User login
Breast cancer now leading cause of cancer death in Black women
Breast cancer has replaced lung cancer as the leading cause of cancer-related death among Black women, but lung cancer remains the leading cause of cancer death in Black men, according to a new report from the American Cancer Society (ACS).
Lung cancer remains the second most commonly diagnosed cancer in both Black women and Black men.
These are among the key findings of the report, Cancer Statistics for African American/Black People 2022 – a triannual compilation of U.S. data on cancer incidence, mortality, survival, screening, and risk factors for Black people – and it marks a major shift as of 2019.
“African American/Black people have a disproportionately high cancer burden compared to other population groups. According to the report, the risk of cancer death for Black individuals remains 19% higher for men and 12% higher for women compared to White individuals,” the ACS says in a statement.
“The gap for breast cancer is more alarming,” it adds. “Black women are 41% more likely to die from breast cancer than White women despite a lower risk of being diagnosed with the disease.”
The new report, published online on Feb. 10 in CA: A Cancer Journal for Clinicians, also notes the following:
An estimated 224,080 new cancer cases and 73,680 cancer deaths will occur among Black people in 2022.
Over the past 5 data years, Black women had an 8% lower overall cancer incidence than White women but 12% higher mortality; Black men have 6% higher cancer incidence than White men but 19% higher cancer mortality.
Prostate cancer mortality among Black men decreased by 1.3% per year from 2015 to 2019 despite a 5% increase in the diagnosis of distant-stage prostate cancer annually since 2012, but the decline was slower than the 5% per year decline from 2010 to 2014.
The overall cancer mortality gap between Black and White people is narrowing. This is due to a steeper drop in prostate, lung, and other smoking-related cancers among Black people.
Colorectal cancer incidence and mortality rates are 21% and 44% higher, respectively, in Black men in comparison with White men and 18% and 31% higher, respectively, in Black women in comparison with White women.
The reasons for the disparities are complex but “largely stem from less access to high-quality care and optimal treatment as a repercussion of long-standing institutional racism,” the report concludes.
“We must address structural racism as a public health issue to close the gaps and advance health equity,” Tawana Thomas-Johnson, senior vice president and chief diversity officer at the ACS, said in the press release.
A version of this article first appeared on Medscape.com.
Breast cancer has replaced lung cancer as the leading cause of cancer-related death among Black women, but lung cancer remains the leading cause of cancer death in Black men, according to a new report from the American Cancer Society (ACS).
Lung cancer remains the second most commonly diagnosed cancer in both Black women and Black men.
These are among the key findings of the report, Cancer Statistics for African American/Black People 2022 – a triannual compilation of U.S. data on cancer incidence, mortality, survival, screening, and risk factors for Black people – and it marks a major shift as of 2019.
“African American/Black people have a disproportionately high cancer burden compared to other population groups. According to the report, the risk of cancer death for Black individuals remains 19% higher for men and 12% higher for women compared to White individuals,” the ACS says in a statement.
“The gap for breast cancer is more alarming,” it adds. “Black women are 41% more likely to die from breast cancer than White women despite a lower risk of being diagnosed with the disease.”
The new report, published online on Feb. 10 in CA: A Cancer Journal for Clinicians, also notes the following:
An estimated 224,080 new cancer cases and 73,680 cancer deaths will occur among Black people in 2022.
Over the past 5 data years, Black women had an 8% lower overall cancer incidence than White women but 12% higher mortality; Black men have 6% higher cancer incidence than White men but 19% higher cancer mortality.
Prostate cancer mortality among Black men decreased by 1.3% per year from 2015 to 2019 despite a 5% increase in the diagnosis of distant-stage prostate cancer annually since 2012, but the decline was slower than the 5% per year decline from 2010 to 2014.
The overall cancer mortality gap between Black and White people is narrowing. This is due to a steeper drop in prostate, lung, and other smoking-related cancers among Black people.
Colorectal cancer incidence and mortality rates are 21% and 44% higher, respectively, in Black men in comparison with White men and 18% and 31% higher, respectively, in Black women in comparison with White women.
The reasons for the disparities are complex but “largely stem from less access to high-quality care and optimal treatment as a repercussion of long-standing institutional racism,” the report concludes.
“We must address structural racism as a public health issue to close the gaps and advance health equity,” Tawana Thomas-Johnson, senior vice president and chief diversity officer at the ACS, said in the press release.
A version of this article first appeared on Medscape.com.
Breast cancer has replaced lung cancer as the leading cause of cancer-related death among Black women, but lung cancer remains the leading cause of cancer death in Black men, according to a new report from the American Cancer Society (ACS).
Lung cancer remains the second most commonly diagnosed cancer in both Black women and Black men.
These are among the key findings of the report, Cancer Statistics for African American/Black People 2022 – a triannual compilation of U.S. data on cancer incidence, mortality, survival, screening, and risk factors for Black people – and it marks a major shift as of 2019.
“African American/Black people have a disproportionately high cancer burden compared to other population groups. According to the report, the risk of cancer death for Black individuals remains 19% higher for men and 12% higher for women compared to White individuals,” the ACS says in a statement.
“The gap for breast cancer is more alarming,” it adds. “Black women are 41% more likely to die from breast cancer than White women despite a lower risk of being diagnosed with the disease.”
The new report, published online on Feb. 10 in CA: A Cancer Journal for Clinicians, also notes the following:
An estimated 224,080 new cancer cases and 73,680 cancer deaths will occur among Black people in 2022.
Over the past 5 data years, Black women had an 8% lower overall cancer incidence than White women but 12% higher mortality; Black men have 6% higher cancer incidence than White men but 19% higher cancer mortality.
Prostate cancer mortality among Black men decreased by 1.3% per year from 2015 to 2019 despite a 5% increase in the diagnosis of distant-stage prostate cancer annually since 2012, but the decline was slower than the 5% per year decline from 2010 to 2014.
The overall cancer mortality gap between Black and White people is narrowing. This is due to a steeper drop in prostate, lung, and other smoking-related cancers among Black people.
Colorectal cancer incidence and mortality rates are 21% and 44% higher, respectively, in Black men in comparison with White men and 18% and 31% higher, respectively, in Black women in comparison with White women.
The reasons for the disparities are complex but “largely stem from less access to high-quality care and optimal treatment as a repercussion of long-standing institutional racism,” the report concludes.
“We must address structural racism as a public health issue to close the gaps and advance health equity,” Tawana Thomas-Johnson, senior vice president and chief diversity officer at the ACS, said in the press release.
A version of this article first appeared on Medscape.com.
Gum disease linked to colorectal cancer: COLDENT study
findings from the population-based case-control COLDENT study suggest.
The rate of new CRC diagnoses among individuals in the study who had a history of PD was nearly 50% higher than in those with no such history, after adjustment for a host of medical and demographic factors, the investigators noted.
This isn’t the first time PD has been linked with extra-oral health outcomes, including gastrointestinal cancers. It has been shown to be associated with several major systemic diseases, such as cardiovascular, respiratory, chronic kidney, and metabolic diseases. Evidence also suggests a link between PD and Alzheimer’s disease.
However, prior studies that looked at the connection between PD and CRC have relied on secondary analyses of data from other studies and are limited by other methodologic shortcomings, noted the researchers, led by Amal Idrissi Janati, DDS, University of Montreal.
To better assess the etiologic role of PD in the development of CRC, Dr. Janati and colleagues analyzed 348 histologically confirmed cases of colon or rectal cancer diagnosed from January 2013 to December 2019 and compared them to 310 matched controls.
The rate of new CRC diagnoses among individuals with a history of PD was 1.4 times higher than among those with no PD history after adjustment for age and gender. It increased to 1.45 times higher when the researchers also adjusted for body mass index, education, income, diabetes, family history of CRC, regular use of aspirin and non-aspirin nonsteroidal anti-inflammatory drugs, and lifetime cumulative smoking, consumption of red and processed meats, alcohol consumption, and total physical activity score.
The findings were published online Jan. 26 in Cancer Causes and Control.
“Our results support the hypothesis of an association between PD and sporadic CRC risk,” the researchers said, adding that further epidemiologic studies are recommended.
They speculated that the “putative mechanism of PD and cancer association involves the spread of periodontal pathogens to extra-oral sites, dissemination of bacteria endotoxins, and release of inflammation products directly into the bloodstream.”
The chronic inflammation associated with PD “promotes carcinogenesis by induction of gene mutations, inhibition of apoptosis, stimulation of angiogenesis, cell proliferation, and epigenetic alterations,” they added.
The COLDENT study was supported by the Cancer Research Society. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
findings from the population-based case-control COLDENT study suggest.
The rate of new CRC diagnoses among individuals in the study who had a history of PD was nearly 50% higher than in those with no such history, after adjustment for a host of medical and demographic factors, the investigators noted.
This isn’t the first time PD has been linked with extra-oral health outcomes, including gastrointestinal cancers. It has been shown to be associated with several major systemic diseases, such as cardiovascular, respiratory, chronic kidney, and metabolic diseases. Evidence also suggests a link between PD and Alzheimer’s disease.
However, prior studies that looked at the connection between PD and CRC have relied on secondary analyses of data from other studies and are limited by other methodologic shortcomings, noted the researchers, led by Amal Idrissi Janati, DDS, University of Montreal.
To better assess the etiologic role of PD in the development of CRC, Dr. Janati and colleagues analyzed 348 histologically confirmed cases of colon or rectal cancer diagnosed from January 2013 to December 2019 and compared them to 310 matched controls.
The rate of new CRC diagnoses among individuals with a history of PD was 1.4 times higher than among those with no PD history after adjustment for age and gender. It increased to 1.45 times higher when the researchers also adjusted for body mass index, education, income, diabetes, family history of CRC, regular use of aspirin and non-aspirin nonsteroidal anti-inflammatory drugs, and lifetime cumulative smoking, consumption of red and processed meats, alcohol consumption, and total physical activity score.
The findings were published online Jan. 26 in Cancer Causes and Control.
“Our results support the hypothesis of an association between PD and sporadic CRC risk,” the researchers said, adding that further epidemiologic studies are recommended.
They speculated that the “putative mechanism of PD and cancer association involves the spread of periodontal pathogens to extra-oral sites, dissemination of bacteria endotoxins, and release of inflammation products directly into the bloodstream.”
The chronic inflammation associated with PD “promotes carcinogenesis by induction of gene mutations, inhibition of apoptosis, stimulation of angiogenesis, cell proliferation, and epigenetic alterations,” they added.
The COLDENT study was supported by the Cancer Research Society. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
findings from the population-based case-control COLDENT study suggest.
The rate of new CRC diagnoses among individuals in the study who had a history of PD was nearly 50% higher than in those with no such history, after adjustment for a host of medical and demographic factors, the investigators noted.
This isn’t the first time PD has been linked with extra-oral health outcomes, including gastrointestinal cancers. It has been shown to be associated with several major systemic diseases, such as cardiovascular, respiratory, chronic kidney, and metabolic diseases. Evidence also suggests a link between PD and Alzheimer’s disease.
However, prior studies that looked at the connection between PD and CRC have relied on secondary analyses of data from other studies and are limited by other methodologic shortcomings, noted the researchers, led by Amal Idrissi Janati, DDS, University of Montreal.
To better assess the etiologic role of PD in the development of CRC, Dr. Janati and colleagues analyzed 348 histologically confirmed cases of colon or rectal cancer diagnosed from January 2013 to December 2019 and compared them to 310 matched controls.
The rate of new CRC diagnoses among individuals with a history of PD was 1.4 times higher than among those with no PD history after adjustment for age and gender. It increased to 1.45 times higher when the researchers also adjusted for body mass index, education, income, diabetes, family history of CRC, regular use of aspirin and non-aspirin nonsteroidal anti-inflammatory drugs, and lifetime cumulative smoking, consumption of red and processed meats, alcohol consumption, and total physical activity score.
The findings were published online Jan. 26 in Cancer Causes and Control.
“Our results support the hypothesis of an association between PD and sporadic CRC risk,” the researchers said, adding that further epidemiologic studies are recommended.
They speculated that the “putative mechanism of PD and cancer association involves the spread of periodontal pathogens to extra-oral sites, dissemination of bacteria endotoxins, and release of inflammation products directly into the bloodstream.”
The chronic inflammation associated with PD “promotes carcinogenesis by induction of gene mutations, inhibition of apoptosis, stimulation of angiogenesis, cell proliferation, and epigenetic alterations,” they added.
The COLDENT study was supported by the Cancer Research Society. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM CANCER CAUSES AND CONTROL
Biomarkers in saliva may detect hepatocellular carcinoma
MicroRNAs (miRNAs) that signal hepatocellular carcinoma (HCC), the most common type of liver cancer, have been detected in saliva for the first time, according to results from a pilot study.
The findings were published online in PeerJ.
The small, noncoding RNAs regulate many cellular functions and affect cancer development and progression.
