specific genes, 50% of BRCA1/2 carriers and 58% of Lynch syndrome patients received targeted treatment. With respect to tier 2 genes, 40% of patients with PALB2, 19% with ATM, and 37% with RAD51C or 51D received a poly (ADP-ribose) polymerase (PARP) inhibitor.

Among patients with a BRCA1/2 mutation who received a PARP inhibitor, 55.1% had breast or ovarian cancer, and 44.8% had other tumor types, including pancreas, prostate, bile duct, gastric cancers. These patients received the drug in a research setting.

For patients with PALB2 alterations who received PARP inhibitors, 53.3% had breast or pancreas cancer, and 46.7% had cancer of the prostate, ovary, or an unknown primary.

Looking ahead

The discussant for the paper, Funda Meric-Bernstam, MD, chair of the Department of Investigational Cancer Therapeutics at the University of Texas MD Anderson Cancer Center, Houston, pointed out that most of the BRCA-positive patients had cancers traditionally associated with the mutation. “There were no patients with PTEN mutations treated, and interestingly, no patients with NF1 were treated,” she said. “But actionability is evolving, as the MEK inhibitor selumitinib was recently approved for NF1.”

Some questions remain unanswered, she noted, such as: “What percentage of patients undergoing tumor-normal testing signed a germline protocol?” and “Does the population introduce a bias – such as younger patients, family history, and so on?”

It is also unknown what percentage of germline alterations were known in comparison with those identified through tumor/normal testing. Also of importance is the fact that in this study, the results of germline testing were delivered in an academic setting, she emphasized. “What if they were delivered elsewhere? What would be the impact of identifying these alterations in an environment with less access to trials?

“But to be fair, it is not easy to seek the germline mutations,” Dr. Meric-Bernstam continued. “These studies were done under institutional review board protocols, and it is important to note that most profiling is done as standard of care without consenting and soliciting patient preference on the return of germline results.”

An infrastructure is needed to return/counsel/offer cascade testing, and “analyses need to be facilitated to ensure that findings can be acted upon in a timely fashion,” she added.

The study was supported by MSKCC internal funding. Dr. Stadler reported relationships (institutional) with Adverum, Alimera Sciences, Allergan, Biomarin, Fortress Biotech, Genentech/Roche, Novartis, Optos, Regeneron, Regenxbio, and Spark Therapeutics. Dr. Meric-Bernstram reported relationships with numerous pharmaceutical companies.

This article first appeared on Medscape.com.

From 7% to nearly 9% of patients with advanced cancer were found to harbor a germline variant with targeted therapeutic actionability in the first study of its kind.

The study involved 11,974 patients with various tumor types. All the patients underwent germline genetic testing from 2015 to 2019 at the Memorial Sloan Kettering Cancer Center (MSKCC) in New York, using the next-generation sequencing panel MSK-IMPACT.

This testing showed that 17.1% of patients had variants in cancer predisposition genes, and 7.1%-8.6% had variants that could potentially be targeted.

“Of course, these numbers are not static,” commented lead author Zsofia K. Stadler, MD, a medical oncologist at MSKCC. “And with the emergence of novel targeted treatments with new FDA indications, the therapeutic actionability of germline variants is likely to increase over time.

“Our study demonstrates the first comprehensive assessment of the clinical utility of germline alterations for therapeutic actionability in a population of patients with advanced cancer,” she added.

Dr. Stadler presented the study results during a virtual scientific program of the American Society of Clinical Oncology 2020.

Testing for somatic mutations is evolving as the standard of care in many cancer types, and somatic genomic testing is rapidly becoming an integral part of the regimen for patients with advanced disease. Some studies suggest that 9%-11% of patients harbor actionable genetic alterations, as determined on the basis of tumor profiling.

“The take-home message from this is that now, more than ever before, germline testing is indicated for the selection of cancer treatment,” said Erin Wysong Hofstatter, MD, from Yale University, New Haven, Conn., in a Highlights of the Day session.

An emerging indication for germline testing is the selection of treatment in the advanced setting, she noted. “And it is important to know your test. Remember that tumor sequencing is not a substitute for comprehensive germline testing.”
 

Implications in cancer treatment

For their study, Dr. Stadler and colleagues reviewed the medical records of patients with likely pathogenic/pathogenic germline (LP/P) alterations in genes that had known therapeutic targets so as to identify germline-targeted treatment either in a clinical or research setting.

“Since 2015, patients undergoing MSK-IMPACT may also choose to provide additional consent for secondary germline genetic analysis, wherein up to 88 genes known to be associated with cancer predisposition are analyzed,” she said. “Likely pathogenic and pathogenic germline alterations identified are disclosed to the patient and treating physician via the Clinical Genetic Service.”

A total of 2043 (17.1%) patients who harbored LP/P variants in a cancer predisposition gene were identified. Of these, 11% of patients harbored pathogenic alterations in high or moderate penetrance cancer predisposition genes. When the analysis was limited to genes with targeted therapeutic actionability, or what the authors defined as tier 1 and tier 2 genes, 7.1% of patients (n = 849) harbored a targetable pathogenic germline alteration.

BRCA alterations accounted for half (52%) of the findings, and 20% were associated with Lynch syndrome.

The tier 2 genes, which included PALB2, ATM, RAD51C, and RAD51D, accounted for about a quarter of the findings. Dr. Hofstatter noted that, using strict criteria, 7.1% of patients (n = 849) were found to harbor a pathogenic alteration and a targetable gene. Using less stringent criteria, additional tier 3 genes and additional genes associated with DNA homologous recombination repair brought the number up to 8.6% (n = 1,003).

Therapeutic action

For determining therapeutic actionability, the strict criteria were used; 593 patients (4.95%) with recurrent or metastatic disease were identified. For these patients, consideration of a targeted therapy, either as part of standard care or as part of an investigation or research protocol, was important.

Of this group, 44% received therapy targeting the germline alteration. Regarding specific genes, 50% of BRCA1/2 carriers and 58% of Lynch syndrome patients received targeted treatment. With respect to tier 2 genes, 40% of patients with PALB2, 19% with ATM, and 37% with RAD51C or 51D received a poly (ADP-ribose) polymerase (PARP) inhibitor.

Among patients with a BRCA1/2 mutation who received a PARP inhibitor, 55.1% had breast or ovarian cancer, and 44.8% had other tumor types, including pancreas, prostate, bile duct, gastric cancers. These patients received the drug in a research setting.

For patients with PALB2 alterations who received PARP inhibitors, 53.3% had breast or pancreas cancer, and 46.7% had cancer of the prostate, ovary, or an unknown primary.

Looking ahead

The discussant for the paper, Funda Meric-Bernstam, MD, chair of the Department of Investigational Cancer Therapeutics at the University of Texas MD Anderson Cancer Center, Houston, pointed out that most of the BRCA-positive patients had cancers traditionally associated with the mutation. “There were no patients with PTEN mutations treated, and interestingly, no patients with NF1 were treated,” she said. “But actionability is evolving, as the MEK inhibitor selumitinib was recently approved for NF1.”

Some questions remain unanswered, she noted, such as: “What percentage of patients undergoing tumor-normal testing signed a germline protocol?” and “Does the population introduce a bias – such as younger patients, family history, and so on?”

It is also unknown what percentage of germline alterations were known in comparison with those identified through tumor/normal testing. Also of importance is the fact that in this study, the results of germline testing were delivered in an academic setting, she emphasized. “What if they were delivered elsewhere? What would be the impact of identifying these alterations in an environment with less access to trials?

“But to be fair, it is not easy to seek the germline mutations,” Dr. Meric-Bernstam continued. “These studies were done under institutional review board protocols, and it is important to note that most profiling is done as standard of care without consenting and soliciting patient preference on the return of germline results.”

An infrastructure is needed to return/counsel/offer cascade testing, and “analyses need to be facilitated to ensure that findings can be acted upon in a timely fashion,” she added.

The study was supported by MSKCC internal funding. Dr. Stadler reported relationships (institutional) with Adverum, Alimera Sciences, Allergan, Biomarin, Fortress Biotech, Genentech/Roche, Novartis, Optos, Regeneron, Regenxbio, and Spark Therapeutics. Dr. Meric-Bernstram reported relationships with numerous pharmaceutical companies.

This article first appeared on Medscape.com.

From 7% to nearly 9% of patients with advanced cancer were found to harbor a germline variant with targeted therapeutic actionability in the first study of its kind.

The study involved 11,974 patients with various tumor types. All the patients underwent germline genetic testing from 2015 to 2019 at the Memorial Sloan Kettering Cancer Center (MSKCC) in New York, using the next-generation sequencing panel MSK-IMPACT.

This testing showed that 17.1% of patients had variants in cancer predisposition genes, and 7.1%-8.6% had variants that could potentially be targeted.

“Of course, these numbers are not static,” commented lead author Zsofia K. Stadler, MD, a medical oncologist at MSKCC. “And with the emergence of novel targeted treatments with new FDA indications, the therapeutic actionability of germline variants is likely to increase over time.

“Our study demonstrates the first comprehensive assessment of the clinical utility of germline alterations for therapeutic actionability in a population of patients with advanced cancer,” she added.

Dr. Stadler presented the study results during a virtual scientific program of the American Society of Clinical Oncology 2020.

Testing for somatic mutations is evolving as the standard of care in many cancer types, and somatic genomic testing is rapidly becoming an integral part of the regimen for patients with advanced disease. Some studies suggest that 9%-11% of patients harbor actionable genetic alterations, as determined on the basis of tumor profiling.

“The take-home message from this is that now, more than ever before, germline testing is indicated for the selection of cancer treatment,” said Erin Wysong Hofstatter, MD, from Yale University, New Haven, Conn., in a Highlights of the Day session.

An emerging indication for germline testing is the selection of treatment in the advanced setting, she noted. “And it is important to know your test. Remember that tumor sequencing is not a substitute for comprehensive germline testing.”
 

Implications in cancer treatment

For their study, Dr. Stadler and colleagues reviewed the medical records of patients with likely pathogenic/pathogenic germline (LP/P) alterations in genes that had known therapeutic targets so as to identify germline-targeted treatment either in a clinical or research setting.

“Since 2015, patients undergoing MSK-IMPACT may also choose to provide additional consent for secondary germline genetic analysis, wherein up to 88 genes known to be associated with cancer predisposition are analyzed,” she said. “Likely pathogenic and pathogenic germline alterations identified are disclosed to the patient and treating physician via the Clinical Genetic Service.”

A total of 2043 (17.1%) patients who harbored LP/P variants in a cancer predisposition gene were identified. Of these, 11% of patients harbored pathogenic alterations in high or moderate penetrance cancer predisposition genes. When the analysis was limited to genes with targeted therapeutic actionability, or what the authors defined as tier 1 and tier 2 genes, 7.1% of patients (n = 849) harbored a targetable pathogenic germline alteration.

BRCA alterations accounted for half (52%) of the findings, and 20% were associated with Lynch syndrome.

The tier 2 genes, which included PALB2, ATM, RAD51C, and RAD51D, accounted for about a quarter of the findings. Dr. Hofstatter noted that, using strict criteria, 7.1% of patients (n = 849) were found to harbor a pathogenic alteration and a targetable gene. Using less stringent criteria, additional tier 3 genes and additional genes associated with DNA homologous recombination repair brought the number up to 8.6% (n = 1,003).

Therapeutic action

For determining therapeutic actionability, the strict criteria were used; 593 patients (4.95%) with recurrent or metastatic disease were identified. For these patients, consideration of a targeted therapy, either as part of standard care or as part of an investigation or research protocol, was important.

Of this group, 44% received therapy targeting the germline alteration. Regarding specific genes, 50% of BRCA1/2 carriers and 58% of Lynch syndrome patients received targeted treatment. With respect to tier 2 genes, 40% of patients with PALB2, 19% with ATM, and 37% with RAD51C or 51D received a poly (ADP-ribose) polymerase (PARP) inhibitor.

Among patients with a BRCA1/2 mutation who received a PARP inhibitor, 55.1% had breast or ovarian cancer, and 44.8% had other tumor types, including pancreas, prostate, bile duct, gastric cancers. These patients received the drug in a research setting.

For patients with PALB2 alterations who received PARP inhibitors, 53.3% had breast or pancreas cancer, and 46.7% had cancer of the prostate, ovary, or an unknown primary.

