Liver transplant might be the next big thing for extensive hepatic metastases in colorectal cancer, according to an editorial published in JAMA Surgery .

“Many centers around the world, including our own, [have] started offering liver transplant to patients with colorectal liver metastases,” write Ralph Quillin III, MD, and Shimul Shah, MD, liver transplant surgeons at the University of Cincinnati.

However, they admit that the concept is controversial. “One need only to go to a tumor board to hear critics of the concept of liver transplant for isolated colorectal liver metastases,” the pair write, adding that opponents might argue that transplant patients could have done as well with chemotherapy.

There’s also the problem of deceased donor organ scarcity, Dr. Quillin and Dr. Shah acknowledge.

Nevertheless, the editorial is effusive about a new comparative effectiveness study that it accompanies in JAMA Surgery from a team at the Oslo University Hospital, led by Svein Dueland, MD, PhD.

The new study shows that for select patients with liver metastases, the 5-year survival rate with transplant is higher than for patients who receive standard of care – portal vein embolization (PVE) and surgical resection.

“[Dr.] Dueland et al. have laid the groundwork for the world to follow and took a concept from being experimental to possibly standard of care: liver transplant for colorectal liver metastases with heavy tumor burden,” the editorialists declare.

Using data from their hospital, the Oslo team compared 50 patients who had colorectal cancer liver metastases from previous liver transplant studies (2006-2019) with a retrospective cohort of 53 patients (2006-2015) from studies with similar selection criteria who underwent PVE with the intent to perform liver resection.

Patients with a high liver-only metastatic load had nine or more tumors, or the largest of their tumors had a diameter of at least 5.5 cm. Among 29 such patients treated with liver transplant, the 5-year overall survival (OS) rate was 33.4%, and the median OS was 40.5 months. Among eight such patients treated with PVE and liver resection, the 5-year OS rate was 12.5%, and the median OS was 29.8 months.

The OS among patients with a high metastatic load who received a transplant may be unprecedented, according to the investigators.

The Oslo team “should be commended for a very aggressive surgical approach” for patients whom “many would deem unresectable and palliative from the start,” comment Dr. Quillin and Dr. Shah.
 

Refining patient selection

In the past, finding the ideal candidate with extensive colorectal liver metastases for liver transplant was like “discovering the proverbial needle in the haystack,” Dr. Quillin and Dr. Shah say. Critics have said the impressive outcomes reported in past studies reflect extreme patient selection.

The new study results make selection easier and may expand the transplant patient population.

The patients in the study had no extrahepatic metastases, and their primary colorectal tumors had been resected. Such patients may represent an expanded transplant population. They were younger than 72 years, and their performance status score was 0-1. They had undergone standard-of-care chemotherapy before their liver procedures.

The high-burden transplant patients were all judged to have nonresectable tumors by the university’s tumor board; 14 of 29 had 16 or more liver lesions.

The maximum number of tumors in the PVE group was 15, so these patients were expected to live longer, owing to the fact that survival is longer for colorectal cancer patients who have fewer liver metastases. However, as noted above, that’s not how it worked out.
 

Different story for low liver burdens

The Oslo investigators caution that, despite the findings, liver transplant for colorectal liver metastases “should still be considered a work in progress.”

The Oslo team says that to avoid “the futile use of liver grafts,” prospective research is needed to clearly identify colorectal liver metastases patients “who would benefit the most” from transplant.

Patients with extensive nonresectable metastases seem to be high on the list, but there might also be a role in resectable disease, say the study authors. One scenario, for instance, would be one in which PVE fails to expand the liver enough to allow resection; this was the case in 15 of the 53 PVE patients in the study.

As for patients with low liver tumor burden, transplant didn’t seem to offer much long-term survival benefit; 5-year OS was 72.4% among 21 low-burden transplant patients, vs. 69.3% among 23 who underwent PVE and resection.

Right-sided disease – having a primary tumor in the ascending colon, a known predictor of worse outcomes – might also prove to be a contraindication. The median OS after liver transplant was 12.2 months among patients with right-sided primaries and high-burden liver metastases. No such patients were alive at 5 years. On the other hand, the median OS was 59.9 months, and the 5-year OS was 45.3% among high-burden patients with left-sided primaries.
 

A call for a consortium

In a second editorial, Yuman Fong, MD, of the City of Hope Medical Center, Duarte, Calif., is less enthusiastic than the pair from Cincinnati. He calls the data “intriguing” but emphasizes that “we must recognize that cadaveric livers for transplant remain a finite resource,” and about 1,000 people die annually while on the waiting list in the United States.

The Cincinnati editorialists call for a multicenter consortium “for the cancer community to increase our understanding of this indication” and “pave the way for liver transplant as an option for colorectal liver metastases, just like we have for hepatocellular carcinoma, unresectable hilar cholangiocarcinoma, and metastatic neuroendocrine tumor.”

The investigators note that survival with transplant might be better because liver resection leaves behind microscopic disease that leads to liver recurrence. Most of the transplant patients in the study also experienced relapse, but recurrence after transplant tends to occur in the lungs with small, slow-growing lesions that are amenable to resection.

The study was funded by Oslo University Hospital, the Norwegian Cancer Society, and the South-Eastern Norway Regional Health Authority. The investigators and the editorialists in Cincinnati have disclosed no relevant financial relationships. Dr. Fong is a consultant for Medtronic and Johnson & Johnson and has received royalties from Merck and Imugene.

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

Liver transplant might be the next big thing for extensive hepatic metastases in colorectal cancer, according to an editorial published in JAMA Surgery .

“Many centers around the world, including our own, [have] started offering liver transplant to patients with colorectal liver metastases,” write Ralph Quillin III, MD, and Shimul Shah, MD, liver transplant surgeons at the University of Cincinnati.

However, they admit that the concept is controversial. “One need only to go to a tumor board to hear critics of the concept of liver transplant for isolated colorectal liver metastases,” the pair write, adding that opponents might argue that transplant patients could have done as well with chemotherapy.

There’s also the problem of deceased donor organ scarcity, Dr. Quillin and Dr. Shah acknowledge.

Nevertheless, the editorial is effusive about a new comparative effectiveness study that it accompanies in JAMA Surgery from a team at the Oslo University Hospital, led by Svein Dueland, MD, PhD.

The new study shows that for select patients with liver metastases, the 5-year survival rate with transplant is higher than for patients who receive standard of care – portal vein embolization (PVE) and surgical resection.

“[Dr.] Dueland et al. have laid the groundwork for the world to follow and took a concept from being experimental to possibly standard of care: liver transplant for colorectal liver metastases with heavy tumor burden,” the editorialists declare.

Using data from their hospital, the Oslo team compared 50 patients who had colorectal cancer liver metastases from previous liver transplant studies (2006-2019) with a retrospective cohort of 53 patients (2006-2015) from studies with similar selection criteria who underwent PVE with the intent to perform liver resection.

Patients with a high liver-only metastatic load had nine or more tumors, or the largest of their tumors had a diameter of at least 5.5 cm. Among 29 such patients treated with liver transplant, the 5-year overall survival (OS) rate was 33.4%, and the median OS was 40.5 months. Among eight such patients treated with PVE and liver resection, the 5-year OS rate was 12.5%, and the median OS was 29.8 months.

The OS among patients with a high metastatic load who received a transplant may be unprecedented, according to the investigators.

The Oslo team “should be commended for a very aggressive surgical approach” for patients whom “many would deem unresectable and palliative from the start,” comment Dr. Quillin and Dr. Shah.
 

Refining patient selection

In the past, finding the ideal candidate with extensive colorectal liver metastases for liver transplant was like “discovering the proverbial needle in the haystack,” Dr. Quillin and Dr. Shah say. Critics have said the impressive outcomes reported in past studies reflect extreme patient selection.

The new study results make selection easier and may expand the transplant patient population.

