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20% with cancer on checkpoint inhibitors get thyroid dysfunction
new research suggests.
Immune checkpoint inhibitors have revolutionized the treatment of many different types of cancers, but can also trigger a variety of immune-related adverse effects. As these drugs become more widely used, rates of these events appear to be more common in the real-world compared with clinical trial settings.
In their new study, Zoe Quandt, MD, of the University of California, San Francisco (UCSF), and colleagues specifically looked at thyroid dysfunction in their own institution’s EHR data and found more than double the rate of hypothyroidism and more than triple the rate of hyperthyroidism, compared with rates in published trials.
Moreover, in contrast to previous studies that have found differences in thyroid dysfunction by checkpoint inhibitor type, Dr. Quandt and colleagues instead found significant differences by cancer type.
Dr. Quandt presented the findings during a virtual press briefing held March 31originally scheduled for ENDO 2020.
“Thyroid dysfunction following checkpoint inhibitor therapy appears to be much more common than was previously reported in clinical trials, and this is one of the first studies to show differences by cancer type rather than by checkpoint inhibitor type,” Dr. Quandt said during the presentation.
However, she also cautioned that there’s “a lot more research to be done to validate case definitions and validate these findings.”
Asked to comment, endocrinologist David C. Lieb, MD, associate professor of medicine at Eastern Virginia Medical School in Norfolk, said in an interview, “These drugs are becoming so much more commonly used, so it’s not surprising that we’re seeing more endocrine complications, especially thyroid disease.”
“Endocrinologists need to work closely with oncologists to make sure patients are being screened and followed appropriately.”
‘A much higher percentage than we were expecting’
Dr. Quandt’s study included 1,146 individuals treated with checkpoint inhibitors at UCSF during 2012-2018 who did not have thyroid cancer or preexisting thyroid dysfunction.
Pembrolizumab (Keytruda) was the most common treatment (45%), followed by nivolumab (Opdivo) (20%). Less than 10% of patients received atezolizumab (Tecentriq), durvalumab (Imfizi), ipilimumab (Yervoy) monotherapy, combined ipilimumab/nivolumab, or other combinations of checkpoint inhibitors.
A total of 19.1% developed thyroid disease, with 13.4% having hypothyroidism and 9.5% hyperthyroidism. These figures far exceed those found in a recent meta-analysis of 38 randomized clinical trials of checkpoint inhibitors that included 7551 patients.
“Using this approach, we found a much higher percentage of patients who developed thyroid dysfunction than we were expecting,” Dr. Quandt said.
In both cases, the two categories – hypothyroidism and hyperthyroidism – aren’t mutually exclusive as hypothyroidism can arise de novo or subsequent to hyperthyroidism.
Dr Lieb commented, “It would be interesting to see what the causes of hyperthyroidism are – thyroiditis or Graves disease.”
Dr. Quandt mentioned a possible reason for the large difference between clinical trial and real-world data.
“Once we’re actually using these drugs outside of clinical trials, some of the restrictions about using them in people with other autoimmune diseases have been lifted, so my guess is that as we give them to a broader population we’re seeing more of these [adverse effects],” she suggested.
Also, “In the initial trials, people weren’t quite as aware of the possibilities of these side effects, so now we’re doing many more labs. Patients get thyroid function tests with every infusion, so I think we’re probably catching more patients who develop disease.”
Differences by cancer type, not checkpoint inhibitor type
And in a new twist, Dr. Quandt found that, in contrast to the differences seen by checkpoint inhibitor type in randomized trials, “surprisingly, we found that this difference did not reach statistical significance.”
“Instead, we saw that cancer type was associated with development of thyroid dysfunction, even after taking checkpoint inhibitor type into account.”
The percentages of patients who developed thyroid dysfunction ranged from 9.7% of those with glioblastoma to 40.0% of those with renal cell carcinoma.
The reason for this is not clear, said Dr. Quandt in an interview.
One possibility relates to other treatments patients with cancer also receive. In renal cell carcinoma, for example, patients also are treated with tyrosine kinase inhibitors, which can also cause thyroid dysfunction, so they may be more susceptible. Or there may be shared antigens activating the immune system.
“That’s definitely one of the questions we’re looking at,” she said.
Dr. Quandt and Dr. Lieb have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
new research suggests.
Immune checkpoint inhibitors have revolutionized the treatment of many different types of cancers, but can also trigger a variety of immune-related adverse effects. As these drugs become more widely used, rates of these events appear to be more common in the real-world compared with clinical trial settings.
In their new study, Zoe Quandt, MD, of the University of California, San Francisco (UCSF), and colleagues specifically looked at thyroid dysfunction in their own institution’s EHR data and found more than double the rate of hypothyroidism and more than triple the rate of hyperthyroidism, compared with rates in published trials.
Moreover, in contrast to previous studies that have found differences in thyroid dysfunction by checkpoint inhibitor type, Dr. Quandt and colleagues instead found significant differences by cancer type.
Dr. Quandt presented the findings during a virtual press briefing held March 31originally scheduled for ENDO 2020.
“Thyroid dysfunction following checkpoint inhibitor therapy appears to be much more common than was previously reported in clinical trials, and this is one of the first studies to show differences by cancer type rather than by checkpoint inhibitor type,” Dr. Quandt said during the presentation.
However, she also cautioned that there’s “a lot more research to be done to validate case definitions and validate these findings.”
Asked to comment, endocrinologist David C. Lieb, MD, associate professor of medicine at Eastern Virginia Medical School in Norfolk, said in an interview, “These drugs are becoming so much more commonly used, so it’s not surprising that we’re seeing more endocrine complications, especially thyroid disease.”
“Endocrinologists need to work closely with oncologists to make sure patients are being screened and followed appropriately.”
‘A much higher percentage than we were expecting’
Dr. Quandt’s study included 1,146 individuals treated with checkpoint inhibitors at UCSF during 2012-2018 who did not have thyroid cancer or preexisting thyroid dysfunction.
Pembrolizumab (Keytruda) was the most common treatment (45%), followed by nivolumab (Opdivo) (20%). Less than 10% of patients received atezolizumab (Tecentriq), durvalumab (Imfizi), ipilimumab (Yervoy) monotherapy, combined ipilimumab/nivolumab, or other combinations of checkpoint inhibitors.
A total of 19.1% developed thyroid disease, with 13.4% having hypothyroidism and 9.5% hyperthyroidism. These figures far exceed those found in a recent meta-analysis of 38 randomized clinical trials of checkpoint inhibitors that included 7551 patients.
“Using this approach, we found a much higher percentage of patients who developed thyroid dysfunction than we were expecting,” Dr. Quandt said.
In both cases, the two categories – hypothyroidism and hyperthyroidism – aren’t mutually exclusive as hypothyroidism can arise de novo or subsequent to hyperthyroidism.
Dr Lieb commented, “It would be interesting to see what the causes of hyperthyroidism are – thyroiditis or Graves disease.”
Dr. Quandt mentioned a possible reason for the large difference between clinical trial and real-world data.
“Once we’re actually using these drugs outside of clinical trials, some of the restrictions about using them in people with other autoimmune diseases have been lifted, so my guess is that as we give them to a broader population we’re seeing more of these [adverse effects],” she suggested.
Also, “In the initial trials, people weren’t quite as aware of the possibilities of these side effects, so now we’re doing many more labs. Patients get thyroid function tests with every infusion, so I think we’re probably catching more patients who develop disease.”
Differences by cancer type, not checkpoint inhibitor type
And in a new twist, Dr. Quandt found that, in contrast to the differences seen by checkpoint inhibitor type in randomized trials, “surprisingly, we found that this difference did not reach statistical significance.”
“Instead, we saw that cancer type was associated with development of thyroid dysfunction, even after taking checkpoint inhibitor type into account.”
The percentages of patients who developed thyroid dysfunction ranged from 9.7% of those with glioblastoma to 40.0% of those with renal cell carcinoma.
The reason for this is not clear, said Dr. Quandt in an interview.
One possibility relates to other treatments patients with cancer also receive. In renal cell carcinoma, for example, patients also are treated with tyrosine kinase inhibitors, which can also cause thyroid dysfunction, so they may be more susceptible. Or there may be shared antigens activating the immune system.
“That’s definitely one of the questions we’re looking at,” she said.
Dr. Quandt and Dr. Lieb have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
new research suggests.
Immune checkpoint inhibitors have revolutionized the treatment of many different types of cancers, but can also trigger a variety of immune-related adverse effects. As these drugs become more widely used, rates of these events appear to be more common in the real-world compared with clinical trial settings.
In their new study, Zoe Quandt, MD, of the University of California, San Francisco (UCSF), and colleagues specifically looked at thyroid dysfunction in their own institution’s EHR data and found more than double the rate of hypothyroidism and more than triple the rate of hyperthyroidism, compared with rates in published trials.
Moreover, in contrast to previous studies that have found differences in thyroid dysfunction by checkpoint inhibitor type, Dr. Quandt and colleagues instead found significant differences by cancer type.
Dr. Quandt presented the findings during a virtual press briefing held March 31originally scheduled for ENDO 2020.
“Thyroid dysfunction following checkpoint inhibitor therapy appears to be much more common than was previously reported in clinical trials, and this is one of the first studies to show differences by cancer type rather than by checkpoint inhibitor type,” Dr. Quandt said during the presentation.
However, she also cautioned that there’s “a lot more research to be done to validate case definitions and validate these findings.”
Asked to comment, endocrinologist David C. Lieb, MD, associate professor of medicine at Eastern Virginia Medical School in Norfolk, said in an interview, “These drugs are becoming so much more commonly used, so it’s not surprising that we’re seeing more endocrine complications, especially thyroid disease.”
“Endocrinologists need to work closely with oncologists to make sure patients are being screened and followed appropriately.”
‘A much higher percentage than we were expecting’
Dr. Quandt’s study included 1,146 individuals treated with checkpoint inhibitors at UCSF during 2012-2018 who did not have thyroid cancer or preexisting thyroid dysfunction.
Pembrolizumab (Keytruda) was the most common treatment (45%), followed by nivolumab (Opdivo) (20%). Less than 10% of patients received atezolizumab (Tecentriq), durvalumab (Imfizi), ipilimumab (Yervoy) monotherapy, combined ipilimumab/nivolumab, or other combinations of checkpoint inhibitors.
A total of 19.1% developed thyroid disease, with 13.4% having hypothyroidism and 9.5% hyperthyroidism. These figures far exceed those found in a recent meta-analysis of 38 randomized clinical trials of checkpoint inhibitors that included 7551 patients.
“Using this approach, we found a much higher percentage of patients who developed thyroid dysfunction than we were expecting,” Dr. Quandt said.
In both cases, the two categories – hypothyroidism and hyperthyroidism – aren’t mutually exclusive as hypothyroidism can arise de novo or subsequent to hyperthyroidism.
Dr Lieb commented, “It would be interesting to see what the causes of hyperthyroidism are – thyroiditis or Graves disease.”
Dr. Quandt mentioned a possible reason for the large difference between clinical trial and real-world data.
“Once we’re actually using these drugs outside of clinical trials, some of the restrictions about using them in people with other autoimmune diseases have been lifted, so my guess is that as we give them to a broader population we’re seeing more of these [adverse effects],” she suggested.
Also, “In the initial trials, people weren’t quite as aware of the possibilities of these side effects, so now we’re doing many more labs. Patients get thyroid function tests with every infusion, so I think we’re probably catching more patients who develop disease.”
Differences by cancer type, not checkpoint inhibitor type
And in a new twist, Dr. Quandt found that, in contrast to the differences seen by checkpoint inhibitor type in randomized trials, “surprisingly, we found that this difference did not reach statistical significance.”
“Instead, we saw that cancer type was associated with development of thyroid dysfunction, even after taking checkpoint inhibitor type into account.”
The percentages of patients who developed thyroid dysfunction ranged from 9.7% of those with glioblastoma to 40.0% of those with renal cell carcinoma.
The reason for this is not clear, said Dr. Quandt in an interview.
One possibility relates to other treatments patients with cancer also receive. In renal cell carcinoma, for example, patients also are treated with tyrosine kinase inhibitors, which can also cause thyroid dysfunction, so they may be more susceptible. Or there may be shared antigens activating the immune system.
“That’s definitely one of the questions we’re looking at,” she said.
Dr. Quandt and Dr. Lieb have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
No staff COVID-19 diagnoses after plan at Chinese cancer center
Short-term results
No staff members or patients were diagnosed with COVID-19 after “strict protective measures” for screening and managing patients were implemented at the National Cancer Center/Cancer Hospital, Chinese Academy of Sciences, in Beijing, according to a report published online April 1 in JAMA Oncology.
However, the time period for the analysis, which included nearly 3000 patients, was short — only about 3 weeks (February 12 to March 3). Also, Beijing is more than 1100 kilometers from Wuhan, the center of the Chinese outbreak of COVID-19.
The Beijing cancer hospital implemented a multipronged safety plan in February in order to “avoid COVID-19 related nosocomial cross-infection between patients and medical staff,” explain the authors, led by medical oncologist Zhijie Wang, MD.
Notably, “all of the measures taken in China are actively being implemented and used in major oncology centers in the United States,” Robert Carlson, MD, chief executive officer, National Comprehensive Cancer Network (NCCN), told Medscape Medical News.
John Greene, MD, section chief, Infectious Disease and Tropical Medicine, Moffitt Cancer Center, Tampa, Florida, pointed out that the Chinese safety plan, which is full of “good measures,” is being largely used at his center. However, he observed that one tool — doing a temperature check at the hospital front door — is not well supported by most of the literature. “It gives good optics and looks like you are doing the most you possibly can, but scientifically it may not be as effective [as other screening measures],” he said.
The Chinese plan consists of four broad elements
First, the above-mentioned on-site temperature tests are performed at the entrances of the hospital, outpatient clinic, and wards. Contact and travel histories related to the Wuhan epidemic area are also established and recorded.
Second, an outpatient appointment scheduling system allows both online scheduling and on-site registration. Online consultation channels are open daily, featuring instruction on medication taking and cancer-related symptom management. These “substantially reduced the flow of people in the hospital,” write the authors. On-site patients must wear a mask and have their own disinfectant.
Third, for patients with cancer preparing to be admitted to hospital, symptoms associated with COVID-19, such as fever and cough, are recorded. Mandatory blood tests and CT scans of the lungs are performed. COVID-19 virus nucleic acid tests are performed for patients with suspected pneumonia on imaging.
Fourth, some anticancer drugs conventionally administered by infusion have been changed to oral administration, such as etoposide and vinorelbine. For adjuvant or maintenance chemotherapy, the infusion intervals were appropriately prolonged depending on patients’ conditions.
Eight out of 2,900 patients had imaging suspicious for infection
The Chinese authors report that a total of 2,944 patients with cancer were seen for clinic consultation and treatment in the wards (2795 outpatients and 149 inpatients).
Patients with cancer are believed to have a higher probability of severe illness and increased mortality compared with the healthy population once infected with COVID-19, point out the authors.
Under the new “strict screening strategy,” 27 patients showed radiologic manifestations of inflammatory changes or multiple-site exudative pneumonia in the lungs, including eight suspected of having COVID-19 infection. “Fortunately, negative results from nucleic acid testing ultimately excluded COVID-19 infection in all these patients,” the authors report.
However, two of these patients “presented with recovered pneumonia after symptomatic treatment.” Commenting on this finding, Moffitt’s Greene said that may mean these two patients were tested and found to be positive but were early in the infection and not yet shedding the virus, or they were infected after the initial negative result.
