Although about two of five physicians report a net worth of between $1 million and $5 million, half are under the million dollars and about half believe in living at or below their means, according to the latest Medscape Physician Debt and Net Worth Report 2020.

43% live below their means

Asked about habits regarding saving, 43% of physicians reported they live below their means. Half said they live at their means, and 7% said they live above their means.

Joel Greenwald, MD, CEO of Greenwald Wealth Management in St. Louis Park, Minn., recommends in the report trying to save 20% of annual gross salary.

More than a third of physicians who responded (39%) said they put more than $2,000/month into tax-deferred retirement or college savings, but Dr. Greenwald acknowledged that this may become more challenging.

“Many have seen the employer match in their retirement plans reduced or eliminated through the end of 2020, with what comes in 2021 as yet undefined,” he said.

A smaller percentage (26%) answered that they put more than $2,000 a month into a taxable retirement or college savings account each month.

Home size by specialty

Mortgages on a primary residence were the top reasons for debt (63%), followed by car loans (37%), personal education loans (26%), and credit card balances (25%).

Half of specialists and 61% of primary care physicians live in homes with up to 3,000 square feet. Only 7% of PCPs and 12% of specialists live in homes with 5000 square feet or more.

At 22%, plastic surgeons and orthopedists were the most likely groups to have houses with the largest square footage, according to the survey.

About one in four physicians in five specialties (urology, cardiology, plastic surgery, otolaryngology, and critical care) reported that they had mortgages of more than $500,000.

Standard financial advice, the report authors note, is that a mortgage should take up no more than 28% of monthly gross income.

Another large source of debt came from student loans. Close to 80% of graduating medical students have educational debt. The average balance for graduating students in 2018 was $196,520, the report authors state.

Those in physical medicine/rehabilitation and family medicine were most likely to still be paying off student debt (34% said they were). Conversely, half as many nephrologists and rheumatologists (15%) and gastroenterologists (14%) reported that they were paying off educational debt.

Only 11% of physicians said they were currently free of any debt.

Most physicians in the survey (72%) reported that they had not experienced a significant financial loss in the past year.

For those who did experience such a loss, the top reason given was related to a bad investment or the stock market (9%).
 

Cost-cutting strategies

Revenue reduction will likely lead to spending less this year as the pandemic challenges continue.

Survey respondents offered their most effective cost-cutting strategies.

A hospitalist said, “Half of every bonus goes into the investment account, no matter how much.”

“We add an extra amount to the principal of our monthly mortgage payment,” an internist said.

A pediatrician offered, “I bring my lunch to work every day and don’t eat in restaurants often.”
 

This article first appeared on Medscape.com.

Although about two of five physicians report a net worth of between $1 million and $5 million, half are under the million dollars and about half believe in living at or below their means, according to the latest Medscape Physician Debt and Net Worth Report 2020.

43% live below their means

Asked about habits regarding saving, 43% of physicians reported they live below their means. Half said they live at their means, and 7% said they live above their means.

Joel Greenwald, MD, CEO of Greenwald Wealth Management in St. Louis Park, Minn., recommends in the report trying to save 20% of annual gross salary.

More than a third of physicians who responded (39%) said they put more than $2,000/month into tax-deferred retirement or college savings, but Dr. Greenwald acknowledged that this may become more challenging.

“Many have seen the employer match in their retirement plans reduced or eliminated through the end of 2020, with what comes in 2021 as yet undefined,” he said.

A smaller percentage (26%) answered that they put more than $2,000 a month into a taxable retirement or college savings account each month.

Home size by specialty

Mortgages on a primary residence were the top reasons for debt (63%), followed by car loans (37%), personal education loans (26%), and credit card balances (25%).

Half of specialists and 61% of primary care physicians live in homes with up to 3,000 square feet. Only 7% of PCPs and 12% of specialists live in homes with 5000 square feet or more.

At 22%, plastic surgeons and orthopedists were the most likely groups to have houses with the largest square footage, according to the survey.

About one in four physicians in five specialties (urology, cardiology, plastic surgery, otolaryngology, and critical care) reported that they had mortgages of more than $500,000.

Standard financial advice, the report authors note, is that a mortgage should take up no more than 28% of monthly gross income.

Another large source of debt came from student loans. Close to 80% of graduating medical students have educational debt. The average balance for graduating students in 2018 was $196,520, the report authors state.

Those in physical medicine/rehabilitation and family medicine were most likely to still be paying off student debt (34% said they were). Conversely, half as many nephrologists and rheumatologists (15%) and gastroenterologists (14%) reported that they were paying off educational debt.

Only 11% of physicians said they were currently free of any debt.

Most physicians in the survey (72%) reported that they had not experienced a significant financial loss in the past year.

For those who did experience such a loss, the top reason given was related to a bad investment or the stock market (9%).
 

Cost-cutting strategies

Revenue reduction will likely lead to spending less this year as the pandemic challenges continue.

Survey respondents offered their most effective cost-cutting strategies.

A hospitalist said, “Half of every bonus goes into the investment account, no matter how much.”

“We add an extra amount to the principal of our monthly mortgage payment,” an internist said.

A pediatrician offered, “I bring my lunch to work every day and don’t eat in restaurants often.”
 

This article first appeared on Medscape.com.

Although about two of five physicians report a net worth of between $1 million and $5 million, half are under the million dollars and about half believe in living at or below their means, according to the latest Medscape Physician Debt and Net Worth Report 2020.

43% live below their means

Asked about habits regarding saving, 43% of physicians reported they live below their means. Half said they live at their means, and 7% said they live above their means.

Joel Greenwald, MD, CEO of Greenwald Wealth Management in St. Louis Park, Minn., recommends in the report trying to save 20% of annual gross salary.

More than a third of physicians who responded (39%) said they put more than $2,000/month into tax-deferred retirement or college savings, but Dr. Greenwald acknowledged that this may become more challenging.

“Many have seen the employer match in their retirement plans reduced or eliminated through the end of 2020, with what comes in 2021 as yet undefined,” he said.

A smaller percentage (26%) answered that they put more than $2,000 a month into a taxable retirement or college savings account each month.

Home size by specialty

Mortgages on a primary residence were the top reasons for debt (63%), followed by car loans (37%), personal education loans (26%), and credit card balances (25%).

Half of specialists and 61% of primary care physicians live in homes with up to 3,000 square feet. Only 7% of PCPs and 12% of specialists live in homes with 5000 square feet or more.

At 22%, plastic surgeons and orthopedists were the most likely groups to have houses with the largest square footage, according to the survey.

About one in four physicians in five specialties (urology, cardiology, plastic surgery, otolaryngology, and critical care) reported that they had mortgages of more than $500,000.

Standard financial advice, the report authors note, is that a mortgage should take up no more than 28% of monthly gross income.

Another large source of debt came from student loans. Close to 80% of graduating medical students have educational debt. The average balance for graduating students in 2018 was $196,520, the report authors state.

Those in physical medicine/rehabilitation and family medicine were most likely to still be paying off student debt (34% said they were). Conversely, half as many nephrologists and rheumatologists (15%) and gastroenterologists (14%) reported that they were paying off educational debt.

Only 11% of physicians said they were currently free of any debt.

Most physicians in the survey (72%) reported that they had not experienced a significant financial loss in the past year.

For those who did experience such a loss, the top reason given was related to a bad investment or the stock market (9%).
 

Cost-cutting strategies

Revenue reduction will likely lead to spending less this year as the pandemic challenges continue.

Survey respondents offered their most effective cost-cutting strategies.

A hospitalist said, “Half of every bonus goes into the investment account, no matter how much.”

“We add an extra amount to the principal of our monthly mortgage payment,” an internist said.

A pediatrician offered, “I bring my lunch to work every day and don’t eat in restaurants often.”
 

This article first appeared on Medscape.com.

For surgical patients on chronic opioid therapy, the goals of pain management are to provide adequate analgesia, prevent withdrawal, and avoid relapse or worsening of opioid use, according to Stephanie B. Jones, MD, professor and chair of anesthesiology at Albany Medical College, New York.

“[With] any patient coming in for any sort of surgery, you should be considering multimodal pain management. That applies to the opioid use disorder patient as well,” Dr. Jones said in a presentation at the virtual Annual Minimally Invasive Surgery Symposium sponsored by Global Academy for Medical Education.

“The challenge of opioid-tolerant patients or opioid abuse patients is twofold – tolerance and hyperalgesia,” Dr. Jones said. Patient tolerance changes how patients perceive pain and respond to medication. Clinicians need to consider the “opioid debt,” defined as the daily amount of opioid medication required by opioid-dependent patients to maintain their usual prehospitalization opioid levels, she explained. Also consider hyperalgesia, a change in pain perception “resulting in an increase in pain sensitivity to painful stimuli, thereby decreasing the analgesic effects of opioids,” Dr. Jones added.

A multimodal approach to pain management in patients on chronic opioids can include some opioids as appropriate, Dr. Jones said. Modulation of pain may draw on epidurals and nerve blocks, as well as managing CNS perception of pain through opioids or acetaminophen, and also using systemic options such as alpha-2 agonists and tramadol, she said.

Studies have shown that opioid abuse or dependence were associated with increased readmission rates, length of stay, and health care costs in surgery patients, said Dr. Jones. However, switching opioids and managing equivalents is complex, and “equianalgesic conversions serve only as a general guide to estimate opioid dose equivalents,” according to UpToDate’s, “Management of acute pain in the patient chronically using opioids,” she said.

Dr. Jones also addressed the issue of using hospitalization as an opportunity to help patients with untreated opioid use disorder. Medication-assisted options include methadone, buprenorphine, and naltrexone.

“One problem with methadone is that there are a lot of medications interactions,” she said. Buprenorphine has the advantage of being long-lasting, and is formulated with naloxone which deters injection. “Because it is a partial agonist, there is a lower risk of overdose and sedation,” and it has fewer medication interactions. However, some doctors are reluctant to prescribe it and there is some risk of medication diversion, she said.

Naltrexone is newer to the role of treating opioid use disorder, Dr. Jones said. “It can cause acute withdrawal because it is a full opioid antagonist,” she noted. However, naltrexone itself causes no withdrawal if stopped, and no respiratory depression or sedation, said Dr. Jones.