The patients in the study had no extrahepatic metastases, and their primary colorectal tumors had been resected. Such patients may represent an expanded transplant population. They were younger than 72 years, and their performance status score was 0-1. They had undergone standard-of-care chemotherapy before their liver procedures.

The high-burden transplant patients were all judged to have nonresectable tumors by the university’s tumor board; 14 of 29 had 16 or more liver lesions.

The maximum number of tumors in the PVE group was 15, so these patients were expected to live longer, owing to the fact that survival is longer for colorectal cancer patients who have fewer liver metastases. However, as noted above, that’s not how it worked out.
 

Different story for low liver burdens

The Oslo investigators caution that, despite the findings, liver transplant for colorectal liver metastases “should still be considered a work in progress.”

The Oslo team says that to avoid “the futile use of liver grafts,” prospective research is needed to clearly identify colorectal liver metastases patients “who would benefit the most” from transplant.

Patients with extensive nonresectable metastases seem to be high on the list, but there might also be a role in resectable disease, say the study authors. One scenario, for instance, would be one in which PVE fails to expand the liver enough to allow resection; this was the case in 15 of the 53 PVE patients in the study.

As for patients with low liver tumor burden, transplant didn’t seem to offer much long-term survival benefit; 5-year OS was 72.4% among 21 low-burden transplant patients, vs. 69.3% among 23 who underwent PVE and resection.

Right-sided disease – having a primary tumor in the ascending colon, a known predictor of worse outcomes – might also prove to be a contraindication. The median OS after liver transplant was 12.2 months among patients with right-sided primaries and high-burden liver metastases. No such patients were alive at 5 years. On the other hand, the median OS was 59.9 months, and the 5-year OS was 45.3% among high-burden patients with left-sided primaries.
 

A call for a consortium

In a second editorial, Yuman Fong, MD, of the City of Hope Medical Center, Duarte, Calif., is less enthusiastic than the pair from Cincinnati. He calls the data “intriguing” but emphasizes that “we must recognize that cadaveric livers for transplant remain a finite resource,” and about 1,000 people die annually while on the waiting list in the United States.

The Cincinnati editorialists call for a multicenter consortium “for the cancer community to increase our understanding of this indication” and “pave the way for liver transplant as an option for colorectal liver metastases, just like we have for hepatocellular carcinoma, unresectable hilar cholangiocarcinoma, and metastatic neuroendocrine tumor.”

The investigators note that survival with transplant might be better because liver resection leaves behind microscopic disease that leads to liver recurrence. Most of the transplant patients in the study also experienced relapse, but recurrence after transplant tends to occur in the lungs with small, slow-growing lesions that are amenable to resection.

The study was funded by Oslo University Hospital, the Norwegian Cancer Society, and the South-Eastern Norway Regional Health Authority. The investigators and the editorialists in Cincinnati have disclosed no relevant financial relationships. Dr. Fong is a consultant for Medtronic and Johnson & Johnson and has received royalties from Merck and Imugene.

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

Liver transplant might be the next big thing for extensive hepatic metastases in colorectal cancer, according to an editorial published in JAMA Surgery .

“Many centers around the world, including our own, [have] started offering liver transplant to patients with colorectal liver metastases,” write Ralph Quillin III, MD, and Shimul Shah, MD, liver transplant surgeons at the University of Cincinnati.

However, they admit that the concept is controversial. “One need only to go to a tumor board to hear critics of the concept of liver transplant for isolated colorectal liver metastases,” the pair write, adding that opponents might argue that transplant patients could have done as well with chemotherapy.

There’s also the problem of deceased donor organ scarcity, Dr. Quillin and Dr. Shah acknowledge.

Nevertheless, the editorial is effusive about a new comparative effectiveness study that it accompanies in JAMA Surgery from a team at the Oslo University Hospital, led by Svein Dueland, MD, PhD.

The new study shows that for select patients with liver metastases, the 5-year survival rate with transplant is higher than for patients who receive standard of care – portal vein embolization (PVE) and surgical resection.

“[Dr.] Dueland et al. have laid the groundwork for the world to follow and took a concept from being experimental to possibly standard of care: liver transplant for colorectal liver metastases with heavy tumor burden,” the editorialists declare.

Using data from their hospital, the Oslo team compared 50 patients who had colorectal cancer liver metastases from previous liver transplant studies (2006-2019) with a retrospective cohort of 53 patients (2006-2015) from studies with similar selection criteria who underwent PVE with the intent to perform liver resection.

Patients with a high liver-only metastatic load had nine or more tumors, or the largest of their tumors had a diameter of at least 5.5 cm. Among 29 such patients treated with liver transplant, the 5-year overall survival (OS) rate was 33.4%, and the median OS was 40.5 months. Among eight such patients treated with PVE and liver resection, the 5-year OS rate was 12.5%, and the median OS was 29.8 months.

The OS among patients with a high metastatic load who received a transplant may be unprecedented, according to the investigators.

The Oslo team “should be commended for a very aggressive surgical approach” for patients whom “many would deem unresectable and palliative from the start,” comment Dr. Quillin and Dr. Shah.
 

Refining patient selection

In the past, finding the ideal candidate with extensive colorectal liver metastases for liver transplant was like “discovering the proverbial needle in the haystack,” Dr. Quillin and Dr. Shah say. Critics have said the impressive outcomes reported in past studies reflect extreme patient selection.

The new study results make selection easier and may expand the transplant patient population.

The patients in the study had no extrahepatic metastases, and their primary colorectal tumors had been resected. Such patients may represent an expanded transplant population. They were younger than 72 years, and their performance status score was 0-1. They had undergone standard-of-care chemotherapy before their liver procedures.

The high-burden transplant patients were all judged to have nonresectable tumors by the university’s tumor board; 14 of 29 had 16 or more liver lesions.

The maximum number of tumors in the PVE group was 15, so these patients were expected to live longer, owing to the fact that survival is longer for colorectal cancer patients who have fewer liver metastases. However, as noted above, that’s not how it worked out.
 

Different story for low liver burdens

The Oslo investigators caution that, despite the findings, liver transplant for colorectal liver metastases “should still be considered a work in progress.”

The Oslo team says that to avoid “the futile use of liver grafts,” prospective research is needed to clearly identify colorectal liver metastases patients “who would benefit the most” from transplant.

Patients with extensive nonresectable metastases seem to be high on the list, but there might also be a role in resectable disease, say the study authors. One scenario, for instance, would be one in which PVE fails to expand the liver enough to allow resection; this was the case in 15 of the 53 PVE patients in the study.

As for patients with low liver tumor burden, transplant didn’t seem to offer much long-term survival benefit; 5-year OS was 72.4% among 21 low-burden transplant patients, vs. 69.3% among 23 who underwent PVE and resection.

Right-sided disease – having a primary tumor in the ascending colon, a known predictor of worse outcomes – might also prove to be a contraindication. The median OS after liver transplant was 12.2 months among patients with right-sided primaries and high-burden liver metastases. No such patients were alive at 5 years. On the other hand, the median OS was 59.9 months, and the 5-year OS was 45.3% among high-burden patients with left-sided primaries.
 

A call for a consortium

In a second editorial, Yuman Fong, MD, of the City of Hope Medical Center, Duarte, Calif., is less enthusiastic than the pair from Cincinnati. He calls the data “intriguing” but emphasizes that “we must recognize that cadaveric livers for transplant remain a finite resource,” and about 1,000 people die annually while on the waiting list in the United States.

The Cincinnati editorialists call for a multicenter consortium “for the cancer community to increase our understanding of this indication” and “pave the way for liver transplant as an option for colorectal liver metastases, just like we have for hepatocellular carcinoma, unresectable hilar cholangiocarcinoma, and metastatic neuroendocrine tumor.”

The investigators note that survival with transplant might be better because liver resection leaves behind microscopic disease that leads to liver recurrence. Most of the transplant patients in the study also experienced relapse, but recurrence after transplant tends to occur in the lungs with small, slow-growing lesions that are amenable to resection.