The discovery has the potential to offer a noninvasive alternative or complement to available detection tools – ultrasound and the blood biomarker alpha fetoprotein (AFP) – which lack sensitivity, said Daniel Rotroff, PhD, MSPH, senior author of the study and a researcher in the Department of Quantitative Health Sciences at the Cleveland Clinic.
“Right now, the current clinical tools are not adequate,” he told this news organization. “They miss approximately 40% to 50% of the patients who have HCC.”
Scientists are interested in finding better ways to detect liver cancer, the rates of which are growing rapidly. HCC represents 80% of all liver cancers.
“HCC and liver cancer are the fastest growing cancers in the United States,” Dr. Rotroff said. “They are the fifth and seventh leading cause of cancer death in men and women, respectively.”
Driving the growth are increases in hepatitis C, obesity, fatty liver disease, and alcoholism.
Nancy Reau, MD, the Richard B. Capps Chair of Hepatology and section chief, Hepatology, at Rush Medical College, Chicago, who was not part of the study, told this news organization that despite the study’s being relatively small in scale, the preliminary information it provides is nonetheless “really attractive.”
If larger studies confirm the results, the discovery could open up the possibility of patients mailing in saliva samples from their homes to screen for liver cancer.
The pandemic, she noted, highlighted the shortcomings of ultrasound in screening for liver cancer, as it required patients to come into a facility.
“You’d love to have a biomarker that was more accessible and accurate,” she said. “It would have lots of applicability where cancer surveillance is less available.”
Dr. Rotroff added that “we do know saliva samples can be stable at room temperature. It opens up possibilities to expand the net of being able to screen a wider number of patients.”
Differentiating HCC from cirrhosis
Investigators at the Cleveland Clinic performed small RNA sequencing in 20 patients with HCC and compared the findings to sequencing of 19 patients with cirrhosis.
Liver cirrhosis is the primary risk factor for developing HCC, so distinguishing patients with HCC from this cohort of high-risk patients serves as a proof of principle.
The sequencing showed that 4,565 precursor and mature miRNAs were detected in saliva and that 365 were significantly different between those with HCC compared to cirrhosis (false discovery rate, P < .05).
“Interestingly, 283 of these miRNAs were significantly downregulated in patients with HCC,” the authors write.
Machine learning found a combination of 10 miRNAs and covariates that accurately classified patients with HCC (area under the curve = 0.87).
The researchers note that miRNAs have been found in saliva and have shown potential as noninvasive biomarkers for a number of other cancers, including breast, oral, and lung cancers.
Additionally, Dr. Rotroff said, microRNAs have been shown to be altered in the tumor tissue of HCC, compared with the surrounding tissue.
Catching cancer early
Dr. Reau noted that a strength of the study is that it validated the biomarker in a diverse group of patients already diagnosed with liver cancer, including people with early-stage cancer, those who underwent transplantation, and those with recurrent cancer.
“Everyone searching for biomarkers is looking to make sure that the surveillance tool identifies the patient when it can pay off with early treatment,” Dr. Reau said.
“You don’t want to identify cancer when it’s bad, and you don’t have any options.
This is a little bit where AFP sometimes fails. Even if ultrasound isn’t that accurate, it still generally identifies people when they fit within curative guidelines.”
Dr. Rotroff also stressed the importance of detecting the cancers early, noting that the prognosis for patients with HCC before it has metastasized is greater than 4 years, but the prognosis drops to less than 1 year if it has metastasized.
Dr. Rotroff has an equity stake in Clarified Precision Medicine. He holds intellectual property related to the detection of HCC. Dr. Reau reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
MicroRNAs (miRNAs) that signal hepatocellular carcinoma (HCC), the most common type of liver cancer, have been detected in saliva for the first time, according to results from a pilot study.
The findings were published online in PeerJ.
The small, noncoding RNAs regulate many cellular functions and affect cancer development and progression.
The discovery has the potential to offer a noninvasive alternative or complement to available detection tools – ultrasound and the blood biomarker alpha fetoprotein (AFP) – which lack sensitivity, said Daniel Rotroff, PhD, MSPH, senior author of the study and a researcher in the Department of Quantitative Health Sciences at the Cleveland Clinic.
“Right now, the current clinical tools are not adequate,” he told this news organization. “They miss approximately 40% to 50% of the patients who have HCC.”
Scientists are interested in finding better ways to detect liver cancer, the rates of which are growing rapidly. HCC represents 80% of all liver cancers.
“HCC and liver cancer are the fastest growing cancers in the United States,” Dr. Rotroff said. “They are the fifth and seventh leading cause of cancer death in men and women, respectively.”
Driving the growth are increases in hepatitis C, obesity, fatty liver disease, and alcoholism.
Nancy Reau, MD, the Richard B. Capps Chair of Hepatology and section chief, Hepatology, at Rush Medical College, Chicago, who was not part of the study, told this news organization that despite the study’s being relatively small in scale, the preliminary information it provides is nonetheless “really attractive.”
If larger studies confirm the results, the discovery could open up the possibility of patients mailing in saliva samples from their homes to screen for liver cancer.
The pandemic, she noted, highlighted the shortcomings of ultrasound in screening for liver cancer, as it required patients to come into a facility.
“You’d love to have a biomarker that was more accessible and accurate,” she said. “It would have lots of applicability where cancer surveillance is less available.”
Dr. Rotroff added that “we do know saliva samples can be stable at room temperature. It opens up possibilities to expand the net of being able to screen a wider number of patients.”
Differentiating HCC from cirrhosis
Investigators at the Cleveland Clinic performed small RNA sequencing in 20 patients with HCC and compared the findings to sequencing of 19 patients with cirrhosis.
Liver cirrhosis is the primary risk factor for developing HCC, so distinguishing patients with HCC from this cohort of high-risk patients serves as a proof of principle.
The sequencing showed that 4,565 precursor and mature miRNAs were detected in saliva and that 365 were significantly different between those with HCC compared to cirrhosis (false discovery rate, P < .05).
“Interestingly, 283 of these miRNAs were significantly downregulated in patients with HCC,” the authors write.
Machine learning found a combination of 10 miRNAs and covariates that accurately classified patients with HCC (area under the curve = 0.87).
The researchers note that miRNAs have been found in saliva and have shown potential as noninvasive biomarkers for a number of other cancers, including breast, oral, and lung cancers.
Additionally, Dr. Rotroff said, microRNAs have been shown to be altered in the tumor tissue of HCC, compared with the surrounding tissue.
Catching cancer early
Dr. Reau noted that a strength of the study is that it validated the biomarker in a diverse group of patients already diagnosed with liver cancer, including people with early-stage cancer, those who underwent transplantation, and those with recurrent cancer.
“Everyone searching for biomarkers is looking to make sure that the surveillance tool identifies the patient when it can pay off with early treatment,” Dr. Reau said.
“You don’t want to identify cancer when it’s bad, and you don’t have any options.
This is a little bit where AFP sometimes fails. Even if ultrasound isn’t that accurate, it still generally identifies people when they fit within curative guidelines.”
Dr. Rotroff also stressed the importance of detecting the cancers early, noting that the prognosis for patients with HCC before it has metastasized is greater than 4 years, but the prognosis drops to less than 1 year if it has metastasized.
Dr. Rotroff has an equity stake in Clarified Precision Medicine. He holds intellectual property related to the detection of HCC. Dr. Reau reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
MicroRNAs (miRNAs) that signal hepatocellular carcinoma (HCC), the most common type of liver cancer, have been detected in saliva for the first time, according to results from a pilot study.
The findings were published online in PeerJ.
The small, noncoding RNAs regulate many cellular functions and affect cancer development and progression.
The discovery has the potential to offer a noninvasive alternative or complement to available detection tools – ultrasound and the blood biomarker alpha fetoprotein (AFP) – which lack sensitivity, said Daniel Rotroff, PhD, MSPH, senior author of the study and a researcher in the Department of Quantitative Health Sciences at the Cleveland Clinic.
“Right now, the current clinical tools are not adequate,” he told this news organization. “They miss approximately 40% to 50% of the patients who have HCC.”
Scientists are interested in finding better ways to detect liver cancer, the rates of which are growing rapidly. HCC represents 80% of all liver cancers.
“HCC and liver cancer are the fastest growing cancers in the United States,” Dr. Rotroff said. “They are the fifth and seventh leading cause of cancer death in men and women, respectively.”
Driving the growth are increases in hepatitis C, obesity, fatty liver disease, and alcoholism.
Nancy Reau, MD, the Richard B. Capps Chair of Hepatology and section chief, Hepatology, at Rush Medical College, Chicago, who was not part of the study, told this news organization that despite the study’s being relatively small in scale, the preliminary information it provides is nonetheless “really attractive.”
If larger studies confirm the results, the discovery could open up the possibility of patients mailing in saliva samples from their homes to screen for liver cancer.
The pandemic, she noted, highlighted the shortcomings of ultrasound in screening for liver cancer, as it required patients to come into a facility.
“You’d love to have a biomarker that was more accessible and accurate,” she said. “It would have lots of applicability where cancer surveillance is less available.”
Dr. Rotroff added that “we do know saliva samples can be stable at room temperature. It opens up possibilities to expand the net of being able to screen a wider number of patients.”
Differentiating HCC from cirrhosis
Investigators at the Cleveland Clinic performed small RNA sequencing in 20 patients with HCC and compared the findings to sequencing of 19 patients with cirrhosis.
Liver cirrhosis is the primary risk factor for developing HCC, so distinguishing patients with HCC from this cohort of high-risk patients serves as a proof of principle.
The sequencing showed that 4,565 precursor and mature miRNAs were detected in saliva and that 365 were significantly different between those with HCC compared to cirrhosis (false discovery rate, P < .05).
“Interestingly, 283 of these miRNAs were significantly downregulated in patients with HCC,” the authors write.
Machine learning found a combination of 10 miRNAs and covariates that accurately classified patients with HCC (area under the curve = 0.87).
The researchers note that miRNAs have been found in saliva and have shown potential as noninvasive biomarkers for a number of other cancers, including breast, oral, and lung cancers.
Additionally, Dr. Rotroff said, microRNAs have been shown to be altered in the tumor tissue of HCC, compared with the surrounding tissue.
Catching cancer early
Dr. Reau noted that a strength of the study is that it validated the biomarker in a diverse group of patients already diagnosed with liver cancer, including people with early-stage cancer, those who underwent transplantation, and those with recurrent cancer.
“Everyone searching for biomarkers is looking to make sure that the surveillance tool identifies the patient when it can pay off with early treatment,” Dr. Reau said.
“You don’t want to identify cancer when it’s bad, and you don’t have any options.
This is a little bit where AFP sometimes fails. Even if ultrasound isn’t that accurate, it still generally identifies people when they fit within curative guidelines.”
Dr. Rotroff also stressed the importance of detecting the cancers early, noting that the prognosis for patients with HCC before it has metastasized is greater than 4 years, but the prognosis drops to less than 1 year if it has metastasized.
Dr. Rotroff has an equity stake in Clarified Precision Medicine. He holds intellectual property related to the detection of HCC. Dr. Reau reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Stopping venetoclax treatment early reduces CLL survival outcomes
“There’s not a lot of awareness about the fact that you’re probably better off not permanently discontinuing treatment,” Anthony R. Mato, first author of the research published in Haematologica, said in an interview.
“Instead, attempting dose reductions with later resumption to complete the planned schedule for treatment probably could improve outcomes,” said Dr. Mato, who is director of the CLL Program at Memorial Sloan Kettering Cancer Center in New York.
Venetoclax, a potent B-cell lymphoma-2 (BCL2) inhibitor, provides a novel, chemotherapy-free treatment option for first-line and r/r CLL. While its safety profile is manageable, treatment interruptions are very common, and premature discontinuations are reported in about a third of patients, often because of adverse events.
Lacking data on the effects of those interruptions on survival outcomes, Dr. Mato and colleagues conducted a post hoc analysis of the phase 3 MURANO trial. In this open-label study, treatment with six cycles of venetoclax in combination with rituximab followed by venetoclax once daily for a total of 2 years showed superior progression-free survival, compared with six cycles of bendamustine plus rituximab in patients with r/r CLL (P < .0001).
The current analysis involved 194 intention-to-treat patients from the trial’s venetoclax arm, among whom 140 (72%) completed 2 years of therapy, and 54 (28%) prematurely discontinued treatment. The most common reasons for discontinuation were adverse events (53.7%) and disease progression (22.2%).
Among those with early discontinuation for any reason except disease progression, the rate of progression-free survival was significantly inferior, compared with those who completed the treatment (hazard ratio, 5.98; P < .0001), as was the rate or discontinuation caused specifically by adverse events, which most commonly involved neutropenia or thrombocytopenia (HR, 5.82; P < .0001).
Those who discontinued had a mean duration of venetoclax therapy of 11.3 months, compared with 24.4 months for all patients. For each additional month of venetoclax therapy, there was a significantly lower risk of a progression-free survival event (P = .0263) and of an overall survival event (P < .0001).