Greene said his center has implemented some measures not mentioned in the Chinese plan. For example, the Florida center no longer allows inpatient visitation. Also, one third of staff now work from home, resulting in less social interaction. Social distancing in meetings, the cafeteria, and hallways is being observed “aggressively,” and most meetings are now on Zoom, he said.
Moffitt has not been hard hit with COVID-19 and is at level one preparedness, the lowest rung. The center has performed 60 tests to date, with only one positive for the virus (< 2%), Greene told Medscape Medical News.
Currently, in the larger Tampa Bay community setting, about 12% of tests are positive.
The low percentage found among the Moffitt patients “tells you that a lot of cancer patients have fever and respiratory symptoms due to other viruses and, more importantly, other reasons, whether it’s their immunotherapy or chemotherapy or their cancer,” said Greene.
NCCN’s Carlson said the publication of the Chinese data was a good sign in terms of international science.
“This is a strong example of how the global oncology community rapidly shares information and experience whenever it makes a difference in patient care,” he commented.
The authors, as well as Carlson and Greene, have reported no relevant financial relationships.
This article first appeared on Medscape.com.
Short-term results
Short-term results
No staff members or patients were diagnosed with COVID-19 after “strict protective measures” for screening and managing patients were implemented at the National Cancer Center/Cancer Hospital, Chinese Academy of Sciences, in Beijing, according to a report published online April 1 in JAMA Oncology.
However, the time period for the analysis, which included nearly 3000 patients, was short — only about 3 weeks (February 12 to March 3). Also, Beijing is more than 1100 kilometers from Wuhan, the center of the Chinese outbreak of COVID-19.
The Beijing cancer hospital implemented a multipronged safety plan in February in order to “avoid COVID-19 related nosocomial cross-infection between patients and medical staff,” explain the authors, led by medical oncologist Zhijie Wang, MD.
Notably, “all of the measures taken in China are actively being implemented and used in major oncology centers in the United States,” Robert Carlson, MD, chief executive officer, National Comprehensive Cancer Network (NCCN), told Medscape Medical News.
John Greene, MD, section chief, Infectious Disease and Tropical Medicine, Moffitt Cancer Center, Tampa, Florida, pointed out that the Chinese safety plan, which is full of “good measures,” is being largely used at his center. However, he observed that one tool — doing a temperature check at the hospital front door — is not well supported by most of the literature. “It gives good optics and looks like you are doing the most you possibly can, but scientifically it may not be as effective [as other screening measures],” he said.
The Chinese plan consists of four broad elements
First, the above-mentioned on-site temperature tests are performed at the entrances of the hospital, outpatient clinic, and wards. Contact and travel histories related to the Wuhan epidemic area are also established and recorded.
Second, an outpatient appointment scheduling system allows both online scheduling and on-site registration. Online consultation channels are open daily, featuring instruction on medication taking and cancer-related symptom management. These “substantially reduced the flow of people in the hospital,” write the authors. On-site patients must wear a mask and have their own disinfectant.
Third, for patients with cancer preparing to be admitted to hospital, symptoms associated with COVID-19, such as fever and cough, are recorded. Mandatory blood tests and CT scans of the lungs are performed. COVID-19 virus nucleic acid tests are performed for patients with suspected pneumonia on imaging.
Fourth, some anticancer drugs conventionally administered by infusion have been changed to oral administration, such as etoposide and vinorelbine. For adjuvant or maintenance chemotherapy, the infusion intervals were appropriately prolonged depending on patients’ conditions.
Eight out of 2,900 patients had imaging suspicious for infection
The Chinese authors report that a total of 2,944 patients with cancer were seen for clinic consultation and treatment in the wards (2795 outpatients and 149 inpatients).
Patients with cancer are believed to have a higher probability of severe illness and increased mortality compared with the healthy population once infected with COVID-19, point out the authors.
Under the new “strict screening strategy,” 27 patients showed radiologic manifestations of inflammatory changes or multiple-site exudative pneumonia in the lungs, including eight suspected of having COVID-19 infection. “Fortunately, negative results from nucleic acid testing ultimately excluded COVID-19 infection in all these patients,” the authors report.
However, two of these patients “presented with recovered pneumonia after symptomatic treatment.” Commenting on this finding, Moffitt’s Greene said that may mean these two patients were tested and found to be positive but were early in the infection and not yet shedding the virus, or they were infected after the initial negative result.
Greene said his center has implemented some measures not mentioned in the Chinese plan. For example, the Florida center no longer allows inpatient visitation. Also, one third of staff now work from home, resulting in less social interaction. Social distancing in meetings, the cafeteria, and hallways is being observed “aggressively,” and most meetings are now on Zoom, he said.
Moffitt has not been hard hit with COVID-19 and is at level one preparedness, the lowest rung. The center has performed 60 tests to date, with only one positive for the virus (< 2%), Greene told Medscape Medical News.
Currently, in the larger Tampa Bay community setting, about 12% of tests are positive.
The low percentage found among the Moffitt patients “tells you that a lot of cancer patients have fever and respiratory symptoms due to other viruses and, more importantly, other reasons, whether it’s their immunotherapy or chemotherapy or their cancer,” said Greene.
NCCN’s Carlson said the publication of the Chinese data was a good sign in terms of international science.
“This is a strong example of how the global oncology community rapidly shares information and experience whenever it makes a difference in patient care,” he commented.
The authors, as well as Carlson and Greene, have reported no relevant financial relationships.
This article first appeared on Medscape.com.
No staff members or patients were diagnosed with COVID-19 after “strict protective measures” for screening and managing patients were implemented at the National Cancer Center/Cancer Hospital, Chinese Academy of Sciences, in Beijing, according to a report published online April 1 in JAMA Oncology.
However, the time period for the analysis, which included nearly 3000 patients, was short — only about 3 weeks (February 12 to March 3). Also, Beijing is more than 1100 kilometers from Wuhan, the center of the Chinese outbreak of COVID-19.
The Beijing cancer hospital implemented a multipronged safety plan in February in order to “avoid COVID-19 related nosocomial cross-infection between patients and medical staff,” explain the authors, led by medical oncologist Zhijie Wang, MD.
Notably, “all of the measures taken in China are actively being implemented and used in major oncology centers in the United States,” Robert Carlson, MD, chief executive officer, National Comprehensive Cancer Network (NCCN), told Medscape Medical News.
John Greene, MD, section chief, Infectious Disease and Tropical Medicine, Moffitt Cancer Center, Tampa, Florida, pointed out that the Chinese safety plan, which is full of “good measures,” is being largely used at his center. However, he observed that one tool — doing a temperature check at the hospital front door — is not well supported by most of the literature. “It gives good optics and looks like you are doing the most you possibly can, but scientifically it may not be as effective [as other screening measures],” he said.
The Chinese plan consists of four broad elements
First, the above-mentioned on-site temperature tests are performed at the entrances of the hospital, outpatient clinic, and wards. Contact and travel histories related to the Wuhan epidemic area are also established and recorded.
Second, an outpatient appointment scheduling system allows both online scheduling and on-site registration. Online consultation channels are open daily, featuring instruction on medication taking and cancer-related symptom management. These “substantially reduced the flow of people in the hospital,” write the authors. On-site patients must wear a mask and have their own disinfectant.
Third, for patients with cancer preparing to be admitted to hospital, symptoms associated with COVID-19, such as fever and cough, are recorded. Mandatory blood tests and CT scans of the lungs are performed. COVID-19 virus nucleic acid tests are performed for patients with suspected pneumonia on imaging.
Fourth, some anticancer drugs conventionally administered by infusion have been changed to oral administration, such as etoposide and vinorelbine. For adjuvant or maintenance chemotherapy, the infusion intervals were appropriately prolonged depending on patients’ conditions.
Eight out of 2,900 patients had imaging suspicious for infection
The Chinese authors report that a total of 2,944 patients with cancer were seen for clinic consultation and treatment in the wards (2795 outpatients and 149 inpatients).
Patients with cancer are believed to have a higher probability of severe illness and increased mortality compared with the healthy population once infected with COVID-19, point out the authors.
Under the new “strict screening strategy,” 27 patients showed radiologic manifestations of inflammatory changes or multiple-site exudative pneumonia in the lungs, including eight suspected of having COVID-19 infection. “Fortunately, negative results from nucleic acid testing ultimately excluded COVID-19 infection in all these patients,” the authors report.
However, two of these patients “presented with recovered pneumonia after symptomatic treatment.” Commenting on this finding, Moffitt’s Greene said that may mean these two patients were tested and found to be positive but were early in the infection and not yet shedding the virus, or they were infected after the initial negative result.
Greene said his center has implemented some measures not mentioned in the Chinese plan. For example, the Florida center no longer allows inpatient visitation. Also, one third of staff now work from home, resulting in less social interaction. Social distancing in meetings, the cafeteria, and hallways is being observed “aggressively,” and most meetings are now on Zoom, he said.
Moffitt has not been hard hit with COVID-19 and is at level one preparedness, the lowest rung. The center has performed 60 tests to date, with only one positive for the virus (< 2%), Greene told Medscape Medical News.
Currently, in the larger Tampa Bay community setting, about 12% of tests are positive.
The low percentage found among the Moffitt patients “tells you that a lot of cancer patients have fever and respiratory symptoms due to other viruses and, more importantly, other reasons, whether it’s their immunotherapy or chemotherapy or their cancer,” said Greene.
NCCN’s Carlson said the publication of the Chinese data was a good sign in terms of international science.
“This is a strong example of how the global oncology community rapidly shares information and experience whenever it makes a difference in patient care,” he commented.
The authors, as well as Carlson and Greene, have reported no relevant financial relationships.
This article first appeared on Medscape.com.
Cardiovascular disease is implicated in link between air pollution and dementia
Virtually all of the association between air pollution and dementia seemed to occur through the presence or the development of cardiovascular disease, which suggests a need to optimize treatment of concurrent cardiovascular disease and risk-factor control in older adults at higher risk for dementia and living in polluted urban areas, said lead author Giulia Grande, MD, a researcher at the Aging Research Center, Karolinska Institutet and Stockholm University, in Solna, Sweden.
In the longitudinal, population-based cohort study, investigators studied 2,927 randomly selected residents in a district of Stockholm who were aged 60 years or older (mean, 74.1 years), lived at home or in institutions, and were free of dementia at baseline (March 2001 through August 2004).
The investigators assessed the participants’ exposure to two major air pollutants – particulate matter ≤2.5 mcm and nitrogen oxide – yearly starting in 1990, from outdoor levels at their residential addresses. Both pollutants are generated by road traffic, among other sources.
Results reported in JAMA Neurology showed that, with a mean follow-up of 6.01 years, 12.4% of the older adults received a dementia diagnosis.
Dementia risk increased with the level of air pollutants at their residential address in the past, with strongest associations seen for exposure in the preceding 5 years: The hazard ratio (HR) for dementia was 1.54 for an interquartile range difference of 0.88 mcg/m3 in particulate matter ≤2.5 mcm and 1.14 for an interquartile range difference of 8.35 mcg/m3 in nitrogen oxide during that time period.
Of note, the study cohort lived in an area having “comparatively good ambient air quality” in which restrictions on air pollution have increased in recent decades, Dr. Grande and coinvestigators noted. “Interestingly, the higher limit reported herein is not only below the current European limit for fine particulate matter but also below the US standard. In other words, we were able to establish harmful effects at levels below current standards,” they wrote.
In analyses of effect modification, the elevation of risk related to particulate matter ≤2.5 mcm exposure and nitrogen oxide exposure was significantly greater among older adults who had heart failure (HRs, 1.93 and 1.43, respectively). Risk was marginally greater among those with ischemic heart disease (HRs, 1.67 and 1.36, respectively).
Analyses of potential mediators showed that preceding stroke accounted for the largest share of all dementia cases related to particulate matter ≤2.5 mcm exposure, at 49.4%.
The stronger association for exposure in the past 5 years is noteworthy for the big picture, they added. “From a policy point of view, this result is encouraging because it might imply that reducing air pollutant levels today could yield better outcomes already in the shorter term, reinforcing the need for appropriately set air quality standards,” they said.
Dr. Grande disclosed no relevant conflicts of interest. The study was funded by the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K); the Swedish Ministry of Health and Social Affairs; the participating County Councils and Municipalities; the Swedish Research Council; funding for doctoral education from the Karolinska Institutet; and the Swedish Research Council for Health, Working Life and Welfare.
SOURCE: Grande G et al. JAMA Neurol. 2020. doi:10.1001/jamaneurol.2019.4914.
Virtually all of the association between air pollution and dementia seemed to occur through the presence or the development of cardiovascular disease, which suggests a need to optimize treatment of concurrent cardiovascular disease and risk-factor control in older adults at higher risk for dementia and living in polluted urban areas, said lead author Giulia Grande, MD, a researcher at the Aging Research Center, Karolinska Institutet and Stockholm University, in Solna, Sweden.
In the longitudinal, population-based cohort study, investigators studied 2,927 randomly selected residents in a district of Stockholm who were aged 60 years or older (mean, 74.1 years), lived at home or in institutions, and were free of dementia at baseline (March 2001 through August 2004).
The investigators assessed the participants’ exposure to two major air pollutants – particulate matter ≤2.5 mcm and nitrogen oxide – yearly starting in 1990, from outdoor levels at their residential addresses. Both pollutants are generated by road traffic, among other sources.
Results reported in JAMA Neurology showed that, with a mean follow-up of 6.01 years, 12.4% of the older adults received a dementia diagnosis.
Dementia risk increased with the level of air pollutants at their residential address in the past, with strongest associations seen for exposure in the preceding 5 years: The hazard ratio (HR) for dementia was 1.54 for an interquartile range difference of 0.88 mcg/m3 in particulate matter ≤2.5 mcm and 1.14 for an interquartile range difference of 8.35 mcg/m3 in nitrogen oxide during that time period.
Of note, the study cohort lived in an area having “comparatively good ambient air quality” in which restrictions on air pollution have increased in recent decades, Dr. Grande and coinvestigators noted. “Interestingly, the higher limit reported herein is not only below the current European limit for fine particulate matter but also below the US standard. In other words, we were able to establish harmful effects at levels below current standards,” they wrote.
In analyses of effect modification, the elevation of risk related to particulate matter ≤2.5 mcm exposure and nitrogen oxide exposure was significantly greater among older adults who had heart failure (HRs, 1.93 and 1.43, respectively). Risk was marginally greater among those with ischemic heart disease (HRs, 1.67 and 1.36, respectively).
Analyses of potential mediators showed that preceding stroke accounted for the largest share of all dementia cases related to particulate matter ≤2.5 mcm exposure, at 49.4%.
The stronger association for exposure in the past 5 years is noteworthy for the big picture, they added. “From a policy point of view, this result is encouraging because it might imply that reducing air pollutant levels today could yield better outcomes already in the shorter term, reinforcing the need for appropriately set air quality standards,” they said.
Dr. Grande disclosed no relevant conflicts of interest. The study was funded by the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K); the Swedish Ministry of Health and Social Affairs; the participating County Councils and Municipalities; the Swedish Research Council; funding for doctoral education from the Karolinska Institutet; and the Swedish Research Council for Health, Working Life and Welfare.
SOURCE: Grande G et al. JAMA Neurol. 2020. doi:10.1001/jamaneurol.2019.4914.