The study was funded by Oslo University Hospital, the Norwegian Cancer Society, and the South-Eastern Norway Regional Health Authority. The investigators and the editorialists in Cincinnati have disclosed no relevant financial relationships. Dr. Fong is a consultant for Medtronic and Johnson & Johnson and has received royalties from Merck and Imugene.

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

Key clinical point: Patients with human epidermal growth factor receptor 2-positive (HER2+) early breast cancer (BC) who achieved a pathologic complete response (pCR) with neoadjuvant pertuzumab, trastuzumab, and chemotherapy (nPTC) and then received adjuvant trastuzumab remained at risk for recurrence, indicating the need for alternative therapies.

Major finding: At 4 years, the invasive disease-free survival rates for the overall, node-positive, and node-negative cohorts were 90.0% (95% confidence interval [CI], 84.6%-93.6%), 86.2% (95% CI, 78.1%-91.4%), and 96.0% (95% CI, 88.0%-98.7%), respectively.

Study details: Findings are from a real-world, retrospective analysis of 217 patients with HER2+ locally advanced, high-risk early-stage BC, including 135 patients with node-positive and 77 with node-negative disease. Patients received nPTC, had pCR, and then received adjuvant trastuzumab.

Disclosures: This study was funded by Genentech, Inc. Some investigators including the lead author reported ties with various pharmaceutical companies, including Genentech. J Sussell, A Cheng, and A Fung declared being employees of Genentech, Inc.

Source: O’Shaughnessy J et al. Breast Cancer Res Treat. 2021 Mar 1. doi: 10.1007/s10549-021-06137-3.

Key clinical point: Patients with human epidermal growth factor receptor 2-positive (HER2+) early breast cancer (BC) who achieved a pathologic complete response (pCR) with neoadjuvant pertuzumab, trastuzumab, and chemotherapy (nPTC) and then received adjuvant trastuzumab remained at risk for recurrence, indicating the need for alternative therapies.

Major finding: At 4 years, the invasive disease-free survival rates for the overall, node-positive, and node-negative cohorts were 90.0% (95% confidence interval [CI], 84.6%-93.6%), 86.2% (95% CI, 78.1%-91.4%), and 96.0% (95% CI, 88.0%-98.7%), respectively.

Study details: Findings are from a real-world, retrospective analysis of 217 patients with HER2+ locally advanced, high-risk early-stage BC, including 135 patients with node-positive and 77 with node-negative disease. Patients received nPTC, had pCR, and then received adjuvant trastuzumab.

Disclosures: This study was funded by Genentech, Inc. Some investigators including the lead author reported ties with various pharmaceutical companies, including Genentech. J Sussell, A Cheng, and A Fung declared being employees of Genentech, Inc.

Source: O’Shaughnessy J et al. Breast Cancer Res Treat. 2021 Mar 1. doi: 10.1007/s10549-021-06137-3.

Key clinical point: Patients with human epidermal growth factor receptor 2-positive (HER2+) early breast cancer (BC) who achieved a pathologic complete response (pCR) with neoadjuvant pertuzumab, trastuzumab, and chemotherapy (nPTC) and then received adjuvant trastuzumab remained at risk for recurrence, indicating the need for alternative therapies.

Major finding: At 4 years, the invasive disease-free survival rates for the overall, node-positive, and node-negative cohorts were 90.0% (95% confidence interval [CI], 84.6%-93.6%), 86.2% (95% CI, 78.1%-91.4%), and 96.0% (95% CI, 88.0%-98.7%), respectively.

Study details: Findings are from a real-world, retrospective analysis of 217 patients with HER2+ locally advanced, high-risk early-stage BC, including 135 patients with node-positive and 77 with node-negative disease. Patients received nPTC, had pCR, and then received adjuvant trastuzumab.

Disclosures: This study was funded by Genentech, Inc. Some investigators including the lead author reported ties with various pharmaceutical companies, including Genentech. J Sussell, A Cheng, and A Fung declared being employees of Genentech, Inc.

Source: O’Shaughnessy J et al. Breast Cancer Res Treat. 2021 Mar 1. doi: 10.1007/s10549-021-06137-3.

The United States saw nearly 23% more deaths than expected during the first 9 months of the pandemic, and almost three-quarters of those deaths involved COVID-19.

For comparison, the death rate increased by 2.5% or less annually in recent years.

At the same time, rates of deaths from heart disease, Alzheimer’s disease or dementia, and diabetes also increased from March 1, 2020, to Jan. 2, 2021, especially during COVID-19 surges.

“Excess deaths surged in the east in April, followed by extended summer and early winter surges concentrated in Southern and Western states, respectively. Many of these states weakly embraced, or discouraged, pandemic control measures and lifted restrictions earlier than other states,” lead author Steven H. Woolf, MD, MPH, from the Virginia Commonwealth University, Richmond, and colleagues wrote in a research letter published online April 2, 2021, in JAMA.

COVID-19 mortality included all deaths for which it was cited as an underlying or contributing cause in records from the District of Columbia and 49 states. North Carolina was excluded for insufficient data.
 

More than half a million excess deaths

Between March 1, 2020, and Jan. 2, 2021, the United States experienced 2,801,439 deaths, or 522,368 excess deaths. A total 72.4% of these events were attributed to COVID-19.

Not all racial and ethnic groups were equally represented. For example, the rate of excess deaths was higher among non-Hispanic Black populations, at 208.4 deaths per 100,000. Non-Hispanic White populations experienced 157 deaths per 100,000, and Hispanic populations experienced 139.8 deaths per 100,000.

Further, non-Hispanic Black individuals accounted for 16.9% of the excess deaths but only 12.5% of the U.S. population, which reflects “racial disparities in COVID-19 mortality,” the authors noted.

Not adjusting for population aging is a potential limitation, as was reliance on provisional data and the likelihood that some death certificates were inaccurate.

In February, Anthony S. Fauci, MD, chief medical adviser to President Joe Biden, stated that political divisions likely played a role in the 500,000-plus COVID-19–related deaths in the United States. 

Then a report came out on March 26 indicating that a different U.S. response to the pandemic could have avoided almost 400,000 COVID-19 deaths. In addition, an April 1 study in the CDC’s Morbidity and Mortality Weekly Report revealed that COVID-19 is now the third leading cause of death in the United States, after heart disease and cancer.
 

‘Massive’ excessive mortality

“There is no more visible or alarming manifestation of the toll of the COVID-19 pandemic than the deaths it has caused. In this issue of JAMA, Dr. Woolf and colleagues provide updated analyses that demonstrate that the excess mortality in the U.S. between March 1, 2020, and Jan. 2, 2021, has been massive,” Alan Garber, MD, PhD, wrote in an accompanying editorial.

“It seems likely that COVID-19 will have contributed to nearly as many deaths in the U.S. as the great influenza pandemic of 1918, and more than in any influenza outbreak in the U.S. since then,” added Dr. Garber, provost of Harvard University in Cambridge, Mass.

This study of excess mortality illustrates what is at stake, he added. “Despite the scientific, medical and public health progress of recent decades, the loss of life attributable to the COVID-19 pandemic exceeds the mortality of major wars. No nation should squander this opportunity to do what it takes to prepare for the next one.”

Dr. Woolf and Dr. Garber disclosed no relevant financial relationships. The National Institutes of Health supported the research through its National Center for Advancing Translational Sciences and the National Institute on Aging.

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

The United States saw nearly 23% more deaths than expected during the first 9 months of the pandemic, and almost three-quarters of those deaths involved COVID-19.

For comparison, the death rate increased by 2.5% or less annually in recent years.

At the same time, rates of deaths from heart disease, Alzheimer’s disease or dementia, and diabetes also increased from March 1, 2020, to Jan. 2, 2021, especially during COVID-19 surges.