Looking ahead

The discussant for the paper, Funda Meric-Bernstam, MD, chair of the Department of Investigational Cancer Therapeutics at the University of Texas MD Anderson Cancer Center, Houston, pointed out that most of the BRCA-positive patients had cancers traditionally associated with the mutation. “There were no patients with PTEN mutations treated, and interestingly, no patients with NF1 were treated,” she said. “But actionability is evolving, as the MEK inhibitor selumitinib was recently approved for NF1.”

Some questions remain unanswered, she noted, such as: “What percentage of patients undergoing tumor-normal testing signed a germline protocol?” and “Does the population introduce a bias – such as younger patients, family history, and so on?”

It is also unknown what percentage of germline alterations were known in comparison with those identified through tumor/normal testing. Also of importance is the fact that in this study, the results of germline testing were delivered in an academic setting, she emphasized. “What if they were delivered elsewhere? What would be the impact of identifying these alterations in an environment with less access to trials?

“But to be fair, it is not easy to seek the germline mutations,” Dr. Meric-Bernstam continued. “These studies were done under institutional review board protocols, and it is important to note that most profiling is done as standard of care without consenting and soliciting patient preference on the return of germline results.”

An infrastructure is needed to return/counsel/offer cascade testing, and “analyses need to be facilitated to ensure that findings can be acted upon in a timely fashion,” she added.

The study was supported by MSKCC internal funding. Dr. Stadler reported relationships (institutional) with Adverum, Alimera Sciences, Allergan, Biomarin, Fortress Biotech, Genentech/Roche, Novartis, Optos, Regeneron, Regenxbio, and Spark Therapeutics. Dr. Meric-Bernstram reported relationships with numerous pharmaceutical companies.

This article first appeared on Medscape.com.

Food allergies among 6- to 10-year-olds may be less common than previously reported, researchers found in a multinational study of European school-age children.

The prevalence was as low as 1.4% and as high as 3.8% using different research methods, and most likely falls somewhere in between. The findings were “considerably lower” than the 16% rate based on parental reports of symptoms such as rash, itching, or diarrhea, Linus Grabenhenrich, MD, MPH, and colleagues reported in Allergy.

In addition, peanut and hazelnut allergens were most common among the 223 children with a positive skin prick allergy assay. A total 5.6% tested sensitive to peanuts and 5.2% to hazelnuts.

Previous research reports of pediatric food allergy prevalence were largely single-center studies with heterogeneous designs, the researchers noted. These prior protocols make comparisons across countries challenging.

In search of a more definitive answer, Dr. Grabenhenrich, of the Robert Koch-Institut in Berlin, and colleagues evaluated 238 children. This group was about 10% of 2,288 children with parental face-to-face interviews and/or skin prick testing from a birth cohort in Germany, Greece, Iceland, Lithuania, the Netherlands, Poland, Spain, and United Kingdom called the EuroPrevall-iFAAM.

All participants had suspected food allergies, and the mean age at follow-up was 8 years. A total 46 children participated in a double-blind, placebo-controlled oral food allergy challenge (DBPCFC). “Most of the positively challenged children reacted only mildly or moderately, except for five children with severe signs or symptoms during DBPCFC,” Dr. Grabenhenrich and associates noted.

A food allergy to at least one allergen was confirmed in 17 children out of 2,097 who completed assessment. This yielded an average raw prevalence of 0.8% across all eight countries. The estimated 1.4%-3.8% food allergy prevalence was based on adjusted analyses that extrapolated findings to all children with questionnaire data or who completed an eligibility assessment.

“Considerable attrition” in all stages of the assessment was a potential limitation. In addition, 192 parents refused to participate in the DBPCFC food challenge component of the research. Studying a birth cohort across European countries was a study strength.

The European Commission supported this study. Dr. Grabenhenrich had no relevant disclosures. Some coauthors reported various ties to pharmaceutical and food companies.

SOURCE: Grabenhenrich L et al. Allergy. 2020 Mar 27. doi: 10.1111/all.14290.
 

Food allergies among 6- to 10-year-olds may be less common than previously reported, researchers found in a multinational study of European school-age children.

The prevalence was as low as 1.4% and as high as 3.8% using different research methods, and most likely falls somewhere in between. The findings were “considerably lower” than the 16% rate based on parental reports of symptoms such as rash, itching, or diarrhea, Linus Grabenhenrich, MD, MPH, and colleagues reported in Allergy.

In addition, peanut and hazelnut allergens were most common among the 223 children with a positive skin prick allergy assay. A total 5.6% tested sensitive to peanuts and 5.2% to hazelnuts.

Previous research reports of pediatric food allergy prevalence were largely single-center studies with heterogeneous designs, the researchers noted. These prior protocols make comparisons across countries challenging.

In search of a more definitive answer, Dr. Grabenhenrich, of the Robert Koch-Institut in Berlin, and colleagues evaluated 238 children. This group was about 10% of 2,288 children with parental face-to-face interviews and/or skin prick testing from a birth cohort in Germany, Greece, Iceland, Lithuania, the Netherlands, Poland, Spain, and United Kingdom called the EuroPrevall-iFAAM.

All participants had suspected food allergies, and the mean age at follow-up was 8 years. A total 46 children participated in a double-blind, placebo-controlled oral food allergy challenge (DBPCFC). “Most of the positively challenged children reacted only mildly or moderately, except for five children with severe signs or symptoms during DBPCFC,” Dr. Grabenhenrich and associates noted.

A food allergy to at least one allergen was confirmed in 17 children out of 2,097 who completed assessment. This yielded an average raw prevalence of 0.8% across all eight countries. The estimated 1.4%-3.8% food allergy prevalence was based on adjusted analyses that extrapolated findings to all children with questionnaire data or who completed an eligibility assessment.

“Considerable attrition” in all stages of the assessment was a potential limitation. In addition, 192 parents refused to participate in the DBPCFC food challenge component of the research. Studying a birth cohort across European countries was a study strength.

The European Commission supported this study. Dr. Grabenhenrich had no relevant disclosures. Some coauthors reported various ties to pharmaceutical and food companies.

SOURCE: Grabenhenrich L et al. Allergy. 2020 Mar 27. doi: 10.1111/all.14290.
 

Food allergies among 6- to 10-year-olds may be less common than previously reported, researchers found in a multinational study of European school-age children.

The prevalence was as low as 1.4% and as high as 3.8% using different research methods, and most likely falls somewhere in between. The findings were “considerably lower” than the 16% rate based on parental reports of symptoms such as rash, itching, or diarrhea, Linus Grabenhenrich, MD, MPH, and colleagues reported in Allergy.

In addition, peanut and hazelnut allergens were most common among the 223 children with a positive skin prick allergy assay. A total 5.6% tested sensitive to peanuts and 5.2% to hazelnuts.

Previous research reports of pediatric food allergy prevalence were largely single-center studies with heterogeneous designs, the researchers noted. These prior protocols make comparisons across countries challenging.

In search of a more definitive answer, Dr. Grabenhenrich, of the Robert Koch-Institut in Berlin, and colleagues evaluated 238 children. This group was about 10% of 2,288 children with parental face-to-face interviews and/or skin prick testing from a birth cohort in Germany, Greece, Iceland, Lithuania, the Netherlands, Poland, Spain, and United Kingdom called the EuroPrevall-iFAAM.

All participants had suspected food allergies, and the mean age at follow-up was 8 years. A total 46 children participated in a double-blind, placebo-controlled oral food allergy challenge (DBPCFC). “Most of the positively challenged children reacted only mildly or moderately, except for five children with severe signs or symptoms during DBPCFC,” Dr. Grabenhenrich and associates noted.

A food allergy to at least one allergen was confirmed in 17 children out of 2,097 who completed assessment. This yielded an average raw prevalence of 0.8% across all eight countries. The estimated 1.4%-3.8% food allergy prevalence was based on adjusted analyses that extrapolated findings to all children with questionnaire data or who completed an eligibility assessment.

“Considerable attrition” in all stages of the assessment was a potential limitation. In addition, 192 parents refused to participate in the DBPCFC food challenge component of the research. Studying a birth cohort across European countries was a study strength.

The European Commission supported this study. Dr. Grabenhenrich had no relevant disclosures. Some coauthors reported various ties to pharmaceutical and food companies.

SOURCE: Grabenhenrich L et al. Allergy. 2020 Mar 27. doi: 10.1111/all.14290.
 

Psoriasis Area and Severity Index (PASI 100) scores were reached by one in four patients after 6 months of therapy in a study that examined six different biologic treatments in biologic-naive and biologic-experienced patients.

The study was published in May in the Journal of the European Academy of Dermatology and Venereology.

High efficacy rates, which include PASI 100 scores, have been reported in randomized trials of biologics that include anti–interleukin (IL)–17A therapies (secukinumab and ixekizumab), anti–IL-17A–receptor therapies (brodalumab), and anti–IL-23 therapies (guselkumab and risankizumab), but information on rates in real-world cohorts has been limited. “Real-world evidence provided by registries is only beginning to emerge, and efficacy data have mostly been derived from clinical trials,” senior author Kristian Reich, MD, PhD, professor for translational research in inflammatory skin diseases at the Institute for Health Services Research in Dermatology and Nursing, University Medical Center Hamburg-Eppendorf (Germany), said in an interview.

He and his coinvestigators conducted the PSO-BIO-REAL (Plaque Psoriasis Treated With Biologics in a Real World Setting) prospective trial in five countries, to evaluate the effectiveness of treatments in patients with moderate to severe plaque psoriasis over a year’s time following administration of a biologic therapy. Patients were 18 years of age or older and had either started a biologic for the first time (biologic-naive) or were transitioning to another biologic (biologic-experienced).

Among 846 participants, 32% were in the United States, followed by France (28%), Italy (22%), the United Kingdom (11%), and Germany (8%). Investigators estimated the proportion of patients achieving a PASI 100 (complete skin clearance) 6 months after starting a biologic as a primary objective, and as secondary objectives, PASI 100 scores at 1 year and PASI 100 maintenance from 6 to 12 months.

Nearly 200 patients withdrew during the course of the study, and 108 switched treatments. Therapies varied among patients: 61% received an anti–tumor necrosis factor agent such as etanercept, infliximab, adalimumab, or certolizumab pegol as an initial biologic treatment, 30% received an anti–IL-12/-23 agent (ustekinumab), and 9% received an anti-IL-17 agent (secukinumab). Additionally, 23% received a concomitant psoriasis medication.

PASI assessments were completed in 603 patients at 6 months, and 522 patients at 12 months. At 6 and 12 months respectively, 23% and 26% of the patients had achieved a PASI 100 score. Investigators noted that the rate of complete skin clearance declined as the number of baseline comorbidities and the number of prior biologics increased.

Biologic-experienced patients at study entry had lower PASI 100 response rates (about 20% at 6 and 12 months) than the biologic-naive patients (25% at 6 months, 30% at 12 months). Dr. Reich pointed out that many biologic-experienced patients often have active disease, despite previous use of biologics, and “they’re likely to represent a more difficult-to-treat population.” Factors such as convenience, safety, and the fact that more complicated patients – those with weight issues, more comorbidities and pretreatments, and lower compliance – are treated in real life than in clinical trials, are likely to influence lack of response in real-world data, Dr. Reich said.

The study’s enrollment period took place from 2014 to 2015, so it did not include patients on newer biologics such as brodalumab, guselkumab, ixekizumab, and tildrakizumab. “Some of these newer therapies have shown greater efficacy than drugs such as ustekinumab and etanercept in clinical trials, and patients are more likely to achieve complete skin clearance. Therefore, real-world rates of complete clearance may have improved since this study concluded,” the investigators pointed out.

Possible limitations of the study include selection bias and possible confounders, they noted.

The study was sponsored by Amgen/AstraZeneca; the manuscript was sponsored by LEO Pharma. One author was an AstraZeneca employee, two are LEO pharma employees, one author had no disclosures, and the remaining authors, including Dr. Reich, disclosed serving as an adviser, paid speaker, consultant, and/or investigator for multiple pharmaceutical companies.

SOURCE: Seneschal J et al. J Eur Acad Dermatol Venereol. 2020 May 4. doi: 10.1111/jdv.16568.

Psoriasis Area and Severity Index (PASI 100) scores were reached by one in four patients after 6 months of therapy in a study that examined six different biologic treatments in biologic-naive and biologic-experienced patients.

The study was published in May in the Journal of the European Academy of Dermatology and Venereology.