The treatment interruption rate was much higher, at 69% (134), involving neutropenia in 43% (84) of instances and requiring dose reductions in 23% (45) of cases.
However, in contrast to permanent discontinuations, the temporary interruptions and dose reductions had no significant effect on progression-free or overall survival, regardless of the duration.
“Improved progression-free and overall survival were associated with greater cumulative venetoclax treatment exposure,” the authors wrote.
“The results of these analyses highlight the importance of appropriately managing treatment modifications to ensure optimal outcomes for patients receiving targeted treatment for CLL,” they said.
Key measures including “better supportive care, use of growth factors, and more aggressive strategies for dose reduction could potentially help to improve or decrease the number of patients discontinuing due to an adverse event,” Dr. Mato added.“We can’t say definitively because this is not a randomized study – it’s a retrospective analysis from a randomized study – but those measures likely could have a positive impact on patient outcomes.”
The study received support from Genentech and AbbVie. Dr. Mato reported consulting or other relationships with AbbVie, AstraZeneca, Celgene, DTRM, Genentech, Janssen, Loxo, PCYC, Sunesis, and TG Therapeutics.
“There’s not a lot of awareness about the fact that you’re probably better off not permanently discontinuing treatment,” Anthony R. Mato, first author of the research published in Haematologica, said in an interview.
“Instead, attempting dose reductions with later resumption to complete the planned schedule for treatment probably could improve outcomes,” said Dr. Mato, who is director of the CLL Program at Memorial Sloan Kettering Cancer Center in New York.
Venetoclax, a potent B-cell lymphoma-2 (BCL2) inhibitor, provides a novel, chemotherapy-free treatment option for first-line and r/r CLL. While its safety profile is manageable, treatment interruptions are very common, and premature discontinuations are reported in about a third of patients, often because of adverse events.
Lacking data on the effects of those interruptions on survival outcomes, Dr. Mato and colleagues conducted a post hoc analysis of the phase 3 MURANO trial. In this open-label study, treatment with six cycles of venetoclax in combination with rituximab followed by venetoclax once daily for a total of 2 years showed superior progression-free survival, compared with six cycles of bendamustine plus rituximab in patients with r/r CLL (P < .0001).
The current analysis involved 194 intention-to-treat patients from the trial’s venetoclax arm, among whom 140 (72%) completed 2 years of therapy, and 54 (28%) prematurely discontinued treatment. The most common reasons for discontinuation were adverse events (53.7%) and disease progression (22.2%).
Among those with early discontinuation for any reason except disease progression, the rate of progression-free survival was significantly inferior, compared with those who completed the treatment (hazard ratio, 5.98; P < .0001), as was the rate or discontinuation caused specifically by adverse events, which most commonly involved neutropenia or thrombocytopenia (HR, 5.82; P < .0001).
Those who discontinued had a mean duration of venetoclax therapy of 11.3 months, compared with 24.4 months for all patients. For each additional month of venetoclax therapy, there was a significantly lower risk of a progression-free survival event (P = .0263) and of an overall survival event (P < .0001).
The treatment interruption rate was much higher, at 69% (134), involving neutropenia in 43% (84) of instances and requiring dose reductions in 23% (45) of cases.
However, in contrast to permanent discontinuations, the temporary interruptions and dose reductions had no significant effect on progression-free or overall survival, regardless of the duration.
“Improved progression-free and overall survival were associated with greater cumulative venetoclax treatment exposure,” the authors wrote.
“The results of these analyses highlight the importance of appropriately managing treatment modifications to ensure optimal outcomes for patients receiving targeted treatment for CLL,” they said.
Key measures including “better supportive care, use of growth factors, and more aggressive strategies for dose reduction could potentially help to improve or decrease the number of patients discontinuing due to an adverse event,” Dr. Mato added.“We can’t say definitively because this is not a randomized study – it’s a retrospective analysis from a randomized study – but those measures likely could have a positive impact on patient outcomes.”
The study received support from Genentech and AbbVie. Dr. Mato reported consulting or other relationships with AbbVie, AstraZeneca, Celgene, DTRM, Genentech, Janssen, Loxo, PCYC, Sunesis, and TG Therapeutics.
“There’s not a lot of awareness about the fact that you’re probably better off not permanently discontinuing treatment,” Anthony R. Mato, first author of the research published in Haematologica, said in an interview.
“Instead, attempting dose reductions with later resumption to complete the planned schedule for treatment probably could improve outcomes,” said Dr. Mato, who is director of the CLL Program at Memorial Sloan Kettering Cancer Center in New York.
Venetoclax, a potent B-cell lymphoma-2 (BCL2) inhibitor, provides a novel, chemotherapy-free treatment option for first-line and r/r CLL. While its safety profile is manageable, treatment interruptions are very common, and premature discontinuations are reported in about a third of patients, often because of adverse events.
Lacking data on the effects of those interruptions on survival outcomes, Dr. Mato and colleagues conducted a post hoc analysis of the phase 3 MURANO trial. In this open-label study, treatment with six cycles of venetoclax in combination with rituximab followed by venetoclax once daily for a total of 2 years showed superior progression-free survival, compared with six cycles of bendamustine plus rituximab in patients with r/r CLL (P < .0001).
The current analysis involved 194 intention-to-treat patients from the trial’s venetoclax arm, among whom 140 (72%) completed 2 years of therapy, and 54 (28%) prematurely discontinued treatment. The most common reasons for discontinuation were adverse events (53.7%) and disease progression (22.2%).
Among those with early discontinuation for any reason except disease progression, the rate of progression-free survival was significantly inferior, compared with those who completed the treatment (hazard ratio, 5.98; P < .0001), as was the rate or discontinuation caused specifically by adverse events, which most commonly involved neutropenia or thrombocytopenia (HR, 5.82; P < .0001).
Those who discontinued had a mean duration of venetoclax therapy of 11.3 months, compared with 24.4 months for all patients. For each additional month of venetoclax therapy, there was a significantly lower risk of a progression-free survival event (P = .0263) and of an overall survival event (P < .0001).
The treatment interruption rate was much higher, at 69% (134), involving neutropenia in 43% (84) of instances and requiring dose reductions in 23% (45) of cases.
However, in contrast to permanent discontinuations, the temporary interruptions and dose reductions had no significant effect on progression-free or overall survival, regardless of the duration.
“Improved progression-free and overall survival were associated with greater cumulative venetoclax treatment exposure,” the authors wrote.
“The results of these analyses highlight the importance of appropriately managing treatment modifications to ensure optimal outcomes for patients receiving targeted treatment for CLL,” they said.
Key measures including “better supportive care, use of growth factors, and more aggressive strategies for dose reduction could potentially help to improve or decrease the number of patients discontinuing due to an adverse event,” Dr. Mato added.“We can’t say definitively because this is not a randomized study – it’s a retrospective analysis from a randomized study – but those measures likely could have a positive impact on patient outcomes.”
The study received support from Genentech and AbbVie. Dr. Mato reported consulting or other relationships with AbbVie, AstraZeneca, Celgene, DTRM, Genentech, Janssen, Loxo, PCYC, Sunesis, and TG Therapeutics.
Primer message boosts colorectal cancer screening rates
Researchers have found a simple, low-cost way to get more adults to complete a fecal immunochemical test (FIT) to screen for colorectal cancer (CRC).
In a randomized controlled trial, patients who received an electronic “primer” message through their patient portal before the test kit arrived in their mailbox were more apt to complete and return the test than peers who didn’t get the electronic message.
“We were thrilled by the magnitude of the impact,” Gregory Goshgarian, MSc, MPH, and Daniel Croymans, MD, with the department of medicine, David Geffen School of Medicine, University of California, Los Angeles, said in a joint email to this news organization.
At UCLA Health, “including a primer patient portal message is now standard practice for our FIT mailer program,” they added.
Their study was published online Feb. 4 in JAMA Network Open.
Heads-up message boosts compliance
CRC screening rates in the United States remain well below the national benchmark of 80%, and COVID-19 hasn’t helped. As a result, multiple medical and professional societies have emphasized the use of a mailed FIT outreach program.
As part of the outreach program, researchers at UCLA Health developed an electronic primer message within the electronic patient portal to alert patients due for CRC screening that they would be receiving a FIT kit in the mail.
They tested the impact of the primer messages in a randomized controlled trial involving 2,339 adults (mean age, 59 years, 57.5% women). Out of these, 1,157 received the standard mailed FIT kit (control group) and 1,182 received the standard mailed FIT kit plus a primer message sent through their personal patient portal.
Adding the primer message significantly increased the FIT completion rate at 6 months by 5.5%, with rates of 37.6% in the intervention group versus 32.1% in the control group.
After adjusting for patient demographics, the primer (versus no primer) led to significantly increased odds of completing CRC screening (adjusted odds ratio: 1.29; 95% confidence interval, 1.08-1.53; P = .004).
The primer message also shortened the time to FIT screening by 3 days (35 days with the primer vs. 38 days without).
Dr. Goshgarian and Dr. Croymans believe the priming messages worked well in their patient population because at the beginning of the intervention they identified a potential lack of awareness of the incoming FIT kit mailer as a barrier to uptake.
“We believe patients were receiving the kits with minimal advanced warning and discarding it as a mistake or hesitant to complete it because they did not understand the value to them,” they told this news organization.
“Therefore, a priming message helped to bridge that gap and allowed patients to be aware of the incoming FIT kits, know why it was important to do the FIT kit, and ultimately led to increasing our FIT kit return rates and thus CRC screening,” they said.
The researchers caution that their findings may be more relevant to patient populations who are more engaged in their health or who are more technologically savvy. In the UCLA Health system, roughly 84% of patients have an activated patient portal.
‘Good enhancement’ for health care systems
Reached for comment, Aasma Shaukat, MD, MPH, professor of medicine, NYU Langone Health, and first author of the American College of Gastroenterology (ACG) 2021 CRC screening guidelines, said the results are “interesting but not entirely surprising.”
“There’s literature supporting that a letter or notification prior to the FIT being mailed improves its uptake. Here, the authors applied it to their health care system in a quality improvement study and demonstrated it works,” Dr. Shaukat said.
“This is a good enhancement for health care systems where most of their patients are using or accessing their health chart portal,” added Dr. Shaukat.
“Caveats are that the generalizability is not known. It requires EHR [electronic health record] support tools and patients with access to a computer and enrolled and able to access their electronic chart, likely those with high literacy and English speaking.”
Funding for the study was provided by the UCLA Health Department of Medicine. Dr. Goshgarian, Dr. Croymans, and Dr. Shaukat have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Researchers have found a simple, low-cost way to get more adults to complete a fecal immunochemical test (FIT) to screen for colorectal cancer (CRC).
In a randomized controlled trial, patients who received an electronic “primer” message through their patient portal before the test kit arrived in their mailbox were more apt to complete and return the test than peers who didn’t get the electronic message.
“We were thrilled by the magnitude of the impact,” Gregory Goshgarian, MSc, MPH, and Daniel Croymans, MD, with the department of medicine, David Geffen School of Medicine, University of California, Los Angeles, said in a joint email to this news organization.
At UCLA Health, “including a primer patient portal message is now standard practice for our FIT mailer program,” they added.
Their study was published online Feb. 4 in JAMA Network Open.
Heads-up message boosts compliance
CRC screening rates in the United States remain well below the national benchmark of 80%, and COVID-19 hasn’t helped. As a result, multiple medical and professional societies have emphasized the use of a mailed FIT outreach program.
As part of the outreach program, researchers at UCLA Health developed an electronic primer message within the electronic patient portal to alert patients due for CRC screening that they would be receiving a FIT kit in the mail.
They tested the impact of the primer messages in a randomized controlled trial involving 2,339 adults (mean age, 59 years, 57.5% women). Out of these, 1,157 received the standard mailed FIT kit (control group) and 1,182 received the standard mailed FIT kit plus a primer message sent through their personal patient portal.
Adding the primer message significantly increased the FIT completion rate at 6 months by 5.5%, with rates of 37.6% in the intervention group versus 32.1% in the control group.
After adjusting for patient demographics, the primer (versus no primer) led to significantly increased odds of completing CRC screening (adjusted odds ratio: 1.29; 95% confidence interval, 1.08-1.53; P = .004).
The primer message also shortened the time to FIT screening by 3 days (35 days with the primer vs. 38 days without).
Dr. Goshgarian and Dr. Croymans believe the priming messages worked well in their patient population because at the beginning of the intervention they identified a potential lack of awareness of the incoming FIT kit mailer as a barrier to uptake.
“We believe patients were receiving the kits with minimal advanced warning and discarding it as a mistake or hesitant to complete it because they did not understand the value to them,” they told this news organization.
“Therefore, a priming message helped to bridge that gap and allowed patients to be aware of the incoming FIT kits, know why it was important to do the FIT kit, and ultimately led to increasing our FIT kit return rates and thus CRC screening,” they said.