“Utilize addiction services in your hospital if you suspect a patient may be at risk for opioid use disorder,” and engage these services early, she emphasized.

Global Academy for Medical Education and this news organization are owned by the same parent company.

Dr. Jones had no financial conflicts to disclose.

For surgical patients on chronic opioid therapy, the goals of pain management are to provide adequate analgesia, prevent withdrawal, and avoid relapse or worsening of opioid use, according to Stephanie B. Jones, MD, professor and chair of anesthesiology at Albany Medical College, New York.

“[With] any patient coming in for any sort of surgery, you should be considering multimodal pain management. That applies to the opioid use disorder patient as well,” Dr. Jones said in a presentation at the virtual Annual Minimally Invasive Surgery Symposium sponsored by Global Academy for Medical Education.

“The challenge of opioid-tolerant patients or opioid abuse patients is twofold – tolerance and hyperalgesia,” Dr. Jones said. Patient tolerance changes how patients perceive pain and respond to medication. Clinicians need to consider the “opioid debt,” defined as the daily amount of opioid medication required by opioid-dependent patients to maintain their usual prehospitalization opioid levels, she explained. Also consider hyperalgesia, a change in pain perception “resulting in an increase in pain sensitivity to painful stimuli, thereby decreasing the analgesic effects of opioids,” Dr. Jones added.

A multimodal approach to pain management in patients on chronic opioids can include some opioids as appropriate, Dr. Jones said. Modulation of pain may draw on epidurals and nerve blocks, as well as managing CNS perception of pain through opioids or acetaminophen, and also using systemic options such as alpha-2 agonists and tramadol, she said.

Studies have shown that opioid abuse or dependence were associated with increased readmission rates, length of stay, and health care costs in surgery patients, said Dr. Jones. However, switching opioids and managing equivalents is complex, and “equianalgesic conversions serve only as a general guide to estimate opioid dose equivalents,” according to UpToDate’s, “Management of acute pain in the patient chronically using opioids,” she said.

Dr. Jones also addressed the issue of using hospitalization as an opportunity to help patients with untreated opioid use disorder. Medication-assisted options include methadone, buprenorphine, and naltrexone.

“One problem with methadone is that there are a lot of medications interactions,” she said. Buprenorphine has the advantage of being long-lasting, and is formulated with naloxone which deters injection. “Because it is a partial agonist, there is a lower risk of overdose and sedation,” and it has fewer medication interactions. However, some doctors are reluctant to prescribe it and there is some risk of medication diversion, she said.

Naltrexone is newer to the role of treating opioid use disorder, Dr. Jones said. “It can cause acute withdrawal because it is a full opioid antagonist,” she noted. However, naltrexone itself causes no withdrawal if stopped, and no respiratory depression or sedation, said Dr. Jones.

“Utilize addiction services in your hospital if you suspect a patient may be at risk for opioid use disorder,” and engage these services early, she emphasized.

Global Academy for Medical Education and this news organization are owned by the same parent company.

Dr. Jones had no financial conflicts to disclose.

For surgical patients on chronic opioid therapy, the goals of pain management are to provide adequate analgesia, prevent withdrawal, and avoid relapse or worsening of opioid use, according to Stephanie B. Jones, MD, professor and chair of anesthesiology at Albany Medical College, New York.

“[With] any patient coming in for any sort of surgery, you should be considering multimodal pain management. That applies to the opioid use disorder patient as well,” Dr. Jones said in a presentation at the virtual Annual Minimally Invasive Surgery Symposium sponsored by Global Academy for Medical Education.

“The challenge of opioid-tolerant patients or opioid abuse patients is twofold – tolerance and hyperalgesia,” Dr. Jones said. Patient tolerance changes how patients perceive pain and respond to medication. Clinicians need to consider the “opioid debt,” defined as the daily amount of opioid medication required by opioid-dependent patients to maintain their usual prehospitalization opioid levels, she explained. Also consider hyperalgesia, a change in pain perception “resulting in an increase in pain sensitivity to painful stimuli, thereby decreasing the analgesic effects of opioids,” Dr. Jones added.

A multimodal approach to pain management in patients on chronic opioids can include some opioids as appropriate, Dr. Jones said. Modulation of pain may draw on epidurals and nerve blocks, as well as managing CNS perception of pain through opioids or acetaminophen, and also using systemic options such as alpha-2 agonists and tramadol, she said.

Studies have shown that opioid abuse or dependence were associated with increased readmission rates, length of stay, and health care costs in surgery patients, said Dr. Jones. However, switching opioids and managing equivalents is complex, and “equianalgesic conversions serve only as a general guide to estimate opioid dose equivalents,” according to UpToDate’s, “Management of acute pain in the patient chronically using opioids,” she said.

Dr. Jones also addressed the issue of using hospitalization as an opportunity to help patients with untreated opioid use disorder. Medication-assisted options include methadone, buprenorphine, and naltrexone.

“One problem with methadone is that there are a lot of medications interactions,” she said. Buprenorphine has the advantage of being long-lasting, and is formulated with naloxone which deters injection. “Because it is a partial agonist, there is a lower risk of overdose and sedation,” and it has fewer medication interactions. However, some doctors are reluctant to prescribe it and there is some risk of medication diversion, she said.

Naltrexone is newer to the role of treating opioid use disorder, Dr. Jones said. “It can cause acute withdrawal because it is a full opioid antagonist,” she noted. However, naltrexone itself causes no withdrawal if stopped, and no respiratory depression or sedation, said Dr. Jones.

“Utilize addiction services in your hospital if you suspect a patient may be at risk for opioid use disorder,” and engage these services early, she emphasized.

Global Academy for Medical Education and this news organization are owned by the same parent company.

Dr. Jones had no financial conflicts to disclose.

The US Food and Drug Administration (FDA) has approved pembrolizumab (Keytruda, Merck) for the first-line treatment of patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) colorectal cancer.

This is the first time that an immunotherapy agent has been approved in this setting and as monotherapy, without added chemotherapy.

“Metastatic colorectal cancer is a serious and life-threatening disease with a poor prognosis,” said Richard Pazdur, MD, director of the FDA Oncology Center of Excellence and acting director of the Office of Oncologic Diseases at the FDA Center for Drug Evaluation and Research, in a statement. “Available current therapy with chemotherapy combinations and other biologics are associated with substantial toxicity.”

“Having a nonchemotherapy option available for selected patients is a noteworthy paradigm shift in treatment,” he commented.

Pembrolizumab is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, and has demonstrated robust antitumor activity and a favorable safety profile in multiple tumor types.

The current approval is based on data from the multicenter, randomized KEYNOTE-177 trial, which found that pembrolizumab more than doubled median progression-free survival (PFS) compared with chemotherapy, the current standard of care. The study results were presented earlier this year at the American Society of Clinical Oncology (ASCO) virtual scientific program, as reported by Medscape Medical News. In a commentary about that study, David Kerr, MD, professor of cancer medicine at the Oxford Cancer Centre, UK, said: “We know that MSI-H/dMMR tumors occur in only 4% or 5% of all patients in the advanced setting. Nevertheless, for that small but important subgroup, we now have a well-tolerated new treatment.”

New standard of care

The KEYNOTE-177 trial involved 307 patients with previously untreated unresectable or metastatic MSI-H or dMMR colorectal cancer. They were randomized to receive either pembrolizumab at 200 mg every 3 weeks for up to 35 cycles (n = 153) or to the investigators’ choice of chemotherapy (n = 154).

Chemotherapy regimens were modified FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) used alone or in combination with either bevacizumab or cetuximab, or FOLFIRI (leucovorin, fluorouracil, irinotecan) alone or in combination with either bevacizumab or cetuximab.

Crossover from the chemotherapy arm to immunotherapy was permitted for up to 35 cycles if the patient experienced disease progression confirmed by central review.

The primary endpoints were PFS and overall survival, and the trial would be considered successful if either primary endpoint was met.

Treatment with pembrolizumab monotherapy significantly reduced the risk of disease progression or death by 40% (HR, 0.60; 95% CI, 0.45 - 0.80; P = .0004), with a median PFS of 16.5 months versus 8.2 months for chemotherapy. At the time of the PFS analysis, overall survival data were not yet mature (66% of the required number of events for final analysis).

The overall response rate with pembrolizumab was 44%, with a complete response achieved in 11% of patients and a partial response rate of 33%. For the chemotherapy arm, the overall response rate was 33%, with a complete response rate of 4% and a partial response rate of 29%.

The median duration of response was not reached in the pembrolizumab arm versus 10.6 months with chemotherapy.

“In the past, no medical treatment has shown such difference in terms of improvement of PFS in metastatic colorectal cancer,” said study investigator Thierry André, MD, of Hôpital Saint Antoine in Paris, France, at a press briefing held prior to the presentation at the ASCO meeting.

At that time, Michael J. Overman, MD, of the University of Texas MD Anderson Cancer Center in Houston, told Medscape Medical News that “I think this is setting a new standard of care.”

Grade 3 or greater treatment-related adverse events occurred in 22% of patients on pembrolizumab and 66% on chemotherapy.

Immune-mediated adverse events and infusion reactions were more common with pembrolizumab than chemotherapy (31% and 13%, respectively). Adverse events that were common with chemotherapy included gastrointestinal events, fatigue, neutropenia, and peripheral sensory neuropathy.

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved pembrolizumab (Keytruda, Merck) for the first-line treatment of patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) colorectal cancer.

This is the first time that an immunotherapy agent has been approved in this setting and as monotherapy, without added chemotherapy.

“Metastatic colorectal cancer is a serious and life-threatening disease with a poor prognosis,” said Richard Pazdur, MD, director of the FDA Oncology Center of Excellence and acting director of the Office of Oncologic Diseases at the FDA Center for Drug Evaluation and Research, in a statement. “Available current therapy with chemotherapy combinations and other biologics are associated with substantial toxicity.”

“Having a nonchemotherapy option available for selected patients is a noteworthy paradigm shift in treatment,” he commented.

Pembrolizumab is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, and has demonstrated robust antitumor activity and a favorable safety profile in multiple tumor types.