“Excess deaths surged in the east in April, followed by extended summer and early winter surges concentrated in Southern and Western states, respectively. Many of these states weakly embraced, or discouraged, pandemic control measures and lifted restrictions earlier than other states,” lead author Steven H. Woolf, MD, MPH, from the Virginia Commonwealth University, Richmond, and colleagues wrote in a research letter published online April 2, 2021, in JAMA.

COVID-19 mortality included all deaths for which it was cited as an underlying or contributing cause in records from the District of Columbia and 49 states. North Carolina was excluded for insufficient data.
 

More than half a million excess deaths

Between March 1, 2020, and Jan. 2, 2021, the United States experienced 2,801,439 deaths, or 522,368 excess deaths. A total 72.4% of these events were attributed to COVID-19.

Not all racial and ethnic groups were equally represented. For example, the rate of excess deaths was higher among non-Hispanic Black populations, at 208.4 deaths per 100,000. Non-Hispanic White populations experienced 157 deaths per 100,000, and Hispanic populations experienced 139.8 deaths per 100,000.

Further, non-Hispanic Black individuals accounted for 16.9% of the excess deaths but only 12.5% of the U.S. population, which reflects “racial disparities in COVID-19 mortality,” the authors noted.

Not adjusting for population aging is a potential limitation, as was reliance on provisional data and the likelihood that some death certificates were inaccurate.

In February, Anthony S. Fauci, MD, chief medical adviser to President Joe Biden, stated that political divisions likely played a role in the 500,000-plus COVID-19–related deaths in the United States. 

Then a report came out on March 26 indicating that a different U.S. response to the pandemic could have avoided almost 400,000 COVID-19 deaths. In addition, an April 1 study in the CDC’s Morbidity and Mortality Weekly Report revealed that COVID-19 is now the third leading cause of death in the United States, after heart disease and cancer.
 

‘Massive’ excessive mortality

“There is no more visible or alarming manifestation of the toll of the COVID-19 pandemic than the deaths it has caused. In this issue of JAMA, Dr. Woolf and colleagues provide updated analyses that demonstrate that the excess mortality in the U.S. between March 1, 2020, and Jan. 2, 2021, has been massive,” Alan Garber, MD, PhD, wrote in an accompanying editorial.

“It seems likely that COVID-19 will have contributed to nearly as many deaths in the U.S. as the great influenza pandemic of 1918, and more than in any influenza outbreak in the U.S. since then,” added Dr. Garber, provost of Harvard University in Cambridge, Mass.

This study of excess mortality illustrates what is at stake, he added. “Despite the scientific, medical and public health progress of recent decades, the loss of life attributable to the COVID-19 pandemic exceeds the mortality of major wars. No nation should squander this opportunity to do what it takes to prepare for the next one.”

Dr. Woolf and Dr. Garber disclosed no relevant financial relationships. The National Institutes of Health supported the research through its National Center for Advancing Translational Sciences and the National Institute on Aging.

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

The United States saw nearly 23% more deaths than expected during the first 9 months of the pandemic, and almost three-quarters of those deaths involved COVID-19.

For comparison, the death rate increased by 2.5% or less annually in recent years.

At the same time, rates of deaths from heart disease, Alzheimer’s disease or dementia, and diabetes also increased from March 1, 2020, to Jan. 2, 2021, especially during COVID-19 surges.

“Excess deaths surged in the east in April, followed by extended summer and early winter surges concentrated in Southern and Western states, respectively. Many of these states weakly embraced, or discouraged, pandemic control measures and lifted restrictions earlier than other states,” lead author Steven H. Woolf, MD, MPH, from the Virginia Commonwealth University, Richmond, and colleagues wrote in a research letter published online April 2, 2021, in JAMA.

COVID-19 mortality included all deaths for which it was cited as an underlying or contributing cause in records from the District of Columbia and 49 states. North Carolina was excluded for insufficient data.
 

More than half a million excess deaths

Between March 1, 2020, and Jan. 2, 2021, the United States experienced 2,801,439 deaths, or 522,368 excess deaths. A total 72.4% of these events were attributed to COVID-19.

Not all racial and ethnic groups were equally represented. For example, the rate of excess deaths was higher among non-Hispanic Black populations, at 208.4 deaths per 100,000. Non-Hispanic White populations experienced 157 deaths per 100,000, and Hispanic populations experienced 139.8 deaths per 100,000.

Further, non-Hispanic Black individuals accounted for 16.9% of the excess deaths but only 12.5% of the U.S. population, which reflects “racial disparities in COVID-19 mortality,” the authors noted.

Not adjusting for population aging is a potential limitation, as was reliance on provisional data and the likelihood that some death certificates were inaccurate.

In February, Anthony S. Fauci, MD, chief medical adviser to President Joe Biden, stated that political divisions likely played a role in the 500,000-plus COVID-19–related deaths in the United States. 

Then a report came out on March 26 indicating that a different U.S. response to the pandemic could have avoided almost 400,000 COVID-19 deaths. In addition, an April 1 study in the CDC’s Morbidity and Mortality Weekly Report revealed that COVID-19 is now the third leading cause of death in the United States, after heart disease and cancer.
 

‘Massive’ excessive mortality

“There is no more visible or alarming manifestation of the toll of the COVID-19 pandemic than the deaths it has caused. In this issue of JAMA, Dr. Woolf and colleagues provide updated analyses that demonstrate that the excess mortality in the U.S. between March 1, 2020, and Jan. 2, 2021, has been massive,” Alan Garber, MD, PhD, wrote in an accompanying editorial.

“It seems likely that COVID-19 will have contributed to nearly as many deaths in the U.S. as the great influenza pandemic of 1918, and more than in any influenza outbreak in the U.S. since then,” added Dr. Garber, provost of Harvard University in Cambridge, Mass.

This study of excess mortality illustrates what is at stake, he added. “Despite the scientific, medical and public health progress of recent decades, the loss of life attributable to the COVID-19 pandemic exceeds the mortality of major wars. No nation should squander this opportunity to do what it takes to prepare for the next one.”

Dr. Woolf and Dr. Garber disclosed no relevant financial relationships. The National Institutes of Health supported the research through its National Center for Advancing Translational Sciences and the National Institute on Aging.

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

Key clinical point: In patients with newly diagnosed breast cancer (BC), the risk of local recurrence (LR) as a first event within 5 years of diagnosis was low and declined further with the number of event-free years.

Major finding: Overall, the incidence of LR as a first event within 5 years of diagnosis was 3.0%, which decreased to 2.4%, 1.6%, 1.0%, and 0.6% after 1, 2, 3, and 4 event-free years, respectively.

Study details: Findings are from the nationwide Netherlands Cancer Registry database, including 34,453 patients with newly diagnosed breast cancer between 2005 and 2008.

Disclosures: This study was supported by CZ fonds 201400316. ML Smidt reported receiving grant from Servier Pharma. Other authors had no disclosures.

Source: Moossdorff M et al. Breast Cancer Res Treat. 2021 Mar 10. doi: 10.1007/s10549-020-06040-3.

Key clinical point: In patients with newly diagnosed breast cancer (BC), the risk of local recurrence (LR) as a first event within 5 years of diagnosis was low and declined further with the number of event-free years.

Major finding: Overall, the incidence of LR as a first event within 5 years of diagnosis was 3.0%, which decreased to 2.4%, 1.6%, 1.0%, and 0.6% after 1, 2, 3, and 4 event-free years, respectively.

Study details: Findings are from the nationwide Netherlands Cancer Registry database, including 34,453 patients with newly diagnosed breast cancer between 2005 and 2008.

Disclosures: This study was supported by CZ fonds 201400316. ML Smidt reported receiving grant from Servier Pharma. Other authors had no disclosures.

Source: Moossdorff M et al. Breast Cancer Res Treat. 2021 Mar 10. doi: 10.1007/s10549-020-06040-3.