High efficacy rates, which include PASI 100 scores, have been reported in randomized trials of biologics that include anti–interleukin (IL)–17A therapies (secukinumab and ixekizumab), anti–IL-17A–receptor therapies (brodalumab), and anti–IL-23 therapies (guselkumab and risankizumab), but information on rates in real-world cohorts has been limited. “Real-world evidence provided by registries is only beginning to emerge, and efficacy data have mostly been derived from clinical trials,” senior author Kristian Reich, MD, PhD, professor for translational research in inflammatory skin diseases at the Institute for Health Services Research in Dermatology and Nursing, University Medical Center Hamburg-Eppendorf (Germany), said in an interview.

He and his coinvestigators conducted the PSO-BIO-REAL (Plaque Psoriasis Treated With Biologics in a Real World Setting) prospective trial in five countries, to evaluate the effectiveness of treatments in patients with moderate to severe plaque psoriasis over a year’s time following administration of a biologic therapy. Patients were 18 years of age or older and had either started a biologic for the first time (biologic-naive) or were transitioning to another biologic (biologic-experienced).

Among 846 participants, 32% were in the United States, followed by France (28%), Italy (22%), the United Kingdom (11%), and Germany (8%). Investigators estimated the proportion of patients achieving a PASI 100 (complete skin clearance) 6 months after starting a biologic as a primary objective, and as secondary objectives, PASI 100 scores at 1 year and PASI 100 maintenance from 6 to 12 months.

Nearly 200 patients withdrew during the course of the study, and 108 switched treatments. Therapies varied among patients: 61% received an anti–tumor necrosis factor agent such as etanercept, infliximab, adalimumab, or certolizumab pegol as an initial biologic treatment, 30% received an anti–IL-12/-23 agent (ustekinumab), and 9% received an anti-IL-17 agent (secukinumab). Additionally, 23% received a concomitant psoriasis medication.

PASI assessments were completed in 603 patients at 6 months, and 522 patients at 12 months. At 6 and 12 months respectively, 23% and 26% of the patients had achieved a PASI 100 score. Investigators noted that the rate of complete skin clearance declined as the number of baseline comorbidities and the number of prior biologics increased.

Biologic-experienced patients at study entry had lower PASI 100 response rates (about 20% at 6 and 12 months) than the biologic-naive patients (25% at 6 months, 30% at 12 months). Dr. Reich pointed out that many biologic-experienced patients often have active disease, despite previous use of biologics, and “they’re likely to represent a more difficult-to-treat population.” Factors such as convenience, safety, and the fact that more complicated patients – those with weight issues, more comorbidities and pretreatments, and lower compliance – are treated in real life than in clinical trials, are likely to influence lack of response in real-world data, Dr. Reich said.

The study’s enrollment period took place from 2014 to 2015, so it did not include patients on newer biologics such as brodalumab, guselkumab, ixekizumab, and tildrakizumab. “Some of these newer therapies have shown greater efficacy than drugs such as ustekinumab and etanercept in clinical trials, and patients are more likely to achieve complete skin clearance. Therefore, real-world rates of complete clearance may have improved since this study concluded,” the investigators pointed out.

Possible limitations of the study include selection bias and possible confounders, they noted.

The study was sponsored by Amgen/AstraZeneca; the manuscript was sponsored by LEO Pharma. One author was an AstraZeneca employee, two are LEO pharma employees, one author had no disclosures, and the remaining authors, including Dr. Reich, disclosed serving as an adviser, paid speaker, consultant, and/or investigator for multiple pharmaceutical companies.

SOURCE: Seneschal J et al. J Eur Acad Dermatol Venereol. 2020 May 4. doi: 10.1111/jdv.16568.

Psoriasis Area and Severity Index (PASI 100) scores were reached by one in four patients after 6 months of therapy in a study that examined six different biologic treatments in biologic-naive and biologic-experienced patients.

The study was published in May in the Journal of the European Academy of Dermatology and Venereology.

High efficacy rates, which include PASI 100 scores, have been reported in randomized trials of biologics that include anti–interleukin (IL)–17A therapies (secukinumab and ixekizumab), anti–IL-17A–receptor therapies (brodalumab), and anti–IL-23 therapies (guselkumab and risankizumab), but information on rates in real-world cohorts has been limited. “Real-world evidence provided by registries is only beginning to emerge, and efficacy data have mostly been derived from clinical trials,” senior author Kristian Reich, MD, PhD, professor for translational research in inflammatory skin diseases at the Institute for Health Services Research in Dermatology and Nursing, University Medical Center Hamburg-Eppendorf (Germany), said in an interview.

He and his coinvestigators conducted the PSO-BIO-REAL (Plaque Psoriasis Treated With Biologics in a Real World Setting) prospective trial in five countries, to evaluate the effectiveness of treatments in patients with moderate to severe plaque psoriasis over a year’s time following administration of a biologic therapy. Patients were 18 years of age or older and had either started a biologic for the first time (biologic-naive) or were transitioning to another biologic (biologic-experienced).

Among 846 participants, 32% were in the United States, followed by France (28%), Italy (22%), the United Kingdom (11%), and Germany (8%). Investigators estimated the proportion of patients achieving a PASI 100 (complete skin clearance) 6 months after starting a biologic as a primary objective, and as secondary objectives, PASI 100 scores at 1 year and PASI 100 maintenance from 6 to 12 months.

Nearly 200 patients withdrew during the course of the study, and 108 switched treatments. Therapies varied among patients: 61% received an anti–tumor necrosis factor agent such as etanercept, infliximab, adalimumab, or certolizumab pegol as an initial biologic treatment, 30% received an anti–IL-12/-23 agent (ustekinumab), and 9% received an anti-IL-17 agent (secukinumab). Additionally, 23% received a concomitant psoriasis medication.

PASI assessments were completed in 603 patients at 6 months, and 522 patients at 12 months. At 6 and 12 months respectively, 23% and 26% of the patients had achieved a PASI 100 score. Investigators noted that the rate of complete skin clearance declined as the number of baseline comorbidities and the number of prior biologics increased.

Biologic-experienced patients at study entry had lower PASI 100 response rates (about 20% at 6 and 12 months) than the biologic-naive patients (25% at 6 months, 30% at 12 months). Dr. Reich pointed out that many biologic-experienced patients often have active disease, despite previous use of biologics, and “they’re likely to represent a more difficult-to-treat population.” Factors such as convenience, safety, and the fact that more complicated patients – those with weight issues, more comorbidities and pretreatments, and lower compliance – are treated in real life than in clinical trials, are likely to influence lack of response in real-world data, Dr. Reich said.

The study’s enrollment period took place from 2014 to 2015, so it did not include patients on newer biologics such as brodalumab, guselkumab, ixekizumab, and tildrakizumab. “Some of these newer therapies have shown greater efficacy than drugs such as ustekinumab and etanercept in clinical trials, and patients are more likely to achieve complete skin clearance. Therefore, real-world rates of complete clearance may have improved since this study concluded,” the investigators pointed out.

Possible limitations of the study include selection bias and possible confounders, they noted.

The study was sponsored by Amgen/AstraZeneca; the manuscript was sponsored by LEO Pharma. One author was an AstraZeneca employee, two are LEO pharma employees, one author had no disclosures, and the remaining authors, including Dr. Reich, disclosed serving as an adviser, paid speaker, consultant, and/or investigator for multiple pharmaceutical companies.

SOURCE: Seneschal J et al. J Eur Acad Dermatol Venereol. 2020 May 4. doi: 10.1111/jdv.16568.

A nutritional intervention with a focus on fatty acids appears to reduce mood swings in patients with bipolar disorder (BD) when used as an adjunct to pharmacotherapy, early research suggests.

copyright/Digital Vision/Thinkstock

In a single-center study, patients with BD who received a diet consisting of high omega-3 plus low omega-6 fatty acids (H3-L6), in addition to usual care, showed significant reductions in mood variability, irritability, and pain, compared with their counterparts who received a diet with usual levels of omega-3 and omega-6 fatty acids commonly consumed in regular U.S. diets.

“Our findings need replication and validation in other studies,” study coinvestigator Erika Saunders, MD, professor and chair of the department of psychiatry and behavioral health at Penn State Health, Hershey, said in an interview.

“While we got really exciting findings, it’s far from confirmatory or the last word on the subject. The fatty acids do two broad things. They incorporate into the membranes of neurons in the brain and they also create signaling molecules throughout the brain and the body that interact with the immune system and the inflammatory system. And we suspect that it is through those mechanisms that this composition of fatty acids is having an effect on mood stability, but lots more work needs to be done to figure that out,” Dr. Saunders added.

The findings were presented at the American Society of Clinical Psychopharmacology 2020 Virtual Conference.
 

Fewer mood swings

Many patients with bipolar disorder do not achieve complete mood stability with medication, making the need for additional treatments imperative, she added.

“We were interested in looking at treatments that improved mood stability in bipolar disorder that are well tolerated by patients and that can be added to pharmacological treatments. We studied this particular nutritional intervention because biologically it does some of the same things that effective medications for bipolar disorder do and it has been investigated as an effective treatment for conditions like migraine headaches, which has a lot of overlap and comorbidity with bipolar disorder.”

The researchers randomized 41 patients with BD to receive the nutritional intervention of high omega-3 plus low omega-6 (H3-L6) and 41 patients with BD to receive a control diet of usual US levels of omega-3 and omega-6 fatty acids.

The patients were aged 20-75 years (mean age, 43.5 +/– 13.9 years) and 83% were women. They had similar mean levels of mood symptoms and pain.

All patients received group-specific study foods and oils, as well as intensive dietary counseling from a dietitian, access to a website with recipes, and guidance for eating in restaurants. All participants were blinded to the composition of the food that they were eating.

Both the interventional diet and the control diet were tailored for the purposes of the study, noted coinvestigator Sarah Shahriar, a research assistant at Penn State.

“The interventional group had more fatty fish such as salmon and tuna, while the control group had more white fish and fish with less fatty acid content. The interventional group also received a different type of cooking oil, which was a blend of olive and macadamia-nut oil, which was specially formulated by a research nutritional service at the University of North Carolina,” Ms. Shahriar said in an interview.

“They also decreased their red meat consumption and received specially formulated snack foods, which were specifically prepared by [the university’s] research nutritional service. It is important to point out that these diets were for a very specific purpose. We are not saying in any way shape or form that this particular nutritional intervention is good in general,” she added.

After 12 weeks, significant reductions were seen in mood variability, energy, irritability, and pain in the H3-L6 group (P < .001). The only symptom that was significantly lowered in the control group was impulsive thoughts (P = .004).

“The best message for doctors to tell their patients at this point is one of general nutritional health and the importance of nutrition in overall body and brain health, and that [this] can be a very important component of mood,” Dr. Saunders said.
 

Diet matters

“Highly unsaturated fatty acids are important components of neuronal cell membranes and in cell signaling,” Jessica M. Gannon, MD, University of Pittsburgh, who was not part of the study, said in an interview.

“Omega-6 fatty acids are precursors to proinflammatory compounds. Omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid are thought to be competitive inhibitors of omega-6 and thought to have anti-inflammatory effects. Supplementation with omega-3 has been explored in cardiovascular disease, diabetes, and in rheumatologic disorders as well as in a host of psychiatric disorders, including bipolar disorders, where a possible treatment effect has been suggested,” Dr. Gannon said.

Dietary interventions targeting not only increasing omega-3 but also decreasing consumption of omega-6 rich foods could be both effective and attractive to patients invested in a healthy lifestyle for promotion of mental health, especially when they are not optimally controlled by prescribed medications, she added.

“This study suggests that such an intervention could prove beneficial, although significant patient support may be necessary to assure adherence to the diet. Patient mood monitoring through a patient’s own personal electronic devices may also enhance buy-in. I would agree that future studies would be worth pursuing,” Dr. Gannon said.

The investigators and Dr. Gannon have reported no relevant financial relationships.

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

A nutritional intervention with a focus on fatty acids appears to reduce mood swings in patients with bipolar disorder (BD) when used as an adjunct to pharmacotherapy, early research suggests.

copyright/Digital Vision/Thinkstock

In a single-center study, patients with BD who received a diet consisting of high omega-3 plus low omega-6 fatty acids (H3-L6), in addition to usual care, showed significant reductions in mood variability, irritability, and pain, compared with their counterparts who received a diet with usual levels of omega-3 and omega-6 fatty acids commonly consumed in regular U.S. diets.

“Our findings need replication and validation in other studies,” study coinvestigator Erika Saunders, MD, professor and chair of the department of psychiatry and behavioral health at Penn State Health, Hershey, said in an interview.