The researchers caution that their findings may be more relevant to patient populations who are more engaged in their health or who are more technologically savvy. In the UCLA Health system, roughly 84% of patients have an activated patient portal.
‘Good enhancement’ for health care systems
Reached for comment, Aasma Shaukat, MD, MPH, professor of medicine, NYU Langone Health, and first author of the American College of Gastroenterology (ACG) 2021 CRC screening guidelines, said the results are “interesting but not entirely surprising.”
“There’s literature supporting that a letter or notification prior to the FIT being mailed improves its uptake. Here, the authors applied it to their health care system in a quality improvement study and demonstrated it works,” Dr. Shaukat said.
“This is a good enhancement for health care systems where most of their patients are using or accessing their health chart portal,” added Dr. Shaukat.
“Caveats are that the generalizability is not known. It requires EHR [electronic health record] support tools and patients with access to a computer and enrolled and able to access their electronic chart, likely those with high literacy and English speaking.”
Funding for the study was provided by the UCLA Health Department of Medicine. Dr. Goshgarian, Dr. Croymans, and Dr. Shaukat have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Researchers have found a simple, low-cost way to get more adults to complete a fecal immunochemical test (FIT) to screen for colorectal cancer (CRC).
In a randomized controlled trial, patients who received an electronic “primer” message through their patient portal before the test kit arrived in their mailbox were more apt to complete and return the test than peers who didn’t get the electronic message.
“We were thrilled by the magnitude of the impact,” Gregory Goshgarian, MSc, MPH, and Daniel Croymans, MD, with the department of medicine, David Geffen School of Medicine, University of California, Los Angeles, said in a joint email to this news organization.
At UCLA Health, “including a primer patient portal message is now standard practice for our FIT mailer program,” they added.
Their study was published online Feb. 4 in JAMA Network Open.
Heads-up message boosts compliance
CRC screening rates in the United States remain well below the national benchmark of 80%, and COVID-19 hasn’t helped. As a result, multiple medical and professional societies have emphasized the use of a mailed FIT outreach program.
As part of the outreach program, researchers at UCLA Health developed an electronic primer message within the electronic patient portal to alert patients due for CRC screening that they would be receiving a FIT kit in the mail.
They tested the impact of the primer messages in a randomized controlled trial involving 2,339 adults (mean age, 59 years, 57.5% women). Out of these, 1,157 received the standard mailed FIT kit (control group) and 1,182 received the standard mailed FIT kit plus a primer message sent through their personal patient portal.
Adding the primer message significantly increased the FIT completion rate at 6 months by 5.5%, with rates of 37.6% in the intervention group versus 32.1% in the control group.
After adjusting for patient demographics, the primer (versus no primer) led to significantly increased odds of completing CRC screening (adjusted odds ratio: 1.29; 95% confidence interval, 1.08-1.53; P = .004).
The primer message also shortened the time to FIT screening by 3 days (35 days with the primer vs. 38 days without).
Dr. Goshgarian and Dr. Croymans believe the priming messages worked well in their patient population because at the beginning of the intervention they identified a potential lack of awareness of the incoming FIT kit mailer as a barrier to uptake.
“We believe patients were receiving the kits with minimal advanced warning and discarding it as a mistake or hesitant to complete it because they did not understand the value to them,” they told this news organization.
“Therefore, a priming message helped to bridge that gap and allowed patients to be aware of the incoming FIT kits, know why it was important to do the FIT kit, and ultimately led to increasing our FIT kit return rates and thus CRC screening,” they said.
The researchers caution that their findings may be more relevant to patient populations who are more engaged in their health or who are more technologically savvy. In the UCLA Health system, roughly 84% of patients have an activated patient portal.
‘Good enhancement’ for health care systems
Reached for comment, Aasma Shaukat, MD, MPH, professor of medicine, NYU Langone Health, and first author of the American College of Gastroenterology (ACG) 2021 CRC screening guidelines, said the results are “interesting but not entirely surprising.”
“There’s literature supporting that a letter or notification prior to the FIT being mailed improves its uptake. Here, the authors applied it to their health care system in a quality improvement study and demonstrated it works,” Dr. Shaukat said.
“This is a good enhancement for health care systems where most of their patients are using or accessing their health chart portal,” added Dr. Shaukat.
“Caveats are that the generalizability is not known. It requires EHR [electronic health record] support tools and patients with access to a computer and enrolled and able to access their electronic chart, likely those with high literacy and English speaking.”
Funding for the study was provided by the UCLA Health Department of Medicine. Dr. Goshgarian, Dr. Croymans, and Dr. Shaukat have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
Alleviating chemo-related nausea is a huge unmet need
This transcript has been edited for clarity. The transcript and an accompanying video first appeared on Medscape.com.
This is Mark Kris from chilly New York and Memorial Sloan Kettering. Today I want to talk about a recent article in the Journal of Clinical Oncology that reported a study of a new neurokinin-1 antagonist called fosnetupitant. This was a well-conducted trial that demonstrates the noninferiority of IV fosnetupitant when compared with IV fosaprepitant. By their study criteria, fosnetupitant was not inferior.
But my reason for discussing this is that the paper and the trial miss the point for the field right now. Although the authors talk about the prevention of nausea and vomiting in the introduction, in the paper itself and in the abstract results section, there’s not a single mention about the medication’s ability to control nausea, which is the critical issue for our patients today. You have to go into the supplementary data to find it mentioned, and what you find is that the prevention of nausea is 50% for both the control and this new drug. We control nausea in only half of the patients who receive cisplatin in 2022. That is a huge issue.
When you ask patients what are the effects of cancer treatment that they fear most, that concerns them most, it’s nausea and emesis; indeed, nausea has replaced emesis as the biggest concern. And although this trial used emesis as the main endpoint, and it was useful in defining the drug, it was not useful in coming up with a new treatment that addresses a huge need. Further, the authors talk about an advantage to fosnetupitant based on infusion reactions, but it is a difference of 0.3% vs. 3%. They talk about that sort of thing in the abstract and in the discussion section but don’t include nausea as part of the key endpoint of this trial. Again, you had to dig deeply to find out that, frankly, fosnetupitant was no better than the drugs we already have.
The other concerning point is that we do have another drug that works well. If you go to the American Society of Clinical Oncology or National Comprehensive Cancer Network guidelines for patients receiving high dosages of cisplatin, you find a four-drug regimen, including olanzapine, and that was not used here. Why is olanzapine so critical? It’s an available drug, it’s an inexpensive drug, it’s a safe drug, and it improves nausea by 15%.
So they did this huge trial to show noninferiority, and they neglected to give a drug that could deal with the most serious side effect of cancer therapy – nausea – and improve things by 15%.
A challenge to people in this field: We have to do better. Nausea is a big problem. While noninferiority trials can be helpful for drug development, they’re not really helpful for the field. With a problem of this magnitude, we need better drugs to control nausea. In the meantime, I urge you all to follow the guidelines for high doses of cisplatin. Please use the four-drug regimen that is recommended in the guidelines and widely used in the United States. Going forward, make sure that when we expend huge amounts of energy to develop new agents and report them in our medical journals, that we look for ways to advance care where there are significant gaps in our ability to deliver what we want. Delivering better control of nausea is something we all need to be committed to. It’s a huge unmet need, and I hope future trials will address that need. Our patients will be better for it and we’ll be better in that we’re delivering what patients deserve, what they need, and what they ask for.
Mark G. Kris, MD, is chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center in New York City. He reported serving as a director, officer, partner, employee, adviser, consultant, or trustee for AstraZeneca, Roche/Genentech, and Ariad Pharmaceuticals, and has received research grants from Pfizer, PUMA, and Roche/Genentech.
This transcript has been edited for clarity. The transcript and an accompanying video first appeared on Medscape.com.
This is Mark Kris from chilly New York and Memorial Sloan Kettering. Today I want to talk about a recent article in the Journal of Clinical Oncology that reported a study of a new neurokinin-1 antagonist called fosnetupitant. This was a well-conducted trial that demonstrates the noninferiority of IV fosnetupitant when compared with IV fosaprepitant. By their study criteria, fosnetupitant was not inferior.
But my reason for discussing this is that the paper and the trial miss the point for the field right now. Although the authors talk about the prevention of nausea and vomiting in the introduction, in the paper itself and in the abstract results section, there’s not a single mention about the medication’s ability to control nausea, which is the critical issue for our patients today. You have to go into the supplementary data to find it mentioned, and what you find is that the prevention of nausea is 50% for both the control and this new drug. We control nausea in only half of the patients who receive cisplatin in 2022. That is a huge issue.
When you ask patients what are the effects of cancer treatment that they fear most, that concerns them most, it’s nausea and emesis; indeed, nausea has replaced emesis as the biggest concern. And although this trial used emesis as the main endpoint, and it was useful in defining the drug, it was not useful in coming up with a new treatment that addresses a huge need. Further, the authors talk about an advantage to fosnetupitant based on infusion reactions, but it is a difference of 0.3% vs. 3%. They talk about that sort of thing in the abstract and in the discussion section but don’t include nausea as part of the key endpoint of this trial. Again, you had to dig deeply to find out that, frankly, fosnetupitant was no better than the drugs we already have.
The other concerning point is that we do have another drug that works well. If you go to the American Society of Clinical Oncology or National Comprehensive Cancer Network guidelines for patients receiving high dosages of cisplatin, you find a four-drug regimen, including olanzapine, and that was not used here. Why is olanzapine so critical? It’s an available drug, it’s an inexpensive drug, it’s a safe drug, and it improves nausea by 15%.
So they did this huge trial to show noninferiority, and they neglected to give a drug that could deal with the most serious side effect of cancer therapy – nausea – and improve things by 15%.
A challenge to people in this field: We have to do better. Nausea is a big problem. While noninferiority trials can be helpful for drug development, they’re not really helpful for the field. With a problem of this magnitude, we need better drugs to control nausea. In the meantime, I urge you all to follow the guidelines for high doses of cisplatin. Please use the four-drug regimen that is recommended in the guidelines and widely used in the United States. Going forward, make sure that when we expend huge amounts of energy to develop new agents and report them in our medical journals, that we look for ways to advance care where there are significant gaps in our ability to deliver what we want. Delivering better control of nausea is something we all need to be committed to. It’s a huge unmet need, and I hope future trials will address that need. Our patients will be better for it and we’ll be better in that we’re delivering what patients deserve, what they need, and what they ask for.
Mark G. Kris, MD, is chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center in New York City. He reported serving as a director, officer, partner, employee, adviser, consultant, or trustee for AstraZeneca, Roche/Genentech, and Ariad Pharmaceuticals, and has received research grants from Pfizer, PUMA, and Roche/Genentech.
This transcript has been edited for clarity. The transcript and an accompanying video first appeared on Medscape.com.
This is Mark Kris from chilly New York and Memorial Sloan Kettering. Today I want to talk about a recent article in the Journal of Clinical Oncology that reported a study of a new neurokinin-1 antagonist called fosnetupitant. This was a well-conducted trial that demonstrates the noninferiority of IV fosnetupitant when compared with IV fosaprepitant. By their study criteria, fosnetupitant was not inferior.
But my reason for discussing this is that the paper and the trial miss the point for the field right now. Although the authors talk about the prevention of nausea and vomiting in the introduction, in the paper itself and in the abstract results section, there’s not a single mention about the medication’s ability to control nausea, which is the critical issue for our patients today. You have to go into the supplementary data to find it mentioned, and what you find is that the prevention of nausea is 50% for both the control and this new drug. We control nausea in only half of the patients who receive cisplatin in 2022. That is a huge issue.
When you ask patients what are the effects of cancer treatment that they fear most, that concerns them most, it’s nausea and emesis; indeed, nausea has replaced emesis as the biggest concern. And although this trial used emesis as the main endpoint, and it was useful in defining the drug, it was not useful in coming up with a new treatment that addresses a huge need. Further, the authors talk about an advantage to fosnetupitant based on infusion reactions, but it is a difference of 0.3% vs. 3%. They talk about that sort of thing in the abstract and in the discussion section but don’t include nausea as part of the key endpoint of this trial. Again, you had to dig deeply to find out that, frankly, fosnetupitant was no better than the drugs we already have.
The other concerning point is that we do have another drug that works well. If you go to the American Society of Clinical Oncology or National Comprehensive Cancer Network guidelines for patients receiving high dosages of cisplatin, you find a four-drug regimen, including olanzapine, and that was not used here. Why is olanzapine so critical? It’s an available drug, it’s an inexpensive drug, it’s a safe drug, and it improves nausea by 15%.
So they did this huge trial to show noninferiority, and they neglected to give a drug that could deal with the most serious side effect of cancer therapy – nausea – and improve things by 15%.
