News from the FDA/CDC

Age-adjusted infant mortality dropped 11% from 2000 to 2017 in the United States, but the even larger decline for infants born to black women still left a death rate more than twice as high as those of white or Hispanic infants, according to a new analysis from the National Center for Health Statistics.

Overall maternal age–adjusted infant mortality decreased 11% from 6.89 per 1,000 births in 2000 to 6.13 per 1,000 in 2017, while the crude mortality rate fell 16% from 6.89 to 5.79, reported Anne K. Driscoll, PhD, and Danielle M. Ely, PhD, of the NCHS.

Over that same time period, age-adjusted infant mortality for births to black women went from 13.59 per 1,000 to 11.19, a drop of 18%. By comparison, age-adjusted mortality declined 7% from 5.59 per 1,000 for infants born to Hispanic women to 5.21 in 2017, they said in a National Vital Statistics Report.

Changes in maternal age distribution had an important effect on infant mortality. Women aged under 25 years, who have higher mortality rates, were less likely to give birth in 2017 than in 2000, and women aged 30-39 years, who have the lowest rates, made up a larger share of births in 2017, they pointed out.

It was, however, changes in age-specific mortality rates (ASMRs) that had the largest influence on the overall drop in the crude mortality rate, accounting for about two-thirds of the overall decline, the NCHS researchers said, noting that the effect varied by race and Hispanic origin.

Births to non-Hispanic white women mirrored the national situation: Approximately two-thirds (68.7%) of the decrease in infant mortality came from changes in ASMRs and one-third (31.3%) from changes in maternal age distribution. Among non-Hispanic black women, the distribution was 95.2% ASMRs and 4.8% age distribution, Dr. Driscoll and Dr. Ely reported based on data from the National Vital Statistics System.

The disparity between the two trends went even further for infants born to Hispanic women. Changes in ASMRs were responsible for 133.7% of the overall change in crude mortality versus –33.7% for changes in maternal age distribution. “If no changes occurred in the ASMRs, the changes in the maternal age distribution would have resulted in a higher mortality rate in 2017,” they explained.

The declines in the ASMRs may be related to incremental improved survival of preterm and low-birthweight infants in certain groups. “While little or no progress has been made to lower [these] two key risk factors for poor birth outcomes, progress has been made in lowering the mortality rates of at-risk infants across maternal age and race and Hispanic origin, resulting in lower ASMRs for all age groups,” the investigators suggested.

It also is possible that “changes in other factors, such as maternal education and cigarette smoking during pregnancy, may have indirectly resulted in declining ASMRs for all age groups over time,” they added.

[email protected]

SOURCE: Driscoll AK, Ely DM. National Vital Statistics Reports. 2020;69(5):1-18.

Age-adjusted infant mortality dropped 11% from 2000 to 2017 in the United States, but the even larger decline for infants born to black women still left a death rate more than twice as high as those of white or Hispanic infants, according to a new analysis from the National Center for Health Statistics.

Overall maternal age–adjusted infant mortality decreased 11% from 6.89 per 1,000 births in 2000 to 6.13 per 1,000 in 2017, while the crude mortality rate fell 16% from 6.89 to 5.79, reported Anne K. Driscoll, PhD, and Danielle M. Ely, PhD, of the NCHS.

Over that same time period, age-adjusted infant mortality for births to black women went from 13.59 per 1,000 to 11.19, a drop of 18%. By comparison, age-adjusted mortality declined 7% from 5.59 per 1,000 for infants born to Hispanic women to 5.21 in 2017, they said in a National Vital Statistics Report.

Changes in maternal age distribution had an important effect on infant mortality. Women aged under 25 years, who have higher mortality rates, were less likely to give birth in 2017 than in 2000, and women aged 30-39 years, who have the lowest rates, made up a larger share of births in 2017, they pointed out.

It was, however, changes in age-specific mortality rates (ASMRs) that had the largest influence on the overall drop in the crude mortality rate, accounting for about two-thirds of the overall decline, the NCHS researchers said, noting that the effect varied by race and Hispanic origin.

Births to non-Hispanic white women mirrored the national situation: Approximately two-thirds (68.7%) of the decrease in infant mortality came from changes in ASMRs and one-third (31.3%) from changes in maternal age distribution. Among non-Hispanic black women, the distribution was 95.2% ASMRs and 4.8% age distribution, Dr. Driscoll and Dr. Ely reported based on data from the National Vital Statistics System.

The disparity between the two trends went even further for infants born to Hispanic women. Changes in ASMRs were responsible for 133.7% of the overall change in crude mortality versus –33.7% for changes in maternal age distribution. “If no changes occurred in the ASMRs, the changes in the maternal age distribution would have resulted in a higher mortality rate in 2017,” they explained.

The declines in the ASMRs may be related to incremental improved survival of preterm and low-birthweight infants in certain groups. “While little or no progress has been made to lower [these] two key risk factors for poor birth outcomes, progress has been made in lowering the mortality rates of at-risk infants across maternal age and race and Hispanic origin, resulting in lower ASMRs for all age groups,” the investigators suggested.

It also is possible that “changes in other factors, such as maternal education and cigarette smoking during pregnancy, may have indirectly resulted in declining ASMRs for all age groups over time,” they added.

[email protected]

SOURCE: Driscoll AK, Ely DM. National Vital Statistics Reports. 2020;69(5):1-18.

Age-adjusted infant mortality dropped 11% from 2000 to 2017 in the United States, but the even larger decline for infants born to black women still left a death rate more than twice as high as those of white or Hispanic infants, according to a new analysis from the National Center for Health Statistics.

Overall maternal age–adjusted infant mortality decreased 11% from 6.89 per 1,000 births in 2000 to 6.13 per 1,000 in 2017, while the crude mortality rate fell 16% from 6.89 to 5.79, reported Anne K. Driscoll, PhD, and Danielle M. Ely, PhD, of the NCHS.

Over that same time period, age-adjusted infant mortality for births to black women went from 13.59 per 1,000 to 11.19, a drop of 18%. By comparison, age-adjusted mortality declined 7% from 5.59 per 1,000 for infants born to Hispanic women to 5.21 in 2017, they said in a National Vital Statistics Report.

Changes in maternal age distribution had an important effect on infant mortality. Women aged under 25 years, who have higher mortality rates, were less likely to give birth in 2017 than in 2000, and women aged 30-39 years, who have the lowest rates, made up a larger share of births in 2017, they pointed out.