“While we got really exciting findings, it’s far from confirmatory or the last word on the subject. The fatty acids do two broad things. They incorporate into the membranes of neurons in the brain and they also create signaling molecules throughout the brain and the body that interact with the immune system and the inflammatory system. And we suspect that it is through those mechanisms that this composition of fatty acids is having an effect on mood stability, but lots more work needs to be done to figure that out,” Dr. Saunders added.

The findings were presented at the American Society of Clinical Psychopharmacology 2020 Virtual Conference.
 

Fewer mood swings

Many patients with bipolar disorder do not achieve complete mood stability with medication, making the need for additional treatments imperative, she added.

“We were interested in looking at treatments that improved mood stability in bipolar disorder that are well tolerated by patients and that can be added to pharmacological treatments. We studied this particular nutritional intervention because biologically it does some of the same things that effective medications for bipolar disorder do and it has been investigated as an effective treatment for conditions like migraine headaches, which has a lot of overlap and comorbidity with bipolar disorder.”

The researchers randomized 41 patients with BD to receive the nutritional intervention of high omega-3 plus low omega-6 (H3-L6) and 41 patients with BD to receive a control diet of usual US levels of omega-3 and omega-6 fatty acids.

The patients were aged 20-75 years (mean age, 43.5 +/– 13.9 years) and 83% were women. They had similar mean levels of mood symptoms and pain.

All patients received group-specific study foods and oils, as well as intensive dietary counseling from a dietitian, access to a website with recipes, and guidance for eating in restaurants. All participants were blinded to the composition of the food that they were eating.

Both the interventional diet and the control diet were tailored for the purposes of the study, noted coinvestigator Sarah Shahriar, a research assistant at Penn State.

“The interventional group had more fatty fish such as salmon and tuna, while the control group had more white fish and fish with less fatty acid content. The interventional group also received a different type of cooking oil, which was a blend of olive and macadamia-nut oil, which was specially formulated by a research nutritional service at the University of North Carolina,” Ms. Shahriar said in an interview.

“They also decreased their red meat consumption and received specially formulated snack foods, which were specifically prepared by [the university’s] research nutritional service. It is important to point out that these diets were for a very specific purpose. We are not saying in any way shape or form that this particular nutritional intervention is good in general,” she added.

After 12 weeks, significant reductions were seen in mood variability, energy, irritability, and pain in the H3-L6 group (P < .001). The only symptom that was significantly lowered in the control group was impulsive thoughts (P = .004).

“The best message for doctors to tell their patients at this point is one of general nutritional health and the importance of nutrition in overall body and brain health, and that [this] can be a very important component of mood,” Dr. Saunders said.
 

Diet matters

“Highly unsaturated fatty acids are important components of neuronal cell membranes and in cell signaling,” Jessica M. Gannon, MD, University of Pittsburgh, who was not part of the study, said in an interview.

“Omega-6 fatty acids are precursors to proinflammatory compounds. Omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid are thought to be competitive inhibitors of omega-6 and thought to have anti-inflammatory effects. Supplementation with omega-3 has been explored in cardiovascular disease, diabetes, and in rheumatologic disorders as well as in a host of psychiatric disorders, including bipolar disorders, where a possible treatment effect has been suggested,” Dr. Gannon said.

Dietary interventions targeting not only increasing omega-3 but also decreasing consumption of omega-6 rich foods could be both effective and attractive to patients invested in a healthy lifestyle for promotion of mental health, especially when they are not optimally controlled by prescribed medications, she added.

“This study suggests that such an intervention could prove beneficial, although significant patient support may be necessary to assure adherence to the diet. Patient mood monitoring through a patient’s own personal electronic devices may also enhance buy-in. I would agree that future studies would be worth pursuing,” Dr. Gannon said.

The investigators and Dr. Gannon have reported no relevant financial relationships.

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

A nutritional intervention with a focus on fatty acids appears to reduce mood swings in patients with bipolar disorder (BD) when used as an adjunct to pharmacotherapy, early research suggests.

copyright/Digital Vision/Thinkstock

In a single-center study, patients with BD who received a diet consisting of high omega-3 plus low omega-6 fatty acids (H3-L6), in addition to usual care, showed significant reductions in mood variability, irritability, and pain, compared with their counterparts who received a diet with usual levels of omega-3 and omega-6 fatty acids commonly consumed in regular U.S. diets.

“Our findings need replication and validation in other studies,” study coinvestigator Erika Saunders, MD, professor and chair of the department of psychiatry and behavioral health at Penn State Health, Hershey, said in an interview.

“While we got really exciting findings, it’s far from confirmatory or the last word on the subject. The fatty acids do two broad things. They incorporate into the membranes of neurons in the brain and they also create signaling molecules throughout the brain and the body that interact with the immune system and the inflammatory system. And we suspect that it is through those mechanisms that this composition of fatty acids is having an effect on mood stability, but lots more work needs to be done to figure that out,” Dr. Saunders added.

The findings were presented at the American Society of Clinical Psychopharmacology 2020 Virtual Conference.
 

Fewer mood swings

Many patients with bipolar disorder do not achieve complete mood stability with medication, making the need for additional treatments imperative, she added.

“We were interested in looking at treatments that improved mood stability in bipolar disorder that are well tolerated by patients and that can be added to pharmacological treatments. We studied this particular nutritional intervention because biologically it does some of the same things that effective medications for bipolar disorder do and it has been investigated as an effective treatment for conditions like migraine headaches, which has a lot of overlap and comorbidity with bipolar disorder.”

The researchers randomized 41 patients with BD to receive the nutritional intervention of high omega-3 plus low omega-6 (H3-L6) and 41 patients with BD to receive a control diet of usual US levels of omega-3 and omega-6 fatty acids.

The patients were aged 20-75 years (mean age, 43.5 +/– 13.9 years) and 83% were women. They had similar mean levels of mood symptoms and pain.

All patients received group-specific study foods and oils, as well as intensive dietary counseling from a dietitian, access to a website with recipes, and guidance for eating in restaurants. All participants were blinded to the composition of the food that they were eating.

Both the interventional diet and the control diet were tailored for the purposes of the study, noted coinvestigator Sarah Shahriar, a research assistant at Penn State.

“The interventional group had more fatty fish such as salmon and tuna, while the control group had more white fish and fish with less fatty acid content. The interventional group also received a different type of cooking oil, which was a blend of olive and macadamia-nut oil, which was specially formulated by a research nutritional service at the University of North Carolina,” Ms. Shahriar said in an interview.

“They also decreased their red meat consumption and received specially formulated snack foods, which were specifically prepared by [the university’s] research nutritional service. It is important to point out that these diets were for a very specific purpose. We are not saying in any way shape or form that this particular nutritional intervention is good in general,” she added.

After 12 weeks, significant reductions were seen in mood variability, energy, irritability, and pain in the H3-L6 group (P < .001). The only symptom that was significantly lowered in the control group was impulsive thoughts (P = .004).

“The best message for doctors to tell their patients at this point is one of general nutritional health and the importance of nutrition in overall body and brain health, and that [this] can be a very important component of mood,” Dr. Saunders said.
 

Diet matters

“Highly unsaturated fatty acids are important components of neuronal cell membranes and in cell signaling,” Jessica M. Gannon, MD, University of Pittsburgh, who was not part of the study, said in an interview.

“Omega-6 fatty acids are precursors to proinflammatory compounds. Omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid are thought to be competitive inhibitors of omega-6 and thought to have anti-inflammatory effects. Supplementation with omega-3 has been explored in cardiovascular disease, diabetes, and in rheumatologic disorders as well as in a host of psychiatric disorders, including bipolar disorders, where a possible treatment effect has been suggested,” Dr. Gannon said.

Dietary interventions targeting not only increasing omega-3 but also decreasing consumption of omega-6 rich foods could be both effective and attractive to patients invested in a healthy lifestyle for promotion of mental health, especially when they are not optimally controlled by prescribed medications, she added.

“This study suggests that such an intervention could prove beneficial, although significant patient support may be necessary to assure adherence to the diet. Patient mood monitoring through a patient’s own personal electronic devices may also enhance buy-in. I would agree that future studies would be worth pursuing,” Dr. Gannon said.

The investigators and Dr. Gannon have reported no relevant financial relationships.

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

Click here to access June 2020 Public Pathogens

Table of Contents

• COVID-19 Data & Trends
• Open Clinical Trials for Patients With COVID-19
• Lessons From the COVID-19 Pandemic: It’s Time to Invest in Public Health
• Gap Analysis for the Conversion to Area Under the Curve Vancomycin Monitoring in a Small Rural Hospital
• Outcomes Comparison of the Veterans’ Choice Program Withthe Veterans Affairs Health Care System for Hepatitis C Treatment

Click here to access June 2020 Public Pathogens

Table of Contents

• COVID-19 Data & Trends
• Open Clinical Trials for Patients With COVID-19
• Lessons From the COVID-19 Pandemic: It’s Time to Invest in Public Health
• Gap Analysis for the Conversion to Area Under the Curve Vancomycin Monitoring in a Small Rural Hospital
• Outcomes Comparison of the Veterans’ Choice Program Withthe Veterans Affairs Health Care System for Hepatitis C Treatment

Click here to access June 2020 Public Pathogens

Table of Contents

• COVID-19 Data & Trends
• Open Clinical Trials for Patients With COVID-19
• Lessons From the COVID-19 Pandemic: It’s Time to Invest in Public Health
• Gap Analysis for the Conversion to Area Under the Curve Vancomycin Monitoring in a Small Rural Hospital
• Outcomes Comparison of the Veterans’ Choice Program Withthe Veterans Affairs Health Care System for Hepatitis C Treatment

The confluence of isolation, excess available time, and anxiety about illness or finances as a result of the COVID-19 pandemic have the potential to increase problem gambling behaviors during this public health emergency, so it’s essential to gather data and supply guidance on this issue, according to a call to action published May 18 in the Journal of Addiction Medicine.

humonia/iStock/Getty Images Plus

“When facing an unforeseen situation with confinement, fear of disease, and financial uncertainty for the future, problem gambling may be an important health hazard to monitor and prevent during and following the COVID-19 crisis, especially given current online gambling availability,” wrote Anders Håkansson, PhD, of Lund University in Sweden and coauthors.

Both stress and trauma have been linked to gambling problems, and both are occurring during the pandemic, said coauthor Marc N. Potenza, MD, PhD, of Yale University, New Haven, Conn., in an interview.

“People are likely to be experiencing stress at levels they haven’t experienced previously,” Dr. Potenza said. While multiple factors can contribute to addictive behaviors, “with respect to the pandemic, one concern is that so-called negative reinforcement motivations – engaging in an addictive behavior to escape from depressed or negative mood states – may be a driving motivation for a significant number of people during this time,” he said.

David Hodgins, PhD, CPsych, a professor of psychology at the University of Calgary in Alberta, who was not involved with the commentary, noted that gambling relapse is triggered by “negative emotional states, interpersonal stress, and financial stress” – all three of which the pandemic contributes to.

Financial stress can especially “inflame erroneous gambling-related cognitions,” he said in an interview, including “beliefs such as the idea that gambling can solve financial problems, even when this is statistically almost impossible as debt increases, and that debt has been caused by gambling.”

Increased social isolation also is particularly problematic, pointed out Shane W. Kraus, PhD, from the University of Nevada, Las Vegas. Dr. Kraus also was not involved with the paper.

“If someone is already struggling with already negative emotions, negative feelings, thoughts, and depression, and you’re now isolating them quite a bit, that’s not going to be a recipe for success,” Dr. Kraus said in an interview.

The mental health effects of the pandemic could be extensive and long-lasting, and such effects often co-occur with addictive behaviors, Dr. Potenza said.

“We should be mindful of ways in which people develop addictions in these settings,” he said. “One of the aspects of the pandemic is that many people are at home for longer periods of time, and they use digital technologies more frequently.”

The use of digital technologies can include interaction on social media platforms and on meeting applications such as Zoom, but such use also offers opportunities for problematic gambling, gaming, and pornography use. The World Health Organization recognizes addiction disorders for gambling and for gaming, and online gaming platforms and pornography sites have reported substantial increases in their traffic during the pandemic, Dr. Potenza said.

The increase in frequency is unsurprising and not necessarily a concern by itself, Dr. Kraus said.

“It’s all about loss of control or difficulty engaging or disengaging,” Dr. Kraus said. “When you can’t stop doing something even if you like it or love it, when it interferes with your day-to-day activities and relationships, that’s when it’s a problem.”
 