Virtually all of the association between air pollution and dementia seemed to occur through the presence or the development of cardiovascular disease, which suggests a need to optimize treatment of concurrent cardiovascular disease and risk-factor control in older adults at higher risk for dementia and living in polluted urban areas, said lead author Giulia Grande, MD, a researcher at the Aging Research Center, Karolinska Institutet and Stockholm University, in Solna, Sweden.
In the longitudinal, population-based cohort study, investigators studied 2,927 randomly selected residents in a district of Stockholm who were aged 60 years or older (mean, 74.1 years), lived at home or in institutions, and were free of dementia at baseline (March 2001 through August 2004).
The investigators assessed the participants’ exposure to two major air pollutants – particulate matter ≤2.5 mcm and nitrogen oxide – yearly starting in 1990, from outdoor levels at their residential addresses. Both pollutants are generated by road traffic, among other sources.
Results reported in JAMA Neurology showed that, with a mean follow-up of 6.01 years, 12.4% of the older adults received a dementia diagnosis.
Dementia risk increased with the level of air pollutants at their residential address in the past, with strongest associations seen for exposure in the preceding 5 years: The hazard ratio (HR) for dementia was 1.54 for an interquartile range difference of 0.88 mcg/m3 in particulate matter ≤2.5 mcm and 1.14 for an interquartile range difference of 8.35 mcg/m3 in nitrogen oxide during that time period.
Of note, the study cohort lived in an area having “comparatively good ambient air quality” in which restrictions on air pollution have increased in recent decades, Dr. Grande and coinvestigators noted. “Interestingly, the higher limit reported herein is not only below the current European limit for fine particulate matter but also below the US standard. In other words, we were able to establish harmful effects at levels below current standards,” they wrote.
In analyses of effect modification, the elevation of risk related to particulate matter ≤2.5 mcm exposure and nitrogen oxide exposure was significantly greater among older adults who had heart failure (HRs, 1.93 and 1.43, respectively). Risk was marginally greater among those with ischemic heart disease (HRs, 1.67 and 1.36, respectively).
Analyses of potential mediators showed that preceding stroke accounted for the largest share of all dementia cases related to particulate matter ≤2.5 mcm exposure, at 49.4%.
The stronger association for exposure in the past 5 years is noteworthy for the big picture, they added. “From a policy point of view, this result is encouraging because it might imply that reducing air pollutant levels today could yield better outcomes already in the shorter term, reinforcing the need for appropriately set air quality standards,” they said.
Dr. Grande disclosed no relevant conflicts of interest. The study was funded by the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K); the Swedish Ministry of Health and Social Affairs; the participating County Councils and Municipalities; the Swedish Research Council; funding for doctoral education from the Karolinska Institutet; and the Swedish Research Council for Health, Working Life and Welfare.
SOURCE: Grande G et al. JAMA Neurol. 2020. doi:10.1001/jamaneurol.2019.4914.
FROM JAMA NEUROLOGY
CARAVAGGIO expands DOAC pool in cancer-related VTE
Oral apixaban (Eliquis, Bristol-Myers Squibb/Pfizer) was as effective as subcutaneous dalteparin (Fragmin, Pfizer) for cancer-related venous thromboembolism (VTE) without an increased risk of major bleeding, the CARAVAGGIO study suggests.
Over 6 months of follow-up, the primary efficacy outcome of recurrent thromboembolism occurred in 32 of 576 patients (5.6%) randomly assigned to apixaban and in 46 of 579 patients (7.9%) assigned dalteparin (hazard ratio, 0.63; 95% confidence interval, 0.37-1.07). The risk difference met the criteria for noninferiority (P < .001) but not for superiority (P = .09).
The risk for major bleeding was similar in the apixaban and dalteparin groups (3.8% and 4.0%; P = .60), including major gastrointestinal (GI) bleeds (11 vs 10 events).
There was a numeric excess of clinically relevant nonmajor bleeding in the apixaban group (9.0% vs 6.0%; HR, 1.42; 95% CI, 0.88-2.30).
However, the site of this bleeding “was essentially the genitourinary tract and the upper respiratory tract, so again there was no increase in gastrointestinal bleeding, even when the clinically relevant major bleeding was considered,” said lead author Giancarlo Agnelli, MD, University of Perugia, Italy.
Taken together, “We believe that the findings of CARAVAGGIO expand the proportion of patients with cancer-associated thrombosis who are eligible for treatment with oral direct anticoagulants, including patients with gastrointestinal cancer,” he concluded.
The findings were presented online March 29 at the American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology (WCC) and published simultaneously in the New England Journal of Medicine.
Major guidelines recommend the use of low-molecular-weight heparin (LMWH) for the treatment of cancer-related VTE but also support the use of edoxaban (Savaysa, Daiichi Sankyo) and rivaroxaban (Xarelto, Janssen Pharmaceuticals) as an alternative based on data from the OKUSAI VTE and SELECT-D trials, respectively. But an increased risk for bleeding was observed among patients with GI cancer in both studies.
“The findings are of clinical relevance because we were able to confirm the efficacy of another [novel oral anticoagulant] NOAC but we have the absence of bleeding, GI bleeding in particular. This is an important point; this is what the clinical community is looking for,” Agnelli told theheart.org | Medscape Cardiology.
The recent ADAM VTE trial testing apixaban, a factor Xa inhibitor, vs dalteparin, a LMWH, reported no major bleeding among patients treated with apixaban (primary safety endpoint) and a significant reduction of VTE (secondary efficacy endpoint). But the trial included only 300 patients with cancer and a more selected population compared with the CARAVAGGIO trial, noted Chiara Melloni, MD, MHS, a cardiologist at Duke Clinical Research Institute, Durham, North Carolina, who was not involved with the trial.
“The trial presented today by Prof. Agnelli provides evidence that apixaban represents an additional valid option, next to edoxaban and rivaroxaban, for the treatment of VTE in cancer patients,” she told theheart.org | Medscape Cardiology in an email. “The subgroup analyses showed consistent results across all different subgroups, but a significant interaction was observed between age groups, with a more favorable profile among those less than 75 years old (and mostly among those <65 years old). This may require more investigation.”
The CARAVAGGIO investigators randomly assigned 576 consecutive patients with cancer who had newly diagnosed symptomatic or incidental acute proximal deep-vein thrombosis or pulmonary embolism to receive apixaban 10 mg twice daily for 7 days followed by 5 mg twice daily or subcutaneous dalteparin 200 IU per kg once daily for 1 month followed by 150 U/kg once daily, both for a total of 6 months. Dose reduction was allowed for dalteparin but not for apixaban during the study.
Various types of cancer were included in the trial, including lung, breast, genitourinary, and upper GI.
The incidence of death was similar in the apixaban and dalteparin groups (23.4% vs 26.4%), with most deaths related to cancer (85.2% vs 88.2%, respectively).
During a discussion of the findings, panelist Bonnie Ky, MD, from the Hospital of the University of Pennsylvania in Philadelphia, and editor in chief of JACC: CardioOncology, congratulated the authors on an “excellent, well-done study” in a high-need cancer population suffering from a clinically significant burden of VTE, reported to be anywhere from 8% to 19% depending on tumor type.
“I was particularly impressed by the low rate of bleeding, which has been traditionally a concern with DOACs, as well the demonstration of noninferiority of apixaban,” she said.
Ky asked why the bleeding rate was lower than observed in other published studies and in whom clinicians shouldn’t be considering apixaban now.
Agnelli said that a head-to-head study is needed to compare the various oral anticoagulant agents but that the gastrointestinal bleeding rate is well known to be reduced with apixaban in patients with atrial fibrillation.
“So whether this is related to the drug or the administration twice daily, it’s something that can be discussed, but honestly the final solution would be to have a comparative study,” he said. “It’s going to be difficult, but it’s what we need.”
As to the clinical application of the data, Agnelli said, “The apixaban data actually extend the number of our patients who could receive the oral agents, including patients with GI cancer. So I do believe this indication about using DOACs in cancer patients will change and the indication expanded. But of course, we are building on something that was already known. We did not discover this all by ourselves.”
Panelist Robert M. Carey, MD, a leader in cardiovascular endocrinology and dean emeritus, University of Virginia School of Medicine in Charlottesville, said the study “conclusively shows noninferiority” but asked for more detail on the subset of patients with GI malignancies and the bleeding rate there.
Agnelli replied that the proportion and number of these patients in CARAVAGGIO is the same as, if not slightly higher than, in other studies. “So we have a population that is representative of all the cancer population, including GI cancer,” he said, adding that subanalyses are underway correlating the site of cancer with the type of bleeding.
Agnes Y.Y. Lee, MD, University of British Columbia, Vancouver Coastal Health, and the British Cancer Agency, all in Vancouver, Canada, notes in a linked editorial that CARAVAGGIO excluded patients with primary and metastatic brain lesions and included few patients with cancers of the upper GI tract, with hematologic cancers, or receiving newer cancer therapies, such as checkpoint inhibitors.
She says clinicians will have to choose carefully which anticoagulant to use but that LMWH is “preferred in patients in whom drug-drug interaction is a concern and in those who have undergone surgery involving the upper gastrointestinal tract because absorption of all direct oral anticoagulants occurs in the stomach or proximal small bowel.”
Warfarin may also be the only option when cost is the “decision driver” in patients with cancer facing major financial healthcare burdens, Lee writes.
Duke’s Melloni also said the cost of oral anticoagulants needs to be taken into account and varies widely for patients based on their insurance and availability of other copay assistance programs. “It is therefore important to discuss with the patients upfront because if the patients are started but cannot afford long term, early discontinuation can impact their safety,” she said.
The trial was sponsored by FADOI (Federazione delle Associazioni dei Dirigenti Ospedalieri Internisti) and was funded by an unrestricted grant from the Bristol-Myers Squibb-Pfizer Alliance. Agnelli reports personal fees from Pfizer and Bayer Healthcare, and “other” from Daiichi Sankyo outside the submitted work. Melloni reports having no relevant conflicts of interest. Lee reports personal fees and nonfinancial support from Bayer; grants, personal fees, and nonfinancial support from Bristol-Myers Squibb; and personal fees from LEO Pharma, Pfizer, and Quercegen Pharmaceuticals outside the submitted work.
This article first appeared on Medscape.com.
Oral apixaban (Eliquis, Bristol-Myers Squibb/Pfizer) was as effective as subcutaneous dalteparin (Fragmin, Pfizer) for cancer-related venous thromboembolism (VTE) without an increased risk of major bleeding, the CARAVAGGIO study suggests.
Over 6 months of follow-up, the primary efficacy outcome of recurrent thromboembolism occurred in 32 of 576 patients (5.6%) randomly assigned to apixaban and in 46 of 579 patients (7.9%) assigned dalteparin (hazard ratio, 0.63; 95% confidence interval, 0.37-1.07). The risk difference met the criteria for noninferiority (P < .001) but not for superiority (P = .09).
The risk for major bleeding was similar in the apixaban and dalteparin groups (3.8% and 4.0%; P = .60), including major gastrointestinal (GI) bleeds (11 vs 10 events).
There was a numeric excess of clinically relevant nonmajor bleeding in the apixaban group (9.0% vs 6.0%; HR, 1.42; 95% CI, 0.88-2.30).
However, the site of this bleeding “was essentially the genitourinary tract and the upper respiratory tract, so again there was no increase in gastrointestinal bleeding, even when the clinically relevant major bleeding was considered,” said lead author Giancarlo Agnelli, MD, University of Perugia, Italy.
Taken together, “We believe that the findings of CARAVAGGIO expand the proportion of patients with cancer-associated thrombosis who are eligible for treatment with oral direct anticoagulants, including patients with gastrointestinal cancer,” he concluded.
The findings were presented online March 29 at the American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology (WCC) and published simultaneously in the New England Journal of Medicine.
Major guidelines recommend the use of low-molecular-weight heparin (LMWH) for the treatment of cancer-related VTE but also support the use of edoxaban (Savaysa, Daiichi Sankyo) and rivaroxaban (Xarelto, Janssen Pharmaceuticals) as an alternative based on data from the OKUSAI VTE and SELECT-D trials, respectively. But an increased risk for bleeding was observed among patients with GI cancer in both studies.
“The findings are of clinical relevance because we were able to confirm the efficacy of another [novel oral anticoagulant] NOAC but we have the absence of bleeding, GI bleeding in particular. This is an important point; this is what the clinical community is looking for,” Agnelli told theheart.org | Medscape Cardiology.
The recent ADAM VTE trial testing apixaban, a factor Xa inhibitor, vs dalteparin, a LMWH, reported no major bleeding among patients treated with apixaban (primary safety endpoint) and a significant reduction of VTE (secondary efficacy endpoint). But the trial included only 300 patients with cancer and a more selected population compared with the CARAVAGGIO trial, noted Chiara Melloni, MD, MHS, a cardiologist at Duke Clinical Research Institute, Durham, North Carolina, who was not involved with the trial.
“The trial presented today by Prof. Agnelli provides evidence that apixaban represents an additional valid option, next to edoxaban and rivaroxaban, for the treatment of VTE in cancer patients,” she told theheart.org | Medscape Cardiology in an email. “The subgroup analyses showed consistent results across all different subgroups, but a significant interaction was observed between age groups, with a more favorable profile among those less than 75 years old (and mostly among those <65 years old). This may require more investigation.”
The CARAVAGGIO investigators randomly assigned 576 consecutive patients with cancer who had newly diagnosed symptomatic or incidental acute proximal deep-vein thrombosis or pulmonary embolism to receive apixaban 10 mg twice daily for 7 days followed by 5 mg twice daily or subcutaneous dalteparin 200 IU per kg once daily for 1 month followed by 150 U/kg once daily, both for a total of 6 months. Dose reduction was allowed for dalteparin but not for apixaban during the study.
Various types of cancer were included in the trial, including lung, breast, genitourinary, and upper GI.
The incidence of death was similar in the apixaban and dalteparin groups (23.4% vs 26.4%), with most deaths related to cancer (85.2% vs 88.2%, respectively).
During a discussion of the findings, panelist Bonnie Ky, MD, from the Hospital of the University of Pennsylvania in Philadelphia, and editor in chief of JACC: CardioOncology, congratulated the authors on an “excellent, well-done study” in a high-need cancer population suffering from a clinically significant burden of VTE, reported to be anywhere from 8% to 19% depending on tumor type.
“I was particularly impressed by the low rate of bleeding, which has been traditionally a concern with DOACs, as well the demonstration of noninferiority of apixaban,” she said.
Ky asked why the bleeding rate was lower than observed in other published studies and in whom clinicians shouldn’t be considering apixaban now.
Agnelli said that a head-to-head study is needed to compare the various oral anticoagulant agents but that the gastrointestinal bleeding rate is well known to be reduced with apixaban in patients with atrial fibrillation.
“So whether this is related to the drug or the administration twice daily, it’s something that can be discussed, but honestly the final solution would be to have a comparative study,” he said. “It’s going to be difficult, but it’s what we need.”
As to the clinical application of the data, Agnelli said, “The apixaban data actually extend the number of our patients who could receive the oral agents, including patients with GI cancer. So I do believe this indication about using DOACs in cancer patients will change and the indication expanded. But of course, we are building on something that was already known. We did not discover this all by ourselves.”
Panelist Robert M. Carey, MD, a leader in cardiovascular endocrinology and dean emeritus, University of Virginia School of Medicine in Charlottesville, said the study “conclusively shows noninferiority” but asked for more detail on the subset of patients with GI malignancies and the bleeding rate there.