It was, however, changes in age-specific mortality rates (ASMRs) that had the largest influence on the overall drop in the crude mortality rate, accounting for about two-thirds of the overall decline, the NCHS researchers said, noting that the effect varied by race and Hispanic origin.

Births to non-Hispanic white women mirrored the national situation: Approximately two-thirds (68.7%) of the decrease in infant mortality came from changes in ASMRs and one-third (31.3%) from changes in maternal age distribution. Among non-Hispanic black women, the distribution was 95.2% ASMRs and 4.8% age distribution, Dr. Driscoll and Dr. Ely reported based on data from the National Vital Statistics System.

The disparity between the two trends went even further for infants born to Hispanic women. Changes in ASMRs were responsible for 133.7% of the overall change in crude mortality versus –33.7% for changes in maternal age distribution. “If no changes occurred in the ASMRs, the changes in the maternal age distribution would have resulted in a higher mortality rate in 2017,” they explained.

The declines in the ASMRs may be related to incremental improved survival of preterm and low-birthweight infants in certain groups. “While little or no progress has been made to lower [these] two key risk factors for poor birth outcomes, progress has been made in lowering the mortality rates of at-risk infants across maternal age and race and Hispanic origin, resulting in lower ASMRs for all age groups,” the investigators suggested.

It also is possible that “changes in other factors, such as maternal education and cigarette smoking during pregnancy, may have indirectly resulted in declining ASMRs for all age groups over time,” they added.

[email protected]

SOURCE: Driscoll AK, Ely DM. National Vital Statistics Reports. 2020;69(5):1-18.

The Food and Administration has approved a new indication for the PD-L1 inhibitor avelumab.

Physicians can now prescribe avelumab (Bavencio) as maintenance treatment for patients with locally advanced or metastatic urothelial carcinoma (UC) that has not progressed after first-line platinum-containing chemotherapy.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The new indication adds to avelumab use in other patient populations, including people with locally advanced or metastatic UC who experience disease progression during or following platinum-containing chemotherapy. The FDA also previously approved avelumab for patients who experienced UC progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

The FDA first approved marketing of avelumab in 2017. Other uses include treatment of metastatic Merkel cell carcinoma and first-line treatment of advanced renal cell carcinoma in combination with axitinib.

The new maintenance therapy indication for avelumab is based on efficacy demonstrated in the JAVELIN Bladder 100 trial. Results from this trial were presented as part of the American Society of Clinical Oncology virtual scientific program.

Investigators randomly assigned 700 patients with unresectable, locally advanced or metastatic UC to intravenous avelumab and best supportive care or best supportive care alone. All participants had UC that had not progressed after first-line platinum-containing chemotherapy.

The median overall survival was 21.4 months in the avelumab arm and 14.3 months in the best supportive care–alone arm (hazard ratio, 0.69; 95% confidence interval, 0.56-0.86). This difference was statistically significant (P = .001).

Avelumab also was associated with significantly longer overall survival in the 51% of participants with PD-L1–positive tumors (hazard ratio, 0.56; 95% confidence interval, 0.40-0.79; P < .001).

Results from the JAVELIN Bladder 100 trial allowed the FDA to convert an initial accelerated approval of avelumab to a regular approval.

Fatigue, musculoskeletal pain, urinary tract infection, and rash were the most common adverse events reported in 20% or more of trial participants. In all, 28% of patients experienced serious adverse events, and one patient died from sepsis during the trial.

Recommended avelumab dosing is 800 mg administered as an intravenous infusion over 60 minutes every 2 weeks until disease progresses or toxicity becomes unacceptable.

See the full prescribing information for more details.

The Food and Administration has approved a new indication for the PD-L1 inhibitor avelumab.

Physicians can now prescribe avelumab (Bavencio) as maintenance treatment for patients with locally advanced or metastatic urothelial carcinoma (UC) that has not progressed after first-line platinum-containing chemotherapy.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The new indication adds to avelumab use in other patient populations, including people with locally advanced or metastatic UC who experience disease progression during or following platinum-containing chemotherapy. The FDA also previously approved avelumab for patients who experienced UC progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

The FDA first approved marketing of avelumab in 2017. Other uses include treatment of metastatic Merkel cell carcinoma and first-line treatment of advanced renal cell carcinoma in combination with axitinib.

The new maintenance therapy indication for avelumab is based on efficacy demonstrated in the JAVELIN Bladder 100 trial. Results from this trial were presented as part of the American Society of Clinical Oncology virtual scientific program.

Investigators randomly assigned 700 patients with unresectable, locally advanced or metastatic UC to intravenous avelumab and best supportive care or best supportive care alone. All participants had UC that had not progressed after first-line platinum-containing chemotherapy.

The median overall survival was 21.4 months in the avelumab arm and 14.3 months in the best supportive care–alone arm (hazard ratio, 0.69; 95% confidence interval, 0.56-0.86). This difference was statistically significant (P = .001).

Avelumab also was associated with significantly longer overall survival in the 51% of participants with PD-L1–positive tumors (hazard ratio, 0.56; 95% confidence interval, 0.40-0.79; P < .001).

Results from the JAVELIN Bladder 100 trial allowed the FDA to convert an initial accelerated approval of avelumab to a regular approval.

Fatigue, musculoskeletal pain, urinary tract infection, and rash were the most common adverse events reported in 20% or more of trial participants. In all, 28% of patients experienced serious adverse events, and one patient died from sepsis during the trial.

Recommended avelumab dosing is 800 mg administered as an intravenous infusion over 60 minutes every 2 weeks until disease progresses or toxicity becomes unacceptable.

See the full prescribing information for more details.

The Food and Administration has approved a new indication for the PD-L1 inhibitor avelumab.

Physicians can now prescribe avelumab (Bavencio) as maintenance treatment for patients with locally advanced or metastatic urothelial carcinoma (UC) that has not progressed after first-line platinum-containing chemotherapy.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The new indication adds to avelumab use in other patient populations, including people with locally advanced or metastatic UC who experience disease progression during or following platinum-containing chemotherapy. The FDA also previously approved avelumab for patients who experienced UC progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

The FDA first approved marketing of avelumab in 2017. Other uses include treatment of metastatic Merkel cell carcinoma and first-line treatment of advanced renal cell carcinoma in combination with axitinib.