Gambling online: Easy, available

The authors note that past research has identified increased gambling problems during economic crises in other countries.

“While currently speculative, financial hardships may promote gambling as individuals may be motivated to gamble to try to win money,” the authors suggested. “Although presently limited, existing data suggest that COVID-19–related financial concerns may increase gambling-related harms, and this possibility merits systematic research.”

But trends and characteristics of the gambling market, including direct effects from the pandemic, can potentially influence behaviors, too. Most casinos have closed during the pandemic, and most of the sports that people bet on have been canceled or postponed.

“Fewer people are gambling on sports, but they turn then to other areas,” Dr. Potenza said. “If they can’t bet on major league type sports, they might gamble on more local sporting events, or they may bet on other activities going on in society during the pandemic.”

But online gambling poses greater risk.

“Properties of online gambling may constitute a particular health hazard when many people are confined to their homes and have had rapid changes in working conditions, psychosocial stress, anxiety, and depression, as has been described in China,” the paper’s authors wrote. “Online gambling may be particularly concerning due to its availability and velocity” and association with higher debt levels.

In addition to online gaming’s ease and availability, past research has found patients report boredom and escapism as reasons they turned to it.

Again, boredom on its own is not necessarily a problem, but for those who already struggle with addictive behaviors, it can be a trigger, Dr. Kraus said.

“Boredom is very tough for them because it’s often associated with negative emotions,” such as dwelling on things not going well in their lives, he said. “In a pandemic, people are by themselves quite a bit, socially isolated, so for those who are struggling already with some depression or anxiety, it’s only going to be increased.”

Online gaming trends may vary with demographics, however. Dr. Kraus noted that his former clinic at the Veterans Administration has been seeing lower gambling in patients with addictive disorders, but those patients are also older and primarily frequented casinos.

“It’s going to depend on age and familiarity with technology,” he said, but even if older problem gamblers are not going to the Internet now, “let’s wait and see what happens in the next 2 or 3 months.”

The authors noted results from a small survey of patients in treatment for gambling addiction at the Bellvitge University Hospital in Barcelona, Spain, where two of the coauthors work. They conducted telephone surveys with 26 patients about the first 4 weeks of sheltering in place because of the coronavirus. All but four of the patients were male, and their average age was 45 years.

“Most presented worries about increased uncertainties, such as the negative impact on their work, risk of COVID-19 infection of themselves or their loved ones and their treatment,” the authors reported.

Although 19% were completely abstinent, an additional 12% (n = 3) reported worsened gambling. In addition, almost half (46%) reported anxiety symptoms and more than a quarter (27%) had depressive symptoms.
 

Appropriate care

A particularly complicating factor of the pandemic is how it has disrupted traditional ways of seeking health care, particularly with how much mental health and other medical care has shifted to telehealth and online delivery, Dr. Potenza pointed out.

“This is a change for many people, and it’s important for both caretakers and people in treatment to be mindful of this and to try to ensure that appropriate services are maintained for people during this time,” he said.

For example, 12-step programs traditionally meet in person, which is largely impossible during the pandemic. Some have moved meetings online, and other programs have turned to apps, such as the Addiction Policy Forum’s app Connections, an empirically validated digital therapy platform that lets patients and clinicians remain connected with remote check-ins.

The move to more telehealth may actually increase access, suggested Dr. Hodgins.

“There is no evidence that this is less effective, and in fact, its convenience might be an advantage in reaching more people,” he said. “More challenging is offering group therapies remotely, but this is also feasible.”

The treatment with the strongest evidence remains cognitive-behavioral therapy (CBT), Dr. Hodgins said.

“This therapy, in part, helps people become aware of their erroneous cognitions and to challenge them, but also helps people restructure their activities to change their habits,” he said. He also noted the rise of online therapy, whether supported by a therapist or entirely self-directed, such as Gambling Self-help.

“These programs typically provide cognitive behavior content but also content that comes from studying how people recover from gambling problems,” he said. “The challenge of completely self-directed approaches is follow-through. Like most online content, people tend to flit around more than they might in therapy.” Still, he added, research has shown good outcomes from these programs.

Dr. Potenza also noted that several organizations, including the International Society of Addiction Medicine and Children and Screens, have been hosting webinars related to COVID-19 coping and/or addiction that clinicians and patients might find helpful.
 

Identification of problematic behaviors

One challenge in watching for problematic gambling behaviors during the pandemic is the set of unusual living circumstances for most people right now. At almost no other time in history have people been primarily confined to their homes, many unable to go to work or working from home, with extra leisure time and nowhere to go.

“With the COVID-19 pandemic, a lot of daily life has changed,” Dr. Potenza said. “It’s unclear whether certain behaviors that have become habitual during the pandemic, such as gaming or online gambling, will then interfere with daily life when the pandemic subsides.”

“The problem is, a small proportion of people who are very vulnerable will develop a disorder and might maintain it,” Dr. Kraus said. Those who already struggle with mental health and may be out of work have greater potential for problematic behaviors.

Dr. Potenza collaborated with other psychiatrists in drafting consensus guidelines on maintaining healthy use of the Internet specifically during the pandemic (Compr Psychiatry. 2020 Jul. doi: 10.10161/comppsych.2020.152180).

“It’s important to think about where one draws the line between normative everyday behaviors – behaviors that are not interfering with life functioning – and those that do interfere with life functioning,” Dr. Potenza said. “If someone is having difficulty making work or family or school obligations, these are important signs that the behavior may be problematic.”

He offered suggestions for things people can do to promote their health during the pandemic, such as having regular routines that include getting physical exercise and social interaction, dining with family if isolating together, and making time for self-care. He also recommended setting limits on the use of digital devices and aiming for a healthy balance in keeping up with the news. The idea is to stay aware of what’s happening without getting burned out or traumatized by news coverage.

Guidance for clinicians

An urgent need for research and guidelines related to gambling and the pandemic exists, the authors argued.

In the meantime, aside from various validated screeners available, Dr. Kraus offered some practical advice for clinicians checking in with their patients: “Ask your patients what they have been doing to cope with this difficult time.”

Some might mention their faith, family, or friends, and others might not have an answer or mention drinking, gaming, or engaging in other activities. “We all do things to cope. Sometimes you use healthy coping and sometimes you use unhealthy coping,” Dr. Kraus said. “I would have a dialogue with my patients around, ‘How are you getting through? What’s helping you? What are some things you’ve tried that are tripping you up?’ ”

If gambling in particular is a possible concern, he encouraged clinicians to ask their patients whether they have tried to quit or what would happen if they stopped gambling.

“What we’d expect is the problem gamblers will have more irritability, crankiness, difficulty with quitting,” he said.

Dr. Hodgins agreed that checking in on how patients’ lives and activities have changed, and their emotion reactions to those changes, is prudent.

“The change in activities might be healthy or might include increased addictive behaviors, including increased use of substances, gaming, pornography, food, and gambling,” he said.

In addition, the paper authors list several examples of guidelines that might be considered in drafting guidance for clinicians, including the following:

• Limiting the extent of gambling
• Not gambling to regulate negative emotions
• Not gambling in order to try to solve financial problems or financial concerns
• Not gambling under the influence of alcohol or drugs
• Carefully monitoring gambling-related time and financial expenditures
• Maintaining and establishing daily routines involving activities other than gambling
• Minding gambling-related attitudes and behaviors in the presence of minors
• Not starting to gamble because of stressors

The research did not receive external funding. Dr. Håkansson has received research funding from the Swedish Sport Foundation, the Swedish alcohol monopoly Systembolaget, and the Swedish state-owned gambling operator AB Svenska Spel. He is working with the company Kontigo Care on devices for gambling addiction follow-up care. Dr. Potenza has received consulting or advisory compensation from several entities, including the Addiction Policy Forum, AXA Gaming, Idorsia, Opiant, and RiverMend Health. Dr. Potenza has received research funding from Mohegan Sun casino and the National Center for Responsible Gaming. No other authors or outside sources had industry-related disclosures.

SOURCE: Håkansson A et al. J Addict Med. 2020 May 18. doi: 10.1097/ADM.0000000000000690.

The confluence of isolation, excess available time, and anxiety about illness or finances as a result of the COVID-19 pandemic have the potential to increase problem gambling behaviors during this public health emergency, so it’s essential to gather data and supply guidance on this issue, according to a call to action published May 18 in the Journal of Addiction Medicine.

humonia/iStock/Getty Images Plus

“When facing an unforeseen situation with confinement, fear of disease, and financial uncertainty for the future, problem gambling may be an important health hazard to monitor and prevent during and following the COVID-19 crisis, especially given current online gambling availability,” wrote Anders Håkansson, PhD, of Lund University in Sweden and coauthors.

Both stress and trauma have been linked to gambling problems, and both are occurring during the pandemic, said coauthor Marc N. Potenza, MD, PhD, of Yale University, New Haven, Conn., in an interview.

“People are likely to be experiencing stress at levels they haven’t experienced previously,” Dr. Potenza said. While multiple factors can contribute to addictive behaviors, “with respect to the pandemic, one concern is that so-called negative reinforcement motivations – engaging in an addictive behavior to escape from depressed or negative mood states – may be a driving motivation for a significant number of people during this time,” he said.

David Hodgins, PhD, CPsych, a professor of psychology at the University of Calgary in Alberta, who was not involved with the commentary, noted that gambling relapse is triggered by “negative emotional states, interpersonal stress, and financial stress” – all three of which the pandemic contributes to.

Financial stress can especially “inflame erroneous gambling-related cognitions,” he said in an interview, including “beliefs such as the idea that gambling can solve financial problems, even when this is statistically almost impossible as debt increases, and that debt has been caused by gambling.”

Increased social isolation also is particularly problematic, pointed out Shane W. Kraus, PhD, from the University of Nevada, Las Vegas. Dr. Kraus also was not involved with the paper.

“If someone is already struggling with already negative emotions, negative feelings, thoughts, and depression, and you’re now isolating them quite a bit, that’s not going to be a recipe for success,” Dr. Kraus said in an interview.

The mental health effects of the pandemic could be extensive and long-lasting, and such effects often co-occur with addictive behaviors, Dr. Potenza said.

“We should be mindful of ways in which people develop addictions in these settings,” he said. “One of the aspects of the pandemic is that many people are at home for longer periods of time, and they use digital technologies more frequently.”

The use of digital technologies can include interaction on social media platforms and on meeting applications such as Zoom, but such use also offers opportunities for problematic gambling, gaming, and pornography use. The World Health Organization recognizes addiction disorders for gambling and for gaming, and online gaming platforms and pornography sites have reported substantial increases in their traffic during the pandemic, Dr. Potenza said.

The increase in frequency is unsurprising and not necessarily a concern by itself, Dr. Kraus said.

“It’s all about loss of control or difficulty engaging or disengaging,” Dr. Kraus said. “When you can’t stop doing something even if you like it or love it, when it interferes with your day-to-day activities and relationships, that’s when it’s a problem.”
 

Gambling online: Easy, available

The authors note that past research has identified increased gambling problems during economic crises in other countries.

“While currently speculative, financial hardships may promote gambling as individuals may be motivated to gamble to try to win money,” the authors suggested. “Although presently limited, existing data suggest that COVID-19–related financial concerns may increase gambling-related harms, and this possibility merits systematic research.”

But trends and characteristics of the gambling market, including direct effects from the pandemic, can potentially influence behaviors, too. Most casinos have closed during the pandemic, and most of the sports that people bet on have been canceled or postponed.

“Fewer people are gambling on sports, but they turn then to other areas,” Dr. Potenza said. “If they can’t bet on major league type sports, they might gamble on more local sporting events, or they may bet on other activities going on in society during the pandemic.”

But online gambling poses greater risk.

“Properties of online gambling may constitute a particular health hazard when many people are confined to their homes and have had rapid changes in working conditions, psychosocial stress, anxiety, and depression, as has been described in China,” the paper’s authors wrote. “Online gambling may be particularly concerning due to its availability and velocity” and association with higher debt levels.

In addition to online gaming’s ease and availability, past research has found patients report boredom and escapism as reasons they turned to it.

Again, boredom on its own is not necessarily a problem, but for those who already struggle with addictive behaviors, it can be a trigger, Dr. Kraus said.

“Boredom is very tough for them because it’s often associated with negative emotions,” such as dwelling on things not going well in their lives, he said. “In a pandemic, people are by themselves quite a bit, socially isolated, so for those who are struggling already with some depression or anxiety, it’s only going to be increased.”