Agnelli replied that the proportion and number of these patients in CARAVAGGIO is the same as, if not slightly higher than, in other studies. “So we have a population that is representative of all the cancer population, including GI cancer,” he said, adding that subanalyses are underway correlating the site of cancer with the type of bleeding.
Agnes Y.Y. Lee, MD, University of British Columbia, Vancouver Coastal Health, and the British Cancer Agency, all in Vancouver, Canada, notes in a linked editorial that CARAVAGGIO excluded patients with primary and metastatic brain lesions and included few patients with cancers of the upper GI tract, with hematologic cancers, or receiving newer cancer therapies, such as checkpoint inhibitors.
She says clinicians will have to choose carefully which anticoagulant to use but that LMWH is “preferred in patients in whom drug-drug interaction is a concern and in those who have undergone surgery involving the upper gastrointestinal tract because absorption of all direct oral anticoagulants occurs in the stomach or proximal small bowel.”
Warfarin may also be the only option when cost is the “decision driver” in patients with cancer facing major financial healthcare burdens, Lee writes.
Duke’s Melloni also said the cost of oral anticoagulants needs to be taken into account and varies widely for patients based on their insurance and availability of other copay assistance programs. “It is therefore important to discuss with the patients upfront because if the patients are started but cannot afford long term, early discontinuation can impact their safety,” she said.
The trial was sponsored by FADOI (Federazione delle Associazioni dei Dirigenti Ospedalieri Internisti) and was funded by an unrestricted grant from the Bristol-Myers Squibb-Pfizer Alliance. Agnelli reports personal fees from Pfizer and Bayer Healthcare, and “other” from Daiichi Sankyo outside the submitted work. Melloni reports having no relevant conflicts of interest. Lee reports personal fees and nonfinancial support from Bayer; grants, personal fees, and nonfinancial support from Bristol-Myers Squibb; and personal fees from LEO Pharma, Pfizer, and Quercegen Pharmaceuticals outside the submitted work.
This article first appeared on Medscape.com.
Oral apixaban (Eliquis, Bristol-Myers Squibb/Pfizer) was as effective as subcutaneous dalteparin (Fragmin, Pfizer) for cancer-related venous thromboembolism (VTE) without an increased risk of major bleeding, the CARAVAGGIO study suggests.
Over 6 months of follow-up, the primary efficacy outcome of recurrent thromboembolism occurred in 32 of 576 patients (5.6%) randomly assigned to apixaban and in 46 of 579 patients (7.9%) assigned dalteparin (hazard ratio, 0.63; 95% confidence interval, 0.37-1.07). The risk difference met the criteria for noninferiority (P < .001) but not for superiority (P = .09).
The risk for major bleeding was similar in the apixaban and dalteparin groups (3.8% and 4.0%; P = .60), including major gastrointestinal (GI) bleeds (11 vs 10 events).
There was a numeric excess of clinically relevant nonmajor bleeding in the apixaban group (9.0% vs 6.0%; HR, 1.42; 95% CI, 0.88-2.30).
However, the site of this bleeding “was essentially the genitourinary tract and the upper respiratory tract, so again there was no increase in gastrointestinal bleeding, even when the clinically relevant major bleeding was considered,” said lead author Giancarlo Agnelli, MD, University of Perugia, Italy.
Taken together, “We believe that the findings of CARAVAGGIO expand the proportion of patients with cancer-associated thrombosis who are eligible for treatment with oral direct anticoagulants, including patients with gastrointestinal cancer,” he concluded.
The findings were presented online March 29 at the American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology (WCC) and published simultaneously in the New England Journal of Medicine.
Major guidelines recommend the use of low-molecular-weight heparin (LMWH) for the treatment of cancer-related VTE but also support the use of edoxaban (Savaysa, Daiichi Sankyo) and rivaroxaban (Xarelto, Janssen Pharmaceuticals) as an alternative based on data from the OKUSAI VTE and SELECT-D trials, respectively. But an increased risk for bleeding was observed among patients with GI cancer in both studies.
“The findings are of clinical relevance because we were able to confirm the efficacy of another [novel oral anticoagulant] NOAC but we have the absence of bleeding, GI bleeding in particular. This is an important point; this is what the clinical community is looking for,” Agnelli told theheart.org | Medscape Cardiology.
The recent ADAM VTE trial testing apixaban, a factor Xa inhibitor, vs dalteparin, a LMWH, reported no major bleeding among patients treated with apixaban (primary safety endpoint) and a significant reduction of VTE (secondary efficacy endpoint). But the trial included only 300 patients with cancer and a more selected population compared with the CARAVAGGIO trial, noted Chiara Melloni, MD, MHS, a cardiologist at Duke Clinical Research Institute, Durham, North Carolina, who was not involved with the trial.
“The trial presented today by Prof. Agnelli provides evidence that apixaban represents an additional valid option, next to edoxaban and rivaroxaban, for the treatment of VTE in cancer patients,” she told theheart.org | Medscape Cardiology in an email. “The subgroup analyses showed consistent results across all different subgroups, but a significant interaction was observed between age groups, with a more favorable profile among those less than 75 years old (and mostly among those <65 years old). This may require more investigation.”
The CARAVAGGIO investigators randomly assigned 576 consecutive patients with cancer who had newly diagnosed symptomatic or incidental acute proximal deep-vein thrombosis or pulmonary embolism to receive apixaban 10 mg twice daily for 7 days followed by 5 mg twice daily or subcutaneous dalteparin 200 IU per kg once daily for 1 month followed by 150 U/kg once daily, both for a total of 6 months. Dose reduction was allowed for dalteparin but not for apixaban during the study.
Various types of cancer were included in the trial, including lung, breast, genitourinary, and upper GI.
The incidence of death was similar in the apixaban and dalteparin groups (23.4% vs 26.4%), with most deaths related to cancer (85.2% vs 88.2%, respectively).
During a discussion of the findings, panelist Bonnie Ky, MD, from the Hospital of the University of Pennsylvania in Philadelphia, and editor in chief of JACC: CardioOncology, congratulated the authors on an “excellent, well-done study” in a high-need cancer population suffering from a clinically significant burden of VTE, reported to be anywhere from 8% to 19% depending on tumor type.
“I was particularly impressed by the low rate of bleeding, which has been traditionally a concern with DOACs, as well the demonstration of noninferiority of apixaban,” she said.
Ky asked why the bleeding rate was lower than observed in other published studies and in whom clinicians shouldn’t be considering apixaban now.
Agnelli said that a head-to-head study is needed to compare the various oral anticoagulant agents but that the gastrointestinal bleeding rate is well known to be reduced with apixaban in patients with atrial fibrillation.
“So whether this is related to the drug or the administration twice daily, it’s something that can be discussed, but honestly the final solution would be to have a comparative study,” he said. “It’s going to be difficult, but it’s what we need.”
As to the clinical application of the data, Agnelli said, “The apixaban data actually extend the number of our patients who could receive the oral agents, including patients with GI cancer. So I do believe this indication about using DOACs in cancer patients will change and the indication expanded. But of course, we are building on something that was already known. We did not discover this all by ourselves.”
Panelist Robert M. Carey, MD, a leader in cardiovascular endocrinology and dean emeritus, University of Virginia School of Medicine in Charlottesville, said the study “conclusively shows noninferiority” but asked for more detail on the subset of patients with GI malignancies and the bleeding rate there.
Agnelli replied that the proportion and number of these patients in CARAVAGGIO is the same as, if not slightly higher than, in other studies. “So we have a population that is representative of all the cancer population, including GI cancer,” he said, adding that subanalyses are underway correlating the site of cancer with the type of bleeding.
Agnes Y.Y. Lee, MD, University of British Columbia, Vancouver Coastal Health, and the British Cancer Agency, all in Vancouver, Canada, notes in a linked editorial that CARAVAGGIO excluded patients with primary and metastatic brain lesions and included few patients with cancers of the upper GI tract, with hematologic cancers, or receiving newer cancer therapies, such as checkpoint inhibitors.
She says clinicians will have to choose carefully which anticoagulant to use but that LMWH is “preferred in patients in whom drug-drug interaction is a concern and in those who have undergone surgery involving the upper gastrointestinal tract because absorption of all direct oral anticoagulants occurs in the stomach or proximal small bowel.”
Warfarin may also be the only option when cost is the “decision driver” in patients with cancer facing major financial healthcare burdens, Lee writes.
Duke’s Melloni also said the cost of oral anticoagulants needs to be taken into account and varies widely for patients based on their insurance and availability of other copay assistance programs. “It is therefore important to discuss with the patients upfront because if the patients are started but cannot afford long term, early discontinuation can impact their safety,” she said.
The trial was sponsored by FADOI (Federazione delle Associazioni dei Dirigenti Ospedalieri Internisti) and was funded by an unrestricted grant from the Bristol-Myers Squibb-Pfizer Alliance. Agnelli reports personal fees from Pfizer and Bayer Healthcare, and “other” from Daiichi Sankyo outside the submitted work. Melloni reports having no relevant conflicts of interest. Lee reports personal fees and nonfinancial support from Bayer; grants, personal fees, and nonfinancial support from Bristol-Myers Squibb; and personal fees from LEO Pharma, Pfizer, and Quercegen Pharmaceuticals outside the submitted work.
This article first appeared on Medscape.com.
CLEOPATRA: Pertuzumab has long-term benefit in HER2+ breast cancer
, with nearly 40% of patients achieving long-term survival, the CLEOPATRA end-of-study analysis shows.
The regimen, combining dual HER2 targeting with chemotherapy, became standard of care in this population as a result of its good efficacy and safety relative to placebo, first established in the phase 3, randomized trial 8 years ago (N Engl J Med. 2012;366:109-19).
Trial updates since then, most recently at a median follow-up of 50 months (N Engl J Med. 2015;372:724-34), have shown clear progression-free and overall survival benefits, with acceptable cardiac and other toxicity.
Investigators led by Sandra M. Swain, MD, of Georgetown University, Washington, performed a final analysis of data from the 808 patients in CLEOPATRA, now at a median follow-up of 99.9 months.
Results reported in The Lancet Oncology showed that, compared with placebo, pertuzumab prolonged investigator-assessed progression-free survival by 6.3 months (the same as that seen in the previous update) and prolonged overall survival by 16.3 months (up from 15.7 months in the previous update).
At 8 years, 37% of patients in the pertuzumab group were still alive, and 16% were still alive without progression.
“The combination of pertuzumab, trastuzumab, and docetaxel remains the standard of care for the first-line treatment of HER2-positive metastatic breast cancer, owing to its overall survival benefits and maintained long-term overall and cardiac safety,” Dr. Swain and coinvestigators concluded. “Prospective identification of patients who will be long-term responders to treatment is an area for future research.”
In an accompanying comment, Matteo Lambertini, MD, PhD, of IRCCS Ospedale Policlinico San Martino in Genova, Italy, and Ines Vaz-Luis, MD, of Institut Gustave Roussy in Villejuif, France, contended that these results, “which are also observed in real-world datasets, challenge the concept of HER2-positive metastatic breast cancer being an incurable disease and open the path to several interconnected clinical and research questions.”
Those questions include the optimal duration of anti-HER2 maintenance therapy in patients without disease progression, best strategies for combining this systemic therapy with local treatment to further improve survival, and new markers to better identify patients likely to be long-term responders, who might benefit from a curative approach, the authors elaborated. They noted that more than half of CLEOPATRA patients had de novo stage IV disease.
“The performance of the current standard pertuzumab-based first-line treatment in patients previously exposed to adjuvant or neoadjuvant anti-HER2 therapy remains to be clarified,” the authors wrote. “Results from several ongoing prospective cohort studies investigating real-world patterns of care and outcomes of patients with HER2-positive metastatic breast cancer will help to clarify this important issue and optimize treatment sequencing.”
Study details
The end-of-study analysis showed that median progression-free survival was 18.7 months with pertuzumab and 12.4 months with placebo (hazard ratio, 0.69; 95% confidence interval, 0.59-0.81). The 8-year landmark progression-free survival rate was 16% with the former and 10% with the latter.
The median overall survival was 57.1 months with pertuzumab and 40.8 months with placebo (HR, 0.69; 95% CI, 0.58-0.82). The 8-year landmark overall survival rate was 37% with the former and 23% with the latter.
A comparison of patients who did and did not achieve long-term response showed that, in both treatment groups, the former more often had tumors that were 3+ positive by HER2 immunohistochemistry and PIK3CA wild-type tumors. The leading grade 3 or 4 adverse event was neutropenia, seen in 49% of patients in the pertuzumab group and 46% of those in the placebo group. The rate of treatment-related death was 1% and 2%, respectively.
Since the last update, only two additional serious adverse events were reported: one case of heart failure and one case of symptomatic left ventricular systolic dysfunction in patients given pertuzumab.
The CLEOPATRA trial was funded by F. Hoffmann-La Roche and Genentech. Dr. Swain and coauthors disclosed relationships with these and other companies. Dr. Lambertini disclosed relationships with Roche, Theramex, and Takeda. Dr. Vaz-Luis disclosed relationships with AstraZeneca, Kephren, and Novartis.
SOURCE: Swain SM et al. Lancet Oncol. 2020 Mar 12. doi: 10.1016/S1470-2045(19)30863-0; Lambertini M et al. Lancet Oncol. 2020 Mar 12. doi: 10.1016/S1470-2045(20)30058-9.
, with nearly 40% of patients achieving long-term survival, the CLEOPATRA end-of-study analysis shows.
The regimen, combining dual HER2 targeting with chemotherapy, became standard of care in this population as a result of its good efficacy and safety relative to placebo, first established in the phase 3, randomized trial 8 years ago (N Engl J Med. 2012;366:109-19).
Trial updates since then, most recently at a median follow-up of 50 months (N Engl J Med. 2015;372:724-34), have shown clear progression-free and overall survival benefits, with acceptable cardiac and other toxicity.
Investigators led by Sandra M. Swain, MD, of Georgetown University, Washington, performed a final analysis of data from the 808 patients in CLEOPATRA, now at a median follow-up of 99.9 months.
Results reported in The Lancet Oncology showed that, compared with placebo, pertuzumab prolonged investigator-assessed progression-free survival by 6.3 months (the same as that seen in the previous update) and prolonged overall survival by 16.3 months (up from 15.7 months in the previous update).
At 8 years, 37% of patients in the pertuzumab group were still alive, and 16% were still alive without progression.
“The combination of pertuzumab, trastuzumab, and docetaxel remains the standard of care for the first-line treatment of HER2-positive metastatic breast cancer, owing to its overall survival benefits and maintained long-term overall and cardiac safety,” Dr. Swain and coinvestigators concluded. “Prospective identification of patients who will be long-term responders to treatment is an area for future research.”
In an accompanying comment, Matteo Lambertini, MD, PhD, of IRCCS Ospedale Policlinico San Martino in Genova, Italy, and Ines Vaz-Luis, MD, of Institut Gustave Roussy in Villejuif, France, contended that these results, “which are also observed in real-world datasets, challenge the concept of HER2-positive metastatic breast cancer being an incurable disease and open the path to several interconnected clinical and research questions.”
Those questions include the optimal duration of anti-HER2 maintenance therapy in patients without disease progression, best strategies for combining this systemic therapy with local treatment to further improve survival, and new markers to better identify patients likely to be long-term responders, who might benefit from a curative approach, the authors elaborated. They noted that more than half of CLEOPATRA patients had de novo stage IV disease.