The new maintenance therapy indication for avelumab is based on efficacy demonstrated in the JAVELIN Bladder 100 trial. Results from this trial were presented as part of the American Society of Clinical Oncology virtual scientific program.

Investigators randomly assigned 700 patients with unresectable, locally advanced or metastatic UC to intravenous avelumab and best supportive care or best supportive care alone. All participants had UC that had not progressed after first-line platinum-containing chemotherapy.

The median overall survival was 21.4 months in the avelumab arm and 14.3 months in the best supportive care–alone arm (hazard ratio, 0.69; 95% confidence interval, 0.56-0.86). This difference was statistically significant (P = .001).

Avelumab also was associated with significantly longer overall survival in the 51% of participants with PD-L1–positive tumors (hazard ratio, 0.56; 95% confidence interval, 0.40-0.79; P < .001).

Results from the JAVELIN Bladder 100 trial allowed the FDA to convert an initial accelerated approval of avelumab to a regular approval.

Fatigue, musculoskeletal pain, urinary tract infection, and rash were the most common adverse events reported in 20% or more of trial participants. In all, 28% of patients experienced serious adverse events, and one patient died from sepsis during the trial.

Recommended avelumab dosing is 800 mg administered as an intravenous infusion over 60 minutes every 2 weeks until disease progresses or toxicity becomes unacceptable.

See the full prescribing information for more details.

The Food and Drug Administration recently announced two new types of cancer that can be treated by the anti–PD-1 antibody pembrolizumab.

The new indications expand the use of pembrolizumab (Keytruda) to include treatment of patients with unresectable or metastatic tumor mutational burden–high (TMB-H) solid tumors as well as patients with cutaneous squamous cell carcinoma (cSCC). The FDA announced the new indications just 8 days apart, on June 16 and June 24.

In addition, on June 29, the FDA approved a third new indication for pembrolizumab, this time as first-line treatment for patients with unresectable or metastatic microsatellite instability–high or mismatch repair–deficient colorectal cancer.



The new approvals add to a wide range of oncology indications for which pembrolizumab can be used.

Accelerated approval to treat solid tumors

The FDA granted accelerated approval for pembrolizumab to treat children and adults with unresectable or metastatic TMB-H solid tumors that progressed after previous treatment or in instances where there are no satisfactory alternative treatment options.

The tumor mutational burden must be confirmed by an FDA-approved test. To that end, the FDA approved the FoundationOneCDx assay, which is designed to help physicians determine which patients meet the threshold for TMB-H malignancies (10 or more mutations per megabase).

The efficacy of pembrolizumab in TMB-H solid tumors was investigated in 10 cohorts from the multicenter, open-label KEYNOTE-158 trial. Participants received 200 mg of pembrolizumab intravenously every 3 weeks until their disease progressed or they experienced unacceptable toxicity.

Within this population, 102 patients had tumors that met the TMB-H definition. In this group, the overall response rate was 29%, including a 25% partial response rate and a 4% complete response rate.

The median duration of response was not reached, but 57% of participants experienced a response lasting 12 months or longer, and 50% had a response lasting 24 months or longer.

The most common adverse events associated with pembrolizumab in this trial were fatigue, musculoskeletal pain, decreased appetite, pruritus, diarrhea, nausea, rash, pyrexia, cough, dyspnea, constipation, pain, and abdominal pain. Pembrolizumab is associated with immune-mediated side effects, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, and skin adverse reactions, the FDA noted.

Safety and efficacy of pembrolizumab in pediatric patients with TMB-H central nervous system cancers have not been established.
 

New option for recurrent or metastatic cSCC

Physicians treating patients with cSCC that is not curable by surgery or radiation now have pembrolizumab to consider as another treatment option.

The cSCC approval is based on results of the multicenter, open-label KEYNOTE-629 trial. The dosage regimen was 200 mg of pembrolizumab intravenously every 3 weeks until cancer progressed, unacceptable toxicity arose, or 24 months of treatment were completed.

The objective response rate was 34%, and the median duration of response was not reached.

Adverse events were similar to those occurring in patients who received pembrolizumab as a single agent in other clinical trials, the FDA noted.

The Food and Drug Administration recently announced two new types of cancer that can be treated by the anti–PD-1 antibody pembrolizumab.

The new indications expand the use of pembrolizumab (Keytruda) to include treatment of patients with unresectable or metastatic tumor mutational burden–high (TMB-H) solid tumors as well as patients with cutaneous squamous cell carcinoma (cSCC). The FDA announced the new indications just 8 days apart, on June 16 and June 24.

In addition, on June 29, the FDA approved a third new indication for pembrolizumab, this time as first-line treatment for patients with unresectable or metastatic microsatellite instability–high or mismatch repair–deficient colorectal cancer.



The new approvals add to a wide range of oncology indications for which pembrolizumab can be used.

Accelerated approval to treat solid tumors

The FDA granted accelerated approval for pembrolizumab to treat children and adults with unresectable or metastatic TMB-H solid tumors that progressed after previous treatment or in instances where there are no satisfactory alternative treatment options.

The tumor mutational burden must be confirmed by an FDA-approved test. To that end, the FDA approved the FoundationOneCDx assay, which is designed to help physicians determine which patients meet the threshold for TMB-H malignancies (10 or more mutations per megabase).

The efficacy of pembrolizumab in TMB-H solid tumors was investigated in 10 cohorts from the multicenter, open-label KEYNOTE-158 trial. Participants received 200 mg of pembrolizumab intravenously every 3 weeks until their disease progressed or they experienced unacceptable toxicity.

Within this population, 102 patients had tumors that met the TMB-H definition. In this group, the overall response rate was 29%, including a 25% partial response rate and a 4% complete response rate.

The median duration of response was not reached, but 57% of participants experienced a response lasting 12 months or longer, and 50% had a response lasting 24 months or longer.

The most common adverse events associated with pembrolizumab in this trial were fatigue, musculoskeletal pain, decreased appetite, pruritus, diarrhea, nausea, rash, pyrexia, cough, dyspnea, constipation, pain, and abdominal pain. Pembrolizumab is associated with immune-mediated side effects, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, and skin adverse reactions, the FDA noted.

Safety and efficacy of pembrolizumab in pediatric patients with TMB-H central nervous system cancers have not been established.
 

New option for recurrent or metastatic cSCC

Physicians treating patients with cSCC that is not curable by surgery or radiation now have pembrolizumab to consider as another treatment option.