The current approval is based on data from the multicenter, randomized KEYNOTE-177 trial, which found that pembrolizumab more than doubled median progression-free survival (PFS) compared with chemotherapy, the current standard of care. The study results were presented earlier this year at the American Society of Clinical Oncology (ASCO) virtual scientific program, as reported by Medscape Medical News. In a commentary about that study, David Kerr, MD, professor of cancer medicine at the Oxford Cancer Centre, UK, said: “We know that MSI-H/dMMR tumors occur in only 4% or 5% of all patients in the advanced setting. Nevertheless, for that small but important subgroup, we now have a well-tolerated new treatment.”

New standard of care

The KEYNOTE-177 trial involved 307 patients with previously untreated unresectable or metastatic MSI-H or dMMR colorectal cancer. They were randomized to receive either pembrolizumab at 200 mg every 3 weeks for up to 35 cycles (n = 153) or to the investigators’ choice of chemotherapy (n = 154).

Chemotherapy regimens were modified FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) used alone or in combination with either bevacizumab or cetuximab, or FOLFIRI (leucovorin, fluorouracil, irinotecan) alone or in combination with either bevacizumab or cetuximab.

Crossover from the chemotherapy arm to immunotherapy was permitted for up to 35 cycles if the patient experienced disease progression confirmed by central review.

The primary endpoints were PFS and overall survival, and the trial would be considered successful if either primary endpoint was met.

Treatment with pembrolizumab monotherapy significantly reduced the risk of disease progression or death by 40% (HR, 0.60; 95% CI, 0.45 - 0.80; P = .0004), with a median PFS of 16.5 months versus 8.2 months for chemotherapy. At the time of the PFS analysis, overall survival data were not yet mature (66% of the required number of events for final analysis).

The overall response rate with pembrolizumab was 44%, with a complete response achieved in 11% of patients and a partial response rate of 33%. For the chemotherapy arm, the overall response rate was 33%, with a complete response rate of 4% and a partial response rate of 29%.

The median duration of response was not reached in the pembrolizumab arm versus 10.6 months with chemotherapy.

“In the past, no medical treatment has shown such difference in terms of improvement of PFS in metastatic colorectal cancer,” said study investigator Thierry André, MD, of Hôpital Saint Antoine in Paris, France, at a press briefing held prior to the presentation at the ASCO meeting.

At that time, Michael J. Overman, MD, of the University of Texas MD Anderson Cancer Center in Houston, told Medscape Medical News that “I think this is setting a new standard of care.”

Grade 3 or greater treatment-related adverse events occurred in 22% of patients on pembrolizumab and 66% on chemotherapy.

Immune-mediated adverse events and infusion reactions were more common with pembrolizumab than chemotherapy (31% and 13%, respectively). Adverse events that were common with chemotherapy included gastrointestinal events, fatigue, neutropenia, and peripheral sensory neuropathy.

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved pembrolizumab (Keytruda, Merck) for the first-line treatment of patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) colorectal cancer.

This is the first time that an immunotherapy agent has been approved in this setting and as monotherapy, without added chemotherapy.

“Metastatic colorectal cancer is a serious and life-threatening disease with a poor prognosis,” said Richard Pazdur, MD, director of the FDA Oncology Center of Excellence and acting director of the Office of Oncologic Diseases at the FDA Center for Drug Evaluation and Research, in a statement. “Available current therapy with chemotherapy combinations and other biologics are associated with substantial toxicity.”

“Having a nonchemotherapy option available for selected patients is a noteworthy paradigm shift in treatment,” he commented.

Pembrolizumab is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, and has demonstrated robust antitumor activity and a favorable safety profile in multiple tumor types.

The current approval is based on data from the multicenter, randomized KEYNOTE-177 trial, which found that pembrolizumab more than doubled median progression-free survival (PFS) compared with chemotherapy, the current standard of care. The study results were presented earlier this year at the American Society of Clinical Oncology (ASCO) virtual scientific program, as reported by Medscape Medical News. In a commentary about that study, David Kerr, MD, professor of cancer medicine at the Oxford Cancer Centre, UK, said: “We know that MSI-H/dMMR tumors occur in only 4% or 5% of all patients in the advanced setting. Nevertheless, for that small but important subgroup, we now have a well-tolerated new treatment.”

New standard of care

The KEYNOTE-177 trial involved 307 patients with previously untreated unresectable or metastatic MSI-H or dMMR colorectal cancer. They were randomized to receive either pembrolizumab at 200 mg every 3 weeks for up to 35 cycles (n = 153) or to the investigators’ choice of chemotherapy (n = 154).

Chemotherapy regimens were modified FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) used alone or in combination with either bevacizumab or cetuximab, or FOLFIRI (leucovorin, fluorouracil, irinotecan) alone or in combination with either bevacizumab or cetuximab.

Crossover from the chemotherapy arm to immunotherapy was permitted for up to 35 cycles if the patient experienced disease progression confirmed by central review.

The primary endpoints were PFS and overall survival, and the trial would be considered successful if either primary endpoint was met.

Treatment with pembrolizumab monotherapy significantly reduced the risk of disease progression or death by 40% (HR, 0.60; 95% CI, 0.45 - 0.80; P = .0004), with a median PFS of 16.5 months versus 8.2 months for chemotherapy. At the time of the PFS analysis, overall survival data were not yet mature (66% of the required number of events for final analysis).

The overall response rate with pembrolizumab was 44%, with a complete response achieved in 11% of patients and a partial response rate of 33%. For the chemotherapy arm, the overall response rate was 33%, with a complete response rate of 4% and a partial response rate of 29%.

The median duration of response was not reached in the pembrolizumab arm versus 10.6 months with chemotherapy.

“In the past, no medical treatment has shown such difference in terms of improvement of PFS in metastatic colorectal cancer,” said study investigator Thierry André, MD, of Hôpital Saint Antoine in Paris, France, at a press briefing held prior to the presentation at the ASCO meeting.

At that time, Michael J. Overman, MD, of the University of Texas MD Anderson Cancer Center in Houston, told Medscape Medical News that “I think this is setting a new standard of care.”

Grade 3 or greater treatment-related adverse events occurred in 22% of patients on pembrolizumab and 66% on chemotherapy.

Immune-mediated adverse events and infusion reactions were more common with pembrolizumab than chemotherapy (31% and 13%, respectively). Adverse events that were common with chemotherapy included gastrointestinal events, fatigue, neutropenia, and peripheral sensory neuropathy.

This article first appeared on Medscape.com.

A novel program that aims to automate the Sharp-van der Heijde scoring of radiographs of patients with rheumatoid arthritis has shown good reliability in identifying regions of interest and matching human reader scoring for joint-space narrowing, according to a report given at the annual European Congress of Rheumatology, held online this year because of COVID-19.

Courtesy Dr. Thomas Deimel

First author and presenter Thomas Deimel, MD, and colleagues at the Medical University of Vienna said their program, called autoscoRA, may be a solution to the problem of readers having to make subjective calls on the severity of damage seen on radiographs.

Although the work continues to be validated, Dr. Deimel, a resident at the university, is confident in the system as is. “I think for joint space narrowing, we’re there at the point where this could be used and could be as good as a human reader in terms of reliability,” he said in an interview. To find out, the group plans to compare the variability between autoscoRA and a gold-standard human reader against the variability seen between human readers. If the two measures of variability are similar, it would provide a strong endorsement.

The effort is far from the first to develop an automatic scoring system for RA images, but no fully automated system has emerged as reliable, according to Dr. Deimel. He thinks one main issue for others has been lack of access to a sufficient data set to train systems. It can be difficult to find enough training images because many types of joint damage are comparatively uncommon. The problem is made even worse because images can be hard to interpret: The shapes that the system must decipher can be misleading, especially in positions of tendon insertion or ligament attachment that can resemble damage. Differing angles of view between various training images can also complicate matters.

The autoscoRA program is based on modifications of a form of convolutional neural network called the VGG16 architecture. The team used 2,207 images from 270 patients to train autoscoRA, 1,150 images from 133 patients for validation, and 1,834 images from 237 patients to test it.

The group had access to a high-quality data set of almost 6,000 hand radiographs from their institution, the result of foresight of principal investigator Daniel Aletaha, MD, and his predecessor Josef Smolen, MD. They “thought ahead and started collecting data and had all of it scored,” Dr. Deimel said. The work wasn’t all completed ahead of time, though. Dr. Deimel had to pull images from the hospital’s system sort through them manually.

The group also benefited from close proximity to computer scientists, including coauthor Georg Langs from the Medical University of Vienna’s computational imaging research lab. “We were lucky that we have a computer science department that is very much involved in medical imaging,” Dr. Deimel said.

The trained system successfully identified regions of interest in 96% of joints. It calculated the same score as the human reader in 80.5% of metacarpophalangeal joints and 72.3% of proximal interphalangeal joints. It deviated by more than 1 point from the gold-standard score in just 1.8% of metacarpophalangeal joints and 1.7% of proximal interphalangeal joints.

The researchers aim next to extend the program to bone erosions and also to images of the wrists and feet. They also hope to use scores from the program in clinical trials to measure a treatment’s effect, in registries of routine patient visits where thousands of such images along with clinical data could form the basis of informative observational studies, and in clinical practice, though likely with human oversight.

The study received no outside financial support. Dr. Deimel had no relevant financial disclosures. Mr. Langs reported being cofounder and shareholder of contextflow and receiving grants from Novartis, Siemens Healthineers, and NVIDIA. Dr. Aletaha reported financial relationships with many companies marketing drugs for rheumatoid arthritis.

SOURCE: Deimel T et al. Ann Rheum Dis. 2020 Jun;79(suppl 1):39-40.

A novel program that aims to automate the Sharp-van der Heijde scoring of radiographs of patients with rheumatoid arthritis has shown good reliability in identifying regions of interest and matching human reader scoring for joint-space narrowing, according to a report given at the annual European Congress of Rheumatology, held online this year because of COVID-19.

Courtesy Dr. Thomas Deimel

First author and presenter Thomas Deimel, MD, and colleagues at the Medical University of Vienna said their program, called autoscoRA, may be a solution to the problem of readers having to make subjective calls on the severity of damage seen on radiographs.

Although the work continues to be validated, Dr. Deimel, a resident at the university, is confident in the system as is. “I think for joint space narrowing, we’re there at the point where this could be used and could be as good as a human reader in terms of reliability,” he said in an interview. To find out, the group plans to compare the variability between autoscoRA and a gold-standard human reader against the variability seen between human readers. If the two measures of variability are similar, it would provide a strong endorsement.