“The performance of the current standard pertuzumab-based first-line treatment in patients previously exposed to adjuvant or neoadjuvant anti-HER2 therapy remains to be clarified,” the authors wrote. “Results from several ongoing prospective cohort studies investigating real-world patterns of care and outcomes of patients with HER2-positive metastatic breast cancer will help to clarify this important issue and optimize treatment sequencing.”
Study details
The end-of-study analysis showed that median progression-free survival was 18.7 months with pertuzumab and 12.4 months with placebo (hazard ratio, 0.69; 95% confidence interval, 0.59-0.81). The 8-year landmark progression-free survival rate was 16% with the former and 10% with the latter.
The median overall survival was 57.1 months with pertuzumab and 40.8 months with placebo (HR, 0.69; 95% CI, 0.58-0.82). The 8-year landmark overall survival rate was 37% with the former and 23% with the latter.
A comparison of patients who did and did not achieve long-term response showed that, in both treatment groups, the former more often had tumors that were 3+ positive by HER2 immunohistochemistry and PIK3CA wild-type tumors. The leading grade 3 or 4 adverse event was neutropenia, seen in 49% of patients in the pertuzumab group and 46% of those in the placebo group. The rate of treatment-related death was 1% and 2%, respectively.
Since the last update, only two additional serious adverse events were reported: one case of heart failure and one case of symptomatic left ventricular systolic dysfunction in patients given pertuzumab.
The CLEOPATRA trial was funded by F. Hoffmann-La Roche and Genentech. Dr. Swain and coauthors disclosed relationships with these and other companies. Dr. Lambertini disclosed relationships with Roche, Theramex, and Takeda. Dr. Vaz-Luis disclosed relationships with AstraZeneca, Kephren, and Novartis.
SOURCE: Swain SM et al. Lancet Oncol. 2020 Mar 12. doi: 10.1016/S1470-2045(19)30863-0; Lambertini M et al. Lancet Oncol. 2020 Mar 12. doi: 10.1016/S1470-2045(20)30058-9.
, with nearly 40% of patients achieving long-term survival, the CLEOPATRA end-of-study analysis shows.
The regimen, combining dual HER2 targeting with chemotherapy, became standard of care in this population as a result of its good efficacy and safety relative to placebo, first established in the phase 3, randomized trial 8 years ago (N Engl J Med. 2012;366:109-19).
Trial updates since then, most recently at a median follow-up of 50 months (N Engl J Med. 2015;372:724-34), have shown clear progression-free and overall survival benefits, with acceptable cardiac and other toxicity.
Investigators led by Sandra M. Swain, MD, of Georgetown University, Washington, performed a final analysis of data from the 808 patients in CLEOPATRA, now at a median follow-up of 99.9 months.
Results reported in The Lancet Oncology showed that, compared with placebo, pertuzumab prolonged investigator-assessed progression-free survival by 6.3 months (the same as that seen in the previous update) and prolonged overall survival by 16.3 months (up from 15.7 months in the previous update).
At 8 years, 37% of patients in the pertuzumab group were still alive, and 16% were still alive without progression.
“The combination of pertuzumab, trastuzumab, and docetaxel remains the standard of care for the first-line treatment of HER2-positive metastatic breast cancer, owing to its overall survival benefits and maintained long-term overall and cardiac safety,” Dr. Swain and coinvestigators concluded. “Prospective identification of patients who will be long-term responders to treatment is an area for future research.”
In an accompanying comment, Matteo Lambertini, MD, PhD, of IRCCS Ospedale Policlinico San Martino in Genova, Italy, and Ines Vaz-Luis, MD, of Institut Gustave Roussy in Villejuif, France, contended that these results, “which are also observed in real-world datasets, challenge the concept of HER2-positive metastatic breast cancer being an incurable disease and open the path to several interconnected clinical and research questions.”
Those questions include the optimal duration of anti-HER2 maintenance therapy in patients without disease progression, best strategies for combining this systemic therapy with local treatment to further improve survival, and new markers to better identify patients likely to be long-term responders, who might benefit from a curative approach, the authors elaborated. They noted that more than half of CLEOPATRA patients had de novo stage IV disease.
“The performance of the current standard pertuzumab-based first-line treatment in patients previously exposed to adjuvant or neoadjuvant anti-HER2 therapy remains to be clarified,” the authors wrote. “Results from several ongoing prospective cohort studies investigating real-world patterns of care and outcomes of patients with HER2-positive metastatic breast cancer will help to clarify this important issue and optimize treatment sequencing.”
Study details
The end-of-study analysis showed that median progression-free survival was 18.7 months with pertuzumab and 12.4 months with placebo (hazard ratio, 0.69; 95% confidence interval, 0.59-0.81). The 8-year landmark progression-free survival rate was 16% with the former and 10% with the latter.
The median overall survival was 57.1 months with pertuzumab and 40.8 months with placebo (HR, 0.69; 95% CI, 0.58-0.82). The 8-year landmark overall survival rate was 37% with the former and 23% with the latter.
A comparison of patients who did and did not achieve long-term response showed that, in both treatment groups, the former more often had tumors that were 3+ positive by HER2 immunohistochemistry and PIK3CA wild-type tumors. The leading grade 3 or 4 adverse event was neutropenia, seen in 49% of patients in the pertuzumab group and 46% of those in the placebo group. The rate of treatment-related death was 1% and 2%, respectively.
Since the last update, only two additional serious adverse events were reported: one case of heart failure and one case of symptomatic left ventricular systolic dysfunction in patients given pertuzumab.
The CLEOPATRA trial was funded by F. Hoffmann-La Roche and Genentech. Dr. Swain and coauthors disclosed relationships with these and other companies. Dr. Lambertini disclosed relationships with Roche, Theramex, and Takeda. Dr. Vaz-Luis disclosed relationships with AstraZeneca, Kephren, and Novartis.
SOURCE: Swain SM et al. Lancet Oncol. 2020 Mar 12. doi: 10.1016/S1470-2045(19)30863-0; Lambertini M et al. Lancet Oncol. 2020 Mar 12. doi: 10.1016/S1470-2045(20)30058-9.
FROM LANCET ONCOLOGY
Guidelines on delaying cancer surgery during COVID-19
Cancer surgeries may need to be delayed as hospitals are forced to allocate resources to a surge of COVID-19 patients, says the American College of Surgeons, as it issues a new set of recommendations in reaction to the crisis.
Most surgeons have already curtailed or have ceased to perform elective operations, the ACS notes, and recommends that surgeons continue to do so in order to preserve the necessary resources for care of critically ill patients during the COVID-19 pandemic. The new clinical guidance for elective surgical case triage during the pandemic includes recommendations for cancer surgery as well as for procedures that are specific to certain cancer types.
“These triage guidelines and joint recommendations are being issued as we appear to be entering a new phase of the COVID-19 pandemic with more hospitals facing a potential push beyond their resources to care for critically ill patients,” commented ACS Executive Director David B. Hoyt, MD, in a statement.
“ACS will continue to monitor the landscape for surgical care but we feel this guidance document provides a good foundation for surgeons to begin enacting these triage recommendations today to help them make the best decisions possible for their patients during COVID-19,” he said.
For cancer surgery, which is often not elective but essential to treatment, ACS has issued general guidance for triaging patients, taking into account the acuity of the local COVID-19 situation.
First, decisions about whether to proceed with elective surgeries must consider the available resources of local facilities. The parties responsible for preparing the facility to manage coronavirus patients should be sharing information at regular intervals about constraints on local resources, especially personal protective equipment (PPE), which is running low in many jurisdictions. For example, if an elective case has a high likelihood of needing postoperative ICU care, it is imperative to balance the risk of delay against the need of availability for patients with COVID-19.
Second, cancer care coordination should use virtual technologies as much as possible, and facilities with tumor boards may find it helpful to locate multidisciplinary experts by virtual means, to assist with decision making and establishing triage criteria.
Three Phases of Pandemic
The ACS has also organized decision making into three phases that reflect the acuity of the local COVID-19 situation:
- Phase I. Semi-Urgent Setting (Preparation Phase) – few COVID-19 patients, hospital resources not exhausted, institution still has ICU ventilator capacity and COVID-19 trajectory not in rapid escalation phase
- Phase II. Urgent Setting – many COVID-19 patients, ICU and ventilator capacity limited, operating room supplies limited
- Phase III. Hospital resources are all routed to COVID-19 patients, no ventilator or ICU capacity, operating room supplies exhausted; patients in whom death is likely within hours if surgery is deferred
Breast Cancer Surgery
The ACS also issued specific guidance for several tumor types, including guidance for breast cancer surgery.
For phase I, surgery should be restricted to patients who are likely to experience compromised survival if it is not performed within next 3 months. This includes patients completing neoadjuvant treatment, those with clinical stage T2 or N1 ERpos/PRpos/HER2-negative tumors, patients with triple negative or HER2-positive tumors, discordant biopsies that are likely to be malignant, and removal of a recurrent lesion.
Phase II would be restricted to patients whose survival is threatened if surgery is not performed within the next few days. These would include incision and drainage of breast abscess, evacuating a hematoma, revision of an ischemic mastectomy flap, and revascularization/revision of an autologous tissue flap (autologous reconstruction should be deferred).
In Phase III, surgical procedures would be restricted to patients who may not survive if surgery is not performed within a few hours. This includes incision and drainage of breast abscess, evacuation of a hematoma, revision of an ischemic mastectomy flap, and revascularization/revision of an autologous tissue flap (autologous reconstruction should be deferred).
Colorectal Cancer Surgery
Guidance for colorectal cancer surgery is also split into the three phases of the pandemic.
Phase I would include cases needing surgical intervention as soon as feasible, while recognizing that the status of each hospital is likely to evolve over the next week or two. These patients would include those with nearly obstructing colon cancer or rectal cancer; cancers that require frequent transfusions; asymptomatic colon cancers; rectal cancers that do not respond to neoadjuvant chemoradiation; malignancies with a risk of local perforation and sepsis; and those with early stage rectal cancers that are not candidates for adjuvant therapy.
Phase II comprises patients needing surgery as soon as feasible, but recognizing that hospital status is likely to progress over the next few days. These cases include patients with a nearly obstructing colon cancer where stenting is not an option; those with nearly obstructing rectal cancer (should be diverted); cancers with high (inpatient) transfusion requirements; and cancers with pending evidence of local perforation and sepsis.
All colorectal procedures typically scheduled as routine should be delayed.
In Phase III, if the status of the facility is likely to progress within hours, the only surgery that should be performed would be for perforated, obstructed, or actively bleeding (inpatient transfusion dependent) cancers or those with sepsis. All other surgeries should be deferred.
Thoracic Cancer Surgery
Thoracic cancer surgery guidelines follow those for breast cancer. Phase I should be restricted to patients whose survival may be impacted if surgery is not performed within next 3 months. These include:
- Cases with solid or predominantly solid (>50%) lung cancer or presumed lung cancer (>2 cm), clinical node negative
- Node positive lung cancer
- Post-induction therapy cancer
- Esophageal cancer T1b or greater
- Chest wall tumors that are potentially aggressive and not manageable by alternative means
- Stenting for obstructing esophageal tumor
- Staging to start treatment (mediastinoscopy, diagnostic VATS for pleural dissemination)
- Symptomatic mediastinal tumors
- Patients who are enrolled in therapeutic clinical trials.
Phase II would permit surgery if survival will be impacted by a delay of a few days. These cases would include nonseptic perforated cancer of esophagus, a tumor-associated infection, and management of surgical complications in a hemodynamically stable patient.
All thoracic procedures considered to be routine/elective would be deferred.
Phase III restricts surgery to patients whose survival will be compromised if they do not undergo surgery within the next few hours. This group would include perforated cancer of esophagus in a septic patient, a patient with a threatened airway, sepsis associated with the cancer, and management of surgical complications in an unstable patient (active bleeding that requires surgery, dehiscence of airway, anastomotic leak with sepsis).
All other cases would be deferred.
Other Cancer Types
Although the ACS doesn’t have specific guidelines for all cancer types, a few are included in their general recommendations for the specialty.
For gynecologic surgeries, ACS lists cancer or suspected cancer as indications where significantly delayed surgery could cause “significant harm.”
Delays, in general, are not recommended for neurosurgery, which would include brain cancers. In pediatrics, most cancer surgery is considered “urgent,” where a delay of days to weeks could prove detrimental to the patient. This would comprise all solid tumors, including the initial biopsy and resection following neoadjuvant therapy.
This article first appeared on Medscape.com.
Cancer surgeries may need to be delayed as hospitals are forced to allocate resources to a surge of COVID-19 patients, says the American College of Surgeons, as it issues a new set of recommendations in reaction to the crisis.
Most surgeons have already curtailed or have ceased to perform elective operations, the ACS notes, and recommends that surgeons continue to do so in order to preserve the necessary resources for care of critically ill patients during the COVID-19 pandemic. The new clinical guidance for elective surgical case triage during the pandemic includes recommendations for cancer surgery as well as for procedures that are specific to certain cancer types.
“These triage guidelines and joint recommendations are being issued as we appear to be entering a new phase of the COVID-19 pandemic with more hospitals facing a potential push beyond their resources to care for critically ill patients,” commented ACS Executive Director David B. Hoyt, MD, in a statement.
“ACS will continue to monitor the landscape for surgical care but we feel this guidance document provides a good foundation for surgeons to begin enacting these triage recommendations today to help them make the best decisions possible for their patients during COVID-19,” he said.
For cancer surgery, which is often not elective but essential to treatment, ACS has issued general guidance for triaging patients, taking into account the acuity of the local COVID-19 situation.
First, decisions about whether to proceed with elective surgeries must consider the available resources of local facilities. The parties responsible for preparing the facility to manage coronavirus patients should be sharing information at regular intervals about constraints on local resources, especially personal protective equipment (PPE), which is running low in many jurisdictions. For example, if an elective case has a high likelihood of needing postoperative ICU care, it is imperative to balance the risk of delay against the need of availability for patients with COVID-19.
Second, cancer care coordination should use virtual technologies as much as possible, and facilities with tumor boards may find it helpful to locate multidisciplinary experts by virtual means, to assist with decision making and establishing triage criteria.
Three Phases of Pandemic
The ACS has also organized decision making into three phases that reflect the acuity of the local COVID-19 situation:
- Phase I. Semi-Urgent Setting (Preparation Phase) – few COVID-19 patients, hospital resources not exhausted, institution still has ICU ventilator capacity and COVID-19 trajectory not in rapid escalation phase
- Phase II. Urgent Setting – many COVID-19 patients, ICU and ventilator capacity limited, operating room supplies limited
- Phase III. Hospital resources are all routed to COVID-19 patients, no ventilator or ICU capacity, operating room supplies exhausted; patients in whom death is likely within hours if surgery is deferred
Breast Cancer Surgery
The ACS also issued specific guidance for several tumor types, including guidance for breast cancer surgery.
For phase I, surgery should be restricted to patients who are likely to experience compromised survival if it is not performed within next 3 months. This includes patients completing neoadjuvant treatment, those with clinical stage T2 or N1 ERpos/PRpos/HER2-negative tumors, patients with triple negative or HER2-positive tumors, discordant biopsies that are likely to be malignant, and removal of a recurrent lesion.
Phase II would be restricted to patients whose survival is threatened if surgery is not performed within the next few days. These would include incision and drainage of breast abscess, evacuating a hematoma, revision of an ischemic mastectomy flap, and revascularization/revision of an autologous tissue flap (autologous reconstruction should be deferred).