The cSCC approval is based on results of the multicenter, open-label KEYNOTE-629 trial. The dosage regimen was 200 mg of pembrolizumab intravenously every 3 weeks until cancer progressed, unacceptable toxicity arose, or 24 months of treatment were completed.

The objective response rate was 34%, and the median duration of response was not reached.

Adverse events were similar to those occurring in patients who received pembrolizumab as a single agent in other clinical trials, the FDA noted.

The Food and Drug Administration recently announced two new types of cancer that can be treated by the anti–PD-1 antibody pembrolizumab.

The new indications expand the use of pembrolizumab (Keytruda) to include treatment of patients with unresectable or metastatic tumor mutational burden–high (TMB-H) solid tumors as well as patients with cutaneous squamous cell carcinoma (cSCC). The FDA announced the new indications just 8 days apart, on June 16 and June 24.

In addition, on June 29, the FDA approved a third new indication for pembrolizumab, this time as first-line treatment for patients with unresectable or metastatic microsatellite instability–high or mismatch repair–deficient colorectal cancer.



The new approvals add to a wide range of oncology indications for which pembrolizumab can be used.

Accelerated approval to treat solid tumors

The FDA granted accelerated approval for pembrolizumab to treat children and adults with unresectable or metastatic TMB-H solid tumors that progressed after previous treatment or in instances where there are no satisfactory alternative treatment options.

The tumor mutational burden must be confirmed by an FDA-approved test. To that end, the FDA approved the FoundationOneCDx assay, which is designed to help physicians determine which patients meet the threshold for TMB-H malignancies (10 or more mutations per megabase).

The efficacy of pembrolizumab in TMB-H solid tumors was investigated in 10 cohorts from the multicenter, open-label KEYNOTE-158 trial. Participants received 200 mg of pembrolizumab intravenously every 3 weeks until their disease progressed or they experienced unacceptable toxicity.

Within this population, 102 patients had tumors that met the TMB-H definition. In this group, the overall response rate was 29%, including a 25% partial response rate and a 4% complete response rate.

The median duration of response was not reached, but 57% of participants experienced a response lasting 12 months or longer, and 50% had a response lasting 24 months or longer.

The most common adverse events associated with pembrolizumab in this trial were fatigue, musculoskeletal pain, decreased appetite, pruritus, diarrhea, nausea, rash, pyrexia, cough, dyspnea, constipation, pain, and abdominal pain. Pembrolizumab is associated with immune-mediated side effects, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, and skin adverse reactions, the FDA noted.

Safety and efficacy of pembrolizumab in pediatric patients with TMB-H central nervous system cancers have not been established.
 

New option for recurrent or metastatic cSCC

Physicians treating patients with cSCC that is not curable by surgery or radiation now have pembrolizumab to consider as another treatment option.

The cSCC approval is based on results of the multicenter, open-label KEYNOTE-629 trial. The dosage regimen was 200 mg of pembrolizumab intravenously every 3 weeks until cancer progressed, unacceptable toxicity arose, or 24 months of treatment were completed.

The objective response rate was 34%, and the median duration of response was not reached.

Adverse events were similar to those occurring in patients who received pembrolizumab as a single agent in other clinical trials, the FDA noted.

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.

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.

Women are much more likely than men to have asthma, and asthma rates among black women are higher than for other races/ethnicities, according to the Centers for Disease Control and Prevention.

Among all women aged 18 years and older, 9.7% reported that they currently had asthma in 2017-2018, compared with 5.5% of men, based on age-adjusted data from the National Health Interview Survey.

The proportion of black, non-Hispanic women with asthma, however, was even higher, at 11.4%. White non-Hispanic women were next at 10.3%, followed by Hispanic (7.8%) and Asian (5.0%) women, the CDC reported June 26 in the Morbidity and Mortality Weekly Report.

The same pattern held for men: 6.2% of black men had asthma in 2017-2018, compared with 5.9% of whites, 3.9% of Hispanics, and 3.3% of Asian men, the CDC said.

[email protected]

SOURCE: MMWR. 2020 Jun 26;69(25):805.

Women are much more likely than men to have asthma, and asthma rates among black women are higher than for other races/ethnicities, according to the Centers for Disease Control and Prevention.

Among all women aged 18 years and older, 9.7% reported that they currently had asthma in 2017-2018, compared with 5.5% of men, based on age-adjusted data from the National Health Interview Survey.

The proportion of black, non-Hispanic women with asthma, however, was even higher, at 11.4%. White non-Hispanic women were next at 10.3%, followed by Hispanic (7.8%) and Asian (5.0%) women, the CDC reported June 26 in the Morbidity and Mortality Weekly Report.

The same pattern held for men: 6.2% of black men had asthma in 2017-2018, compared with 5.9% of whites, 3.9% of Hispanics, and 3.3% of Asian men, the CDC said.

[email protected]

SOURCE: MMWR. 2020 Jun 26;69(25):805.

Women are much more likely than men to have asthma, and asthma rates among black women are higher than for other races/ethnicities, according to the Centers for Disease Control and Prevention.

Among all women aged 18 years and older, 9.7% reported that they currently had asthma in 2017-2018, compared with 5.5% of men, based on age-adjusted data from the National Health Interview Survey.

The proportion of black, non-Hispanic women with asthma, however, was even higher, at 11.4%. White non-Hispanic women were next at 10.3%, followed by Hispanic (7.8%) and Asian (5.0%) women, the CDC reported June 26 in the Morbidity and Mortality Weekly Report.

The same pattern held for men: 6.2% of black men had asthma in 2017-2018, compared with 5.9% of whites, 3.9% of Hispanics, and 3.3% of Asian men, the CDC said.

[email protected]

SOURCE: MMWR. 2020 Jun 26;69(25):805.

A pair of new vaccines for adults aged 65 years and older will be available for the 2020-2021 flu season – Fluzone high-dose quadrivalent, which replaces the trivalent Fluzone high-dose and Fluad quadrivalent (Seqirus), according to the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

At a virtual meeting on June 24, the committee voted unanimously to approve the vaccine recommendations for annual influenza immunization of all individuals aged 6 months and older. They also voted to accept some guidance and language changes to the recommendations.