Key clinical point: In patients with newly diagnosed breast cancer (BC), the risk of local recurrence (LR) as a first event within 5 years of diagnosis was low and declined further with the number of event-free years.

Major finding: Overall, the incidence of LR as a first event within 5 years of diagnosis was 3.0%, which decreased to 2.4%, 1.6%, 1.0%, and 0.6% after 1, 2, 3, and 4 event-free years, respectively.

Study details: Findings are from the nationwide Netherlands Cancer Registry database, including 34,453 patients with newly diagnosed breast cancer between 2005 and 2008.

Disclosures: This study was supported by CZ fonds 201400316. ML Smidt reported receiving grant from Servier Pharma. Other authors had no disclosures.

Source: Moossdorff M et al. Breast Cancer Res Treat. 2021 Mar 10. doi: 10.1007/s10549-020-06040-3.

Key clinical point: Use of female hormones was associated with an increased incidence of breast cancer (BC) in premenopausal women. Among postmenopausal women, older age at first birth increased the incidence of BC, whereas more births decreased it.

Major finding: Use of female hormones significantly increased the incidence of premenopausal breast cancer (adjusted hazard ratio [aHR], 1.53; P = .03). Incidence of postmenopausal breast cancer was higher in women aged 26 years or more vs. 21-25 years at first birth (aHR, 1.34, 1.47, and 1.68 for ages 26-30, 31-35, and 36 years and older, respectively; P less than .001) and lower in women giving more vs. no births (aHR, 0.85, 0.65, and 0.52 for 1, 2, and 3 and more births, respectively; P = .02).

Study details: Findings are from a pooled analysis of 9 population-based cohort studies conducted in Japan including 187,999 women (premenopausal, n=61,113; postmenopausal, n=126,886).

Disclosures: This study was supported by the National Cancer Center Research and Development Fund and the Health and Labour Sciences Research Grants for the Third Term Comprehensive Control Research for Cancer. The authors had no disclosures.

Source: Takeuchi T et al. Cancer Med. 2021 Mar 1. doi: 10.1002/cam4.3752.

Key clinical point: Use of female hormones was associated with an increased incidence of breast cancer (BC) in premenopausal women. Among postmenopausal women, older age at first birth increased the incidence of BC, whereas more births decreased it.

Major finding: Use of female hormones significantly increased the incidence of premenopausal breast cancer (adjusted hazard ratio [aHR], 1.53; P = .03). Incidence of postmenopausal breast cancer was higher in women aged 26 years or more vs. 21-25 years at first birth (aHR, 1.34, 1.47, and 1.68 for ages 26-30, 31-35, and 36 years and older, respectively; P less than .001) and lower in women giving more vs. no births (aHR, 0.85, 0.65, and 0.52 for 1, 2, and 3 and more births, respectively; P = .02).

Study details: Findings are from a pooled analysis of 9 population-based cohort studies conducted in Japan including 187,999 women (premenopausal, n=61,113; postmenopausal, n=126,886).

Disclosures: This study was supported by the National Cancer Center Research and Development Fund and the Health and Labour Sciences Research Grants for the Third Term Comprehensive Control Research for Cancer. The authors had no disclosures.

Source: Takeuchi T et al. Cancer Med. 2021 Mar 1. doi: 10.1002/cam4.3752.

Key clinical point: Use of female hormones was associated with an increased incidence of breast cancer (BC) in premenopausal women. Among postmenopausal women, older age at first birth increased the incidence of BC, whereas more births decreased it.

Major finding: Use of female hormones significantly increased the incidence of premenopausal breast cancer (adjusted hazard ratio [aHR], 1.53; P = .03). Incidence of postmenopausal breast cancer was higher in women aged 26 years or more vs. 21-25 years at first birth (aHR, 1.34, 1.47, and 1.68 for ages 26-30, 31-35, and 36 years and older, respectively; P less than .001) and lower in women giving more vs. no births (aHR, 0.85, 0.65, and 0.52 for 1, 2, and 3 and more births, respectively; P = .02).

Study details: Findings are from a pooled analysis of 9 population-based cohort studies conducted in Japan including 187,999 women (premenopausal, n=61,113; postmenopausal, n=126,886).

Disclosures: This study was supported by the National Cancer Center Research and Development Fund and the Health and Labour Sciences Research Grants for the Third Term Comprehensive Control Research for Cancer. The authors had no disclosures.

Source: Takeuchi T et al. Cancer Med. 2021 Mar 1. doi: 10.1002/cam4.3752.

Key clinical point: Preoperative breast magnetic resonance imaging (MRI) has low accuracy in predicting nodal status after neoadjuvant therapy in patients with invasive lobular carcinoma (ILC), suggesting that axillary findings on posttreatment breast MRI should not be used to plan surgical approach to the axilla.

Major finding: Overall, the accuracy of posttreatment breast MRI in predicting axillary nodal status ranged from 45.5% to 66.7%. The overall accuracy of MRI for predicting nodal status was similar among patients treated with neoadjuvant endocrine therapy (ET) vs. chemotherapy (66.7% vs. 50%; P = .1393).

Study details: Findings are from a retrospective analysis of 79 women with stage I-III ILC who underwent preoperative breast MRI after either neoadjuvant chemotherapy (n=46) or ET (n=33).

Disclosures: This publication was supported by the National Center for Advancing Translational Sciences, National Institute of Health. The authors declared no conflicts of interest.

Source: Abel MK et al. NPJ Breast Cancer. 2021 Mar 5. doi: 10.1038/s41523-021-00233-9.

Key clinical point: Preoperative breast magnetic resonance imaging (MRI) has low accuracy in predicting nodal status after neoadjuvant therapy in patients with invasive lobular carcinoma (ILC), suggesting that axillary findings on posttreatment breast MRI should not be used to plan surgical approach to the axilla.

Major finding: Overall, the accuracy of posttreatment breast MRI in predicting axillary nodal status ranged from 45.5% to 66.7%. The overall accuracy of MRI for predicting nodal status was similar among patients treated with neoadjuvant endocrine therapy (ET) vs. chemotherapy (66.7% vs. 50%; P = .1393).

Study details: Findings are from a retrospective analysis of 79 women with stage I-III ILC who underwent preoperative breast MRI after either neoadjuvant chemotherapy (n=46) or ET (n=33).

Disclosures: This publication was supported by the National Center for Advancing Translational Sciences, National Institute of Health. The authors declared no conflicts of interest.

Source: Abel MK et al. NPJ Breast Cancer. 2021 Mar 5. doi: 10.1038/s41523-021-00233-9.

Key clinical point: Preoperative breast magnetic resonance imaging (MRI) has low accuracy in predicting nodal status after neoadjuvant therapy in patients with invasive lobular carcinoma (ILC), suggesting that axillary findings on posttreatment breast MRI should not be used to plan surgical approach to the axilla.

Major finding: Overall, the accuracy of posttreatment breast MRI in predicting axillary nodal status ranged from 45.5% to 66.7%. The overall accuracy of MRI for predicting nodal status was similar among patients treated with neoadjuvant endocrine therapy (ET) vs. chemotherapy (66.7% vs. 50%; P = .1393).

Study details: Findings are from a retrospective analysis of 79 women with stage I-III ILC who underwent preoperative breast MRI after either neoadjuvant chemotherapy (n=46) or ET (n=33).

Disclosures: This publication was supported by the National Center for Advancing Translational Sciences, National Institute of Health. The authors declared no conflicts of interest.

Source: Abel MK et al. NPJ Breast Cancer. 2021 Mar 5. doi: 10.1038/s41523-021-00233-9.

Patients with COPD may benefit from stepped-up treatment of short-term disease progression with triple therapy to stave off longer-term exacerbations and all-cause mortality.