Online gaming trends may vary with demographics, however. Dr. Kraus noted that his former clinic at the Veterans Administration has been seeing lower gambling in patients with addictive disorders, but those patients are also older and primarily frequented casinos.

“It’s going to depend on age and familiarity with technology,” he said, but even if older problem gamblers are not going to the Internet now, “let’s wait and see what happens in the next 2 or 3 months.”

The authors noted results from a small survey of patients in treatment for gambling addiction at the Bellvitge University Hospital in Barcelona, Spain, where two of the coauthors work. They conducted telephone surveys with 26 patients about the first 4 weeks of sheltering in place because of the coronavirus. All but four of the patients were male, and their average age was 45 years.

“Most presented worries about increased uncertainties, such as the negative impact on their work, risk of COVID-19 infection of themselves or their loved ones and their treatment,” the authors reported.

Although 19% were completely abstinent, an additional 12% (n = 3) reported worsened gambling. In addition, almost half (46%) reported anxiety symptoms and more than a quarter (27%) had depressive symptoms.
 

Appropriate care

A particularly complicating factor of the pandemic is how it has disrupted traditional ways of seeking health care, particularly with how much mental health and other medical care has shifted to telehealth and online delivery, Dr. Potenza pointed out.

“This is a change for many people, and it’s important for both caretakers and people in treatment to be mindful of this and to try to ensure that appropriate services are maintained for people during this time,” he said.

For example, 12-step programs traditionally meet in person, which is largely impossible during the pandemic. Some have moved meetings online, and other programs have turned to apps, such as the Addiction Policy Forum’s app Connections, an empirically validated digital therapy platform that lets patients and clinicians remain connected with remote check-ins.

The move to more telehealth may actually increase access, suggested Dr. Hodgins.

“There is no evidence that this is less effective, and in fact, its convenience might be an advantage in reaching more people,” he said. “More challenging is offering group therapies remotely, but this is also feasible.”

The treatment with the strongest evidence remains cognitive-behavioral therapy (CBT), Dr. Hodgins said.

“This therapy, in part, helps people become aware of their erroneous cognitions and to challenge them, but also helps people restructure their activities to change their habits,” he said. He also noted the rise of online therapy, whether supported by a therapist or entirely self-directed, such as Gambling Self-help.

“These programs typically provide cognitive behavior content but also content that comes from studying how people recover from gambling problems,” he said. “The challenge of completely self-directed approaches is follow-through. Like most online content, people tend to flit around more than they might in therapy.” Still, he added, research has shown good outcomes from these programs.

Dr. Potenza also noted that several organizations, including the International Society of Addiction Medicine and Children and Screens, have been hosting webinars related to COVID-19 coping and/or addiction that clinicians and patients might find helpful.
 

Identification of problematic behaviors

One challenge in watching for problematic gambling behaviors during the pandemic is the set of unusual living circumstances for most people right now. At almost no other time in history have people been primarily confined to their homes, many unable to go to work or working from home, with extra leisure time and nowhere to go.

“With the COVID-19 pandemic, a lot of daily life has changed,” Dr. Potenza said. “It’s unclear whether certain behaviors that have become habitual during the pandemic, such as gaming or online gambling, will then interfere with daily life when the pandemic subsides.”

“The problem is, a small proportion of people who are very vulnerable will develop a disorder and might maintain it,” Dr. Kraus said. Those who already struggle with mental health and may be out of work have greater potential for problematic behaviors.

Dr. Potenza collaborated with other psychiatrists in drafting consensus guidelines on maintaining healthy use of the Internet specifically during the pandemic (Compr Psychiatry. 2020 Jul. doi: 10.10161/comppsych.2020.152180).

“It’s important to think about where one draws the line between normative everyday behaviors – behaviors that are not interfering with life functioning – and those that do interfere with life functioning,” Dr. Potenza said. “If someone is having difficulty making work or family or school obligations, these are important signs that the behavior may be problematic.”

He offered suggestions for things people can do to promote their health during the pandemic, such as having regular routines that include getting physical exercise and social interaction, dining with family if isolating together, and making time for self-care. He also recommended setting limits on the use of digital devices and aiming for a healthy balance in keeping up with the news. The idea is to stay aware of what’s happening without getting burned out or traumatized by news coverage.

Guidance for clinicians

An urgent need for research and guidelines related to gambling and the pandemic exists, the authors argued.

In the meantime, aside from various validated screeners available, Dr. Kraus offered some practical advice for clinicians checking in with their patients: “Ask your patients what they have been doing to cope with this difficult time.”

Some might mention their faith, family, or friends, and others might not have an answer or mention drinking, gaming, or engaging in other activities. “We all do things to cope. Sometimes you use healthy coping and sometimes you use unhealthy coping,” Dr. Kraus said. “I would have a dialogue with my patients around, ‘How are you getting through? What’s helping you? What are some things you’ve tried that are tripping you up?’ ”

If gambling in particular is a possible concern, he encouraged clinicians to ask their patients whether they have tried to quit or what would happen if they stopped gambling.

“What we’d expect is the problem gamblers will have more irritability, crankiness, difficulty with quitting,” he said.

Dr. Hodgins agreed that checking in on how patients’ lives and activities have changed, and their emotion reactions to those changes, is prudent.

“The change in activities might be healthy or might include increased addictive behaviors, including increased use of substances, gaming, pornography, food, and gambling,” he said.

In addition, the paper authors list several examples of guidelines that might be considered in drafting guidance for clinicians, including the following:

• Limiting the extent of gambling
• Not gambling to regulate negative emotions
• Not gambling in order to try to solve financial problems or financial concerns
• Not gambling under the influence of alcohol or drugs
• Carefully monitoring gambling-related time and financial expenditures
• Maintaining and establishing daily routines involving activities other than gambling
• Minding gambling-related attitudes and behaviors in the presence of minors
• Not starting to gamble because of stressors

The research did not receive external funding. Dr. Håkansson has received research funding from the Swedish Sport Foundation, the Swedish alcohol monopoly Systembolaget, and the Swedish state-owned gambling operator AB Svenska Spel. He is working with the company Kontigo Care on devices for gambling addiction follow-up care. Dr. Potenza has received consulting or advisory compensation from several entities, including the Addiction Policy Forum, AXA Gaming, Idorsia, Opiant, and RiverMend Health. Dr. Potenza has received research funding from Mohegan Sun casino and the National Center for Responsible Gaming. No other authors or outside sources had industry-related disclosures.

SOURCE: Håkansson A et al. J Addict Med. 2020 May 18. doi: 10.1097/ADM.0000000000000690.

The confluence of isolation, excess available time, and anxiety about illness or finances as a result of the COVID-19 pandemic have the potential to increase problem gambling behaviors during this public health emergency, so it’s essential to gather data and supply guidance on this issue, according to a call to action published May 18 in the Journal of Addiction Medicine.

humonia/iStock/Getty Images Plus

“When facing an unforeseen situation with confinement, fear of disease, and financial uncertainty for the future, problem gambling may be an important health hazard to monitor and prevent during and following the COVID-19 crisis, especially given current online gambling availability,” wrote Anders Håkansson, PhD, of Lund University in Sweden and coauthors.

Both stress and trauma have been linked to gambling problems, and both are occurring during the pandemic, said coauthor Marc N. Potenza, MD, PhD, of Yale University, New Haven, Conn., in an interview.

“People are likely to be experiencing stress at levels they haven’t experienced previously,” Dr. Potenza said. While multiple factors can contribute to addictive behaviors, “with respect to the pandemic, one concern is that so-called negative reinforcement motivations – engaging in an addictive behavior to escape from depressed or negative mood states – may be a driving motivation for a significant number of people during this time,” he said.

David Hodgins, PhD, CPsych, a professor of psychology at the University of Calgary in Alberta, who was not involved with the commentary, noted that gambling relapse is triggered by “negative emotional states, interpersonal stress, and financial stress” – all three of which the pandemic contributes to.

Financial stress can especially “inflame erroneous gambling-related cognitions,” he said in an interview, including “beliefs such as the idea that gambling can solve financial problems, even when this is statistically almost impossible as debt increases, and that debt has been caused by gambling.”

Increased social isolation also is particularly problematic, pointed out Shane W. Kraus, PhD, from the University of Nevada, Las Vegas. Dr. Kraus also was not involved with the paper.

“If someone is already struggling with already negative emotions, negative feelings, thoughts, and depression, and you’re now isolating them quite a bit, that’s not going to be a recipe for success,” Dr. Kraus said in an interview.

The mental health effects of the pandemic could be extensive and long-lasting, and such effects often co-occur with addictive behaviors, Dr. Potenza said.

“We should be mindful of ways in which people develop addictions in these settings,” he said. “One of the aspects of the pandemic is that many people are at home for longer periods of time, and they use digital technologies more frequently.”

The use of digital technologies can include interaction on social media platforms and on meeting applications such as Zoom, but such use also offers opportunities for problematic gambling, gaming, and pornography use. The World Health Organization recognizes addiction disorders for gambling and for gaming, and online gaming platforms and pornography sites have reported substantial increases in their traffic during the pandemic, Dr. Potenza said.

The increase in frequency is unsurprising and not necessarily a concern by itself, Dr. Kraus said.

“It’s all about loss of control or difficulty engaging or disengaging,” Dr. Kraus said. “When you can’t stop doing something even if you like it or love it, when it interferes with your day-to-day activities and relationships, that’s when it’s a problem.”
 

Gambling online: Easy, available

The authors note that past research has identified increased gambling problems during economic crises in other countries.

“While currently speculative, financial hardships may promote gambling as individuals may be motivated to gamble to try to win money,” the authors suggested. “Although presently limited, existing data suggest that COVID-19–related financial concerns may increase gambling-related harms, and this possibility merits systematic research.”

But trends and characteristics of the gambling market, including direct effects from the pandemic, can potentially influence behaviors, too. Most casinos have closed during the pandemic, and most of the sports that people bet on have been canceled or postponed.

“Fewer people are gambling on sports, but they turn then to other areas,” Dr. Potenza said. “If they can’t bet on major league type sports, they might gamble on more local sporting events, or they may bet on other activities going on in society during the pandemic.”

But online gambling poses greater risk.

“Properties of online gambling may constitute a particular health hazard when many people are confined to their homes and have had rapid changes in working conditions, psychosocial stress, anxiety, and depression, as has been described in China,” the paper’s authors wrote. “Online gambling may be particularly concerning due to its availability and velocity” and association with higher debt levels.

In addition to online gaming’s ease and availability, past research has found patients report boredom and escapism as reasons they turned to it.

Again, boredom on its own is not necessarily a problem, but for those who already struggle with addictive behaviors, it can be a trigger, Dr. Kraus said.

“Boredom is very tough for them because it’s often associated with negative emotions,” such as dwelling on things not going well in their lives, he said. “In a pandemic, people are by themselves quite a bit, socially isolated, so for those who are struggling already with some depression or anxiety, it’s only going to be increased.”

Online gaming trends may vary with demographics, however. Dr. Kraus noted that his former clinic at the Veterans Administration has been seeing lower gambling in patients with addictive disorders, but those patients are also older and primarily frequented casinos.

“It’s going to depend on age and familiarity with technology,” he said, but even if older problem gamblers are not going to the Internet now, “let’s wait and see what happens in the next 2 or 3 months.”

The authors noted results from a small survey of patients in treatment for gambling addiction at the Bellvitge University Hospital in Barcelona, Spain, where two of the coauthors work. They conducted telephone surveys with 26 patients about the first 4 weeks of sheltering in place because of the coronavirus. All but four of the patients were male, and their average age was 45 years.

“Most presented worries about increased uncertainties, such as the negative impact on their work, risk of COVID-19 infection of themselves or their loved ones and their treatment,” the authors reported.

Although 19% were completely abstinent, an additional 12% (n = 3) reported worsened gambling. In addition, almost half (46%) reported anxiety symptoms and more than a quarter (27%) had depressive symptoms.
 

Appropriate care

A particularly complicating factor of the pandemic is how it has disrupted traditional ways of seeking health care, particularly with how much mental health and other medical care has shifted to telehealth and online delivery, Dr. Potenza pointed out.

“This is a change for many people, and it’s important for both caretakers and people in treatment to be mindful of this and to try to ensure that appropriate services are maintained for people during this time,” he said.

For example, 12-step programs traditionally meet in person, which is largely impossible during the pandemic. Some have moved meetings online, and other programs have turned to apps, such as the Addiction Policy Forum’s app Connections, an empirically validated digital therapy platform that lets patients and clinicians remain connected with remote check-ins.