The past flu season was unique in its overlap with the emergence of the COVID-19 coronavirus, which likely contributed to a third peak in reported cases of influenza-like illness at approximately week 14 of last season, said Lisa Grohskopf, MD, of the CDC’s influenza division, who presented data on last year’s activity and the updates for next season.

The CDC estimates that 39,000,000-56,000,000 flu illnesses occurred in the United States from Oct. 1, 2019, to April 4, 2020, said Dr. Grohskopf. Estimates also suggest as many as 740,000 hospitalizations and 62,000 deaths related to the seasonal flu.

Preliminary results of vaccine effectiveness showed 39% overall for the 2019-2020 season, with more substantial protection against influenza B and lower protection against A/H1N1pmd09.

Vaccine safety data from the Vaccine Adverse Event Reporting System and Vaccine Safety Datalink showed no new safety concerns for any flu vaccine types used last year, Dr. Grohskopf noted.

Based on this information, three components (A/H1N1pdm09, A/H3N2, and B/Victoria) have been updated for the 2020-2021 vaccines, said Dr. Grohskopf. The egg-based influenza vaccines will include hemagglutinin derived from an A/Guangdong-Maonan/SWL1536/2019(H1N1)pdm09–like virus, an A/Hong Kong/2671/2019(H3N2)–like virus and a B/Washington/02/2019 (Victoria lineage)–like virus, and (for quadrivalent vaccines) a B/Phuket/3073/2013 (Yamagata lineage)–like virus.

Nonegg vaccines will contain hemagglutinin derived from an A/Hawaii/70/2019 (H1N1)pdm09–like virus, an A/Hong Kong/45/2019 (H3N2)–like virus, a B/Washington/02/2019 (Victoria lineage)–like virus, and a B/Phuket/3073/2013 (Yamagata lineage)–like virus.

New guidance for next year’s flu season includes a change to the language in the contraindications and precautions table to simply read “Contraindications,” with more details in the text explaining package insert contraindications and ACIP recommendations, Dr. Grohskopf said. In addition, updated guidance clarifies that live-attenuated influenza vaccine quadravalents (LAIV4) should not be used in patients with cochlear implants, active cerebrospinal fluid leaks, and anatomical or functional asplenia, based on ACIP’s review of the latest evidence and the availability of alternative vaccines.

ACIP also updated guidance on the use of antivirals and LAIV4. Based on half-lives, language was added indicating that clinicians should assume interference if antivirals are given within certain intervals of LAIV4, Dr. Grohskopf explained. “Newer antivirals peramivir and baloxavir have longer half-lives than oseltamivir and zanamivir, and insufficient data are available on the use of LAIV4 in the setting of antiviral use.”

The ACIP members had no financial conflicts to disclose.
 

A pair of new vaccines for adults aged 65 years and older will be available for the 2020-2021 flu season – Fluzone high-dose quadrivalent, which replaces the trivalent Fluzone high-dose and Fluad quadrivalent (Seqirus), according to the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

At a virtual meeting on June 24, the committee voted unanimously to approve the vaccine recommendations for annual influenza immunization of all individuals aged 6 months and older. They also voted to accept some guidance and language changes to the recommendations.

The past flu season was unique in its overlap with the emergence of the COVID-19 coronavirus, which likely contributed to a third peak in reported cases of influenza-like illness at approximately week 14 of last season, said Lisa Grohskopf, MD, of the CDC’s influenza division, who presented data on last year’s activity and the updates for next season.

The CDC estimates that 39,000,000-56,000,000 flu illnesses occurred in the United States from Oct. 1, 2019, to April 4, 2020, said Dr. Grohskopf. Estimates also suggest as many as 740,000 hospitalizations and 62,000 deaths related to the seasonal flu.

Preliminary results of vaccine effectiveness showed 39% overall for the 2019-2020 season, with more substantial protection against influenza B and lower protection against A/H1N1pmd09.

Vaccine safety data from the Vaccine Adverse Event Reporting System and Vaccine Safety Datalink showed no new safety concerns for any flu vaccine types used last year, Dr. Grohskopf noted.

Based on this information, three components (A/H1N1pdm09, A/H3N2, and B/Victoria) have been updated for the 2020-2021 vaccines, said Dr. Grohskopf. The egg-based influenza vaccines will include hemagglutinin derived from an A/Guangdong-Maonan/SWL1536/2019(H1N1)pdm09–like virus, an A/Hong Kong/2671/2019(H3N2)–like virus and a B/Washington/02/2019 (Victoria lineage)–like virus, and (for quadrivalent vaccines) a B/Phuket/3073/2013 (Yamagata lineage)–like virus.

Nonegg vaccines will contain hemagglutinin derived from an A/Hawaii/70/2019 (H1N1)pdm09–like virus, an A/Hong Kong/45/2019 (H3N2)–like virus, a B/Washington/02/2019 (Victoria lineage)–like virus, and a B/Phuket/3073/2013 (Yamagata lineage)–like virus.

New guidance for next year’s flu season includes a change to the language in the contraindications and precautions table to simply read “Contraindications,” with more details in the text explaining package insert contraindications and ACIP recommendations, Dr. Grohskopf said. In addition, updated guidance clarifies that live-attenuated influenza vaccine quadravalents (LAIV4) should not be used in patients with cochlear implants, active cerebrospinal fluid leaks, and anatomical or functional asplenia, based on ACIP’s review of the latest evidence and the availability of alternative vaccines.

ACIP also updated guidance on the use of antivirals and LAIV4. Based on half-lives, language was added indicating that clinicians should assume interference if antivirals are given within certain intervals of LAIV4, Dr. Grohskopf explained. “Newer antivirals peramivir and baloxavir have longer half-lives than oseltamivir and zanamivir, and insufficient data are available on the use of LAIV4 in the setting of antiviral use.”

The ACIP members had no financial conflicts to disclose.
 

A pair of new vaccines for adults aged 65 years and older will be available for the 2020-2021 flu season – Fluzone high-dose quadrivalent, which replaces the trivalent Fluzone high-dose and Fluad quadrivalent (Seqirus), according to the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

At a virtual meeting on June 24, the committee voted unanimously to approve the vaccine recommendations for annual influenza immunization of all individuals aged 6 months and older. They also voted to accept some guidance and language changes to the recommendations.

The past flu season was unique in its overlap with the emergence of the COVID-19 coronavirus, which likely contributed to a third peak in reported cases of influenza-like illness at approximately week 14 of last season, said Lisa Grohskopf, MD, of the CDC’s influenza division, who presented data on last year’s activity and the updates for next season.