The effort is far from the first to develop an automatic scoring system for RA images, but no fully automated system has emerged as reliable, according to Dr. Deimel. He thinks one main issue for others has been lack of access to a sufficient data set to train systems. It can be difficult to find enough training images because many types of joint damage are comparatively uncommon. The problem is made even worse because images can be hard to interpret: The shapes that the system must decipher can be misleading, especially in positions of tendon insertion or ligament attachment that can resemble damage. Differing angles of view between various training images can also complicate matters.

The autoscoRA program is based on modifications of a form of convolutional neural network called the VGG16 architecture. The team used 2,207 images from 270 patients to train autoscoRA, 1,150 images from 133 patients for validation, and 1,834 images from 237 patients to test it.

The group had access to a high-quality data set of almost 6,000 hand radiographs from their institution, the result of foresight of principal investigator Daniel Aletaha, MD, and his predecessor Josef Smolen, MD. They “thought ahead and started collecting data and had all of it scored,” Dr. Deimel said. The work wasn’t all completed ahead of time, though. Dr. Deimel had to pull images from the hospital’s system sort through them manually.

The group also benefited from close proximity to computer scientists, including coauthor Georg Langs from the Medical University of Vienna’s computational imaging research lab. “We were lucky that we have a computer science department that is very much involved in medical imaging,” Dr. Deimel said.

The trained system successfully identified regions of interest in 96% of joints. It calculated the same score as the human reader in 80.5% of metacarpophalangeal joints and 72.3% of proximal interphalangeal joints. It deviated by more than 1 point from the gold-standard score in just 1.8% of metacarpophalangeal joints and 1.7% of proximal interphalangeal joints.

The researchers aim next to extend the program to bone erosions and also to images of the wrists and feet. They also hope to use scores from the program in clinical trials to measure a treatment’s effect, in registries of routine patient visits where thousands of such images along with clinical data could form the basis of informative observational studies, and in clinical practice, though likely with human oversight.

The study received no outside financial support. Dr. Deimel had no relevant financial disclosures. Mr. Langs reported being cofounder and shareholder of contextflow and receiving grants from Novartis, Siemens Healthineers, and NVIDIA. Dr. Aletaha reported financial relationships with many companies marketing drugs for rheumatoid arthritis.

SOURCE: Deimel T et al. Ann Rheum Dis. 2020 Jun;79(suppl 1):39-40.

A novel program that aims to automate the Sharp-van der Heijde scoring of radiographs of patients with rheumatoid arthritis has shown good reliability in identifying regions of interest and matching human reader scoring for joint-space narrowing, according to a report given at the annual European Congress of Rheumatology, held online this year because of COVID-19.

Courtesy Dr. Thomas Deimel

First author and presenter Thomas Deimel, MD, and colleagues at the Medical University of Vienna said their program, called autoscoRA, may be a solution to the problem of readers having to make subjective calls on the severity of damage seen on radiographs.

Although the work continues to be validated, Dr. Deimel, a resident at the university, is confident in the system as is. “I think for joint space narrowing, we’re there at the point where this could be used and could be as good as a human reader in terms of reliability,” he said in an interview. To find out, the group plans to compare the variability between autoscoRA and a gold-standard human reader against the variability seen between human readers. If the two measures of variability are similar, it would provide a strong endorsement.

The effort is far from the first to develop an automatic scoring system for RA images, but no fully automated system has emerged as reliable, according to Dr. Deimel. He thinks one main issue for others has been lack of access to a sufficient data set to train systems. It can be difficult to find enough training images because many types of joint damage are comparatively uncommon. The problem is made even worse because images can be hard to interpret: The shapes that the system must decipher can be misleading, especially in positions of tendon insertion or ligament attachment that can resemble damage. Differing angles of view between various training images can also complicate matters.

The autoscoRA program is based on modifications of a form of convolutional neural network called the VGG16 architecture. The team used 2,207 images from 270 patients to train autoscoRA, 1,150 images from 133 patients for validation, and 1,834 images from 237 patients to test it.

The group had access to a high-quality data set of almost 6,000 hand radiographs from their institution, the result of foresight of principal investigator Daniel Aletaha, MD, and his predecessor Josef Smolen, MD. They “thought ahead and started collecting data and had all of it scored,” Dr. Deimel said. The work wasn’t all completed ahead of time, though. Dr. Deimel had to pull images from the hospital’s system sort through them manually.

The group also benefited from close proximity to computer scientists, including coauthor Georg Langs from the Medical University of Vienna’s computational imaging research lab. “We were lucky that we have a computer science department that is very much involved in medical imaging,” Dr. Deimel said.

The trained system successfully identified regions of interest in 96% of joints. It calculated the same score as the human reader in 80.5% of metacarpophalangeal joints and 72.3% of proximal interphalangeal joints. It deviated by more than 1 point from the gold-standard score in just 1.8% of metacarpophalangeal joints and 1.7% of proximal interphalangeal joints.

The researchers aim next to extend the program to bone erosions and also to images of the wrists and feet. They also hope to use scores from the program in clinical trials to measure a treatment’s effect, in registries of routine patient visits where thousands of such images along with clinical data could form the basis of informative observational studies, and in clinical practice, though likely with human oversight.

The study received no outside financial support. Dr. Deimel had no relevant financial disclosures. Mr. Langs reported being cofounder and shareholder of contextflow and receiving grants from Novartis, Siemens Healthineers, and NVIDIA. Dr. Aletaha reported financial relationships with many companies marketing drugs for rheumatoid arthritis.

SOURCE: Deimel T et al. Ann Rheum Dis. 2020 Jun;79(suppl 1):39-40.

ACE levels are lower in individuals with first episode psychosis (FEP) and even lower in those with resistant disease, suggesting the enzyme may be a biomarker of disease severity.

In a longitudinal cohort study, investigators found patients with FEP had significantly reduced ACE levels compared with their healthy peers.

With blood concentrations of the enzyme significantly reduced in those who were treatment-resistant, “ACE alterations appear to be already present at the disease onset” and results suggest “a possible relationship with disease severity,” noted the researchers, led by investigator Luisa Longo, MD, a resident in psychiatry, University of Bari Aldo Moro in Italy.

Moreover, the finding that lower ACE levels were associated with greater cognitive impairment on neuropsychological tests indicates the enzyme plays a role in “the alteration of neurocognitive abilities” in patients with FEP.

Taken together, the results “highlight ACE as a promising peripheral biomarker to identify patients at risk of treatment resistance to antipsychotics,” the investigators reported.

The findings were presented at the annual congress of the Schizophrenia International Research Society.
 

Mechanisms “poorly understood”

Previous studies suggest ACE may play a role in neurologic and psychiatric conditions, including schizophrenia, through alterations in function or blood concentrations.

However, the molecular mechanisms underlying disease onset and response to antipsychotics in patients with FEP “remain poorly understood,” the researchers noted. In addition, “despite adequate antipsychotic treatment, 20% of patients have persistent symptoms.”

To determine whether ACE levels are already altered in FEP patients, the investigators examined data on 138 patients with FEP and 115 healthy controls.

After measuring blood concentrations in 122 of the patients and 78 controls, they found that ACE levels were significantly lower in FEP patients (P = 4.1x10-13) after controlling for age, sex, ethnicity, duration of illness, smoking status, and chlorpromazine equivalents.

Cerebrospinal fluid (CSF) levels, which were measured in 19 patients and 18 controls, were also significantly lower in individuals with FEP (P = .01), with a strong correlation observed between blood and CSF levels (P = .0005).

Next, the team used Treatment Response and Resistance in Psychosis criteria to compare ACE levels in 32 treatment-resistant patients and 106 non–treatment-resistant patients. Results showed that ACE blood levels were significantly lower in the treatment-resistant patients (P = .03).

Finally, the association between ACE blood levels and range of clinical and neurocognitive variables were examined across all FEP patients.

The Scale for the Assessment of Negative and Positive Symptoms was administered, along with a battery of tests looking at processing speed, working memory, verbal learning and memory, visual learning and memory, ideational fluency, and executive function. All were combined into a composite score.

While there was no association between ACE blood levels and symptom severity in the patients, there was a significant association between levels and verbal memory (P = .007) and composite cognitive score (P = .04).
 

Notable finding

In an interview, Thomas W. Sedlak, MD, PhD, assistant professor of psychiatry and behavioral health, Johns Hopkins University, Baltimore, said the finding that ACE levels were associated with lower cognition scores is “notable in that we don’t really have any treatments for cognition.

“Antipsychotic drugs treat more of the famous symptoms of hallucinations and delusions and disordered speech, but they don›t really help cognition a whole lot — and too much medicine might even make that worse,” said Dr. Sedlak, who was not involved with the research.

“So it’s interesting to have another biomarker that might relate a symptom of schizophrenia that we don’t really have a good grip on addressing,” he said.

However, he noted that this study is “preliminary,” has not looked at longitudinal changes in ACE in the same patients, and is one of “many” correlation studies.

“I like to say you can pretty much Google any chemical in the body and somebody has a claim about it and schizophrenia,” Dr. Sedlak said.

Nevertheless, the current analysis is “convergent” with past studies on ACE, including those that have found associations between polymorphisms in the enzyme and schizophrenia, he noted.

Moreover, research has shown that ACE facilitates glutamate transmission, specifically via N-methyl-D-aspartate (NMDA) receptors in the prefrontal cortex, “which is probably the brain region most tied to schizophrenia abnormalities,” Dr. Sedlak said.
 

No tie to inflammation

The findings do contrast, however, with the increasing body of evidence linking schizophrenia to inflammation.

Dr. Sedlak said that is not surprising, as the more that is learned about schizophrenia, “the less it is likely to be a single homogeneous entity but something more akin to intellectual disability.

“We’re finding that there are different subtypes of schizophrenia, some of which might have more of an inflammatory tie and others which don’t.”

He added that it might be possible over the longer term to cluster patients by ACE levels and other biomarkers and then follow them long term to “see if we can predict outcomes better than purely clinical terms.”

In this way, Dr. Sedlak said he believes that psychiatry may become more like rheumatology, “which I’d say is the area of medicine, at least in terms of making diagnoses, most similar.”

The etiology of conditions such as lupus and rheumatoid arthritis is “not absolutely known” and there is “probably no single cause,” with the diagnosis relying on clinical findings alongside biomarker tests.