©moodboard/thinkstockphotos.com

Clinically important deterioration was a significant predictor of worsening disease and all-cause mortality in chronic obstructive pulmonary disease, a study based on data from more than 10,000 patients has shown.

For this study, clinically important deterioration (CID) as a measure of COPD is defined as a combination of change in lung function and/or health status, or a first acute moderate to severe COPD exacerbation, wrote MeiLan K. Han, MD, of the University of Michigan, Ann Arbor, and colleagues.

The study was published in ERJ Open Research The investigators analyzed data from the IMPACT trial, a phase III, double-blind, multicenter, 52-week study of symptomatic COPD patients aged 40 years and older.

In the intent-to-treat population, patients with symptomatic COPD and at least one moderate or severe exacerbation in the past year were randomized to a once-daily dose of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 mcg (4,151 patients); FF/VI 100/25 mcg (4,134 patients); or UMEC/VI 62.5/25 mcg using a single dry-power inhaler (2,070 patients).

The researchers explored both the prognostic value of a CID event on future clinical outcomes and the impact of single-inhaler triple versus dual therapy on reducing CID risk. CID was defined as any of the following: moderate/severe exacerbation; deterioration in lung function (defined as a decrease of 100 mL or more from baseline in trough forced expiratory volume per second); or deterioration in health status based on increases of 4.0 units or more on the St George’s Respiratory Questionnaire (SGRQ) total score or 2.0 units or more on the COPD Assessment Test (CAT) score.

Overall, patients with a CID by 28 weeks had significantly increased exacerbation rates after week 28, as well as smaller improvements in lung function and health status at week 52 (P < .001 for all). In addition, CID patients had an increased risk of all-cause mortality after 28 weeks, compared with patients without CID. However, FF/UMEC/VI significantly reduced CID risk, compared with dual therapies, the researchers noted.

Based on the CID SGRQ definition, patients with CID had a 75% increase in moderate to severe exacerbations by week 28 and a 96% in severe exacerbations over weeks 29-52. The increases were similar using the CID CAT definition (72% and 91%, respectively).

Patients with CID also showed significantly reduced improvements in both lung function and health status after 1 year, and a significantly increased risk of all-cause mortality compared to patients without CID.

In comparing triple vs. double therapies, FF/UMEC/VI patients showed significant reductions in CID risk by 52 weeks, compared with patients treated with FF/VI and UMEC/VI. This difference was true across all subgroups, except for the subgroup of patients who were on long-acting beta2-agonist (LABA) and long-acting muscarinic antagonist (LAMA) therapy prior to screening, the researchers said.

In addition, “treatment effect was greater at higher blood eosinophil counts for FF/UMEC/VI versus UMEC/VI,” the researchers noted.

The study findings were limited by several factors including the lack of CID as a primary endpoint, the relatively short 5-month follow-up period, and the use of a symptomatic patient population with an established risk of exacerbation, which could limit generalizability, the researchers noted. However, the findings support the value of preventing short-term CID and adding inhaled corticosteroids (ICS) or bronchodilation for patients in this study population, they said.
 

Data may help drive tailored treatments

“This study is a post hoc analysis of data from the IMPACT trial, an RCT examining triple therapy vs ICS/LABA vs LABA/LAMA,” Dr. Han, lead and corresponding author, said in an interview. “In this particular paper, we conducted a treatment independent analysis examining individuals who experienced clinically important deteriorations at week 28 and then compared outcomes at week 52 based on CID status at week 28. Patients with a CID by week 28 had significantly increased exacerbation rates after week 28, smaller improvements in lung function and health status at week 52, and increased risk of all-cause mortality after week 28 versus patients who were CID free,” she emphasized. “We also saw that FF/UMEC/VI significantly reduced CID risk versus dual therapies.” These data suggest that shorter-term changes are associated with longer term outcomes, and provide important information both for the purposes of clinical trials design as well as patient clinical assessments, she added.

Dr. Han said she was not surprised by the findings. “I think these results are consistent with prior analyses but suggest that short-term outcomes relate to longer-term ones,” she said. However, she stressed the need for individualized treatment.

“While there are relationships between symptoms, lung function, and exacerbations as demonstrated by these analyses, in any individual patient sometimes these three disease axes do not perfectly align,” she explained. Dr. Han’s main message for clinicians in practice is that optimization of triple therapy in patients with severe disease and high risk for exacerbations was associated not only with short-term improvements in symptoms and lung function, but also with longer-term reductions in exacerbations and mortality.

As for additional research, prospective studies using CID as a primary or secondary outcome would help validate the composite outcome in this study, as regulatory agencies have been slow to adopt composite outcomes, Dr. Han said.

Dr. Han disclosed relationships with GlaxoSmithKline, which funded the study, as well as AstraZeneca, Boehringer Ingelheim, Novartis, Sunovion, Mylan, Merck, and Verona.

Patients with COPD may benefit from stepped-up treatment of short-term disease progression with triple therapy to stave off longer-term exacerbations and all-cause mortality.

©moodboard/thinkstockphotos.com

Clinically important deterioration was a significant predictor of worsening disease and all-cause mortality in chronic obstructive pulmonary disease, a study based on data from more than 10,000 patients has shown.

For this study, clinically important deterioration (CID) as a measure of COPD is defined as a combination of change in lung function and/or health status, or a first acute moderate to severe COPD exacerbation, wrote MeiLan K. Han, MD, of the University of Michigan, Ann Arbor, and colleagues.

The study was published in ERJ Open Research The investigators analyzed data from the IMPACT trial, a phase III, double-blind, multicenter, 52-week study of symptomatic COPD patients aged 40 years and older.

In the intent-to-treat population, patients with symptomatic COPD and at least one moderate or severe exacerbation in the past year were randomized to a once-daily dose of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 mcg (4,151 patients); FF/VI 100/25 mcg (4,134 patients); or UMEC/VI 62.5/25 mcg using a single dry-power inhaler (2,070 patients).

The researchers explored both the prognostic value of a CID event on future clinical outcomes and the impact of single-inhaler triple versus dual therapy on reducing CID risk. CID was defined as any of the following: moderate/severe exacerbation; deterioration in lung function (defined as a decrease of 100 mL or more from baseline in trough forced expiratory volume per second); or deterioration in health status based on increases of 4.0 units or more on the St George’s Respiratory Questionnaire (SGRQ) total score or 2.0 units or more on the COPD Assessment Test (CAT) score.

Overall, patients with a CID by 28 weeks had significantly increased exacerbation rates after week 28, as well as smaller improvements in lung function and health status at week 52 (P < .001 for all). In addition, CID patients had an increased risk of all-cause mortality after 28 weeks, compared with patients without CID. However, FF/UMEC/VI significantly reduced CID risk, compared with dual therapies, the researchers noted.

Based on the CID SGRQ definition, patients with CID had a 75% increase in moderate to severe exacerbations by week 28 and a 96% in severe exacerbations over weeks 29-52. The increases were similar using the CID CAT definition (72% and 91%, respectively).

Patients with CID also showed significantly reduced improvements in both lung function and health status after 1 year, and a significantly increased risk of all-cause mortality compared to patients without CID.

In comparing triple vs. double therapies, FF/UMEC/VI patients showed significant reductions in CID risk by 52 weeks, compared with patients treated with FF/VI and UMEC/VI. This difference was true across all subgroups, except for the subgroup of patients who were on long-acting beta2-agonist (LABA) and long-acting muscarinic antagonist (LAMA) therapy prior to screening, the researchers said.

In addition, “treatment effect was greater at higher blood eosinophil counts for FF/UMEC/VI versus UMEC/VI,” the researchers noted.

The study findings were limited by several factors including the lack of CID as a primary endpoint, the relatively short 5-month follow-up period, and the use of a symptomatic patient population with an established risk of exacerbation, which could limit generalizability, the researchers noted. However, the findings support the value of preventing short-term CID and adding inhaled corticosteroids (ICS) or bronchodilation for patients in this study population, they said.
 