The CDC estimates that 39,000,000-56,000,000 flu illnesses occurred in the United States from Oct. 1, 2019, to April 4, 2020, said Dr. Grohskopf. Estimates also suggest as many as 740,000 hospitalizations and 62,000 deaths related to the seasonal flu.

Preliminary results of vaccine effectiveness showed 39% overall for the 2019-2020 season, with more substantial protection against influenza B and lower protection against A/H1N1pmd09.

Vaccine safety data from the Vaccine Adverse Event Reporting System and Vaccine Safety Datalink showed no new safety concerns for any flu vaccine types used last year, Dr. Grohskopf noted.

Based on this information, three components (A/H1N1pdm09, A/H3N2, and B/Victoria) have been updated for the 2020-2021 vaccines, said Dr. Grohskopf. The egg-based influenza vaccines will include hemagglutinin derived from an A/Guangdong-Maonan/SWL1536/2019(H1N1)pdm09–like virus, an A/Hong Kong/2671/2019(H3N2)–like virus and a B/Washington/02/2019 (Victoria lineage)–like virus, and (for quadrivalent vaccines) a B/Phuket/3073/2013 (Yamagata lineage)–like virus.

Nonegg vaccines will contain hemagglutinin derived from an A/Hawaii/70/2019 (H1N1)pdm09–like virus, an A/Hong Kong/45/2019 (H3N2)–like virus, a B/Washington/02/2019 (Victoria lineage)–like virus, and a B/Phuket/3073/2013 (Yamagata lineage)–like virus.

New guidance for next year’s flu season includes a change to the language in the contraindications and precautions table to simply read “Contraindications,” with more details in the text explaining package insert contraindications and ACIP recommendations, Dr. Grohskopf said. In addition, updated guidance clarifies that live-attenuated influenza vaccine quadravalents (LAIV4) should not be used in patients with cochlear implants, active cerebrospinal fluid leaks, and anatomical or functional asplenia, based on ACIP’s review of the latest evidence and the availability of alternative vaccines.

ACIP also updated guidance on the use of antivirals and LAIV4. Based on half-lives, language was added indicating that clinicians should assume interference if antivirals are given within certain intervals of LAIV4, Dr. Grohskopf explained. “Newer antivirals peramivir and baloxavir have longer half-lives than oseltamivir and zanamivir, and insufficient data are available on the use of LAIV4 in the setting of antiviral use.”

The ACIP members had no financial conflicts to disclose.
 

Half of all COVID-19 hospitalizations among Medicare beneficiaries last 8 days or longer, according to a new analysis by the Centers for Medicare & Medicaid Services.

CMS encounter and claims data show almost 110,000 hospital stays for COVID-19 from Jan. 1 to May 16, 2020. Of the longer admissions, 18% were 8-10 days, 16% were 11-15 days, and another 16% were 16 days or longer, the CMS reported in a preliminary data snapshot released June 22.

The hospitalization rate for the Medicare population was 175 per 100,000 as of May 16, but the CMS data show a number of disparities involving race/ethnicity and other demographic characteristics were uncovered, such as the following:

• Black patients were hospitalized for COVID-19 at a much higher rate, at 465 per 100,000 beneficiaries, than were Hispanics (258), Asians (187), and whites (123).
• Residents of urban/suburban areas had a much higher hospitalization rate than did those living in rural areas: 205 versus 57 per 100,000.
• Beneficiaries enrolled in both Medicare and Medicaid had 473 hospitalizations per 100,000, but the rate for those with Medicare only was 112.

“The disparities in the data reflect longstanding challenges facing minority communities and low-income older adults, many of whom face structural challenges to their health that go far beyond what is traditionally considered ‘medical,’ ” CMS Administrator Seema Verma said in a separate statement.

[email protected]

Half of all COVID-19 hospitalizations among Medicare beneficiaries last 8 days or longer, according to a new analysis by the Centers for Medicare & Medicaid Services.

CMS encounter and claims data show almost 110,000 hospital stays for COVID-19 from Jan. 1 to May 16, 2020. Of the longer admissions, 18% were 8-10 days, 16% were 11-15 days, and another 16% were 16 days or longer, the CMS reported in a preliminary data snapshot released June 22.

The hospitalization rate for the Medicare population was 175 per 100,000 as of May 16, but the CMS data show a number of disparities involving race/ethnicity and other demographic characteristics were uncovered, such as the following:

• Black patients were hospitalized for COVID-19 at a much higher rate, at 465 per 100,000 beneficiaries, than were Hispanics (258), Asians (187), and whites (123).
• Residents of urban/suburban areas had a much higher hospitalization rate than did those living in rural areas: 205 versus 57 per 100,000.
• Beneficiaries enrolled in both Medicare and Medicaid had 473 hospitalizations per 100,000, but the rate for those with Medicare only was 112.

“The disparities in the data reflect longstanding challenges facing minority communities and low-income older adults, many of whom face structural challenges to their health that go far beyond what is traditionally considered ‘medical,’ ” CMS Administrator Seema Verma said in a separate statement.

[email protected]

Half of all COVID-19 hospitalizations among Medicare beneficiaries last 8 days or longer, according to a new analysis by the Centers for Medicare & Medicaid Services.

CMS encounter and claims data show almost 110,000 hospital stays for COVID-19 from Jan. 1 to May 16, 2020. Of the longer admissions, 18% were 8-10 days, 16% were 11-15 days, and another 16% were 16 days or longer, the CMS reported in a preliminary data snapshot released June 22.

The hospitalization rate for the Medicare population was 175 per 100,000 as of May 16, but the CMS data show a number of disparities involving race/ethnicity and other demographic characteristics were uncovered, such as the following:

• Black patients were hospitalized for COVID-19 at a much higher rate, at 465 per 100,000 beneficiaries, than were Hispanics (258), Asians (187), and whites (123).
• Residents of urban/suburban areas had a much higher hospitalization rate than did those living in rural areas: 205 versus 57 per 100,000.
• Beneficiaries enrolled in both Medicare and Medicaid had 473 hospitalizations per 100,000, but the rate for those with Medicare only was 112.

“The disparities in the data reflect longstanding challenges facing minority communities and low-income older adults, many of whom face structural challenges to their health that go far beyond what is traditionally considered ‘medical,’ ” CMS Administrator Seema Verma said in a separate statement.