The move to more telehealth may actually increase access, suggested Dr. Hodgins.

“There is no evidence that this is less effective, and in fact, its convenience might be an advantage in reaching more people,” he said. “More challenging is offering group therapies remotely, but this is also feasible.”

The treatment with the strongest evidence remains cognitive-behavioral therapy (CBT), Dr. Hodgins said.

“This therapy, in part, helps people become aware of their erroneous cognitions and to challenge them, but also helps people restructure their activities to change their habits,” he said. He also noted the rise of online therapy, whether supported by a therapist or entirely self-directed, such as Gambling Self-help.

“These programs typically provide cognitive behavior content but also content that comes from studying how people recover from gambling problems,” he said. “The challenge of completely self-directed approaches is follow-through. Like most online content, people tend to flit around more than they might in therapy.” Still, he added, research has shown good outcomes from these programs.

Dr. Potenza also noted that several organizations, including the International Society of Addiction Medicine and Children and Screens, have been hosting webinars related to COVID-19 coping and/or addiction that clinicians and patients might find helpful.
 

Identification of problematic behaviors

One challenge in watching for problematic gambling behaviors during the pandemic is the set of unusual living circumstances for most people right now. At almost no other time in history have people been primarily confined to their homes, many unable to go to work or working from home, with extra leisure time and nowhere to go.

“With the COVID-19 pandemic, a lot of daily life has changed,” Dr. Potenza said. “It’s unclear whether certain behaviors that have become habitual during the pandemic, such as gaming or online gambling, will then interfere with daily life when the pandemic subsides.”

“The problem is, a small proportion of people who are very vulnerable will develop a disorder and might maintain it,” Dr. Kraus said. Those who already struggle with mental health and may be out of work have greater potential for problematic behaviors.

Dr. Potenza collaborated with other psychiatrists in drafting consensus guidelines on maintaining healthy use of the Internet specifically during the pandemic (Compr Psychiatry. 2020 Jul. doi: 10.10161/comppsych.2020.152180).

“It’s important to think about where one draws the line between normative everyday behaviors – behaviors that are not interfering with life functioning – and those that do interfere with life functioning,” Dr. Potenza said. “If someone is having difficulty making work or family or school obligations, these are important signs that the behavior may be problematic.”

He offered suggestions for things people can do to promote their health during the pandemic, such as having regular routines that include getting physical exercise and social interaction, dining with family if isolating together, and making time for self-care. He also recommended setting limits on the use of digital devices and aiming for a healthy balance in keeping up with the news. The idea is to stay aware of what’s happening without getting burned out or traumatized by news coverage.

Guidance for clinicians

An urgent need for research and guidelines related to gambling and the pandemic exists, the authors argued.

In the meantime, aside from various validated screeners available, Dr. Kraus offered some practical advice for clinicians checking in with their patients: “Ask your patients what they have been doing to cope with this difficult time.”

Some might mention their faith, family, or friends, and others might not have an answer or mention drinking, gaming, or engaging in other activities. “We all do things to cope. Sometimes you use healthy coping and sometimes you use unhealthy coping,” Dr. Kraus said. “I would have a dialogue with my patients around, ‘How are you getting through? What’s helping you? What are some things you’ve tried that are tripping you up?’ ”

If gambling in particular is a possible concern, he encouraged clinicians to ask their patients whether they have tried to quit or what would happen if they stopped gambling.

“What we’d expect is the problem gamblers will have more irritability, crankiness, difficulty with quitting,” he said.

Dr. Hodgins agreed that checking in on how patients’ lives and activities have changed, and their emotion reactions to those changes, is prudent.

“The change in activities might be healthy or might include increased addictive behaviors, including increased use of substances, gaming, pornography, food, and gambling,” he said.

In addition, the paper authors list several examples of guidelines that might be considered in drafting guidance for clinicians, including the following:

• Limiting the extent of gambling
• Not gambling to regulate negative emotions
• Not gambling in order to try to solve financial problems or financial concerns
• Not gambling under the influence of alcohol or drugs
• Carefully monitoring gambling-related time and financial expenditures
• Maintaining and establishing daily routines involving activities other than gambling
• Minding gambling-related attitudes and behaviors in the presence of minors
• Not starting to gamble because of stressors

The research did not receive external funding. Dr. Håkansson has received research funding from the Swedish Sport Foundation, the Swedish alcohol monopoly Systembolaget, and the Swedish state-owned gambling operator AB Svenska Spel. He is working with the company Kontigo Care on devices for gambling addiction follow-up care. Dr. Potenza has received consulting or advisory compensation from several entities, including the Addiction Policy Forum, AXA Gaming, Idorsia, Opiant, and RiverMend Health. Dr. Potenza has received research funding from Mohegan Sun casino and the National Center for Responsible Gaming. No other authors or outside sources had industry-related disclosures.

SOURCE: Håkansson A et al. J Addict Med. 2020 May 18. doi: 10.1097/ADM.0000000000000690.

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Addressing racism in the maternal mortality crisis

The emerging racial disparities in COVID-19 incidence and outcomes in the United States are on a collision course with long-standing racial disparities in U.S. maternal care and mortality. “The saying is that ‘the virus doesn’t discriminate,’ but it understands our biases, right? So, the virus takes advantage of the weaknesses in our system,” said Joia A. Crear-Perry, MD, an ob.gyn. and founder and president of the National Birth Equity Collaborative, a New Orleans–based research, training, and advocacy organization working to optimize black maternal and infant health. This article is part of an ongoing feature series on the crisis in maternal mortality in the United States. Here we explore potential solutions for addressing the inequities as proposed by thought leaders and key stakeholders. Read more.

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COVID-19 ravages the Navajo Nation

The Navajo Nation has the most cases of the COVID-19 virus of any tribe in the United States, and numbers as of May 31, 2020, are 5,348, with 246 confirmed deaths. These devastating numbers, which might be leveling off, are associated with Navajo people having higher-than-average rates of diabetes, heart disease, and cancer. This is compounded with 30%-40% of homes having no electricity or running water, and a poverty rate of about 38%. “We endured and learned from each Naayee, hunger, and death to name a few adversities. The COVID-19 pandemic, or “Big Cough” (Dikos Nitsaa’igii -19 in Navajo language), is a monster confronting the Navajo today. It has had significant impact on our nation and people,” Mary Hasbah Roessel, MD, a Navajo board-certified psychiatrist practicing in Santa Fe, N.M., wrote in a commentary on MDedge. Read more.

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In an update of the PREDIX-HER2 trial, trastuzumab emtansine (T-DM1) remained equivalent to standard neoadjuvant chemotherapy plus dual-targeted HER2 therapy in producing pathologic complete remissions (pCRs) among patients with HER2-positive, metastatic breast cancer.

The new data also suggest tumor-infiltrating lymphocytes (TILs) and dramatic improvements in PET-CT scans can predict favorable outcomes in both treatment groups. Though these findings will be useful for research purposes, they likely won’t influence routine clinical practice.

Thomas Hatschek, MD, PhD, of Karolinska Institutet in Stockholm, presented the updated results from PREDIX-HER2 during the European Society for Medical Oncology: Breast Cancer virtual meeting.

PREDIX-HER2 included patients with HER2-positive breast cancer and tumor size greater than 20 mm or lymph node metastases.

Patients received neoadjuvant therapy (NAT) with docetaxel and trastuzumab plus pertuzumab (DTP) or T-DM1 every 3 weeks for a planned total of six courses. The protocol permitted switching to the competing treatment for progression, lack of response, or drug-related severe toxicity.

Postoperatively, all patients received triweekly epirubicin plus cyclophosphamide – four courses for the T-DM1 arm and two courses for the DTP arm. All patients then received triweekly adjuvant trastuzumab for 11 courses. The 62% of patients whose tumors were hormone receptor (HR)–positive received standard endocrine therapy postoperatively.
 

Updated results, predictors of pCR

At the 2019 ASCO annual meeting, PREDIX-HER2 investigators reported that, when compared with DTP, T-DM1 produced the same likelihood of pCR with less toxicity (ASCO 2019, Abstract 501). Updated data presented at ESMO Breast Cancer 2020 showed similar results.

The pCR rate was 45.5% in the DTP arm and 43.9% in the T-DM1 arm (P = .824). pCR rates were higher for HR-negative tumors – 63.6% in the DTP arm and 59% in the T-DM1 arm – than for HR-positive tumors – 36.4% in the DTP arm and 33.9% in the TDM-1 arm.

Three patients had disease progression with T-DM1, and none progressed with DTP. However, almost twice as many patients switched from DTP to T-DM1, compared with the other sequence.

Dr. Hatschek reported that the presence of at least 10% TILs predicted pCR in both treatment groups. Among patients who achieved a pCR, 52.2% had at least 10% TILs in baseline biopsies, and 30.4% had less than 10% TILs.

In addition, a decrease of FDG maximum standardized uptake value by more than 75% on protocol-required PET-CT scans was highly predictive of pCR. Among patients who achieved a pCR, 70.3% had a maximum standardized uptake value decrease of more than 75%, and 22.5% had a decrease of 75% or less.

At median follow-up of 28.5 months, event-free survival was similar between the treatment arms. Overall, there were 13 cases of progression, relapse, contralateral breast cancer, distant metastases, or death from any cause. There were five such events in the DTP arm and eight in the TDM-1 arm.

Dr. Hatschek concluded that neoadjuvant T-DM1 may be as effective as standard NAT in all clinical subgroups evaluated. Both TILs and PET-CT showed the potential to predict pCR and merit further study in the NAT setting.
 

An imperfect surrogate

By definition, a surrogate is “one appointed to act in place of another.” In the case of PREDIX-HER2 and most other NAT studies in HER2-positive breast cancer patients, pCR is a surrogate for the endpoint about which doctors and patients really care – cancer-free survival.

As such, pCR is not a perfect surrogate. Reproducibly, pCR has been highly predictive of disease-free survival and overall survival, especially in the HR-negative subset of HER2-positive patients.

However, despite improvements with dual targeting of HER2 in the TRYPHAENA trial (Eur J Cancer. 2018;89:27-35) and the use of T-DM1 for patients failing to achieve pCR in the immediately practice-changing KATHERINE trial (N Engl J Med. 2019;380:617-28), eventual relapse is seen in 10%-20% of patients in various clinical-pathologic subgroups.

In PREDIX-HER2, the pCR rate for node-positive patients was considerably lower with T-DM1 than with DTP (54.1% vs. 38%), noted Valentina Guarneri, MD, of the University of Padova (Italy), in her discussion of the trial at ESMO Breast Cancer 2020.

Patients with larger initial tumor size and multiple involved axillary nodes at diagnosis remain at increased risk of death because of cancer relapse.

Central nervous system relapse remains a vexing problem. Among patients with triple-positive breast cancer, relapses may occur late, despite pCR.

Patients whose tumors transform from HER2 positive to HER2 negative with NAT, seen in approximately 8% of cases in the KATHERINE trial (ESMO Breast Cancer 2020, Abstract 96O), may be another poor-risk group.
 

Clinical implications

PREDIX-HER2 is an important study. At the early time point of 2.4 years (especially early since most patients were HR-positive), if pCR is achieved, event-free survival is excellent with T-DM1 or an aggressive multiagent cytotoxic combination plus dual HER2 targeting followed by anthracyclines.

It is ideal to have clinical-pathologic tests to distinguish those patients destined to achieve the surrogate endpoint of pCR from those who will not achieve it.

Despite linkage of TILs to improved outcome for triple-negative and HER2-enriched molecular subtypes (Lancet Oncol. 2018 Jan;19[1]:40-50), analysis of TILs is not standard practice in HER2-positive breast cancer in community settings. Optimal cutoffs are not well established, and TILs have not been linked to the choice of particular treatment options.

Currently, PET-CT scans are not part of National Comprehensive Cancer Network guidelines for pretreatment evaluation, except in patients for whom there is clinical suspicion of distant disease.

For those reasons, the main results of PREDIX-HER2 remain research tools that will focus our attention on the clinical-pathologic correlations Dr. Hatschek highlighted, but the results should have no influence on routine clinical practice at this time.

PREDIX-HER2 was funded by the Swedish Cancer Society, Radiumhemmet of Karolinska Institutet, Region Stockholm, and Roche Sweden. Dr. Hatschek disclosed relationships with Roche Sweden, Pfizer Sweden, and Pierre Fabre Sweden. Dr. Guarneri disclosed relationships with Roche, Novartis, and Eli Lilly.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

SOURCE: Hatschek T et al. ESMO Breast Cancer 2020, Abstract 97O.