A challenge to people in this field: We have to do better. Nausea is a big problem. While noninferiority trials can be helpful for drug development, they’re not really helpful for the field. With a problem of this magnitude, we need better drugs to control nausea. In the meantime, I urge you all to follow the guidelines for high doses of cisplatin. Please use the four-drug regimen that is recommended in the guidelines and widely used in the United States. Going forward, make sure that when we expend huge amounts of energy to develop new agents and report them in our medical journals, that we look for ways to advance care where there are significant gaps in our ability to deliver what we want. Delivering better control of nausea is something we all need to be committed to. It’s a huge unmet need, and I hope future trials will address that need. Our patients will be better for it and we’ll be better in that we’re delivering what patients deserve, what they need, and what they ask for.
Mark G. Kris, MD, is chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center in New York City. He reported serving as a director, officer, partner, employee, adviser, consultant, or trustee for AstraZeneca, Roche/Genentech, and Ariad Pharmaceuticals, and has received research grants from Pfizer, PUMA, and Roche/Genentech.
“I didn’t want to meet you.” Dispelling myths about palliative care
The names of health care professionals and patients cited within the dialogue text have been changed to protect their privacy.
but over the years I have come to realize that she was right – most people, including many within health care, don’t have a good appreciation of what palliative care is or how it can help patients and health care teams.
A recent national survey about cancer-related health information found that of more than 1,000 surveyed Americans, less than 30% professed any knowledge of palliative care. Of those who had some knowledge of palliative care, around 30% believed palliative care was synonymous with hospice.1 Another 15% believed that a patient would have to give up cancer-directed treatments to receive palliative care.1
It’s not giving up
This persistent belief that palliative care is equivalent to hospice, or is tantamount to “giving up,” is one of the most commonly held myths I encounter in everyday practice.
I knock on the exam door and walk in.
A small, trim woman in her late 50s is sitting in a chair, arms folded across her chest, face drawn in.
“Hi,” I start. “I’m Sarah, the palliative care nurse practitioner who works in this clinic. I work closely with Dr. Smith.”
Dr. Smith is the patient’s oncologist.
“I really didn’t want to meet you,” she says in a quiet voice, her eyes large with concern.
I don’t take it personally. Few patients really want to be in the position of needing to meet the palliative care team.
“I looked up palliative care on Google and saw the word hospice.”
“Yeah,” I say. “I hear that a lot. Well, I can reassure you that this isn’t hospice.
In this clinic, our focus is on your cancer symptoms, your treatment side effects, and your quality of life.”
She looks visibly relieved. “Quality of life,” she echoes. “I need more of that.”
“OK,” I say. “So, tell me what you’re struggling with the most right now.”
That’s how many palliative care visits start. I actually prefer if patients haven’t heard of palliative care because it allows me to frame it for them, rather than having to start by addressing a myth or a prior negative experience. Even when patients haven’t had a negative experience with palliative care per se, typically, if they’ve interacted with palliative care in the past, it’s usually because someone they loved died in a hospital setting and it is the memory of that terrible loss that becomes synonymous with their recollection of palliative care.
Many patients I meet have never seen another outpatient palliative care practitioner – and this makes sense – we are still too few and far between. Most established palliative care teams are hospital based and many patients seen in the community do not have easy access to palliative care teams where they receive oncologic care.2 As an embedded practitioner, I see patients in the same exam rooms and infusion centers where they receive their cancer therapies, so I’m effectively woven into the fabric of their oncology experience. Just being there in the cancer center allows me to be in the right place at the right time for the right patients and their care teams.
More than pain management
Another myth I tend to dispel a lot is that palliative care is just a euphemism for “pain management.” I have seen this less lately, but still occasionally in the chart I’ll see documented in a note, “patient is seeing palliative/pain management,” when a patient is seeing me or one of my colleagues. Unfortunately, when providers have limited or outdated views of what palliative care is or the value it brings to patient-centered cancer care, referrals to palliative care tend to be delayed.3
“I really think Ms. Lopez could benefit from seeing palliative care,” an oncology nurse practitioner says to an oncologist.
I’m standing nearby, about to see another patient in one of the exam rooms in our clinic.
“But I don’t think she’s ready. And besides, she doesn’t have any pain,” he says.
He turns to me quizzically. “What do you think?”
“Tell me about the patient,” I ask, taking a few steps in their direction.
“Well, she’s a 64-year-old woman with metastatic cancer.
She has a really poor appetite and is losing some weight.
Seems a bit down, kind of pessimistic about things.
Her scan showed some new growth, so guess I’m not surprised by that.”
“I might be able to help her with the appetite and the mood changes.
I can at least talk with her and see where she’s at,” I offer.
“Alright,” he says. “We’ll put the palliative referral in.”
He hesitates. “But are you sure you want to see her?
She doesn’t have any pain.” He sounds skeptical.
“Yeah, I mean, it sounds like she has symptoms that are bothering her, so I’d be happy to see her. She sounds completely appropriate for palliative care.”
I hear this assumption a lot – that palliative care is somehow equivalent to pain management and that unless a patient’s pain is severe, it’s not worth referring the patient to palliative care. Don’t get me wrong – we do a lot of pain management, but at its heart, palliative care is an interdisciplinary specialty focused on improving or maintaining quality of life for people with serious illness. Because the goal is so broad, care can take many shapes.4
In addition to pain, palliative care clinicians commonly treat nausea, shortness of breath, constipation or diarrhea, poor appetite, fatigue, anxiety, depression, and insomnia.
Palliative care is more than medical or nursing care
A related misconception about palliative care held by many lay people and health care workers alike is that palliative care is primarily medical or nursing care focused mostly on alleviating physical symptoms such as pain or nausea. This couldn’t be further from the truth.
We’ve been talking for a while.
Ms. Lopez tells me about her struggles to maintain her weight while undergoing chemotherapy. She has low-grade nausea that is impacting her ability and desire to eat more and didn’t think that her weight loss was severe enough to warrant taking medication.
We talk about how she may be able to use antinausea medication sparingly to alleviate nausea while also limiting side effects from the medications—which was a big concern for her.
I ask her what else is bothering her.
She tells me that she has always been a strong Catholic and even when life has gotten tough, her faith was never shaken – until now.
She is struggling to understand why she ended up with metastatic cancer at such a relatively young age—why would God do this to her?
She had plans for retirement that have since evaporated in the face of a foreshortened life.
Why did this happen to her of all people? She was completely healthy until her diagnosis.
Her face is wet with tears.
We talk a little about how a diagnosis like this can change so much of a person’s life and identity. I try to validate her experience. She’s clearly suffering from a sense that her life is not what she expected, and she is struggling to integrate how her future looks at this point.
I ask her what conversations with her priest have been like.
At this point you may be wondering where this conversation is going. Why are we talking about Ms. Lopez’s religion? Palliative care is best delivered through high functioning interdisciplinary teams that can include other supportive people in a patient’s life. We work in concert to try to bring comfort to a patient and their family.4 That support network can include nurses, physicians, social workers, and chaplains. In this case, Ms. Lopez had not yet reached out to her priest. She hasn’t had the time or energy to contact her priest given her symptoms.
“Can I contact your priest for you?
Maybe he can visit or call and chat with you?”
She nods and wipes tears away.
“That would be really nice,” she says. “I’d love it if he could pray with me.”
A few hours after the visit, I call Ms. Lopez’s priest.
I ask him to reach out to her and about her request for prayer.
He says he’s been thinking about her and that her presence has been missed at weekly Mass. He thanks me for the call and says he’ll call her tomorrow.
I say my own small prayer for Ms. Lopez and head home, the day’s work completed.
Sarah D'Ambruoso was born and raised in Maine. She completed her undergraduate and graduate nursing education at New York University and UCLA, respectively, and currently works as a palliative care nurse practitioner in an oncology clinic in Los Angeles.
References
1. Cheng BT et al. Patterns of palliative care beliefs among adults in the U.S.: Analysis of a National Cancer Database. J Pain Symptom Manage. 2019 Aug 10. doi: 10.1016/j.jpainsymman.2019.07.030.
2. Finlay E et al. Filling the gap: Creating an outpatient palliative care program in your institution. Am Soc Clin Oncol Educ Book. 2018 May 23. doi: 10.1200/EDBK_200775.
3. Von Roenn JH et al. Barriers and approaches to the successful integration of palliative care and oncology practice. J Natl Compr Canc Netw. 2013 Mar. doi: 10.6004/jnccn.2013.0209.
4. Ferrell BR et al. Integration of palliative care into standard oncology care: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol. 2016 Oct 31. doi: 10.1200/JCO.2016.70.1474.
The names of health care professionals and patients cited within the dialogue text have been changed to protect their privacy.
but over the years I have come to realize that she was right – most people, including many within health care, don’t have a good appreciation of what palliative care is or how it can help patients and health care teams.
A recent national survey about cancer-related health information found that of more than 1,000 surveyed Americans, less than 30% professed any knowledge of palliative care. Of those who had some knowledge of palliative care, around 30% believed palliative care was synonymous with hospice.1 Another 15% believed that a patient would have to give up cancer-directed treatments to receive palliative care.1
It’s not giving up
This persistent belief that palliative care is equivalent to hospice, or is tantamount to “giving up,” is one of the most commonly held myths I encounter in everyday practice.
I knock on the exam door and walk in.
A small, trim woman in her late 50s is sitting in a chair, arms folded across her chest, face drawn in.
“Hi,” I start. “I’m Sarah, the palliative care nurse practitioner who works in this clinic. I work closely with Dr. Smith.”
Dr. Smith is the patient’s oncologist.
“I really didn’t want to meet you,” she says in a quiet voice, her eyes large with concern.
I don’t take it personally. Few patients really want to be in the position of needing to meet the palliative care team.
“I looked up palliative care on Google and saw the word hospice.”
“Yeah,” I say. “I hear that a lot. Well, I can reassure you that this isn’t hospice.
In this clinic, our focus is on your cancer symptoms, your treatment side effects, and your quality of life.”
She looks visibly relieved. “Quality of life,” she echoes. “I need more of that.”
“OK,” I say. “So, tell me what you’re struggling with the most right now.”
That’s how many palliative care visits start. I actually prefer if patients haven’t heard of palliative care because it allows me to frame it for them, rather than having to start by addressing a myth or a prior negative experience. Even when patients haven’t had a negative experience with palliative care per se, typically, if they’ve interacted with palliative care in the past, it’s usually because someone they loved died in a hospital setting and it is the memory of that terrible loss that becomes synonymous with their recollection of palliative care.
Many patients I meet have never seen another outpatient palliative care practitioner – and this makes sense – we are still too few and far between. Most established palliative care teams are hospital based and many patients seen in the community do not have easy access to palliative care teams where they receive oncologic care.2 As an embedded practitioner, I see patients in the same exam rooms and infusion centers where they receive their cancer therapies, so I’m effectively woven into the fabric of their oncology experience. Just being there in the cancer center allows me to be in the right place at the right time for the right patients and their care teams.
More than pain management
Another myth I tend to dispel a lot is that palliative care is just a euphemism for “pain management.” I have seen this less lately, but still occasionally in the chart I’ll see documented in a note, “patient is seeing palliative/pain management,” when a patient is seeing me or one of my colleagues. Unfortunately, when providers have limited or outdated views of what palliative care is or the value it brings to patient-centered cancer care, referrals to palliative care tend to be delayed.3
“I really think Ms. Lopez could benefit from seeing palliative care,” an oncology nurse practitioner says to an oncologist.
I’m standing nearby, about to see another patient in one of the exam rooms in our clinic.
“But I don’t think she’s ready. And besides, she doesn’t have any pain,” he says.
He turns to me quizzically. “What do you think?”
“Tell me about the patient,” I ask, taking a few steps in their direction.
“Well, she’s a 64-year-old woman with metastatic cancer.
She has a really poor appetite and is losing some weight.
Seems a bit down, kind of pessimistic about things.
Her scan showed some new growth, so guess I’m not surprised by that.”
“I might be able to help her with the appetite and the mood changes.
I can at least talk with her and see where she’s at,” I offer.
“Alright,” he says. “We’ll put the palliative referral in.”
He hesitates. “But are you sure you want to see her?
She doesn’t have any pain.” He sounds skeptical.
“Yeah, I mean, it sounds like she has symptoms that are bothering her, so I’d be happy to see her. She sounds completely appropriate for palliative care.”
I hear this assumption a lot – that palliative care is somehow equivalent to pain management and that unless a patient’s pain is severe, it’s not worth referring the patient to palliative care. Don’t get me wrong – we do a lot of pain management, but at its heart, palliative care is an interdisciplinary specialty focused on improving or maintaining quality of life for people with serious illness. Because the goal is so broad, care can take many shapes.4
In addition to pain, palliative care clinicians commonly treat nausea, shortness of breath, constipation or diarrhea, poor appetite, fatigue, anxiety, depression, and insomnia.