[email protected]

The Food and Drug Administration has granted accelerated approval of selinexor, a nuclear transport inhibitor, for the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL).

Selinexor (marketed as XPOVIO by Karyopharm Therapeutics) is intended for adult patients with relapsed/refractory DLBCL, not otherwise specified, including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy, according to the FDA’s announcement.

The FDA granted selinexor accelerated approval for this indication based on the response rate seen in the SADAL trial. Continued approval for this indication “may be contingent upon verification and description of clinical benefit in confirmatory trials,” according to the FDA.

The SADAL trial (NCT02227251) was a phase 2, single-arm, open-label study of patients with DLBCL who had previously received two to five systemic regimens. The patients received selinexor at 60 mg orally on days 1 and 3 of each week.

Results in 134 patients showed an overall response rate of 29% (95% confidence interval: 22-38), with complete responses in 13% of patients. Of 39 patients who achieved a partial or complete response, 38% had a response duration of at least 6 months, and 15% had a response duration of at least 12 months, according to the FDA announcement.

The most common adverse reactions in this trial were fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3-4 laboratory abnormalities occurred in 15% or more of the patients, and comprised thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia.

Serious adverse reactions occurred in 46% of patients, most often from infection. Gastrointestinal toxicity occurred in 80% of patients, and any-grade hyponatremia occurred in 61%. Central neurological adverse reactions occurred in 25% of patients, including dizziness and mental status changes, according to the announcement.

Warnings and precautions for adverse events – including thrombocytopenia, neutropenia, gastrointestinal toxicity, hyponatremia, serious infection, neurological toxicity, and embryo-fetal toxicity – are provided in the prescribing information.

Selinexor acts through the inhibition of exportin-1 and leads to an accumulation of tumor suppressor proteins, a reduction in oncoproteins, and apoptosis of cancer cells. The drug was previously approved in 2019 for the treatment of relapsed/refractory multiple myeloma.

The SADAL trial was sponsored by Karyopharm Therapeutics.

[email protected]

SOURCE: U.S. Food and Drug Administration. 2020. Approval announcement.

The Food and Drug Administration has granted accelerated approval of selinexor, a nuclear transport inhibitor, for the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL).

Selinexor (marketed as XPOVIO by Karyopharm Therapeutics) is intended for adult patients with relapsed/refractory DLBCL, not otherwise specified, including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy, according to the FDA’s announcement.

The FDA granted selinexor accelerated approval for this indication based on the response rate seen in the SADAL trial. Continued approval for this indication “may be contingent upon verification and description of clinical benefit in confirmatory trials,” according to the FDA.

The SADAL trial (NCT02227251) was a phase 2, single-arm, open-label study of patients with DLBCL who had previously received two to five systemic regimens. The patients received selinexor at 60 mg orally on days 1 and 3 of each week.

Results in 134 patients showed an overall response rate of 29% (95% confidence interval: 22-38), with complete responses in 13% of patients. Of 39 patients who achieved a partial or complete response, 38% had a response duration of at least 6 months, and 15% had a response duration of at least 12 months, according to the FDA announcement.

The most common adverse reactions in this trial were fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3-4 laboratory abnormalities occurred in 15% or more of the patients, and comprised thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia.

Serious adverse reactions occurred in 46% of patients, most often from infection. Gastrointestinal toxicity occurred in 80% of patients, and any-grade hyponatremia occurred in 61%. Central neurological adverse reactions occurred in 25% of patients, including dizziness and mental status changes, according to the announcement.

Warnings and precautions for adverse events – including thrombocytopenia, neutropenia, gastrointestinal toxicity, hyponatremia, serious infection, neurological toxicity, and embryo-fetal toxicity – are provided in the prescribing information.

Selinexor acts through the inhibition of exportin-1 and leads to an accumulation of tumor suppressor proteins, a reduction in oncoproteins, and apoptosis of cancer cells. The drug was previously approved in 2019 for the treatment of relapsed/refractory multiple myeloma.

The SADAL trial was sponsored by Karyopharm Therapeutics.

[email protected]

SOURCE: U.S. Food and Drug Administration. 2020. Approval announcement.

The Food and Drug Administration has granted accelerated approval of selinexor, a nuclear transport inhibitor, for the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL).

Selinexor (marketed as XPOVIO by Karyopharm Therapeutics) is intended for adult patients with relapsed/refractory DLBCL, not otherwise specified, including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy, according to the FDA’s announcement.

The FDA granted selinexor accelerated approval for this indication based on the response rate seen in the SADAL trial. Continued approval for this indication “may be contingent upon verification and description of clinical benefit in confirmatory trials,” according to the FDA.

The SADAL trial (NCT02227251) was a phase 2, single-arm, open-label study of patients with DLBCL who had previously received two to five systemic regimens. The patients received selinexor at 60 mg orally on days 1 and 3 of each week.

Results in 134 patients showed an overall response rate of 29% (95% confidence interval: 22-38), with complete responses in 13% of patients. Of 39 patients who achieved a partial or complete response, 38% had a response duration of at least 6 months, and 15% had a response duration of at least 12 months, according to the FDA announcement.

The most common adverse reactions in this trial were fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3-4 laboratory abnormalities occurred in 15% or more of the patients, and comprised thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia.

Serious adverse reactions occurred in 46% of patients, most often from infection. Gastrointestinal toxicity occurred in 80% of patients, and any-grade hyponatremia occurred in 61%. Central neurological adverse reactions occurred in 25% of patients, including dizziness and mental status changes, according to the announcement.

Warnings and precautions for adverse events – including thrombocytopenia, neutropenia, gastrointestinal toxicity, hyponatremia, serious infection, neurological toxicity, and embryo-fetal toxicity – are provided in the prescribing information.

Selinexor acts through the inhibition of exportin-1 and leads to an accumulation of tumor suppressor proteins, a reduction in oncoproteins, and apoptosis of cancer cells. The drug was previously approved in 2019 for the treatment of relapsed/refractory multiple myeloma.

The SADAL trial was sponsored by Karyopharm Therapeutics.

[email protected]

SOURCE: U.S. Food and Drug Administration. 2020. Approval announcement.

ED visits for myocardial infarction, stroke, and hyperglycemic crisis dropped substantially in the 10 weeks after COVID-19 was declared a national emergency on March 13, according to the Centers for Disease Control and Prevention.