“I think psychiatry is, long term, hoping to discover some biomarkers ... that would be used together with the clinical findings to help come to more clinical agreement on how to define cases – and would be predictive long term in terms of the course of illness,” Dr. Sedlak concluded.

The study had no specific funding. The study investigators and Dr. Sedlak have disclosed no relevant financial relationships.
 

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

ACE levels are lower in individuals with first episode psychosis (FEP) and even lower in those with resistant disease, suggesting the enzyme may be a biomarker of disease severity.

In a longitudinal cohort study, investigators found patients with FEP had significantly reduced ACE levels compared with their healthy peers.

With blood concentrations of the enzyme significantly reduced in those who were treatment-resistant, “ACE alterations appear to be already present at the disease onset” and results suggest “a possible relationship with disease severity,” noted the researchers, led by investigator Luisa Longo, MD, a resident in psychiatry, University of Bari Aldo Moro in Italy.

Moreover, the finding that lower ACE levels were associated with greater cognitive impairment on neuropsychological tests indicates the enzyme plays a role in “the alteration of neurocognitive abilities” in patients with FEP.

Taken together, the results “highlight ACE as a promising peripheral biomarker to identify patients at risk of treatment resistance to antipsychotics,” the investigators reported.

The findings were presented at the annual congress of the Schizophrenia International Research Society.
 

Mechanisms “poorly understood”

Previous studies suggest ACE may play a role in neurologic and psychiatric conditions, including schizophrenia, through alterations in function or blood concentrations.

However, the molecular mechanisms underlying disease onset and response to antipsychotics in patients with FEP “remain poorly understood,” the researchers noted. In addition, “despite adequate antipsychotic treatment, 20% of patients have persistent symptoms.”

To determine whether ACE levels are already altered in FEP patients, the investigators examined data on 138 patients with FEP and 115 healthy controls.

After measuring blood concentrations in 122 of the patients and 78 controls, they found that ACE levels were significantly lower in FEP patients (P = 4.1x10-13) after controlling for age, sex, ethnicity, duration of illness, smoking status, and chlorpromazine equivalents.

Cerebrospinal fluid (CSF) levels, which were measured in 19 patients and 18 controls, were also significantly lower in individuals with FEP (P = .01), with a strong correlation observed between blood and CSF levels (P = .0005).

Next, the team used Treatment Response and Resistance in Psychosis criteria to compare ACE levels in 32 treatment-resistant patients and 106 non–treatment-resistant patients. Results showed that ACE blood levels were significantly lower in the treatment-resistant patients (P = .03).

Finally, the association between ACE blood levels and range of clinical and neurocognitive variables were examined across all FEP patients.

The Scale for the Assessment of Negative and Positive Symptoms was administered, along with a battery of tests looking at processing speed, working memory, verbal learning and memory, visual learning and memory, ideational fluency, and executive function. All were combined into a composite score.

While there was no association between ACE blood levels and symptom severity in the patients, there was a significant association between levels and verbal memory (P = .007) and composite cognitive score (P = .04).
 

Notable finding

In an interview, Thomas W. Sedlak, MD, PhD, assistant professor of psychiatry and behavioral health, Johns Hopkins University, Baltimore, said the finding that ACE levels were associated with lower cognition scores is “notable in that we don’t really have any treatments for cognition.

“Antipsychotic drugs treat more of the famous symptoms of hallucinations and delusions and disordered speech, but they don›t really help cognition a whole lot — and too much medicine might even make that worse,” said Dr. Sedlak, who was not involved with the research.

“So it’s interesting to have another biomarker that might relate a symptom of schizophrenia that we don’t really have a good grip on addressing,” he said.

However, he noted that this study is “preliminary,” has not looked at longitudinal changes in ACE in the same patients, and is one of “many” correlation studies.

“I like to say you can pretty much Google any chemical in the body and somebody has a claim about it and schizophrenia,” Dr. Sedlak said.

Nevertheless, the current analysis is “convergent” with past studies on ACE, including those that have found associations between polymorphisms in the enzyme and schizophrenia, he noted.

Moreover, research has shown that ACE facilitates glutamate transmission, specifically via N-methyl-D-aspartate (NMDA) receptors in the prefrontal cortex, “which is probably the brain region most tied to schizophrenia abnormalities,” Dr. Sedlak said.
 

No tie to inflammation

The findings do contrast, however, with the increasing body of evidence linking schizophrenia to inflammation.

Dr. Sedlak said that is not surprising, as the more that is learned about schizophrenia, “the less it is likely to be a single homogeneous entity but something more akin to intellectual disability.

“We’re finding that there are different subtypes of schizophrenia, some of which might have more of an inflammatory tie and others which don’t.”

He added that it might be possible over the longer term to cluster patients by ACE levels and other biomarkers and then follow them long term to “see if we can predict outcomes better than purely clinical terms.”

In this way, Dr. Sedlak said he believes that psychiatry may become more like rheumatology, “which I’d say is the area of medicine, at least in terms of making diagnoses, most similar.”

The etiology of conditions such as lupus and rheumatoid arthritis is “not absolutely known” and there is “probably no single cause,” with the diagnosis relying on clinical findings alongside biomarker tests.

“I think psychiatry is, long term, hoping to discover some biomarkers ... that would be used together with the clinical findings to help come to more clinical agreement on how to define cases – and would be predictive long term in terms of the course of illness,” Dr. Sedlak concluded.

The study had no specific funding. The study investigators and Dr. Sedlak have disclosed no relevant financial relationships.
 

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

ACE levels are lower in individuals with first episode psychosis (FEP) and even lower in those with resistant disease, suggesting the enzyme may be a biomarker of disease severity.

In a longitudinal cohort study, investigators found patients with FEP had significantly reduced ACE levels compared with their healthy peers.

With blood concentrations of the enzyme significantly reduced in those who were treatment-resistant, “ACE alterations appear to be already present at the disease onset” and results suggest “a possible relationship with disease severity,” noted the researchers, led by investigator Luisa Longo, MD, a resident in psychiatry, University of Bari Aldo Moro in Italy.

Moreover, the finding that lower ACE levels were associated with greater cognitive impairment on neuropsychological tests indicates the enzyme plays a role in “the alteration of neurocognitive abilities” in patients with FEP.

Taken together, the results “highlight ACE as a promising peripheral biomarker to identify patients at risk of treatment resistance to antipsychotics,” the investigators reported.

The findings were presented at the annual congress of the Schizophrenia International Research Society.
 

Mechanisms “poorly understood”

Previous studies suggest ACE may play a role in neurologic and psychiatric conditions, including schizophrenia, through alterations in function or blood concentrations.

However, the molecular mechanisms underlying disease onset and response to antipsychotics in patients with FEP “remain poorly understood,” the researchers noted. In addition, “despite adequate antipsychotic treatment, 20% of patients have persistent symptoms.”

To determine whether ACE levels are already altered in FEP patients, the investigators examined data on 138 patients with FEP and 115 healthy controls.

After measuring blood concentrations in 122 of the patients and 78 controls, they found that ACE levels were significantly lower in FEP patients (P = 4.1x10-13) after controlling for age, sex, ethnicity, duration of illness, smoking status, and chlorpromazine equivalents.

Cerebrospinal fluid (CSF) levels, which were measured in 19 patients and 18 controls, were also significantly lower in individuals with FEP (P = .01), with a strong correlation observed between blood and CSF levels (P = .0005).

Next, the team used Treatment Response and Resistance in Psychosis criteria to compare ACE levels in 32 treatment-resistant patients and 106 non–treatment-resistant patients. Results showed that ACE blood levels were significantly lower in the treatment-resistant patients (P = .03).

Finally, the association between ACE blood levels and range of clinical and neurocognitive variables were examined across all FEP patients.

The Scale for the Assessment of Negative and Positive Symptoms was administered, along with a battery of tests looking at processing speed, working memory, verbal learning and memory, visual learning and memory, ideational fluency, and executive function. All were combined into a composite score.

While there was no association between ACE blood levels and symptom severity in the patients, there was a significant association between levels and verbal memory (P = .007) and composite cognitive score (P = .04).
 

Notable finding

In an interview, Thomas W. Sedlak, MD, PhD, assistant professor of psychiatry and behavioral health, Johns Hopkins University, Baltimore, said the finding that ACE levels were associated with lower cognition scores is “notable in that we don’t really have any treatments for cognition.

“Antipsychotic drugs treat more of the famous symptoms of hallucinations and delusions and disordered speech, but they don›t really help cognition a whole lot — and too much medicine might even make that worse,” said Dr. Sedlak, who was not involved with the research.

“So it’s interesting to have another biomarker that might relate a symptom of schizophrenia that we don’t really have a good grip on addressing,” he said.

However, he noted that this study is “preliminary,” has not looked at longitudinal changes in ACE in the same patients, and is one of “many” correlation studies.

“I like to say you can pretty much Google any chemical in the body and somebody has a claim about it and schizophrenia,” Dr. Sedlak said.

Nevertheless, the current analysis is “convergent” with past studies on ACE, including those that have found associations between polymorphisms in the enzyme and schizophrenia, he noted.

Moreover, research has shown that ACE facilitates glutamate transmission, specifically via N-methyl-D-aspartate (NMDA) receptors in the prefrontal cortex, “which is probably the brain region most tied to schizophrenia abnormalities,” Dr. Sedlak said.
 

No tie to inflammation

The findings do contrast, however, with the increasing body of evidence linking schizophrenia to inflammation.

Dr. Sedlak said that is not surprising, as the more that is learned about schizophrenia, “the less it is likely to be a single homogeneous entity but something more akin to intellectual disability.

“We’re finding that there are different subtypes of schizophrenia, some of which might have more of an inflammatory tie and others which don’t.”

He added that it might be possible over the longer term to cluster patients by ACE levels and other biomarkers and then follow them long term to “see if we can predict outcomes better than purely clinical terms.”

In this way, Dr. Sedlak said he believes that psychiatry may become more like rheumatology, “which I’d say is the area of medicine, at least in terms of making diagnoses, most similar.”

The etiology of conditions such as lupus and rheumatoid arthritis is “not absolutely known” and there is “probably no single cause,” with the diagnosis relying on clinical findings alongside biomarker tests.