In Phase III, surgical procedures would be restricted to patients who may not survive if surgery is not performed within a few hours. This includes incision and drainage of breast abscess, evacuation of a hematoma, revision of an ischemic mastectomy flap, and revascularization/revision of an autologous tissue flap (autologous reconstruction should be deferred).
Colorectal Cancer Surgery
Guidance for colorectal cancer surgery is also split into the three phases of the pandemic.
Phase I would include cases needing surgical intervention as soon as feasible, while recognizing that the status of each hospital is likely to evolve over the next week or two. These patients would include those with nearly obstructing colon cancer or rectal cancer; cancers that require frequent transfusions; asymptomatic colon cancers; rectal cancers that do not respond to neoadjuvant chemoradiation; malignancies with a risk of local perforation and sepsis; and those with early stage rectal cancers that are not candidates for adjuvant therapy.
Phase II comprises patients needing surgery as soon as feasible, but recognizing that hospital status is likely to progress over the next few days. These cases include patients with a nearly obstructing colon cancer where stenting is not an option; those with nearly obstructing rectal cancer (should be diverted); cancers with high (inpatient) transfusion requirements; and cancers with pending evidence of local perforation and sepsis.
All colorectal procedures typically scheduled as routine should be delayed.
In Phase III, if the status of the facility is likely to progress within hours, the only surgery that should be performed would be for perforated, obstructed, or actively bleeding (inpatient transfusion dependent) cancers or those with sepsis. All other surgeries should be deferred.
Thoracic Cancer Surgery
Thoracic cancer surgery guidelines follow those for breast cancer. Phase I should be restricted to patients whose survival may be impacted if surgery is not performed within next 3 months. These include:
- Cases with solid or predominantly solid (>50%) lung cancer or presumed lung cancer (>2 cm), clinical node negative
- Node positive lung cancer
- Post-induction therapy cancer
- Esophageal cancer T1b or greater
- Chest wall tumors that are potentially aggressive and not manageable by alternative means
- Stenting for obstructing esophageal tumor
- Staging to start treatment (mediastinoscopy, diagnostic VATS for pleural dissemination)
- Symptomatic mediastinal tumors
- Patients who are enrolled in therapeutic clinical trials.
Phase II would permit surgery if survival will be impacted by a delay of a few days. These cases would include nonseptic perforated cancer of esophagus, a tumor-associated infection, and management of surgical complications in a hemodynamically stable patient.
All thoracic procedures considered to be routine/elective would be deferred.
Phase III restricts surgery to patients whose survival will be compromised if they do not undergo surgery within the next few hours. This group would include perforated cancer of esophagus in a septic patient, a patient with a threatened airway, sepsis associated with the cancer, and management of surgical complications in an unstable patient (active bleeding that requires surgery, dehiscence of airway, anastomotic leak with sepsis).
All other cases would be deferred.
Other Cancer Types
Although the ACS doesn’t have specific guidelines for all cancer types, a few are included in their general recommendations for the specialty.
For gynecologic surgeries, ACS lists cancer or suspected cancer as indications where significantly delayed surgery could cause “significant harm.”
Delays, in general, are not recommended for neurosurgery, which would include brain cancers. In pediatrics, most cancer surgery is considered “urgent,” where a delay of days to weeks could prove detrimental to the patient. This would comprise all solid tumors, including the initial biopsy and resection following neoadjuvant therapy.
This article first appeared on Medscape.com.
Cancer surgeries may need to be delayed as hospitals are forced to allocate resources to a surge of COVID-19 patients, says the American College of Surgeons, as it issues a new set of recommendations in reaction to the crisis.
Most surgeons have already curtailed or have ceased to perform elective operations, the ACS notes, and recommends that surgeons continue to do so in order to preserve the necessary resources for care of critically ill patients during the COVID-19 pandemic. The new clinical guidance for elective surgical case triage during the pandemic includes recommendations for cancer surgery as well as for procedures that are specific to certain cancer types.
“These triage guidelines and joint recommendations are being issued as we appear to be entering a new phase of the COVID-19 pandemic with more hospitals facing a potential push beyond their resources to care for critically ill patients,” commented ACS Executive Director David B. Hoyt, MD, in a statement.
“ACS will continue to monitor the landscape for surgical care but we feel this guidance document provides a good foundation for surgeons to begin enacting these triage recommendations today to help them make the best decisions possible for their patients during COVID-19,” he said.
For cancer surgery, which is often not elective but essential to treatment, ACS has issued general guidance for triaging patients, taking into account the acuity of the local COVID-19 situation.
First, decisions about whether to proceed with elective surgeries must consider the available resources of local facilities. The parties responsible for preparing the facility to manage coronavirus patients should be sharing information at regular intervals about constraints on local resources, especially personal protective equipment (PPE), which is running low in many jurisdictions. For example, if an elective case has a high likelihood of needing postoperative ICU care, it is imperative to balance the risk of delay against the need of availability for patients with COVID-19.
Second, cancer care coordination should use virtual technologies as much as possible, and facilities with tumor boards may find it helpful to locate multidisciplinary experts by virtual means, to assist with decision making and establishing triage criteria.
Three Phases of Pandemic
The ACS has also organized decision making into three phases that reflect the acuity of the local COVID-19 situation:
- Phase I. Semi-Urgent Setting (Preparation Phase) – few COVID-19 patients, hospital resources not exhausted, institution still has ICU ventilator capacity and COVID-19 trajectory not in rapid escalation phase
- Phase II. Urgent Setting – many COVID-19 patients, ICU and ventilator capacity limited, operating room supplies limited
- Phase III. Hospital resources are all routed to COVID-19 patients, no ventilator or ICU capacity, operating room supplies exhausted; patients in whom death is likely within hours if surgery is deferred
Breast Cancer Surgery
The ACS also issued specific guidance for several tumor types, including guidance for breast cancer surgery.
For phase I, surgery should be restricted to patients who are likely to experience compromised survival if it is not performed within next 3 months. This includes patients completing neoadjuvant treatment, those with clinical stage T2 or N1 ERpos/PRpos/HER2-negative tumors, patients with triple negative or HER2-positive tumors, discordant biopsies that are likely to be malignant, and removal of a recurrent lesion.
Phase II would be restricted to patients whose survival is threatened if surgery is not performed within the next few days. These would include incision and drainage of breast abscess, evacuating a hematoma, revision of an ischemic mastectomy flap, and revascularization/revision of an autologous tissue flap (autologous reconstruction should be deferred).
In Phase III, surgical procedures would be restricted to patients who may not survive if surgery is not performed within a few hours. This includes incision and drainage of breast abscess, evacuation of a hematoma, revision of an ischemic mastectomy flap, and revascularization/revision of an autologous tissue flap (autologous reconstruction should be deferred).
Colorectal Cancer Surgery
Guidance for colorectal cancer surgery is also split into the three phases of the pandemic.
Phase I would include cases needing surgical intervention as soon as feasible, while recognizing that the status of each hospital is likely to evolve over the next week or two. These patients would include those with nearly obstructing colon cancer or rectal cancer; cancers that require frequent transfusions; asymptomatic colon cancers; rectal cancers that do not respond to neoadjuvant chemoradiation; malignancies with a risk of local perforation and sepsis; and those with early stage rectal cancers that are not candidates for adjuvant therapy.
Phase II comprises patients needing surgery as soon as feasible, but recognizing that hospital status is likely to progress over the next few days. These cases include patients with a nearly obstructing colon cancer where stenting is not an option; those with nearly obstructing rectal cancer (should be diverted); cancers with high (inpatient) transfusion requirements; and cancers with pending evidence of local perforation and sepsis.
All colorectal procedures typically scheduled as routine should be delayed.
In Phase III, if the status of the facility is likely to progress within hours, the only surgery that should be performed would be for perforated, obstructed, or actively bleeding (inpatient transfusion dependent) cancers or those with sepsis. All other surgeries should be deferred.
Thoracic Cancer Surgery
Thoracic cancer surgery guidelines follow those for breast cancer. Phase I should be restricted to patients whose survival may be impacted if surgery is not performed within next 3 months. These include:
- Cases with solid or predominantly solid (>50%) lung cancer or presumed lung cancer (>2 cm), clinical node negative
- Node positive lung cancer
- Post-induction therapy cancer
- Esophageal cancer T1b or greater
- Chest wall tumors that are potentially aggressive and not manageable by alternative means
- Stenting for obstructing esophageal tumor
- Staging to start treatment (mediastinoscopy, diagnostic VATS for pleural dissemination)
- Symptomatic mediastinal tumors
- Patients who are enrolled in therapeutic clinical trials.
Phase II would permit surgery if survival will be impacted by a delay of a few days. These cases would include nonseptic perforated cancer of esophagus, a tumor-associated infection, and management of surgical complications in a hemodynamically stable patient.
All thoracic procedures considered to be routine/elective would be deferred.
Phase III restricts surgery to patients whose survival will be compromised if they do not undergo surgery within the next few hours. This group would include perforated cancer of esophagus in a septic patient, a patient with a threatened airway, sepsis associated with the cancer, and management of surgical complications in an unstable patient (active bleeding that requires surgery, dehiscence of airway, anastomotic leak with sepsis).
All other cases would be deferred.
Other Cancer Types
Although the ACS doesn’t have specific guidelines for all cancer types, a few are included in their general recommendations for the specialty.
For gynecologic surgeries, ACS lists cancer or suspected cancer as indications where significantly delayed surgery could cause “significant harm.”
Delays, in general, are not recommended for neurosurgery, which would include brain cancers. In pediatrics, most cancer surgery is considered “urgent,” where a delay of days to weeks could prove detrimental to the patient. This would comprise all solid tumors, including the initial biopsy and resection following neoadjuvant therapy.
This article first appeared on Medscape.com.
FDA approves ozanimod for relapsing and secondary progressive forms of MS
The Food and Drug Administration has approved the oral medication ozanimod (Zeposia) for relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, according to a release from Bristol-Myers Squibb.
Ozanimod is a sphingosine 1-phosphate (S1P) receptor modulator that binds with high affinity to S1P receptors 1 and 5. It blocks the capacity of lymphocytes to egress from lymph nodes, reducing the number of lymphocytes in peripheral blood. Although its therapeutic mechanism of action in MS is unknown, it may involve the reduction of lymphocyte migration into the central nervous system. A genetic test is not required to start the drug, and no patient observation is required for the first dose, although up-titration of initial doses are required to reach the maintenance dose because a transient decrease in heart rate and atrioventricular conduction delays may occur, according to the company.
The approval is based on a pair of head-to-head studies that compared it with interferon beta-1a (Avonex) and together included more than 2,600 patients. It delivered better efficacy in terms of relative reduction in annualized relapse rate (48% at 1 year and 38% at 2 years). It also demonstrated better relative reduction of the number of T1-weighted gadolinium-enhanced brain lesions (63% fewer at 1 year and 53% fewer at 2 years) and number of new or enlarging T2 lesions (48% fewer at 1 year and 42% at 2 years).
Ozanimod is contraindicated in patients who, in the past 6 months, experienced a myocardial infarction, unstable angina, stroke, or other conditions. It is associated with other health risks, including infections, liver injury, additive immunosuppressive effects from prior immune-modulating therapies, and increased blood pressure. Certain assessments, such as recent complete blood count, ECG, liver function test, and current and prior medications and vaccinations, are required before initiation of treatment.
In its announcement, Bristol-Myers Squibb said that it has decided to delay the commercial launch of ozanimod during the COVID-19 pandemic until a later date.
The drug is also in development for additional immune-inflammatory indications, including ulcerative colitis and Crohn’s disease.
The full prescribing information can be found on the company’s website.
The Food and Drug Administration has approved the oral medication ozanimod (Zeposia) for relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, according to a release from Bristol-Myers Squibb.
Ozanimod is a sphingosine 1-phosphate (S1P) receptor modulator that binds with high affinity to S1P receptors 1 and 5. It blocks the capacity of lymphocytes to egress from lymph nodes, reducing the number of lymphocytes in peripheral blood. Although its therapeutic mechanism of action in MS is unknown, it may involve the reduction of lymphocyte migration into the central nervous system. A genetic test is not required to start the drug, and no patient observation is required for the first dose, although up-titration of initial doses are required to reach the maintenance dose because a transient decrease in heart rate and atrioventricular conduction delays may occur, according to the company.
The approval is based on a pair of head-to-head studies that compared it with interferon beta-1a (Avonex) and together included more than 2,600 patients. It delivered better efficacy in terms of relative reduction in annualized relapse rate (48% at 1 year and 38% at 2 years). It also demonstrated better relative reduction of the number of T1-weighted gadolinium-enhanced brain lesions (63% fewer at 1 year and 53% fewer at 2 years) and number of new or enlarging T2 lesions (48% fewer at 1 year and 42% at 2 years).
Ozanimod is contraindicated in patients who, in the past 6 months, experienced a myocardial infarction, unstable angina, stroke, or other conditions. It is associated with other health risks, including infections, liver injury, additive immunosuppressive effects from prior immune-modulating therapies, and increased blood pressure. Certain assessments, such as recent complete blood count, ECG, liver function test, and current and prior medications and vaccinations, are required before initiation of treatment.
In its announcement, Bristol-Myers Squibb said that it has decided to delay the commercial launch of ozanimod during the COVID-19 pandemic until a later date.
The drug is also in development for additional immune-inflammatory indications, including ulcerative colitis and Crohn’s disease.
The full prescribing information can be found on the company’s website.
The Food and Drug Administration has approved the oral medication ozanimod (Zeposia) for relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, according to a release from Bristol-Myers Squibb.
Ozanimod is a sphingosine 1-phosphate (S1P) receptor modulator that binds with high affinity to S1P receptors 1 and 5. It blocks the capacity of lymphocytes to egress from lymph nodes, reducing the number of lymphocytes in peripheral blood. Although its therapeutic mechanism of action in MS is unknown, it may involve the reduction of lymphocyte migration into the central nervous system. A genetic test is not required to start the drug, and no patient observation is required for the first dose, although up-titration of initial doses are required to reach the maintenance dose because a transient decrease in heart rate and atrioventricular conduction delays may occur, according to the company.
The approval is based on a pair of head-to-head studies that compared it with interferon beta-1a (Avonex) and together included more than 2,600 patients. It delivered better efficacy in terms of relative reduction in annualized relapse rate (48% at 1 year and 38% at 2 years). It also demonstrated better relative reduction of the number of T1-weighted gadolinium-enhanced brain lesions (63% fewer at 1 year and 53% fewer at 2 years) and number of new or enlarging T2 lesions (48% fewer at 1 year and 42% at 2 years).
Ozanimod is contraindicated in patients who, in the past 6 months, experienced a myocardial infarction, unstable angina, stroke, or other conditions. It is associated with other health risks, including infections, liver injury, additive immunosuppressive effects from prior immune-modulating therapies, and increased blood pressure. Certain assessments, such as recent complete blood count, ECG, liver function test, and current and prior medications and vaccinations, are required before initiation of treatment.
In its announcement, Bristol-Myers Squibb said that it has decided to delay the commercial launch of ozanimod during the COVID-19 pandemic until a later date.
The drug is also in development for additional immune-inflammatory indications, including ulcerative colitis and Crohn’s disease.
The full prescribing information can be found on the company’s website.