Compared with the 10-week period from Jan. 5 to March 14, ED visits were down by 23% for MI, 20% for stroke, and 10% for hyperglycemic crisis from March 15 to May 23, Samantha J. Lange, MPH, and associates at the CDC reported June 22 in the Morbidity and Mortality Weekly Report.

“A short-term decline of this magnitude … is biologically implausible for MI and stroke, especially for older adults, and unlikely for hyperglycemic crisis, and the finding suggests that patients with these conditions either could not access care or were delaying or avoiding seeking care during the early pandemic period,” they wrote.

The largest decreases in the actual number of visits for MI occurred among both men (down by 2,114, –24%) and women (down by 1,459, –25%) aged 65-74 years. For stroke, men aged 65-74 years had 1,406 (–19%) fewer visits to the ED and women 75-84 years had 1,642 (–23%) fewer visits, the CDC researchers said.

For hypoglycemic crisis, the largest declines during the early pandemic period occurred among younger adults: ED visits for men and women aged 18-44 years were down, respectively, by 419 (–8%) and 775 (–16%), they reported based on data from the National Syndromic Surveillance Program.

“Decreases in ED visits for hyperglycemic crisis might be less striking because patient recognition of this crisis is typically augmented by home glucose monitoring and not reliant upon symptoms alone, as is the case for MI and stroke,” Ms. Lange and her associates noted.

Charting weekly visit numbers showed that the drop for all three conditions actually started the week before the emergency was declared and reached its nadir the week after (March 22) for MI and 2 weeks later (March 29) for stroke and hypoglycemic crisis.

Visits for hypoglycemic crisis have largely returned to normal since those low points, but MI and stroke visits “remain below prepandemic levels” despite gradual increases through April and May, they said.

It has been reported that “deaths not associated with confirmed or probable COVID-19 might have been directly or indirectly attributed to the pandemic. The striking decline in ED visits for acute life-threatening conditions might partially explain observed excess mortality not associated with COVID-19,” the investigators wrote.

[email protected]

ED visits for myocardial infarction, stroke, and hyperglycemic crisis dropped substantially in the 10 weeks after COVID-19 was declared a national emergency on March 13, according to the Centers for Disease Control and Prevention.

Compared with the 10-week period from Jan. 5 to March 14, ED visits were down by 23% for MI, 20% for stroke, and 10% for hyperglycemic crisis from March 15 to May 23, Samantha J. Lange, MPH, and associates at the CDC reported June 22 in the Morbidity and Mortality Weekly Report.

“A short-term decline of this magnitude … is biologically implausible for MI and stroke, especially for older adults, and unlikely for hyperglycemic crisis, and the finding suggests that patients with these conditions either could not access care or were delaying or avoiding seeking care during the early pandemic period,” they wrote.

The largest decreases in the actual number of visits for MI occurred among both men (down by 2,114, –24%) and women (down by 1,459, –25%) aged 65-74 years. For stroke, men aged 65-74 years had 1,406 (–19%) fewer visits to the ED and women 75-84 years had 1,642 (–23%) fewer visits, the CDC researchers said.

For hypoglycemic crisis, the largest declines during the early pandemic period occurred among younger adults: ED visits for men and women aged 18-44 years were down, respectively, by 419 (–8%) and 775 (–16%), they reported based on data from the National Syndromic Surveillance Program.

“Decreases in ED visits for hyperglycemic crisis might be less striking because patient recognition of this crisis is typically augmented by home glucose monitoring and not reliant upon symptoms alone, as is the case for MI and stroke,” Ms. Lange and her associates noted.

Charting weekly visit numbers showed that the drop for all three conditions actually started the week before the emergency was declared and reached its nadir the week after (March 22) for MI and 2 weeks later (March 29) for stroke and hypoglycemic crisis.

Visits for hypoglycemic crisis have largely returned to normal since those low points, but MI and stroke visits “remain below prepandemic levels” despite gradual increases through April and May, they said.

It has been reported that “deaths not associated with confirmed or probable COVID-19 might have been directly or indirectly attributed to the pandemic. The striking decline in ED visits for acute life-threatening conditions might partially explain observed excess mortality not associated with COVID-19,” the investigators wrote.

[email protected]

ED visits for myocardial infarction, stroke, and hyperglycemic crisis dropped substantially in the 10 weeks after COVID-19 was declared a national emergency on March 13, according to the Centers for Disease Control and Prevention.

Compared with the 10-week period from Jan. 5 to March 14, ED visits were down by 23% for MI, 20% for stroke, and 10% for hyperglycemic crisis from March 15 to May 23, Samantha J. Lange, MPH, and associates at the CDC reported June 22 in the Morbidity and Mortality Weekly Report.

“A short-term decline of this magnitude … is biologically implausible for MI and stroke, especially for older adults, and unlikely for hyperglycemic crisis, and the finding suggests that patients with these conditions either could not access care or were delaying or avoiding seeking care during the early pandemic period,” they wrote.

The largest decreases in the actual number of visits for MI occurred among both men (down by 2,114, –24%) and women (down by 1,459, –25%) aged 65-74 years. For stroke, men aged 65-74 years had 1,406 (–19%) fewer visits to the ED and women 75-84 years had 1,642 (–23%) fewer visits, the CDC researchers said.

For hypoglycemic crisis, the largest declines during the early pandemic period occurred among younger adults: ED visits for men and women aged 18-44 years were down, respectively, by 419 (–8%) and 775 (–16%), they reported based on data from the National Syndromic Surveillance Program.

“Decreases in ED visits for hyperglycemic crisis might be less striking because patient recognition of this crisis is typically augmented by home glucose monitoring and not reliant upon symptoms alone, as is the case for MI and stroke,” Ms. Lange and her associates noted.

Charting weekly visit numbers showed that the drop for all three conditions actually started the week before the emergency was declared and reached its nadir the week after (March 22) for MI and 2 weeks later (March 29) for stroke and hypoglycemic crisis.

Visits for hypoglycemic crisis have largely returned to normal since those low points, but MI and stroke visits “remain below prepandemic levels” despite gradual increases through April and May, they said.

It has been reported that “deaths not associated with confirmed or probable COVID-19 might have been directly or indirectly attributed to the pandemic. The striking decline in ED visits for acute life-threatening conditions might partially explain observed excess mortality not associated with COVID-19,” the investigators wrote.

[email protected]