Palliative care is more than medical or nursing care
A related misconception about palliative care held by many lay people and health care workers alike is that palliative care is primarily medical or nursing care focused mostly on alleviating physical symptoms such as pain or nausea. This couldn’t be further from the truth.
We’ve been talking for a while.
Ms. Lopez tells me about her struggles to maintain her weight while undergoing chemotherapy. She has low-grade nausea that is impacting her ability and desire to eat more and didn’t think that her weight loss was severe enough to warrant taking medication.
We talk about how she may be able to use antinausea medication sparingly to alleviate nausea while also limiting side effects from the medications—which was a big concern for her.
I ask her what else is bothering her.
She tells me that she has always been a strong Catholic and even when life has gotten tough, her faith was never shaken – until now.
She is struggling to understand why she ended up with metastatic cancer at such a relatively young age—why would God do this to her?
She had plans for retirement that have since evaporated in the face of a foreshortened life.
Why did this happen to her of all people? She was completely healthy until her diagnosis.
Her face is wet with tears.
We talk a little about how a diagnosis like this can change so much of a person’s life and identity. I try to validate her experience. She’s clearly suffering from a sense that her life is not what she expected, and she is struggling to integrate how her future looks at this point.
I ask her what conversations with her priest have been like.
At this point you may be wondering where this conversation is going. Why are we talking about Ms. Lopez’s religion? Palliative care is best delivered through high functioning interdisciplinary teams that can include other supportive people in a patient’s life. We work in concert to try to bring comfort to a patient and their family.4 That support network can include nurses, physicians, social workers, and chaplains. In this case, Ms. Lopez had not yet reached out to her priest. She hasn’t had the time or energy to contact her priest given her symptoms.
“Can I contact your priest for you?
Maybe he can visit or call and chat with you?”
She nods and wipes tears away.
“That would be really nice,” she says. “I’d love it if he could pray with me.”
A few hours after the visit, I call Ms. Lopez’s priest.
I ask him to reach out to her and about her request for prayer.
He says he’s been thinking about her and that her presence has been missed at weekly Mass. He thanks me for the call and says he’ll call her tomorrow.
I say my own small prayer for Ms. Lopez and head home, the day’s work completed.
Sarah D'Ambruoso was born and raised in Maine. She completed her undergraduate and graduate nursing education at New York University and UCLA, respectively, and currently works as a palliative care nurse practitioner in an oncology clinic in Los Angeles.
References
1. Cheng BT et al. Patterns of palliative care beliefs among adults in the U.S.: Analysis of a National Cancer Database. J Pain Symptom Manage. 2019 Aug 10. doi: 10.1016/j.jpainsymman.2019.07.030.
2. Finlay E et al. Filling the gap: Creating an outpatient palliative care program in your institution. Am Soc Clin Oncol Educ Book. 2018 May 23. doi: 10.1200/EDBK_200775.
3. Von Roenn JH et al. Barriers and approaches to the successful integration of palliative care and oncology practice. J Natl Compr Canc Netw. 2013 Mar. doi: 10.6004/jnccn.2013.0209.
4. Ferrell BR et al. Integration of palliative care into standard oncology care: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol. 2016 Oct 31. doi: 10.1200/JCO.2016.70.1474.
The names of health care professionals and patients cited within the dialogue text have been changed to protect their privacy.
but over the years I have come to realize that she was right – most people, including many within health care, don’t have a good appreciation of what palliative care is or how it can help patients and health care teams.
A recent national survey about cancer-related health information found that of more than 1,000 surveyed Americans, less than 30% professed any knowledge of palliative care. Of those who had some knowledge of palliative care, around 30% believed palliative care was synonymous with hospice.1 Another 15% believed that a patient would have to give up cancer-directed treatments to receive palliative care.1
It’s not giving up
This persistent belief that palliative care is equivalent to hospice, or is tantamount to “giving up,” is one of the most commonly held myths I encounter in everyday practice.
I knock on the exam door and walk in.
A small, trim woman in her late 50s is sitting in a chair, arms folded across her chest, face drawn in.
“Hi,” I start. “I’m Sarah, the palliative care nurse practitioner who works in this clinic. I work closely with Dr. Smith.”
Dr. Smith is the patient’s oncologist.
“I really didn’t want to meet you,” she says in a quiet voice, her eyes large with concern.
I don’t take it personally. Few patients really want to be in the position of needing to meet the palliative care team.
“I looked up palliative care on Google and saw the word hospice.”
“Yeah,” I say. “I hear that a lot. Well, I can reassure you that this isn’t hospice.
In this clinic, our focus is on your cancer symptoms, your treatment side effects, and your quality of life.”
She looks visibly relieved. “Quality of life,” she echoes. “I need more of that.”
“OK,” I say. “So, tell me what you’re struggling with the most right now.”
That’s how many palliative care visits start. I actually prefer if patients haven’t heard of palliative care because it allows me to frame it for them, rather than having to start by addressing a myth or a prior negative experience. Even when patients haven’t had a negative experience with palliative care per se, typically, if they’ve interacted with palliative care in the past, it’s usually because someone they loved died in a hospital setting and it is the memory of that terrible loss that becomes synonymous with their recollection of palliative care.
Many patients I meet have never seen another outpatient palliative care practitioner – and this makes sense – we are still too few and far between. Most established palliative care teams are hospital based and many patients seen in the community do not have easy access to palliative care teams where they receive oncologic care.2 As an embedded practitioner, I see patients in the same exam rooms and infusion centers where they receive their cancer therapies, so I’m effectively woven into the fabric of their oncology experience. Just being there in the cancer center allows me to be in the right place at the right time for the right patients and their care teams.
More than pain management
Another myth I tend to dispel a lot is that palliative care is just a euphemism for “pain management.” I have seen this less lately, but still occasionally in the chart I’ll see documented in a note, “patient is seeing palliative/pain management,” when a patient is seeing me or one of my colleagues. Unfortunately, when providers have limited or outdated views of what palliative care is or the value it brings to patient-centered cancer care, referrals to palliative care tend to be delayed.3
“I really think Ms. Lopez could benefit from seeing palliative care,” an oncology nurse practitioner says to an oncologist.
I’m standing nearby, about to see another patient in one of the exam rooms in our clinic.
“But I don’t think she’s ready. And besides, she doesn’t have any pain,” he says.
He turns to me quizzically. “What do you think?”
“Tell me about the patient,” I ask, taking a few steps in their direction.
“Well, she’s a 64-year-old woman with metastatic cancer.
She has a really poor appetite and is losing some weight.
Seems a bit down, kind of pessimistic about things.
Her scan showed some new growth, so guess I’m not surprised by that.”
“I might be able to help her with the appetite and the mood changes.
I can at least talk with her and see where she’s at,” I offer.
“Alright,” he says. “We’ll put the palliative referral in.”
He hesitates. “But are you sure you want to see her?
She doesn’t have any pain.” He sounds skeptical.
“Yeah, I mean, it sounds like she has symptoms that are bothering her, so I’d be happy to see her. She sounds completely appropriate for palliative care.”
I hear this assumption a lot – that palliative care is somehow equivalent to pain management and that unless a patient’s pain is severe, it’s not worth referring the patient to palliative care. Don’t get me wrong – we do a lot of pain management, but at its heart, palliative care is an interdisciplinary specialty focused on improving or maintaining quality of life for people with serious illness. Because the goal is so broad, care can take many shapes.4
In addition to pain, palliative care clinicians commonly treat nausea, shortness of breath, constipation or diarrhea, poor appetite, fatigue, anxiety, depression, and insomnia.
Palliative care is more than medical or nursing care
A related misconception about palliative care held by many lay people and health care workers alike is that palliative care is primarily medical or nursing care focused mostly on alleviating physical symptoms such as pain or nausea. This couldn’t be further from the truth.
We’ve been talking for a while.
Ms. Lopez tells me about her struggles to maintain her weight while undergoing chemotherapy. She has low-grade nausea that is impacting her ability and desire to eat more and didn’t think that her weight loss was severe enough to warrant taking medication.
We talk about how she may be able to use antinausea medication sparingly to alleviate nausea while also limiting side effects from the medications—which was a big concern for her.
I ask her what else is bothering her.
She tells me that she has always been a strong Catholic and even when life has gotten tough, her faith was never shaken – until now.
She is struggling to understand why she ended up with metastatic cancer at such a relatively young age—why would God do this to her?
She had plans for retirement that have since evaporated in the face of a foreshortened life.
Why did this happen to her of all people? She was completely healthy until her diagnosis.
Her face is wet with tears.
We talk a little about how a diagnosis like this can change so much of a person’s life and identity. I try to validate her experience. She’s clearly suffering from a sense that her life is not what she expected, and she is struggling to integrate how her future looks at this point.
I ask her what conversations with her priest have been like.
At this point you may be wondering where this conversation is going. Why are we talking about Ms. Lopez’s religion? Palliative care is best delivered through high functioning interdisciplinary teams that can include other supportive people in a patient’s life. We work in concert to try to bring comfort to a patient and their family.4 That support network can include nurses, physicians, social workers, and chaplains. In this case, Ms. Lopez had not yet reached out to her priest. She hasn’t had the time or energy to contact her priest given her symptoms.
“Can I contact your priest for you?
Maybe he can visit or call and chat with you?”
She nods and wipes tears away.
“That would be really nice,” she says. “I’d love it if he could pray with me.”
A few hours after the visit, I call Ms. Lopez’s priest.
I ask him to reach out to her and about her request for prayer.
He says he’s been thinking about her and that her presence has been missed at weekly Mass. He thanks me for the call and says he’ll call her tomorrow.
I say my own small prayer for Ms. Lopez and head home, the day’s work completed.
Sarah D'Ambruoso was born and raised in Maine. She completed her undergraduate and graduate nursing education at New York University and UCLA, respectively, and currently works as a palliative care nurse practitioner in an oncology clinic in Los Angeles.
References
1. Cheng BT et al. Patterns of palliative care beliefs among adults in the U.S.: Analysis of a National Cancer Database. J Pain Symptom Manage. 2019 Aug 10. doi: 10.1016/j.jpainsymman.2019.07.030.
2. Finlay E et al. Filling the gap: Creating an outpatient palliative care program in your institution. Am Soc Clin Oncol Educ Book. 2018 May 23. doi: 10.1200/EDBK_200775.
3. Von Roenn JH et al. Barriers and approaches to the successful integration of palliative care and oncology practice. J Natl Compr Canc Netw. 2013 Mar. doi: 10.6004/jnccn.2013.0209.
4. Ferrell BR et al. Integration of palliative care into standard oncology care: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol. 2016 Oct 31. doi: 10.1200/JCO.2016.70.1474.
Confirmed: Pembro plus chemo as first-line standard of care for esophageal cancer
An interim analysis of the KEYNOTE-590 study, published in 2020, found that the combination of pembrolizumab and chemotherapy in the first-line setting proved superior to chemotherapy alone in all outcome measures.
The updated analysis, which adds 12 months of follow-up data, shows “first-line pembrolizumab plus chemotherapy continued to provide clinically meaningful benefits in all patients with locally advanced and metastatic esophageal cancer, including [gastroesophageal junction] adenocarcinoma,” said lead author Jean-Philippe Metges, MD, of the CHU Brest-Institut de Cancerologie et d’Hematologie ARPEGO Network, Brest, France.
Similar quality of life and safety data were also observed with pembrolizumab plus chemotherapy versus chemotherapy alone, Dr. Metges added.
“These longer-term data further support first-line pembrolizumab plus chemotherapy as a new standard of care in patients with locally advanced and metastatic esophageal cancer,” he said.
The updated analysis was presented at the 2022 Gastrointestinal Cancers Symposium.
Pembro for esophageal cancer
Pembrolizumab first received regulatory approval in 2019 as monotherapy in the second-line setting to treat recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus in tumors with programmed death–ligand 1 (PD-L1) expression.
In response to the interim KEYNOTE-590 data, the FDA expanded the indication in 2021, granting accelerated approval for pembrolizumab in combination with platinum and fluoropyrimidine-based chemotherapy in the first-line setting for patients who were not candidates for surgical resection or definitive chemoradiotherapy.
The updated KEYNOTE-590 data lend greater weight for the use of pembrolizumab plus chemotherapy as first-line standard of care in advanced esophageal cancer.
In the analysis, a total of 749 eligible patients with previously untreated locally advanced, unresectable, or metastatic esophageal squamous cell carcinoma (ESCC), adenocarcinoma, or Siewert type 1 esophagogastric junction adenocarcinoma, regardless of PD-L1 status, were randomly assigned (1:1) to pembrolizumab 200 mg or placebo plus 5-fluorouracil and cisplatin once every 3 weeks for up to 35 cycles.
The authors evaluated overall survival in all patients as well as subgroups including those with ESCC, ESCC PD-L1 combined positive score ≥10 tumors, and PD-L1 CPS ≥10 tumors. The research team also looked at progression-free survival in most groups and overall response rate, duration of response, safety, and health-related quality of life.