Perspective from the heartland: Cancer care and research during a public health crisis
I have no knowledge of, or experience with, managing a cancer patient during a pandemic. However, from the published and otherwise shared experience of others, we should not allow ourselves to underestimate the voracity of the coronavirus pandemic on our patients, communities, and health care systems.
Data from China suggest cancer patients infected with SARS-CoV-2 face a 3.5 times higher risk of mechanical ventilation, intensive care unit admission, or death, compared with infected patients without cancer (Lancet Oncol 2020;21:335-7).
Health care workers in Seattle have also shared their experiences battling coronavirus infections in cancer patients (J Natl Compr Canc Netw. 2020 Mar 20. doi: 10.6004/jnccn.2020.7560). Masumi Ueda, MD, of Seattle Cancer Care Alliance, and colleagues reviewed their decisions in multiple domains over a 7-week period, during which the state of Washington went from a single case of SARS-CoV-2 infection to nearly 650 cases and 40 deaths.
Making tough treatment decisions
Dr. Ueda and colleagues contrasted their customary resource-rich, innovation-oriented, cancer-combatting environment with their current circumstance, in which they must prioritize treatment for patients for whom the risk-reward balance has tilted substantially toward “risk.”
The authors noted that their most difficult decisions were those regarding delay of cancer treatment. They suggested that plans for potentially curative adjuvant therapy should likely proceed, but, for patients with metastatic disease, the equation is more nuanced.
In some cases, treatment should be delayed or interrupted with recognition of how that could result in worsening performance status and admission for symptom palliation, further stressing inpatient resources.
The authors suggested scenarios for prioritizing cancer surgery. For example, several months of systemic therapy (ideally, low-risk systemic therapy such as hormone therapy for breast or prostate cancer) and surgical delay may be worthwhile, without compromising patient care.
Patients with aggressive hematologic malignancy requiring urgent systemic treatment (potentially stem cell transplantation and cellular immunotherapies) should be treated promptly. However, even in those cases, opportunities should be sought to lessen immunosuppression and transition care as quickly as possible to the outpatient clinic, according to guidelines from the American Society of Transplantation and Cellular Therapy.
See one, do one, teach one
Rendering patient care during a pandemic would be unique for me. However, I, like all physicians, am familiar with feelings of inadequacy at times of professional challenge. On countless occasions, I have started my day or walked into a patient’s room wondering whether I will have the fortitude, knowledge, creativity, or help I need to get through that day or make that patient “better” by any definition of that word.
We all know the formula: “Work hard. Make evidence-based, personalized decisions for those who have entrusted their care to us. Learn from those encounters. Teach from our knowledge and experience – that is, ‘See one, do one, teach one.’ ”
The Seattle oncologists are living the lives of first responders and deserve our admiration for putting pen to paper so we can learn from their considerable, relevant experience.
Similar admiration is due to Giuseppe Curigliano, MD, of the European Institute of Oncology in Milan. In the ASCO Daily News, Dr. Curigliano described an epidemic that, within 3 weeks, overloaded the health care system across northern Italy.
Hospitalization was needed for over 60% of infected patients, and nearly 15% of those patients needed intensive care unit services for respiratory distress. The Italians centralized oncology care in specialized hubs, with spokes of institutions working in parallel to provide cancer-specific care in a COVID-free environment.
To build upon cancer-specific information from Italy and other areas hard-hit by COVID-19, more than 30 cancer centers have joined together to form the COVID-19 and Cancer Consortium. The consortium’s website hosts a survey designed to “capture details related to cancer patients presumed to have COVID-19.”
Calculating deaths and long-term consequences for cancer care delivery
It is proper that the authors from China, Italy, and Seattle did not focus attention on the case fatality rate from the COVID-19 pandemic among cancer patients. To say the least, it would be complicated to tally the direct mortality – either overall or in clinically important subsets of patients, including country-specific cohorts.
What we know from published reports is that, in Italy, cancer patients account for about 20% of deaths from coronavirus. In China, the case-fatality rate for patients with cancer was 5.6% (JAMA. 2020 Feb 24. doi: 10.1001/jama.2020.2648).
However, we know nothing about the indirect death toll from malignancy (without coronavirus infection) that was untreated or managed less than optimally because of personnel and physical resources that were diverted to COVID-19–associated cases.
Similarly, we cannot begin to estimate indirect consequences of the pandemic to oncology practices, such as accelerated burnout and posttraumatic stress disorder, as well as the long-range effects of economic turmoil on patients, health care workers, and provider organizations.
What happens to cancer trials?
From China, Italy, and Seattle, thus far, there is little information about how the pandemic will affect the vital clinical research endeavor. The Seattle physicians did say they plan to enroll patients on clinical trials only when the trial offers a high chance of benefiting the patient over standard therapy alone.
Fortunately, the National Institutes of Health and Food and Drug Administration have released guidance documents related to clinical trials.
The National Cancer Institute (NCI) has also released guidance documents (March 13 guidance; March 23 guidance) for patients on clinical trials supported by the NCI Cancer Therapy Evaluation Program (CTEP) and the NCI Community Oncology Research Program (NCORP).
CTEP and NCORP are making reasonable accommodations to suspend monitoring visits and audits, allow tele–follow-up visits for patients, and permit local physicians to provide care for patients on study. In addition, with appropriate procedural adherence and documentation, CTEP and NCORP will allow oral investigational medicines to be mailed directly to patients’ homes.
Planned NCI National Clinical Trials Network meetings will be conducted via remote access webinars, conference calls, and similar technology. These adjustments – and probably many more to come – are geared toward facilitating ongoing care to proceed safely and with minimal risk for patients currently receiving investigational therapies and for the sites and investigators engaged in those studies.
Each of us has probably faced a personal “defining professional moment,” when we had to utilize every skill in our arsenal and examine the motivations that led us to a career in oncology. However, it is clear from the forgoing clinical and research processes and guidelines that the COVID-19 pandemic is such a defining professional moment for each of us, in every community we serve.
Critical junctures like this cause more rapid behavior change and innovation than the slow-moving pace that characterizes our idealized preferences. As oncologists who embrace new data and behavioral change, we stand to learn processes that will facilitate more perfected systems of care than the one that preceded this unprecedented crisis, promote more efficient sharing of high-quality information, and improve the outcome for our future patients.
Dr. Lyss was an oncologist and researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
I have no knowledge of, or experience with, managing a cancer patient during a pandemic. However, from the published and otherwise shared experience of others, we should not allow ourselves to underestimate the voracity of the coronavirus pandemic on our patients, communities, and health care systems.
Data from China suggest cancer patients infected with SARS-CoV-2 face a 3.5 times higher risk of mechanical ventilation, intensive care unit admission, or death, compared with infected patients without cancer (Lancet Oncol 2020;21:335-7).
Health care workers in Seattle have also shared their experiences battling coronavirus infections in cancer patients (J Natl Compr Canc Netw. 2020 Mar 20. doi: 10.6004/jnccn.2020.7560). Masumi Ueda, MD, of Seattle Cancer Care Alliance, and colleagues reviewed their decisions in multiple domains over a 7-week period, during which the state of Washington went from a single case of SARS-CoV-2 infection to nearly 650 cases and 40 deaths.
Making tough treatment decisions
Dr. Ueda and colleagues contrasted their customary resource-rich, innovation-oriented, cancer-combatting environment with their current circumstance, in which they must prioritize treatment for patients for whom the risk-reward balance has tilted substantially toward “risk.”
The authors noted that their most difficult decisions were those regarding delay of cancer treatment. They suggested that plans for potentially curative adjuvant therapy should likely proceed, but, for patients with metastatic disease, the equation is more nuanced.
In some cases, treatment should be delayed or interrupted with recognition of how that could result in worsening performance status and admission for symptom palliation, further stressing inpatient resources.
The authors suggested scenarios for prioritizing cancer surgery. For example, several months of systemic therapy (ideally, low-risk systemic therapy such as hormone therapy for breast or prostate cancer) and surgical delay may be worthwhile, without compromising patient care.
Patients with aggressive hematologic malignancy requiring urgent systemic treatment (potentially stem cell transplantation and cellular immunotherapies) should be treated promptly. However, even in those cases, opportunities should be sought to lessen immunosuppression and transition care as quickly as possible to the outpatient clinic, according to guidelines from the American Society of Transplantation and Cellular Therapy.
See one, do one, teach one
Rendering patient care during a pandemic would be unique for me. However, I, like all physicians, am familiar with feelings of inadequacy at times of professional challenge. On countless occasions, I have started my day or walked into a patient’s room wondering whether I will have the fortitude, knowledge, creativity, or help I need to get through that day or make that patient “better” by any definition of that word.
We all know the formula: “Work hard. Make evidence-based, personalized decisions for those who have entrusted their care to us. Learn from those encounters. Teach from our knowledge and experience – that is, ‘See one, do one, teach one.’ ”
The Seattle oncologists are living the lives of first responders and deserve our admiration for putting pen to paper so we can learn from their considerable, relevant experience.
Similar admiration is due to Giuseppe Curigliano, MD, of the European Institute of Oncology in Milan. In the ASCO Daily News, Dr. Curigliano described an epidemic that, within 3 weeks, overloaded the health care system across northern Italy.
Hospitalization was needed for over 60% of infected patients, and nearly 15% of those patients needed intensive care unit services for respiratory distress. The Italians centralized oncology care in specialized hubs, with spokes of institutions working in parallel to provide cancer-specific care in a COVID-free environment.
To build upon cancer-specific information from Italy and other areas hard-hit by COVID-19, more than 30 cancer centers have joined together to form the COVID-19 and Cancer Consortium. The consortium’s website hosts a survey designed to “capture details related to cancer patients presumed to have COVID-19.”
Calculating deaths and long-term consequences for cancer care delivery
It is proper that the authors from China, Italy, and Seattle did not focus attention on the case fatality rate from the COVID-19 pandemic among cancer patients. To say the least, it would be complicated to tally the direct mortality – either overall or in clinically important subsets of patients, including country-specific cohorts.
What we know from published reports is that, in Italy, cancer patients account for about 20% of deaths from coronavirus. In China, the case-fatality rate for patients with cancer was 5.6% (JAMA. 2020 Feb 24. doi: 10.1001/jama.2020.2648).
However, we know nothing about the indirect death toll from malignancy (without coronavirus infection) that was untreated or managed less than optimally because of personnel and physical resources that were diverted to COVID-19–associated cases.
Similarly, we cannot begin to estimate indirect consequences of the pandemic to oncology practices, such as accelerated burnout and posttraumatic stress disorder, as well as the long-range effects of economic turmoil on patients, health care workers, and provider organizations.
What happens to cancer trials?
From China, Italy, and Seattle, thus far, there is little information about how the pandemic will affect the vital clinical research endeavor. The Seattle physicians did say they plan to enroll patients on clinical trials only when the trial offers a high chance of benefiting the patient over standard therapy alone.
Fortunately, the National Institutes of Health and Food and Drug Administration have released guidance documents related to clinical trials.
The National Cancer Institute (NCI) has also released guidance documents (March 13 guidance; March 23 guidance) for patients on clinical trials supported by the NCI Cancer Therapy Evaluation Program (CTEP) and the NCI Community Oncology Research Program (NCORP).
CTEP and NCORP are making reasonable accommodations to suspend monitoring visits and audits, allow tele–follow-up visits for patients, and permit local physicians to provide care for patients on study. In addition, with appropriate procedural adherence and documentation, CTEP and NCORP will allow oral investigational medicines to be mailed directly to patients’ homes.
Planned NCI National Clinical Trials Network meetings will be conducted via remote access webinars, conference calls, and similar technology. These adjustments – and probably many more to come – are geared toward facilitating ongoing care to proceed safely and with minimal risk for patients currently receiving investigational therapies and for the sites and investigators engaged in those studies.
Each of us has probably faced a personal “defining professional moment,” when we had to utilize every skill in our arsenal and examine the motivations that led us to a career in oncology. However, it is clear from the forgoing clinical and research processes and guidelines that the COVID-19 pandemic is such a defining professional moment for each of us, in every community we serve.
Critical junctures like this cause more rapid behavior change and innovation than the slow-moving pace that characterizes our idealized preferences. As oncologists who embrace new data and behavioral change, we stand to learn processes that will facilitate more perfected systems of care than the one that preceded this unprecedented crisis, promote more efficient sharing of high-quality information, and improve the outcome for our future patients.
Dr. Lyss was an oncologist and researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
I have no knowledge of, or experience with, managing a cancer patient during a pandemic. However, from the published and otherwise shared experience of others, we should not allow ourselves to underestimate the voracity of the coronavirus pandemic on our patients, communities, and health care systems.
Data from China suggest cancer patients infected with SARS-CoV-2 face a 3.5 times higher risk of mechanical ventilation, intensive care unit admission, or death, compared with infected patients without cancer (Lancet Oncol 2020;21:335-7).
Health care workers in Seattle have also shared their experiences battling coronavirus infections in cancer patients (J Natl Compr Canc Netw. 2020 Mar 20. doi: 10.6004/jnccn.2020.7560). Masumi Ueda, MD, of Seattle Cancer Care Alliance, and colleagues reviewed their decisions in multiple domains over a 7-week period, during which the state of Washington went from a single case of SARS-CoV-2 infection to nearly 650 cases and 40 deaths.
Making tough treatment decisions
Dr. Ueda and colleagues contrasted their customary resource-rich, innovation-oriented, cancer-combatting environment with their current circumstance, in which they must prioritize treatment for patients for whom the risk-reward balance has tilted substantially toward “risk.”
The authors noted that their most difficult decisions were those regarding delay of cancer treatment. They suggested that plans for potentially curative adjuvant therapy should likely proceed, but, for patients with metastatic disease, the equation is more nuanced.
In some cases, treatment should be delayed or interrupted with recognition of how that could result in worsening performance status and admission for symptom palliation, further stressing inpatient resources.
The authors suggested scenarios for prioritizing cancer surgery. For example, several months of systemic therapy (ideally, low-risk systemic therapy such as hormone therapy for breast or prostate cancer) and surgical delay may be worthwhile, without compromising patient care.
Patients with aggressive hematologic malignancy requiring urgent systemic treatment (potentially stem cell transplantation and cellular immunotherapies) should be treated promptly. However, even in those cases, opportunities should be sought to lessen immunosuppression and transition care as quickly as possible to the outpatient clinic, according to guidelines from the American Society of Transplantation and Cellular Therapy.
See one, do one, teach one
Rendering patient care during a pandemic would be unique for me. However, I, like all physicians, am familiar with feelings of inadequacy at times of professional challenge. On countless occasions, I have started my day or walked into a patient’s room wondering whether I will have the fortitude, knowledge, creativity, or help I need to get through that day or make that patient “better” by any definition of that word.
We all know the formula: “Work hard. Make evidence-based, personalized decisions for those who have entrusted their care to us. Learn from those encounters. Teach from our knowledge and experience – that is, ‘See one, do one, teach one.’ ”
The Seattle oncologists are living the lives of first responders and deserve our admiration for putting pen to paper so we can learn from their considerable, relevant experience.
Similar admiration is due to Giuseppe Curigliano, MD, of the European Institute of Oncology in Milan. In the ASCO Daily News, Dr. Curigliano described an epidemic that, within 3 weeks, overloaded the health care system across northern Italy.
Hospitalization was needed for over 60% of infected patients, and nearly 15% of those patients needed intensive care unit services for respiratory distress. The Italians centralized oncology care in specialized hubs, with spokes of institutions working in parallel to provide cancer-specific care in a COVID-free environment.