“I think psychiatry is, long term, hoping to discover some biomarkers ... that would be used together with the clinical findings to help come to more clinical agreement on how to define cases – and would be predictive long term in terms of the course of illness,” Dr. Sedlak concluded.

The study had no specific funding. The study investigators and Dr. Sedlak have disclosed no relevant financial relationships.
 

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

Targeting TIGIT, an inhibitory receptor expressed on immune cells, could complement activity of anti–programmed death–ligand 1/PD-1 antibodies in patients with solid tumors, results of a phase 1 study suggest.

The combination of the anti-TIGIT antibody tiragolumab with the PD-L1 inhibitor atezolizumab was well tolerated and showed preliminary activity in the phase 1b portion of the study, according to investigator Johanna C. Bendell, MD, of Sarah Cannon Research Institute/Tennessee Oncology in Nashville, Tenn.

Objective responses occurred mainly in chemoimmunotherapy-naive, PD-L1-positive tumors. In an expansion cohort of 13 patients with PD-L1-positive non–small cell lung cancer (NSCLC), the confirmed overall response rate was 46%, with several responses demonstrating durability.

Dr. Bendell reported these results at the AACR virtual meeting II.

While several important research questions remain, the results in the lung cancer expansion cohort were encouraging, particularly in patients who were smokers and previous smokers, said invited discussant Michele Teng, PhD, of QIMR Berghofer Medical Research Institute in Brisbane, Australia.

“Although it was [a] small cohort, the data suggest promising duration of response in some of the patients [n = 4] who have been under study for more than 700 days,” Dr. Teng said.

Based on the preliminary safety and activity seen in this study, the combination of tiragolumab and atezolizumab is being evaluated in a randomized, placebo-controlled phase 2 study, and a phase 3 study is recruiting.
 

Rationale, design, and safety

TIGIT is a novel inhibitory receptor expressed on multiple immune cells, especially CD8-positive T cells and natural killer cells, Dr. Bendell explained. She added that TIGIT is coexpressed with PD-1 on immune cells.

“Using anti-TIGIT antibodies to prevent TIGIT from binding, and cotargeting TIGIT and PD-L1, may restore antitumor response and enhance anti-PD-L1 effect,” Dr. Bendell said.

The phase 1 study Dr. Bendell presented, known as GO30103, was designed to evaluate tiragolumab as a single agent and in combination with atezolizumab in advanced solid tumors.

There were 24 patients in the phase 1a portion of GO30103, which was intended to determine the preliminary safety, tolerability, and recommended phase 2 dose of tiragolumab. There were 49 patients treated with tiragolumab plus atezolizumab in the phase 1b portion, which was intended to provide data on pharmacokinetics as well as preliminary antitumor activity of the combination.

No dose-limiting toxicities were seen in either cohort. The recommended phase 2 dose of tiragolumab was 600 mg every 3 weeks.

Tiragolumab was well tolerated in the phase 1a and 1b portions of the trial, according to Dr. Bendell.

“Immune-related adverse events were seen, but their incidence was not out of proportion to events seen with atezolizumab alone,” she said.

Treatment-related grade 3-4 adverse events occurred in one patient (4%) in the phase 1a portion of the trial and two patients (4%) in the phase 1b portion. There were no grade 5 adverse events related to treatment.

Efficacy and next steps

No objective responses were seen with tiragolumab monotherapy, although several patients did exhibit tumor reduction.

“We were not really expecting much single-agent activity of the anti-TIGIT drug,” Dr. Bendell said. “There’s some preclinical data that suggests that TIGIT may be more important as a single agent in earlier stages of cancer.”

In contrast, the combination of tiragolumab and atezolizumab resulted in several responses, including one in a patient with PD-L1-positive NSCLC who was previously treated with immunotherapy, according to Dr. Bendell.

The 13-patient expansion cohort of patients with PD-L1-positive NSCLC were treated at the recommended phase 2 dose of tiragolumab and atezolizumab. In these chemoimmunotherapy-naive patients, the overall response rate was 46%. Responses occurred in 6 of 13 patients and included 2 complete responses. Four patients had stable disease, so the disease control rate was 85% (11/13).

Based on that expansion cohort, a randomized, phase 2 study called CITYSCAPE was initiated. Results of CITYSCAPE were recently presented as part of the American Society of Clinical Oncology virtual scientific program.

In that study, tiragolumab plus atezolizumab improved the overall response rate and progression-free survival when compared with placebo plus atezolizumab. More substantial improvement was seen in the subgroup of patients with PD-L1 tumor proportion scores of 50% or greater.

The activity and safety of tiragolumab plus atezolizumab will be confirmed in the ongoing SKYSCRAPER-01 trial (NCT04294810), a phase 3 study of first-line treatment in patients with NSCLC and a PD-L1 tumor proportion score of 50% or greater, according to investigators.

The phase 1 study presented by Dr. Bendell was sponsored by Genentech. Dr. Bendell disclosed relationships with Genentech/Roche, Gilead, Five Prime, Lilly, and other companies.
 

SOURCE: Bendell JC et al. AACR 2020, Abstract CT302.

Targeting TIGIT, an inhibitory receptor expressed on immune cells, could complement activity of anti–programmed death–ligand 1/PD-1 antibodies in patients with solid tumors, results of a phase 1 study suggest.

The combination of the anti-TIGIT antibody tiragolumab with the PD-L1 inhibitor atezolizumab was well tolerated and showed preliminary activity in the phase 1b portion of the study, according to investigator Johanna C. Bendell, MD, of Sarah Cannon Research Institute/Tennessee Oncology in Nashville, Tenn.

Objective responses occurred mainly in chemoimmunotherapy-naive, PD-L1-positive tumors. In an expansion cohort of 13 patients with PD-L1-positive non–small cell lung cancer (NSCLC), the confirmed overall response rate was 46%, with several responses demonstrating durability.

Dr. Bendell reported these results at the AACR virtual meeting II.

While several important research questions remain, the results in the lung cancer expansion cohort were encouraging, particularly in patients who were smokers and previous smokers, said invited discussant Michele Teng, PhD, of QIMR Berghofer Medical Research Institute in Brisbane, Australia.

“Although it was [a] small cohort, the data suggest promising duration of response in some of the patients [n = 4] who have been under study for more than 700 days,” Dr. Teng said.

Based on the preliminary safety and activity seen in this study, the combination of tiragolumab and atezolizumab is being evaluated in a randomized, placebo-controlled phase 2 study, and a phase 3 study is recruiting.
 

Rationale, design, and safety

TIGIT is a novel inhibitory receptor expressed on multiple immune cells, especially CD8-positive T cells and natural killer cells, Dr. Bendell explained. She added that TIGIT is coexpressed with PD-1 on immune cells.

“Using anti-TIGIT antibodies to prevent TIGIT from binding, and cotargeting TIGIT and PD-L1, may restore antitumor response and enhance anti-PD-L1 effect,” Dr. Bendell said.

The phase 1 study Dr. Bendell presented, known as GO30103, was designed to evaluate tiragolumab as a single agent and in combination with atezolizumab in advanced solid tumors.

There were 24 patients in the phase 1a portion of GO30103, which was intended to determine the preliminary safety, tolerability, and recommended phase 2 dose of tiragolumab. There were 49 patients treated with tiragolumab plus atezolizumab in the phase 1b portion, which was intended to provide data on pharmacokinetics as well as preliminary antitumor activity of the combination.

No dose-limiting toxicities were seen in either cohort. The recommended phase 2 dose of tiragolumab was 600 mg every 3 weeks.

Tiragolumab was well tolerated in the phase 1a and 1b portions of the trial, according to Dr. Bendell.

“Immune-related adverse events were seen, but their incidence was not out of proportion to events seen with atezolizumab alone,” she said.

Treatment-related grade 3-4 adverse events occurred in one patient (4%) in the phase 1a portion of the trial and two patients (4%) in the phase 1b portion. There were no grade 5 adverse events related to treatment.

Efficacy and next steps

No objective responses were seen with tiragolumab monotherapy, although several patients did exhibit tumor reduction.

“We were not really expecting much single-agent activity of the anti-TIGIT drug,” Dr. Bendell said. “There’s some preclinical data that suggests that TIGIT may be more important as a single agent in earlier stages of cancer.”

In contrast, the combination of tiragolumab and atezolizumab resulted in several responses, including one in a patient with PD-L1-positive NSCLC who was previously treated with immunotherapy, according to Dr. Bendell.

The 13-patient expansion cohort of patients with PD-L1-positive NSCLC were treated at the recommended phase 2 dose of tiragolumab and atezolizumab. In these chemoimmunotherapy-naive patients, the overall response rate was 46%. Responses occurred in 6 of 13 patients and included 2 complete responses. Four patients had stable disease, so the disease control rate was 85% (11/13).

Based on that expansion cohort, a randomized, phase 2 study called CITYSCAPE was initiated. Results of CITYSCAPE were recently presented as part of the American Society of Clinical Oncology virtual scientific program.

In that study, tiragolumab plus atezolizumab improved the overall response rate and progression-free survival when compared with placebo plus atezolizumab. More substantial improvement was seen in the subgroup of patients with PD-L1 tumor proportion scores of 50% or greater.

The activity and safety of tiragolumab plus atezolizumab will be confirmed in the ongoing SKYSCRAPER-01 trial (NCT04294810), a phase 3 study of first-line treatment in patients with NSCLC and a PD-L1 tumor proportion score of 50% or greater, according to investigators.

The phase 1 study presented by Dr. Bendell was sponsored by Genentech. Dr. Bendell disclosed relationships with Genentech/Roche, Gilead, Five Prime, Lilly, and other companies.
 

SOURCE: Bendell JC et al. AACR 2020, Abstract CT302.

Targeting TIGIT, an inhibitory receptor expressed on immune cells, could complement activity of anti–programmed death–ligand 1/PD-1 antibodies in patients with solid tumors, results of a phase 1 study suggest.

The combination of the anti-TIGIT antibody tiragolumab with the PD-L1 inhibitor atezolizumab was well tolerated and showed preliminary activity in the phase 1b portion of the study, according to investigator Johanna C. Bendell, MD, of Sarah Cannon Research Institute/Tennessee Oncology in Nashville, Tenn.