In an update of the PREDIX-HER2 trial, trastuzumab emtansine (T-DM1) remained equivalent to standard neoadjuvant chemotherapy plus dual-targeted HER2 therapy in producing pathologic complete remissions (pCRs) among patients with HER2-positive, metastatic breast cancer.

The new data also suggest tumor-infiltrating lymphocytes (TILs) and dramatic improvements in PET-CT scans can predict favorable outcomes in both treatment groups. Though these findings will be useful for research purposes, they likely won’t influence routine clinical practice.

Thomas Hatschek, MD, PhD, of Karolinska Institutet in Stockholm, presented the updated results from PREDIX-HER2 during the European Society for Medical Oncology: Breast Cancer virtual meeting.

PREDIX-HER2 included patients with HER2-positive breast cancer and tumor size greater than 20 mm or lymph node metastases.

Patients received neoadjuvant therapy (NAT) with docetaxel and trastuzumab plus pertuzumab (DTP) or T-DM1 every 3 weeks for a planned total of six courses. The protocol permitted switching to the competing treatment for progression, lack of response, or drug-related severe toxicity.

Postoperatively, all patients received triweekly epirubicin plus cyclophosphamide – four courses for the T-DM1 arm and two courses for the DTP arm. All patients then received triweekly adjuvant trastuzumab for 11 courses. The 62% of patients whose tumors were hormone receptor (HR)–positive received standard endocrine therapy postoperatively.
 

Updated results, predictors of pCR

At the 2019 ASCO annual meeting, PREDIX-HER2 investigators reported that, when compared with DTP, T-DM1 produced the same likelihood of pCR with less toxicity (ASCO 2019, Abstract 501). Updated data presented at ESMO Breast Cancer 2020 showed similar results.

The pCR rate was 45.5% in the DTP arm and 43.9% in the T-DM1 arm (P = .824). pCR rates were higher for HR-negative tumors – 63.6% in the DTP arm and 59% in the T-DM1 arm – than for HR-positive tumors – 36.4% in the DTP arm and 33.9% in the TDM-1 arm.

Three patients had disease progression with T-DM1, and none progressed with DTP. However, almost twice as many patients switched from DTP to T-DM1, compared with the other sequence.

Dr. Hatschek reported that the presence of at least 10% TILs predicted pCR in both treatment groups. Among patients who achieved a pCR, 52.2% had at least 10% TILs in baseline biopsies, and 30.4% had less than 10% TILs.

In addition, a decrease of FDG maximum standardized uptake value by more than 75% on protocol-required PET-CT scans was highly predictive of pCR. Among patients who achieved a pCR, 70.3% had a maximum standardized uptake value decrease of more than 75%, and 22.5% had a decrease of 75% or less.

At median follow-up of 28.5 months, event-free survival was similar between the treatment arms. Overall, there were 13 cases of progression, relapse, contralateral breast cancer, distant metastases, or death from any cause. There were five such events in the DTP arm and eight in the TDM-1 arm.

Dr. Hatschek concluded that neoadjuvant T-DM1 may be as effective as standard NAT in all clinical subgroups evaluated. Both TILs and PET-CT showed the potential to predict pCR and merit further study in the NAT setting.
 

An imperfect surrogate

By definition, a surrogate is “one appointed to act in place of another.” In the case of PREDIX-HER2 and most other NAT studies in HER2-positive breast cancer patients, pCR is a surrogate for the endpoint about which doctors and patients really care – cancer-free survival.

As such, pCR is not a perfect surrogate. Reproducibly, pCR has been highly predictive of disease-free survival and overall survival, especially in the HR-negative subset of HER2-positive patients.

However, despite improvements with dual targeting of HER2 in the TRYPHAENA trial (Eur J Cancer. 2018;89:27-35) and the use of T-DM1 for patients failing to achieve pCR in the immediately practice-changing KATHERINE trial (N Engl J Med. 2019;380:617-28), eventual relapse is seen in 10%-20% of patients in various clinical-pathologic subgroups.

In PREDIX-HER2, the pCR rate for node-positive patients was considerably lower with T-DM1 than with DTP (54.1% vs. 38%), noted Valentina Guarneri, MD, of the University of Padova (Italy), in her discussion of the trial at ESMO Breast Cancer 2020.

Patients with larger initial tumor size and multiple involved axillary nodes at diagnosis remain at increased risk of death because of cancer relapse.

Central nervous system relapse remains a vexing problem. Among patients with triple-positive breast cancer, relapses may occur late, despite pCR.

Patients whose tumors transform from HER2 positive to HER2 negative with NAT, seen in approximately 8% of cases in the KATHERINE trial (ESMO Breast Cancer 2020, Abstract 96O), may be another poor-risk group.
 

Clinical implications

PREDIX-HER2 is an important study. At the early time point of 2.4 years (especially early since most patients were HR-positive), if pCR is achieved, event-free survival is excellent with T-DM1 or an aggressive multiagent cytotoxic combination plus dual HER2 targeting followed by anthracyclines.

It is ideal to have clinical-pathologic tests to distinguish those patients destined to achieve the surrogate endpoint of pCR from those who will not achieve it.

Despite linkage of TILs to improved outcome for triple-negative and HER2-enriched molecular subtypes (Lancet Oncol. 2018 Jan;19[1]:40-50), analysis of TILs is not standard practice in HER2-positive breast cancer in community settings. Optimal cutoffs are not well established, and TILs have not been linked to the choice of particular treatment options.

Currently, PET-CT scans are not part of National Comprehensive Cancer Network guidelines for pretreatment evaluation, except in patients for whom there is clinical suspicion of distant disease.

For those reasons, the main results of PREDIX-HER2 remain research tools that will focus our attention on the clinical-pathologic correlations Dr. Hatschek highlighted, but the results should have no influence on routine clinical practice at this time.

PREDIX-HER2 was funded by the Swedish Cancer Society, Radiumhemmet of Karolinska Institutet, Region Stockholm, and Roche Sweden. Dr. Hatschek disclosed relationships with Roche Sweden, Pfizer Sweden, and Pierre Fabre Sweden. Dr. Guarneri disclosed relationships with Roche, Novartis, and Eli Lilly.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

SOURCE: Hatschek T et al. ESMO Breast Cancer 2020, Abstract 97O.

In an update of the PREDIX-HER2 trial, trastuzumab emtansine (T-DM1) remained equivalent to standard neoadjuvant chemotherapy plus dual-targeted HER2 therapy in producing pathologic complete remissions (pCRs) among patients with HER2-positive, metastatic breast cancer.

The new data also suggest tumor-infiltrating lymphocytes (TILs) and dramatic improvements in PET-CT scans can predict favorable outcomes in both treatment groups. Though these findings will be useful for research purposes, they likely won’t influence routine clinical practice.

Thomas Hatschek, MD, PhD, of Karolinska Institutet in Stockholm, presented the updated results from PREDIX-HER2 during the European Society for Medical Oncology: Breast Cancer virtual meeting.

PREDIX-HER2 included patients with HER2-positive breast cancer and tumor size greater than 20 mm or lymph node metastases.

Patients received neoadjuvant therapy (NAT) with docetaxel and trastuzumab plus pertuzumab (DTP) or T-DM1 every 3 weeks for a planned total of six courses. The protocol permitted switching to the competing treatment for progression, lack of response, or drug-related severe toxicity.

Postoperatively, all patients received triweekly epirubicin plus cyclophosphamide – four courses for the T-DM1 arm and two courses for the DTP arm. All patients then received triweekly adjuvant trastuzumab for 11 courses. The 62% of patients whose tumors were hormone receptor (HR)–positive received standard endocrine therapy postoperatively.
 

Updated results, predictors of pCR

At the 2019 ASCO annual meeting, PREDIX-HER2 investigators reported that, when compared with DTP, T-DM1 produced the same likelihood of pCR with less toxicity (ASCO 2019, Abstract 501). Updated data presented at ESMO Breast Cancer 2020 showed similar results.

The pCR rate was 45.5% in the DTP arm and 43.9% in the T-DM1 arm (P = .824). pCR rates were higher for HR-negative tumors – 63.6% in the DTP arm and 59% in the T-DM1 arm – than for HR-positive tumors – 36.4% in the DTP arm and 33.9% in the TDM-1 arm.

Three patients had disease progression with T-DM1, and none progressed with DTP. However, almost twice as many patients switched from DTP to T-DM1, compared with the other sequence.

Dr. Hatschek reported that the presence of at least 10% TILs predicted pCR in both treatment groups. Among patients who achieved a pCR, 52.2% had at least 10% TILs in baseline biopsies, and 30.4% had less than 10% TILs.

In addition, a decrease of FDG maximum standardized uptake value by more than 75% on protocol-required PET-CT scans was highly predictive of pCR. Among patients who achieved a pCR, 70.3% had a maximum standardized uptake value decrease of more than 75%, and 22.5% had a decrease of 75% or less.

At median follow-up of 28.5 months, event-free survival was similar between the treatment arms. Overall, there were 13 cases of progression, relapse, contralateral breast cancer, distant metastases, or death from any cause. There were five such events in the DTP arm and eight in the TDM-1 arm.

Dr. Hatschek concluded that neoadjuvant T-DM1 may be as effective as standard NAT in all clinical subgroups evaluated. Both TILs and PET-CT showed the potential to predict pCR and merit further study in the NAT setting.
 

An imperfect surrogate

By definition, a surrogate is “one appointed to act in place of another.” In the case of PREDIX-HER2 and most other NAT studies in HER2-positive breast cancer patients, pCR is a surrogate for the endpoint about which doctors and patients really care – cancer-free survival.

As such, pCR is not a perfect surrogate. Reproducibly, pCR has been highly predictive of disease-free survival and overall survival, especially in the HR-negative subset of HER2-positive patients.

However, despite improvements with dual targeting of HER2 in the TRYPHAENA trial (Eur J Cancer. 2018;89:27-35) and the use of T-DM1 for patients failing to achieve pCR in the immediately practice-changing KATHERINE trial (N Engl J Med. 2019;380:617-28), eventual relapse is seen in 10%-20% of patients in various clinical-pathologic subgroups.

In PREDIX-HER2, the pCR rate for node-positive patients was considerably lower with T-DM1 than with DTP (54.1% vs. 38%), noted Valentina Guarneri, MD, of the University of Padova (Italy), in her discussion of the trial at ESMO Breast Cancer 2020.

Patients with larger initial tumor size and multiple involved axillary nodes at diagnosis remain at increased risk of death because of cancer relapse.

Central nervous system relapse remains a vexing problem. Among patients with triple-positive breast cancer, relapses may occur late, despite pCR.

Patients whose tumors transform from HER2 positive to HER2 negative with NAT, seen in approximately 8% of cases in the KATHERINE trial (ESMO Breast Cancer 2020, Abstract 96O), may be another poor-risk group.
 

Clinical implications

PREDIX-HER2 is an important study. At the early time point of 2.4 years (especially early since most patients were HR-positive), if pCR is achieved, event-free survival is excellent with T-DM1 or an aggressive multiagent cytotoxic combination plus dual HER2 targeting followed by anthracyclines.

It is ideal to have clinical-pathologic tests to distinguish those patients destined to achieve the surrogate endpoint of pCR from those who will not achieve it.

Despite linkage of TILs to improved outcome for triple-negative and HER2-enriched molecular subtypes (Lancet Oncol. 2018 Jan;19[1]:40-50), analysis of TILs is not standard practice in HER2-positive breast cancer in community settings. Optimal cutoffs are not well established, and TILs have not been linked to the choice of particular treatment options.

Currently, PET-CT scans are not part of National Comprehensive Cancer Network guidelines for pretreatment evaluation, except in patients for whom there is clinical suspicion of distant disease.

For those reasons, the main results of PREDIX-HER2 remain research tools that will focus our attention on the clinical-pathologic correlations Dr. Hatschek highlighted, but the results should have no influence on routine clinical practice at this time.

PREDIX-HER2 was funded by the Swedish Cancer Society, Radiumhemmet of Karolinska Institutet, Region Stockholm, and Roche Sweden. Dr. Hatschek disclosed relationships with Roche Sweden, Pfizer Sweden, and Pierre Fabre Sweden. Dr. Guarneri disclosed relationships with Roche, Novartis, and Eli Lilly.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

SOURCE: Hatschek T et al. ESMO Breast Cancer 2020, Abstract 97O.