Treatment continued until progression, unacceptable toxicity, withdrawal, or until 2 years, with no crossover permitted.
At the median follow-up of 34.8 months, median overall survival was longer for all patients receiving the combination therapy (hazard ratio, 0.73) as well as patients with ESCC (HR, 0.73), ESCC CPS ≥10 (HR, 0.59), CPS ≥10 (HR, 0.64), and adenocarcinoma (HR, 0.73).
For progression-free survival, pembrolizumab plus chemotherapy was superior in all patients (HR, 0.64), the ESCC group (HR, 0.65), as well as the PD-L1 CPS ≥10 tumor group (HR, 0.51).
The 24-month overall survival in all patients was also notably higher for those receiving the combination therapy – 26.3% versus 16.1% – as was 24-month progression-free survival – 11.6% versus 3.3%.
The overall response rate was 45.0% in the combination group, with 25 complete responses (6.7%), versus 29.3% in the control group, with 9 complete responses (2.4%). The median duration of response was 8.3 months in the combination group versus 6.0 months in the chemotherapy group. About 20% of patients in the combination group had a response rate lasting 24 months or longer, compared with 6% who received chemotherapy alone.
As for safety, grade 3-5 drug-related adverse events were similar in both arms – 72% for the combination versus 68% for chemotherapy alone. However, more patients in the combination group discontinued treatment because of drug-related adverse events – 21% versus 12%.
No additional or surprise adverse events occurred with the longer follow-up, plus quality of life was comparable between groups, Dr. Metges noted.
Stefano Cascinu, MD, Università Vita-Salute, San Raffaele Hospital, Milan, who was not involved in the analysis, reiterated that this update confirms the findings from earlier analyses and shows a benefit across all subgroups.
“One of the most relevant findings was that 20% of patients were responding for more than 24 months,” he said. “It is also important that a similar quality of life was maintained.”
Although Dr. Cascinu emphasized that this is a landmark trial in advanced esophageal and gastric cancers, he indicated to several points that remain to be investigated. These include the reproducibility of the findings in common clinical situations – such as a patient with impaired performance status, malnutrition, or peritoneal involvement – as well as the role of PD-L1.
The efficacy of the combination therapy across all subgroups led to a wide FDA approval, though the European Medicines Agency limited its approval to patients with PD-L1 CPS ≥10 tumors.
“Even though all subgroups did well, patients with [PD-L1] CPS ≥10 did better,” said Dr. Cascinu. “[And] in reality, the benefit may only be driven by a specific subpopulation.”
Dr. Cascinu added: “PD-L1 may be a negative biomarker and may be informative about the magnitude of benefit. This may be useful to discuss with patients regarding the expected benefit [of this therapeutic option].”
The study was supported by Merck & Co. Dr. Metges reported receiving payment for travel, accommodations, expenses from Amgen, LEO Pharma, and MSD Oncology, and receiving honoraria from Bristol-Myers Squibb, Lilly, Novartis, Sanofi, and Syncore. Dr. Cascinu has disclosed honoraria from BMS, Lilly, MSD Oncology, and others, as well as a consulting or advisory role for many of these same manufacturers and serving on the speakers’ bureau of Lilly and SERVIER. The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
A version of this article first appeared on Medscape.com.
An interim analysis of the KEYNOTE-590 study, published in 2020, found that the combination of pembrolizumab and chemotherapy in the first-line setting proved superior to chemotherapy alone in all outcome measures.
The updated analysis, which adds 12 months of follow-up data, shows “first-line pembrolizumab plus chemotherapy continued to provide clinically meaningful benefits in all patients with locally advanced and metastatic esophageal cancer, including [gastroesophageal junction] adenocarcinoma,” said lead author Jean-Philippe Metges, MD, of the CHU Brest-Institut de Cancerologie et d’Hematologie ARPEGO Network, Brest, France.
Similar quality of life and safety data were also observed with pembrolizumab plus chemotherapy versus chemotherapy alone, Dr. Metges added.
“These longer-term data further support first-line pembrolizumab plus chemotherapy as a new standard of care in patients with locally advanced and metastatic esophageal cancer,” he said.
The updated analysis was presented at the 2022 Gastrointestinal Cancers Symposium.
Pembro for esophageal cancer
Pembrolizumab first received regulatory approval in 2019 as monotherapy in the second-line setting to treat recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus in tumors with programmed death–ligand 1 (PD-L1) expression.
In response to the interim KEYNOTE-590 data, the FDA expanded the indication in 2021, granting accelerated approval for pembrolizumab in combination with platinum and fluoropyrimidine-based chemotherapy in the first-line setting for patients who were not candidates for surgical resection or definitive chemoradiotherapy.
The updated KEYNOTE-590 data lend greater weight for the use of pembrolizumab plus chemotherapy as first-line standard of care in advanced esophageal cancer.
In the analysis, a total of 749 eligible patients with previously untreated locally advanced, unresectable, or metastatic esophageal squamous cell carcinoma (ESCC), adenocarcinoma, or Siewert type 1 esophagogastric junction adenocarcinoma, regardless of PD-L1 status, were randomly assigned (1:1) to pembrolizumab 200 mg or placebo plus 5-fluorouracil and cisplatin once every 3 weeks for up to 35 cycles.
The authors evaluated overall survival in all patients as well as subgroups including those with ESCC, ESCC PD-L1 combined positive score ≥10 tumors, and PD-L1 CPS ≥10 tumors. The research team also looked at progression-free survival in most groups and overall response rate, duration of response, safety, and health-related quality of life.
Treatment continued until progression, unacceptable toxicity, withdrawal, or until 2 years, with no crossover permitted.
At the median follow-up of 34.8 months, median overall survival was longer for all patients receiving the combination therapy (hazard ratio, 0.73) as well as patients with ESCC (HR, 0.73), ESCC CPS ≥10 (HR, 0.59), CPS ≥10 (HR, 0.64), and adenocarcinoma (HR, 0.73).
For progression-free survival, pembrolizumab plus chemotherapy was superior in all patients (HR, 0.64), the ESCC group (HR, 0.65), as well as the PD-L1 CPS ≥10 tumor group (HR, 0.51).
The 24-month overall survival in all patients was also notably higher for those receiving the combination therapy – 26.3% versus 16.1% – as was 24-month progression-free survival – 11.6% versus 3.3%.
The overall response rate was 45.0% in the combination group, with 25 complete responses (6.7%), versus 29.3% in the control group, with 9 complete responses (2.4%). The median duration of response was 8.3 months in the combination group versus 6.0 months in the chemotherapy group. About 20% of patients in the combination group had a response rate lasting 24 months or longer, compared with 6% who received chemotherapy alone.
As for safety, grade 3-5 drug-related adverse events were similar in both arms – 72% for the combination versus 68% for chemotherapy alone. However, more patients in the combination group discontinued treatment because of drug-related adverse events – 21% versus 12%.
No additional or surprise adverse events occurred with the longer follow-up, plus quality of life was comparable between groups, Dr. Metges noted.
Stefano Cascinu, MD, Università Vita-Salute, San Raffaele Hospital, Milan, who was not involved in the analysis, reiterated that this update confirms the findings from earlier analyses and shows a benefit across all subgroups.
“One of the most relevant findings was that 20% of patients were responding for more than 24 months,” he said. “It is also important that a similar quality of life was maintained.”
Although Dr. Cascinu emphasized that this is a landmark trial in advanced esophageal and gastric cancers, he indicated to several points that remain to be investigated. These include the reproducibility of the findings in common clinical situations – such as a patient with impaired performance status, malnutrition, or peritoneal involvement – as well as the role of PD-L1.
The efficacy of the combination therapy across all subgroups led to a wide FDA approval, though the European Medicines Agency limited its approval to patients with PD-L1 CPS ≥10 tumors.
“Even though all subgroups did well, patients with [PD-L1] CPS ≥10 did better,” said Dr. Cascinu. “[And] in reality, the benefit may only be driven by a specific subpopulation.”
Dr. Cascinu added: “PD-L1 may be a negative biomarker and may be informative about the magnitude of benefit. This may be useful to discuss with patients regarding the expected benefit [of this therapeutic option].”
The study was supported by Merck & Co. Dr. Metges reported receiving payment for travel, accommodations, expenses from Amgen, LEO Pharma, and MSD Oncology, and receiving honoraria from Bristol-Myers Squibb, Lilly, Novartis, Sanofi, and Syncore. Dr. Cascinu has disclosed honoraria from BMS, Lilly, MSD Oncology, and others, as well as a consulting or advisory role for many of these same manufacturers and serving on the speakers’ bureau of Lilly and SERVIER. The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
A version of this article first appeared on Medscape.com.
An interim analysis of the KEYNOTE-590 study, published in 2020, found that the combination of pembrolizumab and chemotherapy in the first-line setting proved superior to chemotherapy alone in all outcome measures.
The updated analysis, which adds 12 months of follow-up data, shows “first-line pembrolizumab plus chemotherapy continued to provide clinically meaningful benefits in all patients with locally advanced and metastatic esophageal cancer, including [gastroesophageal junction] adenocarcinoma,” said lead author Jean-Philippe Metges, MD, of the CHU Brest-Institut de Cancerologie et d’Hematologie ARPEGO Network, Brest, France.
Similar quality of life and safety data were also observed with pembrolizumab plus chemotherapy versus chemotherapy alone, Dr. Metges added.
“These longer-term data further support first-line pembrolizumab plus chemotherapy as a new standard of care in patients with locally advanced and metastatic esophageal cancer,” he said.
The updated analysis was presented at the 2022 Gastrointestinal Cancers Symposium.
Pembro for esophageal cancer
Pembrolizumab first received regulatory approval in 2019 as monotherapy in the second-line setting to treat recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus in tumors with programmed death–ligand 1 (PD-L1) expression.
In response to the interim KEYNOTE-590 data, the FDA expanded the indication in 2021, granting accelerated approval for pembrolizumab in combination with platinum and fluoropyrimidine-based chemotherapy in the first-line setting for patients who were not candidates for surgical resection or definitive chemoradiotherapy.
The updated KEYNOTE-590 data lend greater weight for the use of pembrolizumab plus chemotherapy as first-line standard of care in advanced esophageal cancer.
In the analysis, a total of 749 eligible patients with previously untreated locally advanced, unresectable, or metastatic esophageal squamous cell carcinoma (ESCC), adenocarcinoma, or Siewert type 1 esophagogastric junction adenocarcinoma, regardless of PD-L1 status, were randomly assigned (1:1) to pembrolizumab 200 mg or placebo plus 5-fluorouracil and cisplatin once every 3 weeks for up to 35 cycles.
The authors evaluated overall survival in all patients as well as subgroups including those with ESCC, ESCC PD-L1 combined positive score ≥10 tumors, and PD-L1 CPS ≥10 tumors. The research team also looked at progression-free survival in most groups and overall response rate, duration of response, safety, and health-related quality of life.
Treatment continued until progression, unacceptable toxicity, withdrawal, or until 2 years, with no crossover permitted.
At the median follow-up of 34.8 months, median overall survival was longer for all patients receiving the combination therapy (hazard ratio, 0.73) as well as patients with ESCC (HR, 0.73), ESCC CPS ≥10 (HR, 0.59), CPS ≥10 (HR, 0.64), and adenocarcinoma (HR, 0.73).
For progression-free survival, pembrolizumab plus chemotherapy was superior in all patients (HR, 0.64), the ESCC group (HR, 0.65), as well as the PD-L1 CPS ≥10 tumor group (HR, 0.51).
The 24-month overall survival in all patients was also notably higher for those receiving the combination therapy – 26.3% versus 16.1% – as was 24-month progression-free survival – 11.6% versus 3.3%.
The overall response rate was 45.0% in the combination group, with 25 complete responses (6.7%), versus 29.3% in the control group, with 9 complete responses (2.4%). The median duration of response was 8.3 months in the combination group versus 6.0 months in the chemotherapy group. About 20% of patients in the combination group had a response rate lasting 24 months or longer, compared with 6% who received chemotherapy alone.
As for safety, grade 3-5 drug-related adverse events were similar in both arms – 72% for the combination versus 68% for chemotherapy alone. However, more patients in the combination group discontinued treatment because of drug-related adverse events – 21% versus 12%.
No additional or surprise adverse events occurred with the longer follow-up, plus quality of life was comparable between groups, Dr. Metges noted.
Stefano Cascinu, MD, Università Vita-Salute, San Raffaele Hospital, Milan, who was not involved in the analysis, reiterated that this update confirms the findings from earlier analyses and shows a benefit across all subgroups.
“One of the most relevant findings was that 20% of patients were responding for more than 24 months,” he said. “It is also important that a similar quality of life was maintained.”
Although Dr. Cascinu emphasized that this is a landmark trial in advanced esophageal and gastric cancers, he indicated to several points that remain to be investigated. These include the reproducibility of the findings in common clinical situations – such as a patient with impaired performance status, malnutrition, or peritoneal involvement – as well as the role of PD-L1.