Objective responses occurred mainly in chemoimmunotherapy-naive, PD-L1-positive tumors. In an expansion cohort of 13 patients with PD-L1-positive non–small cell lung cancer (NSCLC), the confirmed overall response rate was 46%, with several responses demonstrating durability.

Dr. Bendell reported these results at the AACR virtual meeting II.

While several important research questions remain, the results in the lung cancer expansion cohort were encouraging, particularly in patients who were smokers and previous smokers, said invited discussant Michele Teng, PhD, of QIMR Berghofer Medical Research Institute in Brisbane, Australia.

“Although it was [a] small cohort, the data suggest promising duration of response in some of the patients [n = 4] who have been under study for more than 700 days,” Dr. Teng said.

Based on the preliminary safety and activity seen in this study, the combination of tiragolumab and atezolizumab is being evaluated in a randomized, placebo-controlled phase 2 study, and a phase 3 study is recruiting.
 

Rationale, design, and safety

TIGIT is a novel inhibitory receptor expressed on multiple immune cells, especially CD8-positive T cells and natural killer cells, Dr. Bendell explained. She added that TIGIT is coexpressed with PD-1 on immune cells.

“Using anti-TIGIT antibodies to prevent TIGIT from binding, and cotargeting TIGIT and PD-L1, may restore antitumor response and enhance anti-PD-L1 effect,” Dr. Bendell said.

The phase 1 study Dr. Bendell presented, known as GO30103, was designed to evaluate tiragolumab as a single agent and in combination with atezolizumab in advanced solid tumors.

There were 24 patients in the phase 1a portion of GO30103, which was intended to determine the preliminary safety, tolerability, and recommended phase 2 dose of tiragolumab. There were 49 patients treated with tiragolumab plus atezolizumab in the phase 1b portion, which was intended to provide data on pharmacokinetics as well as preliminary antitumor activity of the combination.

No dose-limiting toxicities were seen in either cohort. The recommended phase 2 dose of tiragolumab was 600 mg every 3 weeks.

Tiragolumab was well tolerated in the phase 1a and 1b portions of the trial, according to Dr. Bendell.

“Immune-related adverse events were seen, but their incidence was not out of proportion to events seen with atezolizumab alone,” she said.

Treatment-related grade 3-4 adverse events occurred in one patient (4%) in the phase 1a portion of the trial and two patients (4%) in the phase 1b portion. There were no grade 5 adverse events related to treatment.

Efficacy and next steps

No objective responses were seen with tiragolumab monotherapy, although several patients did exhibit tumor reduction.

“We were not really expecting much single-agent activity of the anti-TIGIT drug,” Dr. Bendell said. “There’s some preclinical data that suggests that TIGIT may be more important as a single agent in earlier stages of cancer.”

In contrast, the combination of tiragolumab and atezolizumab resulted in several responses, including one in a patient with PD-L1-positive NSCLC who was previously treated with immunotherapy, according to Dr. Bendell.

The 13-patient expansion cohort of patients with PD-L1-positive NSCLC were treated at the recommended phase 2 dose of tiragolumab and atezolizumab. In these chemoimmunotherapy-naive patients, the overall response rate was 46%. Responses occurred in 6 of 13 patients and included 2 complete responses. Four patients had stable disease, so the disease control rate was 85% (11/13).

Based on that expansion cohort, a randomized, phase 2 study called CITYSCAPE was initiated. Results of CITYSCAPE were recently presented as part of the American Society of Clinical Oncology virtual scientific program.

In that study, tiragolumab plus atezolizumab improved the overall response rate and progression-free survival when compared with placebo plus atezolizumab. More substantial improvement was seen in the subgroup of patients with PD-L1 tumor proportion scores of 50% or greater.

The activity and safety of tiragolumab plus atezolizumab will be confirmed in the ongoing SKYSCRAPER-01 trial (NCT04294810), a phase 3 study of first-line treatment in patients with NSCLC and a PD-L1 tumor proportion score of 50% or greater, according to investigators.

The phase 1 study presented by Dr. Bendell was sponsored by Genentech. Dr. Bendell disclosed relationships with Genentech/Roche, Gilead, Five Prime, Lilly, and other companies.
 

SOURCE: Bendell JC et al. AACR 2020, Abstract CT302.

Background: oHCM is characterized by mutations in sarcomeric proteins. Mavacamten is a ­small-molecule modulator of cardiac myosin, commonly affected in oHCM.

Dr. Blount is a hospitalist at the University of Colorado at Denver, Aurora.

Background: oHCM is characterized by mutations in sarcomeric proteins. Mavacamten is a ­small-molecule modulator of cardiac myosin, commonly affected in oHCM.

Dr. Blount is a hospitalist at the University of Colorado at Denver, Aurora.

Background: oHCM is characterized by mutations in sarcomeric proteins. Mavacamten is a ­small-molecule modulator of cardiac myosin, commonly affected in oHCM.

Dr. Blount is a hospitalist at the University of Colorado at Denver, Aurora.

The Diagnosis: Eruptive Syringoma 

A punch biopsy of a lesion on the penis was performed. Histopathologic examination revealed many tadpole-shaped cords of epithelial cells and small ducts in the dermis (Figure). Based on clinical and histopathological findings, a diagnosis of eruptive syringoma was made. The patient declined treatment.  

Syringomas are common benign eccrine neoplasms. They present clinically as small flesh-colored to brownish papules symmetrically distributed on the face, neck, trunk, pubic area, arms, and legs.^1-3 Classic syringoma occurs more frequently in young adult women.¹ Eruptive syringoma is a rare variant, and the age of onset ranges from 3 to 50 years.^1-13  Eruptive syringoma is the term for multiple lesions that occur synchronously in any part of the body.^1,4,13 The term eruptive is not the opposite of localized and refers to the time of onset of the lesion. There may be both a generalized eruptive syringoma or a localized eruptive syringoma depending on the distribution of the lesions.¹ The most common site for syringoma occurrence is the eyelid; penile syringoma is extremely rare. Several cases of penile syringoma have been reported, but eruptive penile syringoma is rare.^3,5-10,12,13  

Histopathology is essential for the diagnosis of syringoma. Hematoxylin and eosin stain shows multiple small cystic ducts and epithelial cell nests in the dermis. Ductal structures sometimes appear tadpolelike or comma shaped depending on the section.^1,2,7,12 

The clinical differential diagnosis of syringoma includes sebaceous hyperplasia, verruca plana, molluscum contagiosum, bowenoid papulosis, condyloma acuminatum, lichen planus, lichen nitidus, milia, angiofibroma, epidermal cyst, calcinosis cutis, granuloma annulare, and sarcoidosis.^3,8,12 

Because syringoma is benign, treatment is not necessary unless there is a cosmetic problem.^3,5,7,8,12 There is no satisfactory treatment of eruptive penile syringoma. Treatment options include topical tretinoin and adapalene, oral isotretinoin, cryotherapy, microelectrodesiccation with an epilating needle, dermabrasion, CO₂ laser, and surgical excision.^2,3,7,8,12  

Adult patients with penile syringoma may be concerned about sexually transmitted diseases due to the appearance of the papules. If cosmesis is not an issue, clinicians should reassure the patient after a biopsy that the lesions are benign and self-limiting without recommending treatment.  

The Diagnosis: Eruptive Syringoma 

A punch biopsy of a lesion on the penis was performed. Histopathologic examination revealed many tadpole-shaped cords of epithelial cells and small ducts in the dermis (Figure). Based on clinical and histopathological findings, a diagnosis of eruptive syringoma was made. The patient declined treatment.  

Syringomas are common benign eccrine neoplasms. They present clinically as small flesh-colored to brownish papules symmetrically distributed on the face, neck, trunk, pubic area, arms, and legs.^1-3 Classic syringoma occurs more frequently in young adult women.¹ Eruptive syringoma is a rare variant, and the age of onset ranges from 3 to 50 years.^1-13  Eruptive syringoma is the term for multiple lesions that occur synchronously in any part of the body.^1,4,13 The term eruptive is not the opposite of localized and refers to the time of onset of the lesion. There may be both a generalized eruptive syringoma or a localized eruptive syringoma depending on the distribution of the lesions.¹ The most common site for syringoma occurrence is the eyelid; penile syringoma is extremely rare. Several cases of penile syringoma have been reported, but eruptive penile syringoma is rare.^3,5-10,12,13  

Histopathology is essential for the diagnosis of syringoma. Hematoxylin and eosin stain shows multiple small cystic ducts and epithelial cell nests in the dermis. Ductal structures sometimes appear tadpolelike or comma shaped depending on the section.^1,2,7,12 

The clinical differential diagnosis of syringoma includes sebaceous hyperplasia, verruca plana, molluscum contagiosum, bowenoid papulosis, condyloma acuminatum, lichen planus, lichen nitidus, milia, angiofibroma, epidermal cyst, calcinosis cutis, granuloma annulare, and sarcoidosis.^3,8,12 

Because syringoma is benign, treatment is not necessary unless there is a cosmetic problem.^3,5,7,8,12 There is no satisfactory treatment of eruptive penile syringoma. Treatment options include topical tretinoin and adapalene, oral isotretinoin, cryotherapy, microelectrodesiccation with an epilating needle, dermabrasion, CO₂ laser, and surgical excision.^2,3,7,8,12  

Adult patients with penile syringoma may be concerned about sexually transmitted diseases due to the appearance of the papules. If cosmesis is not an issue, clinicians should reassure the patient after a biopsy that the lesions are benign and self-limiting without recommending treatment.  

The Diagnosis: Eruptive Syringoma 

A punch biopsy of a lesion on the penis was performed. Histopathologic examination revealed many tadpole-shaped cords of epithelial cells and small ducts in the dermis (Figure). Based on clinical and histopathological findings, a diagnosis of eruptive syringoma was made. The patient declined treatment.  