To build upon cancer-specific information from Italy and other areas hard-hit by COVID-19, more than 30 cancer centers have joined together to form the COVID-19 and Cancer Consortium. The consortium’s website hosts a survey designed to “capture details related to cancer patients presumed to have COVID-19.”
Calculating deaths and long-term consequences for cancer care delivery
It is proper that the authors from China, Italy, and Seattle did not focus attention on the case fatality rate from the COVID-19 pandemic among cancer patients. To say the least, it would be complicated to tally the direct mortality – either overall or in clinically important subsets of patients, including country-specific cohorts.
What we know from published reports is that, in Italy, cancer patients account for about 20% of deaths from coronavirus. In China, the case-fatality rate for patients with cancer was 5.6% (JAMA. 2020 Feb 24. doi: 10.1001/jama.2020.2648).
However, we know nothing about the indirect death toll from malignancy (without coronavirus infection) that was untreated or managed less than optimally because of personnel and physical resources that were diverted to COVID-19–associated cases.
Similarly, we cannot begin to estimate indirect consequences of the pandemic to oncology practices, such as accelerated burnout and posttraumatic stress disorder, as well as the long-range effects of economic turmoil on patients, health care workers, and provider organizations.
What happens to cancer trials?
From China, Italy, and Seattle, thus far, there is little information about how the pandemic will affect the vital clinical research endeavor. The Seattle physicians did say they plan to enroll patients on clinical trials only when the trial offers a high chance of benefiting the patient over standard therapy alone.
Fortunately, the National Institutes of Health and Food and Drug Administration have released guidance documents related to clinical trials.
The National Cancer Institute (NCI) has also released guidance documents (March 13 guidance; March 23 guidance) for patients on clinical trials supported by the NCI Cancer Therapy Evaluation Program (CTEP) and the NCI Community Oncology Research Program (NCORP).
CTEP and NCORP are making reasonable accommodations to suspend monitoring visits and audits, allow tele–follow-up visits for patients, and permit local physicians to provide care for patients on study. In addition, with appropriate procedural adherence and documentation, CTEP and NCORP will allow oral investigational medicines to be mailed directly to patients’ homes.
Planned NCI National Clinical Trials Network meetings will be conducted via remote access webinars, conference calls, and similar technology. These adjustments – and probably many more to come – are geared toward facilitating ongoing care to proceed safely and with minimal risk for patients currently receiving investigational therapies and for the sites and investigators engaged in those studies.
Each of us has probably faced a personal “defining professional moment,” when we had to utilize every skill in our arsenal and examine the motivations that led us to a career in oncology. However, it is clear from the forgoing clinical and research processes and guidelines that the COVID-19 pandemic is such a defining professional moment for each of us, in every community we serve.
Critical junctures like this cause more rapid behavior change and innovation than the slow-moving pace that characterizes our idealized preferences. As oncologists who embrace new data and behavioral change, we stand to learn processes that will facilitate more perfected systems of care than the one that preceded this unprecedented crisis, promote more efficient sharing of high-quality information, and improve the outcome for our future patients.
Dr. Lyss was an oncologist and researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
Study finds spironolactone doesn’t boost breast cancer recurrence
in a large retrospective study, Chapman Wei said in a in a virtual meeting held by the George Washington University department of dermatology in Washington. The virtual meeting included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled due to the COVID-19 pandemic.
Spironolactone is an aldosterone antagonist and heart failure medication that, because of its peripheral antiandrogen effects, is often used off-label to treat female androgenetic hair loss. Although it has been available for nigh on half a century and has a well-established favorable safety profile, with no indication of carcinogenic effects, little is known about its use in treating alopecia in breast cancer survivors on endocrine therapies, where there has been a theoretic possibility that the drug’s antiandrogen effects could promote breast cancer recurrence.
Not so, said Mr. Wei, from George Washington University.
He presented a retrospective, propensity score–matched, case-control study that used the Humana Insurance database. The initial comparison was between 746 women who went on spironolactone after their breast cancer diagnosis versus 28,400 female breast cancer patients who didn’t take the drug. The primary outcome was recurrent breast cancer within 2 years after diagnosis.
“We chose 2 years because most breast cancer relapses occur within that time,” Mr. Wei explained.
In the initial unadjusted between-group comparison, the breast cancer recurrence rate was 16.5% in the spironolactone group, significantly higher than the 12.8% rate in more than 28,000 controls. However, in a comparison between the spironolactone group and 746 controls extensively propensity score–matched for acne, hypertension, hirsutism, smoking, illicit drug use, heart failure, primary aldosteronism, and other potential confounding variables, there was no significant difference between spironolactone users and controls, with 2-year breast cancer recurrence rates of 16.5% and 15.8%, respectively.
In a multivariate Cox regression analysis, the stand-out finding was that alcohol abuse was independently associated with a 2.3-fold increased risk of breast cancer recurrence.
Mr. Wei noted that these findings confirm those in a recent literature review by investigators at Memorial Sloan Kettering Cancer Center in New York who found no increase in estrogen levels with spironolactone and no heightened risk of female breast cancer while on the drug in three studies totaling 49,298 patients.
“Spironolactone has the potential to be used as a relatively safe systemic treatment option for the management of [endocrine therapy–induced alopecia] in female breast cancer patients and survivors on endocrine therapies who respond poorly to monotherapy with topical minoxidil,” the Sloan Kettering researchers declared (Breast Cancer Res Treat. 2019 Feb;174[1]:15-26).
Mr. Wei reported having no financial conflicts regarding his unfunded study.
in a large retrospective study, Chapman Wei said in a in a virtual meeting held by the George Washington University department of dermatology in Washington. The virtual meeting included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled due to the COVID-19 pandemic.
Spironolactone is an aldosterone antagonist and heart failure medication that, because of its peripheral antiandrogen effects, is often used off-label to treat female androgenetic hair loss. Although it has been available for nigh on half a century and has a well-established favorable safety profile, with no indication of carcinogenic effects, little is known about its use in treating alopecia in breast cancer survivors on endocrine therapies, where there has been a theoretic possibility that the drug’s antiandrogen effects could promote breast cancer recurrence.
Not so, said Mr. Wei, from George Washington University.
He presented a retrospective, propensity score–matched, case-control study that used the Humana Insurance database. The initial comparison was between 746 women who went on spironolactone after their breast cancer diagnosis versus 28,400 female breast cancer patients who didn’t take the drug. The primary outcome was recurrent breast cancer within 2 years after diagnosis.
“We chose 2 years because most breast cancer relapses occur within that time,” Mr. Wei explained.
In the initial unadjusted between-group comparison, the breast cancer recurrence rate was 16.5% in the spironolactone group, significantly higher than the 12.8% rate in more than 28,000 controls. However, in a comparison between the spironolactone group and 746 controls extensively propensity score–matched for acne, hypertension, hirsutism, smoking, illicit drug use, heart failure, primary aldosteronism, and other potential confounding variables, there was no significant difference between spironolactone users and controls, with 2-year breast cancer recurrence rates of 16.5% and 15.8%, respectively.
In a multivariate Cox regression analysis, the stand-out finding was that alcohol abuse was independently associated with a 2.3-fold increased risk of breast cancer recurrence.
Mr. Wei noted that these findings confirm those in a recent literature review by investigators at Memorial Sloan Kettering Cancer Center in New York who found no increase in estrogen levels with spironolactone and no heightened risk of female breast cancer while on the drug in three studies totaling 49,298 patients.
“Spironolactone has the potential to be used as a relatively safe systemic treatment option for the management of [endocrine therapy–induced alopecia] in female breast cancer patients and survivors on endocrine therapies who respond poorly to monotherapy with topical minoxidil,” the Sloan Kettering researchers declared (Breast Cancer Res Treat. 2019 Feb;174[1]:15-26).
Mr. Wei reported having no financial conflicts regarding his unfunded study.
in a large retrospective study, Chapman Wei said in a in a virtual meeting held by the George Washington University department of dermatology in Washington. The virtual meeting included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled due to the COVID-19 pandemic.
Spironolactone is an aldosterone antagonist and heart failure medication that, because of its peripheral antiandrogen effects, is often used off-label to treat female androgenetic hair loss. Although it has been available for nigh on half a century and has a well-established favorable safety profile, with no indication of carcinogenic effects, little is known about its use in treating alopecia in breast cancer survivors on endocrine therapies, where there has been a theoretic possibility that the drug’s antiandrogen effects could promote breast cancer recurrence.
Not so, said Mr. Wei, from George Washington University.
He presented a retrospective, propensity score–matched, case-control study that used the Humana Insurance database. The initial comparison was between 746 women who went on spironolactone after their breast cancer diagnosis versus 28,400 female breast cancer patients who didn’t take the drug. The primary outcome was recurrent breast cancer within 2 years after diagnosis.
“We chose 2 years because most breast cancer relapses occur within that time,” Mr. Wei explained.
In the initial unadjusted between-group comparison, the breast cancer recurrence rate was 16.5% in the spironolactone group, significantly higher than the 12.8% rate in more than 28,000 controls. However, in a comparison between the spironolactone group and 746 controls extensively propensity score–matched for acne, hypertension, hirsutism, smoking, illicit drug use, heart failure, primary aldosteronism, and other potential confounding variables, there was no significant difference between spironolactone users and controls, with 2-year breast cancer recurrence rates of 16.5% and 15.8%, respectively.
In a multivariate Cox regression analysis, the stand-out finding was that alcohol abuse was independently associated with a 2.3-fold increased risk of breast cancer recurrence.
Mr. Wei noted that these findings confirm those in a recent literature review by investigators at Memorial Sloan Kettering Cancer Center in New York who found no increase in estrogen levels with spironolactone and no heightened risk of female breast cancer while on the drug in three studies totaling 49,298 patients.
“Spironolactone has the potential to be used as a relatively safe systemic treatment option for the management of [endocrine therapy–induced alopecia] in female breast cancer patients and survivors on endocrine therapies who respond poorly to monotherapy with topical minoxidil,” the Sloan Kettering researchers declared (Breast Cancer Res Treat. 2019 Feb;174[1]:15-26).
Mr. Wei reported having no financial conflicts regarding his unfunded study.
CLL and breast cancer differ in the expression of regulatory microRNAs
Expression of three microRNAs (miR-155, miR-29a, and miR-27b) was detectable in patients with chronic lymphocytic leukemia (CLL) and in breast cancer (BC) patients, but not in healthy subjects, according to a molecular analysis of patients reported in Molecular Therapy Oncolytics. In addition, circulating microarrays were found to be able to differentiate between both CLL and BC patients and healthy subjects.
The researchers obtained blood samples from 15 CLL patients and tissue samples from 15 BC patients, all from a single center.
The use of quantitative reverse transcription polymerase chain reaction (qRT-PCR) demonstrated a significant increase in the expression of all three miRNAs in patients with BC and CLL, compared with respective healthy groups (P less than .001).
In BC patients, there was a significant difference between the expression of miR-155 and miR-29a (P less than .05), miR-155 and miR-27b (P less than .01), and miR-27b and miR-29a (P less than .001). In CLL patients, the qRT-PCR results showed a significant difference between expression of both miR-27b and miR-29a, compared with expression of miR-155 (P less than .001). In addition, there was a significant association between miR-155 and prevascular invasion (P = .013), but no significant association with other clinical variables (age, tumor grade, nuclear grade, tumor stage, tumor size, area of invasive component, tumor side, margin, or preneural invasion), according to the researchers.
Results also showed that elevated circulating miRNAs were BC specific and could differentiate BC tissues from the controls, and comparing expression of miRNAs between BC and CLL patients, there was also a significant difference for all miRNAs (P less than .001) between them.
“Our results suggest that miR-27b, miR-29a, and miR-155 could be potential new biomarkers for diagnosis, as well as a therapeutic target for CLL and BC,” the researchers concluded.
The authors reported that they had no competing interests.
SOURCE: Raeisi F et al. Mol Ther Oncolytics. 2020;16:230-7.
Expression of three microRNAs (miR-155, miR-29a, and miR-27b) was detectable in patients with chronic lymphocytic leukemia (CLL) and in breast cancer (BC) patients, but not in healthy subjects, according to a molecular analysis of patients reported in Molecular Therapy Oncolytics. In addition, circulating microarrays were found to be able to differentiate between both CLL and BC patients and healthy subjects.
The researchers obtained blood samples from 15 CLL patients and tissue samples from 15 BC patients, all from a single center.
The use of quantitative reverse transcription polymerase chain reaction (qRT-PCR) demonstrated a significant increase in the expression of all three miRNAs in patients with BC and CLL, compared with respective healthy groups (P less than .001).
In BC patients, there was a significant difference between the expression of miR-155 and miR-29a (P less than .05), miR-155 and miR-27b (P less than .01), and miR-27b and miR-29a (P less than .001). In CLL patients, the qRT-PCR results showed a significant difference between expression of both miR-27b and miR-29a, compared with expression of miR-155 (P less than .001). In addition, there was a significant association between miR-155 and prevascular invasion (P = .013), but no significant association with other clinical variables (age, tumor grade, nuclear grade, tumor stage, tumor size, area of invasive component, tumor side, margin, or preneural invasion), according to the researchers.
Results also showed that elevated circulating miRNAs were BC specific and could differentiate BC tissues from the controls, and comparing expression of miRNAs between BC and CLL patients, there was also a significant difference for all miRNAs (P less than .001) between them.
“Our results suggest that miR-27b, miR-29a, and miR-155 could be potential new biomarkers for diagnosis, as well as a therapeutic target for CLL and BC,” the researchers concluded.
The authors reported that they had no competing interests.
SOURCE: Raeisi F et al. Mol Ther Oncolytics. 2020;16:230-7.
Expression of three microRNAs (miR-155, miR-29a, and miR-27b) was detectable in patients with chronic lymphocytic leukemia (CLL) and in breast cancer (BC) patients, but not in healthy subjects, according to a molecular analysis of patients reported in Molecular Therapy Oncolytics. In addition, circulating microarrays were found to be able to differentiate between both CLL and BC patients and healthy subjects.
The researchers obtained blood samples from 15 CLL patients and tissue samples from 15 BC patients, all from a single center.
The use of quantitative reverse transcription polymerase chain reaction (qRT-PCR) demonstrated a significant increase in the expression of all three miRNAs in patients with BC and CLL, compared with respective healthy groups (P less than .001).
In BC patients, there was a significant difference between the expression of miR-155 and miR-29a (P less than .05), miR-155 and miR-27b (P less than .01), and miR-27b and miR-29a (P less than .001). In CLL patients, the qRT-PCR results showed a significant difference between expression of both miR-27b and miR-29a, compared with expression of miR-155 (P less than .001). In addition, there was a significant association between miR-155 and prevascular invasion (P = .013), but no significant association with other clinical variables (age, tumor grade, nuclear grade, tumor stage, tumor size, area of invasive component, tumor side, margin, or preneural invasion), according to the researchers.
Results also showed that elevated circulating miRNAs were BC specific and could differentiate BC tissues from the controls, and comparing expression of miRNAs between BC and CLL patients, there was also a significant difference for all miRNAs (P less than .001) between them.
“Our results suggest that miR-27b, miR-29a, and miR-155 could be potential new biomarkers for diagnosis, as well as a therapeutic target for CLL and BC,” the researchers concluded.
The authors reported that they had no competing interests.
SOURCE: Raeisi F et al. Mol Ther Oncolytics. 2020;16:230-7.
FROM MOLECULAR THERAPY ONCOLYTICS