Data may help drive tailored treatments

“This study is a post hoc analysis of data from the IMPACT trial, an RCT examining triple therapy vs ICS/LABA vs LABA/LAMA,” Dr. Han, lead and corresponding author, said in an interview. “In this particular paper, we conducted a treatment independent analysis examining individuals who experienced clinically important deteriorations at week 28 and then compared outcomes at week 52 based on CID status at week 28. Patients with a CID by week 28 had significantly increased exacerbation rates after week 28, smaller improvements in lung function and health status at week 52, and increased risk of all-cause mortality after week 28 versus patients who were CID free,” she emphasized. “We also saw that FF/UMEC/VI significantly reduced CID risk versus dual therapies.” These data suggest that shorter-term changes are associated with longer term outcomes, and provide important information both for the purposes of clinical trials design as well as patient clinical assessments, she added.

Dr. Han said she was not surprised by the findings. “I think these results are consistent with prior analyses but suggest that short-term outcomes relate to longer-term ones,” she said. However, she stressed the need for individualized treatment.

“While there are relationships between symptoms, lung function, and exacerbations as demonstrated by these analyses, in any individual patient sometimes these three disease axes do not perfectly align,” she explained. Dr. Han’s main message for clinicians in practice is that optimization of triple therapy in patients with severe disease and high risk for exacerbations was associated not only with short-term improvements in symptoms and lung function, but also with longer-term reductions in exacerbations and mortality.

As for additional research, prospective studies using CID as a primary or secondary outcome would help validate the composite outcome in this study, as regulatory agencies have been slow to adopt composite outcomes, Dr. Han said.

Dr. Han disclosed relationships with GlaxoSmithKline, which funded the study, as well as AstraZeneca, Boehringer Ingelheim, Novartis, Sunovion, Mylan, Merck, and Verona.

Patients with COPD may benefit from stepped-up treatment of short-term disease progression with triple therapy to stave off longer-term exacerbations and all-cause mortality.

©moodboard/thinkstockphotos.com

Clinically important deterioration was a significant predictor of worsening disease and all-cause mortality in chronic obstructive pulmonary disease, a study based on data from more than 10,000 patients has shown.

For this study, clinically important deterioration (CID) as a measure of COPD is defined as a combination of change in lung function and/or health status, or a first acute moderate to severe COPD exacerbation, wrote MeiLan K. Han, MD, of the University of Michigan, Ann Arbor, and colleagues.

The study was published in ERJ Open Research The investigators analyzed data from the IMPACT trial, a phase III, double-blind, multicenter, 52-week study of symptomatic COPD patients aged 40 years and older.

In the intent-to-treat population, patients with symptomatic COPD and at least one moderate or severe exacerbation in the past year were randomized to a once-daily dose of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 mcg (4,151 patients); FF/VI 100/25 mcg (4,134 patients); or UMEC/VI 62.5/25 mcg using a single dry-power inhaler (2,070 patients).

The researchers explored both the prognostic value of a CID event on future clinical outcomes and the impact of single-inhaler triple versus dual therapy on reducing CID risk. CID was defined as any of the following: moderate/severe exacerbation; deterioration in lung function (defined as a decrease of 100 mL or more from baseline in trough forced expiratory volume per second); or deterioration in health status based on increases of 4.0 units or more on the St George’s Respiratory Questionnaire (SGRQ) total score or 2.0 units or more on the COPD Assessment Test (CAT) score.

Overall, patients with a CID by 28 weeks had significantly increased exacerbation rates after week 28, as well as smaller improvements in lung function and health status at week 52 (P < .001 for all). In addition, CID patients had an increased risk of all-cause mortality after 28 weeks, compared with patients without CID. However, FF/UMEC/VI significantly reduced CID risk, compared with dual therapies, the researchers noted.

Based on the CID SGRQ definition, patients with CID had a 75% increase in moderate to severe exacerbations by week 28 and a 96% in severe exacerbations over weeks 29-52. The increases were similar using the CID CAT definition (72% and 91%, respectively).

Patients with CID also showed significantly reduced improvements in both lung function and health status after 1 year, and a significantly increased risk of all-cause mortality compared to patients without CID.

In comparing triple vs. double therapies, FF/UMEC/VI patients showed significant reductions in CID risk by 52 weeks, compared with patients treated with FF/VI and UMEC/VI. This difference was true across all subgroups, except for the subgroup of patients who were on long-acting beta2-agonist (LABA) and long-acting muscarinic antagonist (LAMA) therapy prior to screening, the researchers said.

In addition, “treatment effect was greater at higher blood eosinophil counts for FF/UMEC/VI versus UMEC/VI,” the researchers noted.

The study findings were limited by several factors including the lack of CID as a primary endpoint, the relatively short 5-month follow-up period, and the use of a symptomatic patient population with an established risk of exacerbation, which could limit generalizability, the researchers noted. However, the findings support the value of preventing short-term CID and adding inhaled corticosteroids (ICS) or bronchodilation for patients in this study population, they said.
 

Data may help drive tailored treatments

“This study is a post hoc analysis of data from the IMPACT trial, an RCT examining triple therapy vs ICS/LABA vs LABA/LAMA,” Dr. Han, lead and corresponding author, said in an interview. “In this particular paper, we conducted a treatment independent analysis examining individuals who experienced clinically important deteriorations at week 28 and then compared outcomes at week 52 based on CID status at week 28. Patients with a CID by week 28 had significantly increased exacerbation rates after week 28, smaller improvements in lung function and health status at week 52, and increased risk of all-cause mortality after week 28 versus patients who were CID free,” she emphasized. “We also saw that FF/UMEC/VI significantly reduced CID risk versus dual therapies.” These data suggest that shorter-term changes are associated with longer term outcomes, and provide important information both for the purposes of clinical trials design as well as patient clinical assessments, she added.

Dr. Han said she was not surprised by the findings. “I think these results are consistent with prior analyses but suggest that short-term outcomes relate to longer-term ones,” she said. However, she stressed the need for individualized treatment.

“While there are relationships between symptoms, lung function, and exacerbations as demonstrated by these analyses, in any individual patient sometimes these three disease axes do not perfectly align,” she explained. Dr. Han’s main message for clinicians in practice is that optimization of triple therapy in patients with severe disease and high risk for exacerbations was associated not only with short-term improvements in symptoms and lung function, but also with longer-term reductions in exacerbations and mortality.

As for additional research, prospective studies using CID as a primary or secondary outcome would help validate the composite outcome in this study, as regulatory agencies have been slow to adopt composite outcomes, Dr. Han said.

Dr. Han disclosed relationships with GlaxoSmithKline, which funded the study, as well as AstraZeneca, Boehringer Ingelheim, Novartis, Sunovion, Mylan, Merck, and Verona.

Key clinical point: The overall incidence of cutaneous adverse events (AEs) was low and manageable, rarely needing treatment cessation, in patients with advanced hormone receptor-positive, human epidermal growth receptor 2-negative breast cancer (HR+HER2−BC) receiving palbociclib and endocrine therapy (ET).

Major finding: The incidence of treatment-related cutaneous AEs was 14.2%, of which only 15.0% and 4.0% required temporary treatment suspension and discontinuation, respectively. The mean time to AE onset was 168 days (6 cycles) of treatment.

Study details: Findings are from a retrospective analysis of 324 adult patients with advanced HR+HER2−BC who received oral palbociclib (mean treatment cycles, 9) and ET.

Disclosures: This study did not declare any specific funding. The authors declared no conflicts of interest.

Source: Chawla S et al. Breast Cancer Res Treat. 2021 Mar 8. doi: 10.1007/s10549-021-06169-9.

Key clinical point: The overall incidence of cutaneous adverse events (AEs) was low and manageable, rarely needing treatment cessation, in patients with advanced hormone receptor-positive, human epidermal growth receptor 2-negative breast cancer (HR+HER2−BC) receiving palbociclib and endocrine therapy (ET).