Syringomas are common benign eccrine neoplasms. They present clinically as small flesh-colored to brownish papules symmetrically distributed on the face, neck, trunk, pubic area, arms, and legs.^1-3 Classic syringoma occurs more frequently in young adult women.¹ Eruptive syringoma is a rare variant, and the age of onset ranges from 3 to 50 years.^1-13  Eruptive syringoma is the term for multiple lesions that occur synchronously in any part of the body.^1,4,13 The term eruptive is not the opposite of localized and refers to the time of onset of the lesion. There may be both a generalized eruptive syringoma or a localized eruptive syringoma depending on the distribution of the lesions.¹ The most common site for syringoma occurrence is the eyelid; penile syringoma is extremely rare. Several cases of penile syringoma have been reported, but eruptive penile syringoma is rare.^3,5-10,12,13  

Histopathology is essential for the diagnosis of syringoma. Hematoxylin and eosin stain shows multiple small cystic ducts and epithelial cell nests in the dermis. Ductal structures sometimes appear tadpolelike or comma shaped depending on the section.^1,2,7,12 

The clinical differential diagnosis of syringoma includes sebaceous hyperplasia, verruca plana, molluscum contagiosum, bowenoid papulosis, condyloma acuminatum, lichen planus, lichen nitidus, milia, angiofibroma, epidermal cyst, calcinosis cutis, granuloma annulare, and sarcoidosis.^3,8,12 

Because syringoma is benign, treatment is not necessary unless there is a cosmetic problem.^3,5,7,8,12 There is no satisfactory treatment of eruptive penile syringoma. Treatment options include topical tretinoin and adapalene, oral isotretinoin, cryotherapy, microelectrodesiccation with an epilating needle, dermabrasion, CO₂ laser, and surgical excision.^2,3,7,8,12  

Adult patients with penile syringoma may be concerned about sexually transmitted diseases due to the appearance of the papules. If cosmesis is not an issue, clinicians should reassure the patient after a biopsy that the lesions are benign and self-limiting without recommending treatment.  

The Food and Drug Administration approved a combination of pertuzumab (Perjeta, Genentech/Roche), trastuzumab (Herceptin, Genentech/Roche) and hyaluronidase (Phesgo, Genentech/Roche) that is administered subcutaneously – rather than intravenously – for the treatment of early and metastatic HER2-positive breast cancers.

Phesgo is initially used in combination with chemotherapy at an infusion center but could continue to be administered in a patient’s home by a qualified health care professional once chemotherapy is complete, according to the FDA.

Administration takes approximately 8 minutes for the initial loading dose and approximately 5 minutes for maintenance doses, according to a Genentech press statement. This compares favorably with the 150 minutes needed for the combined loading dose of intravenous pertuzumab and trastuzumab, and the 60-150 minutes for intravenous maintenance infusions, the company said.

“Currently, most patients with HER2-positive breast cancer receive trastuzumab and pertuzumab at infusion centers. With a new administration route, Phesgo offers an outpatient option for patients to receive trastuzumab and pertuzumab,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, in an agency press release.

“The fixed-dose combination of trastuzumab and pertuzumab offers a simpler, faster, and easier treatment experience for patients with HER2-positive breast cancer,” said Antoinette Tan, MD, MHSc, chief of breast medical oncology at Levine Cancer Institute, Charlotte, N.C., in the company statement.

Dr. Tan also said that home administration “can be advantageous for patients and infusion centers.”

However, in April, the Community Oncology Alliance strenuously objected to this type of treatment in a patient’s home, as reported by Medscape Medical News.

The group, which represents U.S. community-based practices, said it “fundamentally opposes home infusion of chemotherapy, cancer immunotherapy, and cancer treatment supportive drugs because of serious patient safety concerns.”

The FDA’s approval was based on the results of the pivotal phase 3 FeDeriCa trial, a noninferiority study in patients with HER2-positive early breast cancer, which demonstrated that the new product had comparable efficacy and safety as intravenous pertuzumab and intravenous trastuzumab.

In terms of efficacy, the subcutaneous product demonstrated noninferior plasma levels of pertuzumab, which was the primary endpoint, when compared with IV administration of pertuzumab.

Safety was comparable between the two approaches, with no new safety signals using the subcutaneous delivery method, including no “meaningful difference” in cardiac toxicity, according to Genentech. However, there were more administration-related reactions with the new product. The most common adverse events in both groups were alopecia, nausea, diarrhea, and anemia.

The new product uses a drug delivery technology (Enhanze, Halozyme Therapeutics) that employs a proprietary enzyme that temporarily degrades hyaluronan, a glycosaminoglycan or chain of natural sugars in the body, to facilitate the dispersion and absorption of injected therapeutic drugs, according to Genentech.

In May, at the European Society for Medical Oncology Breast Cancer Virtual Meeting 2020, investigators of the phase 2 PHranceSCa study reported that “more than 80%” of patients preferred subcutaneous to intravenous administration of pertuzumab and trastuzumab.

This article first appeared on Medscape.com.

The Food and Drug Administration approved a combination of pertuzumab (Perjeta, Genentech/Roche), trastuzumab (Herceptin, Genentech/Roche) and hyaluronidase (Phesgo, Genentech/Roche) that is administered subcutaneously – rather than intravenously – for the treatment of early and metastatic HER2-positive breast cancers.

Phesgo is initially used in combination with chemotherapy at an infusion center but could continue to be administered in a patient’s home by a qualified health care professional once chemotherapy is complete, according to the FDA.

Administration takes approximately 8 minutes for the initial loading dose and approximately 5 minutes for maintenance doses, according to a Genentech press statement. This compares favorably with the 150 minutes needed for the combined loading dose of intravenous pertuzumab and trastuzumab, and the 60-150 minutes for intravenous maintenance infusions, the company said.

“Currently, most patients with HER2-positive breast cancer receive trastuzumab and pertuzumab at infusion centers. With a new administration route, Phesgo offers an outpatient option for patients to receive trastuzumab and pertuzumab,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, in an agency press release.

“The fixed-dose combination of trastuzumab and pertuzumab offers a simpler, faster, and easier treatment experience for patients with HER2-positive breast cancer,” said Antoinette Tan, MD, MHSc, chief of breast medical oncology at Levine Cancer Institute, Charlotte, N.C., in the company statement.

Dr. Tan also said that home administration “can be advantageous for patients and infusion centers.”

However, in April, the Community Oncology Alliance strenuously objected to this type of treatment in a patient’s home, as reported by Medscape Medical News.

The group, which represents U.S. community-based practices, said it “fundamentally opposes home infusion of chemotherapy, cancer immunotherapy, and cancer treatment supportive drugs because of serious patient safety concerns.”

The FDA’s approval was based on the results of the pivotal phase 3 FeDeriCa trial, a noninferiority study in patients with HER2-positive early breast cancer, which demonstrated that the new product had comparable efficacy and safety as intravenous pertuzumab and intravenous trastuzumab.

In terms of efficacy, the subcutaneous product demonstrated noninferior plasma levels of pertuzumab, which was the primary endpoint, when compared with IV administration of pertuzumab.

Safety was comparable between the two approaches, with no new safety signals using the subcutaneous delivery method, including no “meaningful difference” in cardiac toxicity, according to Genentech. However, there were more administration-related reactions with the new product. The most common adverse events in both groups were alopecia, nausea, diarrhea, and anemia.

The new product uses a drug delivery technology (Enhanze, Halozyme Therapeutics) that employs a proprietary enzyme that temporarily degrades hyaluronan, a glycosaminoglycan or chain of natural sugars in the body, to facilitate the dispersion and absorption of injected therapeutic drugs, according to Genentech.

In May, at the European Society for Medical Oncology Breast Cancer Virtual Meeting 2020, investigators of the phase 2 PHranceSCa study reported that “more than 80%” of patients preferred subcutaneous to intravenous administration of pertuzumab and trastuzumab.

This article first appeared on Medscape.com.

The Food and Drug Administration approved a combination of pertuzumab (Perjeta, Genentech/Roche), trastuzumab (Herceptin, Genentech/Roche) and hyaluronidase (Phesgo, Genentech/Roche) that is administered subcutaneously – rather than intravenously – for the treatment of early and metastatic HER2-positive breast cancers.

Phesgo is initially used in combination with chemotherapy at an infusion center but could continue to be administered in a patient’s home by a qualified health care professional once chemotherapy is complete, according to the FDA.

Administration takes approximately 8 minutes for the initial loading dose and approximately 5 minutes for maintenance doses, according to a Genentech press statement. This compares favorably with the 150 minutes needed for the combined loading dose of intravenous pertuzumab and trastuzumab, and the 60-150 minutes for intravenous maintenance infusions, the company said.

“Currently, most patients with HER2-positive breast cancer receive trastuzumab and pertuzumab at infusion centers. With a new administration route, Phesgo offers an outpatient option for patients to receive trastuzumab and pertuzumab,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, in an agency press release.

“The fixed-dose combination of trastuzumab and pertuzumab offers a simpler, faster, and easier treatment experience for patients with HER2-positive breast cancer,” said Antoinette Tan, MD, MHSc, chief of breast medical oncology at Levine Cancer Institute, Charlotte, N.C., in the company statement.

Dr. Tan also said that home administration “can be advantageous for patients and infusion centers.”

However, in April, the Community Oncology Alliance strenuously objected to this type of treatment in a patient’s home, as reported by Medscape Medical News.

The group, which represents U.S. community-based practices, said it “fundamentally opposes home infusion of chemotherapy, cancer immunotherapy, and cancer treatment supportive drugs because of serious patient safety concerns.”

The FDA’s approval was based on the results of the pivotal phase 3 FeDeriCa trial, a noninferiority study in patients with HER2-positive early breast cancer, which demonstrated that the new product had comparable efficacy and safety as intravenous pertuzumab and intravenous trastuzumab.

In terms of efficacy, the subcutaneous product demonstrated noninferior plasma levels of pertuzumab, which was the primary endpoint, when compared with IV administration of pertuzumab.

Safety was comparable between the two approaches, with no new safety signals using the subcutaneous delivery method, including no “meaningful difference” in cardiac toxicity, according to Genentech. However, there were more administration-related reactions with the new product. The most common adverse events in both groups were alopecia, nausea, diarrhea, and anemia.

The new product uses a drug delivery technology (Enhanze, Halozyme Therapeutics) that employs a proprietary enzyme that temporarily degrades hyaluronan, a glycosaminoglycan or chain of natural sugars in the body, to facilitate the dispersion and absorption of injected therapeutic drugs, according to Genentech.

In May, at the European Society for Medical Oncology Breast Cancer Virtual Meeting 2020, investigators of the phase 2 PHranceSCa study reported that “more than 80%” of patients preferred subcutaneous to intravenous administration of pertuzumab and trastuzumab.

This article first appeared on Medscape.com.