Major finding: The incidence of treatment-related cutaneous AEs was 14.2%, of which only 15.0% and 4.0% required temporary treatment suspension and discontinuation, respectively. The mean time to AE onset was 168 days (6 cycles) of treatment.

Study details: Findings are from a retrospective analysis of 324 adult patients with advanced HR+HER2−BC who received oral palbociclib (mean treatment cycles, 9) and ET.

Disclosures: This study did not declare any specific funding. The authors declared no conflicts of interest.

Source: Chawla S et al. Breast Cancer Res Treat. 2021 Mar 8. doi: 10.1007/s10549-021-06169-9.

Key clinical point: The overall incidence of cutaneous adverse events (AEs) was low and manageable, rarely needing treatment cessation, in patients with advanced hormone receptor-positive, human epidermal growth receptor 2-negative breast cancer (HR+HER2−BC) receiving palbociclib and endocrine therapy (ET).

Major finding: The incidence of treatment-related cutaneous AEs was 14.2%, of which only 15.0% and 4.0% required temporary treatment suspension and discontinuation, respectively. The mean time to AE onset was 168 days (6 cycles) of treatment.

Study details: Findings are from a retrospective analysis of 324 adult patients with advanced HR+HER2−BC who received oral palbociclib (mean treatment cycles, 9) and ET.

Disclosures: This study did not declare any specific funding. The authors declared no conflicts of interest.

Source: Chawla S et al. Breast Cancer Res Treat. 2021 Mar 8. doi: 10.1007/s10549-021-06169-9.

Key clinical point: Adjuvant endocrine therapy (ET) was associated with improved overall survival (OS) in older patients with node-negative, estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2−) invasive breast cancer with multiple comorbidities.

Major finding: During median follow-up of 43.6 months, median OS was higher in patients who received ET vs. those who did not (79.2 months vs. 67.7 months; P less than .0001).

Study details: Findings are from a retrospective, matched cohort analysis of 1,972 older patients (age, 70 years or more) with Charlson/Deyo comorbidity scores of 2 or 3 who received breast and axillary surgery for ER+/HER2−, pathologic node-negative breast cancer.

Disclosures: This work was partly supported by the National Cancer Institute. MS Karuturi reported support from Pfizer. The remaining authors had no disclosures.

Source: Tamirisa N et al. Cancer. 2021 Mar 18. doi: 10.1002/cncr.33489.

Key clinical point: Adjuvant endocrine therapy (ET) was associated with improved overall survival (OS) in older patients with node-negative, estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2−) invasive breast cancer with multiple comorbidities.

Major finding: During median follow-up of 43.6 months, median OS was higher in patients who received ET vs. those who did not (79.2 months vs. 67.7 months; P less than .0001).

Study details: Findings are from a retrospective, matched cohort analysis of 1,972 older patients (age, 70 years or more) with Charlson/Deyo comorbidity scores of 2 or 3 who received breast and axillary surgery for ER+/HER2−, pathologic node-negative breast cancer.

Disclosures: This work was partly supported by the National Cancer Institute. MS Karuturi reported support from Pfizer. The remaining authors had no disclosures.

Source: Tamirisa N et al. Cancer. 2021 Mar 18. doi: 10.1002/cncr.33489.

Key clinical point: Adjuvant endocrine therapy (ET) was associated with improved overall survival (OS) in older patients with node-negative, estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2−) invasive breast cancer with multiple comorbidities.

Major finding: During median follow-up of 43.6 months, median OS was higher in patients who received ET vs. those who did not (79.2 months vs. 67.7 months; P less than .0001).

Study details: Findings are from a retrospective, matched cohort analysis of 1,972 older patients (age, 70 years or more) with Charlson/Deyo comorbidity scores of 2 or 3 who received breast and axillary surgery for ER+/HER2−, pathologic node-negative breast cancer.

Disclosures: This work was partly supported by the National Cancer Institute. MS Karuturi reported support from Pfizer. The remaining authors had no disclosures.

Source: Tamirisa N et al. Cancer. 2021 Mar 18. doi: 10.1002/cncr.33489.

Key clinical point: Pembrolizumab monotherapy as second- or third-line treatment did not improve overall survival (OS) in patients with previously treated metastatic triple-negative breast cancer (TNBC) compared with chemotherapy.

Major finding: Median OS was similar with pembrolizumab vs. chemotherapy in patients with programmed death-ligand 1 combined positive score of 1 or more (10.7 months vs. 10.2 months; P = .073) or 10 or more (12.7 months vs. 11.6 months; P = .057). Dose modification, reduction, interruption, or withdrawal because of adverse events was lower in pembrolizumab (21%) vs. chemotherapy (45%) groups.

Study details: Findings are from phase 3 KEYNOTE-119 trial including 622 patients with metastatic TNBC who underwent 1 or 2 previous treatments, experienced progression on most recent therapy, and received previous treatment with an anthracycline or taxane. Patients were randomly allocated to receive either intravenous pembrolizumab (n=312) or investigator-choice chemotherapy (n=310).

Disclosures: This study was funded by Merck Sharp and Dohme. Some investigators, including the lead author, reported ties with various pharmaceutical companies including Merck Sharp and Dohme.

Source: Winer EP et al. Lancet Oncol. 2021 Mar 4. doi: 10.1016/S1470-2045(20)30754-3.

Key clinical point: Pembrolizumab monotherapy as second- or third-line treatment did not improve overall survival (OS) in patients with previously treated metastatic triple-negative breast cancer (TNBC) compared with chemotherapy.

Major finding: Median OS was similar with pembrolizumab vs. chemotherapy in patients with programmed death-ligand 1 combined positive score of 1 or more (10.7 months vs. 10.2 months; P = .073) or 10 or more (12.7 months vs. 11.6 months; P = .057). Dose modification, reduction, interruption, or withdrawal because of adverse events was lower in pembrolizumab (21%) vs. chemotherapy (45%) groups.

Study details: Findings are from phase 3 KEYNOTE-119 trial including 622 patients with metastatic TNBC who underwent 1 or 2 previous treatments, experienced progression on most recent therapy, and received previous treatment with an anthracycline or taxane. Patients were randomly allocated to receive either intravenous pembrolizumab (n=312) or investigator-choice chemotherapy (n=310).

Disclosures: This study was funded by Merck Sharp and Dohme. Some investigators, including the lead author, reported ties with various pharmaceutical companies including Merck Sharp and Dohme.

Source: Winer EP et al. Lancet Oncol. 2021 Mar 4. doi: 10.1016/S1470-2045(20)30754-3.

Key clinical point: Pembrolizumab monotherapy as second- or third-line treatment did not improve overall survival (OS) in patients with previously treated metastatic triple-negative breast cancer (TNBC) compared with chemotherapy.

Major finding: Median OS was similar with pembrolizumab vs. chemotherapy in patients with programmed death-ligand 1 combined positive score of 1 or more (10.7 months vs. 10.2 months; P = .073) or 10 or more (12.7 months vs. 11.6 months; P = .057). Dose modification, reduction, interruption, or withdrawal because of adverse events was lower in pembrolizumab (21%) vs. chemotherapy (45%) groups.

Study details: Findings are from phase 3 KEYNOTE-119 trial including 622 patients with metastatic TNBC who underwent 1 or 2 previous treatments, experienced progression on most recent therapy, and received previous treatment with an anthracycline or taxane. Patients were randomly allocated to receive either intravenous pembrolizumab (n=312) or investigator-choice chemotherapy (n=310).

Disclosures: This study was funded by Merck Sharp and Dohme. Some investigators, including the lead author, reported ties with various pharmaceutical companies including Merck Sharp and Dohme.

Source: Winer EP et al. Lancet Oncol. 2021 Mar 4. doi: 10.1016/S1470-2045(20)30754-3.