The efficacy of the combination therapy across all subgroups led to a wide FDA approval, though the European Medicines Agency limited its approval to patients with PD-L1 CPS ≥10 tumors.
“Even though all subgroups did well, patients with [PD-L1] CPS ≥10 did better,” said Dr. Cascinu. “[And] in reality, the benefit may only be driven by a specific subpopulation.”
Dr. Cascinu added: “PD-L1 may be a negative biomarker and may be informative about the magnitude of benefit. This may be useful to discuss with patients regarding the expected benefit [of this therapeutic option].”
The study was supported by Merck & Co. Dr. Metges reported receiving payment for travel, accommodations, expenses from Amgen, LEO Pharma, and MSD Oncology, and receiving honoraria from Bristol-Myers Squibb, Lilly, Novartis, Sanofi, and Syncore. Dr. Cascinu has disclosed honoraria from BMS, Lilly, MSD Oncology, and others, as well as a consulting or advisory role for many of these same manufacturers and serving on the speakers’ bureau of Lilly and SERVIER. The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
A version of this article first appeared on Medscape.com.
FROM GI CANCERS SYMPOSIUM 2022
Cancer, infection risk higher in transplant patients than rejection
“It’s important to have immunosuppression to protect people from rejection, but we wanted to be able to say, ‘What are the other causes of kidney failure that we might be able to identify that help improve longer-term outcomes’,” coauthor Andrew Bentall, MBChB, MD, a Mayo Clinic nephrologist, told this news organization.
“And I think the main thing we found is that we need to differentiate people into two groups,” he said, including younger, nondiabetic patients who develop graft failure due to alloimmunity and older often diabetic patients “who are less likely to have a rejection episode but who are still at high risk for death from a malignancy or infection so maybe we can modify their immunosuppression, for example, and reduce their mortality risk which could be very helpful.”
The study was published online Jan. 17 in Transplantation Direct.
Cohort study
The cohort was made up of 5,752 consecutive kidney transplant recipients treated at one of three Mayo Clinic sites. The mean age of recipients was 53.8 years and one-quarter were 65 years of age or older. “At the time of transplantation, 69.8% were on dialysis, and 10.3% had received a prior kidney,” of which half were from a deceased donor, the authors note.
Almost all patients received tacrolimus as part of their maintenance immunosuppressive regimen. At a median follow-up of 3.5 years, overall graft failure occurred in 21.6% of patients, including death with a functioning graft (DWFG) in 12% and graft failure in 9.6% of patients. The most common causes of DWFG included malignancy at 20.0%, followed closely by infection at 19.7%, investigators note.
Cardiac disease was the cause of DWFG in 12.6% of patients, and the cause was unknown in 37%. Of those patients who died with a functioning graft, 12.3% died within the first year of transplantation. Roughly 45% died between 1 and 5 years later, and 42% died more than 5 years after transplantation.
On multivariable analysis, independent predictors of DWFG included:
- Older age at transplantation (hazard ratio, 1.75; P < .001)
- Male sex (HR, 1.34; P < .001)
- Dialysis prior to transplant (HR, 1.49; P < .001)
- Diabetes as a cause of end-stage renal disease (ESRD) (HR, 1.88; P < .001)
- Prednisone use as maintenance therapy (HR, 1.34; P = .008)
Graft failure
Of patients who had graft failure, almost one-quarter occurred within the first year of transplantation, about 42% occurred 1 to 5 years later, and a third occurred more than 5 years later.
Most patients (39%) who went on to graft failure did so as a result of “alloimmunity”, a term investigators used to cover all types of rejection, with a smaller number of graft failures being caused by glomerular diseases, at 18.6%, and renal tubular injury, at 13.9%.
“In the first year after transplantation, surgical complications and primary nonfunction of the allograft caused 60.3% ... of graft losses,” the authors point out. Beyond the first year, alloimmunity accounted for approximately half of the cases of graft failure, investigators note.
In the multivariable analysis for overall graft failure, risk factors included:
- Young recipient age (HR, 0.80; P < .001)
- History of a previous kidney transplant (HR, 1.33; P = .042)
- Dialysis at time of transplantation (HR, 1.54; P < .001)
- Black recipient race (HR, 1.40; P = .006)
- Black donor race (HR, 1.35; P = .038)
- Diabetes as a cause of ESRD (HR, 1.40; P = .002)
- HLA mismatch (HR, 1.27; P < .001)
- Delayed graft function (HR, 2.20; P < .001)
“Over time, DWFG was more common than graft failure,” the authors note.
Modifiable risk factors
As Dr. Bentall acknowledged, not all risk factors contributing to DWFG or graft failure are modifiable. However, diabetes – which stood out as a risk factor for both DWFG and graft failure – is potentially modifiable before patients reach ESRD, as he suggested. Diabetes is currently a cause for up to 40% of all ESRD cases in the United States.
“We can’t necessarily always reverse the diabetes, but there are significant new medications that can be used along with weight loss strategies to improve diabetes control,” he noted.
Similarly, it’s well established that patients who come into transplantation with a body mass index in excess of 30 kg/m2 have more scarring and damage to the kidney 5- and 10-years post-transplantation than healthy weight patients, as Dr. Bentall observed. “Again, this is a key modifiable component, and it fits into diabetes intervention strategies as well,” he emphasized. The use of prednisone as maintenance immunosuppressive therapy similarly emerged as a risk factor for DWFG.
Transplant recipients who receive prednisone may well be a higher risk population to begin with, “but we are also using prednisone in our older patients because we try to use less induction immunosuppression at the time of transplantation. So if we can try and get people off prednisone, that may lessen their risk of infection and subsequent mortality,” Dr. Bentall noted.
A version of this article first appeared on Medscape.com.
“It’s important to have immunosuppression to protect people from rejection, but we wanted to be able to say, ‘What are the other causes of kidney failure that we might be able to identify that help improve longer-term outcomes’,” coauthor Andrew Bentall, MBChB, MD, a Mayo Clinic nephrologist, told this news organization.
“And I think the main thing we found is that we need to differentiate people into two groups,” he said, including younger, nondiabetic patients who develop graft failure due to alloimmunity and older often diabetic patients “who are less likely to have a rejection episode but who are still at high risk for death from a malignancy or infection so maybe we can modify their immunosuppression, for example, and reduce their mortality risk which could be very helpful.”
The study was published online Jan. 17 in Transplantation Direct.
Cohort study
The cohort was made up of 5,752 consecutive kidney transplant recipients treated at one of three Mayo Clinic sites. The mean age of recipients was 53.8 years and one-quarter were 65 years of age or older. “At the time of transplantation, 69.8% were on dialysis, and 10.3% had received a prior kidney,” of which half were from a deceased donor, the authors note.
Almost all patients received tacrolimus as part of their maintenance immunosuppressive regimen. At a median follow-up of 3.5 years, overall graft failure occurred in 21.6% of patients, including death with a functioning graft (DWFG) in 12% and graft failure in 9.6% of patients. The most common causes of DWFG included malignancy at 20.0%, followed closely by infection at 19.7%, investigators note.
Cardiac disease was the cause of DWFG in 12.6% of patients, and the cause was unknown in 37%. Of those patients who died with a functioning graft, 12.3% died within the first year of transplantation. Roughly 45% died between 1 and 5 years later, and 42% died more than 5 years after transplantation.
On multivariable analysis, independent predictors of DWFG included:
- Older age at transplantation (hazard ratio, 1.75; P < .001)
- Male sex (HR, 1.34; P < .001)
- Dialysis prior to transplant (HR, 1.49; P < .001)
- Diabetes as a cause of end-stage renal disease (ESRD) (HR, 1.88; P < .001)
- Prednisone use as maintenance therapy (HR, 1.34; P = .008)
Graft failure
Of patients who had graft failure, almost one-quarter occurred within the first year of transplantation, about 42% occurred 1 to 5 years later, and a third occurred more than 5 years later.
Most patients (39%) who went on to graft failure did so as a result of “alloimmunity”, a term investigators used to cover all types of rejection, with a smaller number of graft failures being caused by glomerular diseases, at 18.6%, and renal tubular injury, at 13.9%.
“In the first year after transplantation, surgical complications and primary nonfunction of the allograft caused 60.3% ... of graft losses,” the authors point out. Beyond the first year, alloimmunity accounted for approximately half of the cases of graft failure, investigators note.
In the multivariable analysis for overall graft failure, risk factors included:
- Young recipient age (HR, 0.80; P < .001)
- History of a previous kidney transplant (HR, 1.33; P = .042)
- Dialysis at time of transplantation (HR, 1.54; P < .001)
- Black recipient race (HR, 1.40; P = .006)
- Black donor race (HR, 1.35; P = .038)
- Diabetes as a cause of ESRD (HR, 1.40; P = .002)
- HLA mismatch (HR, 1.27; P < .001)
- Delayed graft function (HR, 2.20; P < .001)
“Over time, DWFG was more common than graft failure,” the authors note.
Modifiable risk factors
As Dr. Bentall acknowledged, not all risk factors contributing to DWFG or graft failure are modifiable. However, diabetes – which stood out as a risk factor for both DWFG and graft failure – is potentially modifiable before patients reach ESRD, as he suggested. Diabetes is currently a cause for up to 40% of all ESRD cases in the United States.
“We can’t necessarily always reverse the diabetes, but there are significant new medications that can be used along with weight loss strategies to improve diabetes control,” he noted.
Similarly, it’s well established that patients who come into transplantation with a body mass index in excess of 30 kg/m2 have more scarring and damage to the kidney 5- and 10-years post-transplantation than healthy weight patients, as Dr. Bentall observed. “Again, this is a key modifiable component, and it fits into diabetes intervention strategies as well,” he emphasized. The use of prednisone as maintenance immunosuppressive therapy similarly emerged as a risk factor for DWFG.
Transplant recipients who receive prednisone may well be a higher risk population to begin with, “but we are also using prednisone in our older patients because we try to use less induction immunosuppression at the time of transplantation. So if we can try and get people off prednisone, that may lessen their risk of infection and subsequent mortality,” Dr. Bentall noted.
A version of this article first appeared on Medscape.com.
“It’s important to have immunosuppression to protect people from rejection, but we wanted to be able to say, ‘What are the other causes of kidney failure that we might be able to identify that help improve longer-term outcomes’,” coauthor Andrew Bentall, MBChB, MD, a Mayo Clinic nephrologist, told this news organization.
“And I think the main thing we found is that we need to differentiate people into two groups,” he said, including younger, nondiabetic patients who develop graft failure due to alloimmunity and older often diabetic patients “who are less likely to have a rejection episode but who are still at high risk for death from a malignancy or infection so maybe we can modify their immunosuppression, for example, and reduce their mortality risk which could be very helpful.”
The study was published online Jan. 17 in Transplantation Direct.
Cohort study
The cohort was made up of 5,752 consecutive kidney transplant recipients treated at one of three Mayo Clinic sites. The mean age of recipients was 53.8 years and one-quarter were 65 years of age or older. “At the time of transplantation, 69.8% were on dialysis, and 10.3% had received a prior kidney,” of which half were from a deceased donor, the authors note.
Almost all patients received tacrolimus as part of their maintenance immunosuppressive regimen. At a median follow-up of 3.5 years, overall graft failure occurred in 21.6% of patients, including death with a functioning graft (DWFG) in 12% and graft failure in 9.6% of patients. The most common causes of DWFG included malignancy at 20.0%, followed closely by infection at 19.7%, investigators note.
Cardiac disease was the cause of DWFG in 12.6% of patients, and the cause was unknown in 37%. Of those patients who died with a functioning graft, 12.3% died within the first year of transplantation. Roughly 45% died between 1 and 5 years later, and 42% died more than 5 years after transplantation.
On multivariable analysis, independent predictors of DWFG included:
- Older age at transplantation (hazard ratio, 1.75; P < .001)
- Male sex (HR, 1.34; P < .001)
- Dialysis prior to transplant (HR, 1.49; P < .001)
- Diabetes as a cause of end-stage renal disease (ESRD) (HR, 1.88; P < .001)
- Prednisone use as maintenance therapy (HR, 1.34; P = .008)
Graft failure
Of patients who had graft failure, almost one-quarter occurred within the first year of transplantation, about 42% occurred 1 to 5 years later, and a third occurred more than 5 years later.
Most patients (39%) who went on to graft failure did so as a result of “alloimmunity”, a term investigators used to cover all types of rejection, with a smaller number of graft failures being caused by glomerular diseases, at 18.6%, and renal tubular injury, at 13.9%.
“In the first year after transplantation, surgical complications and primary nonfunction of the allograft caused 60.3% ... of graft losses,” the authors point out. Beyond the first year, alloimmunity accounted for approximately half of the cases of graft failure, investigators note.
In the multivariable analysis for overall graft failure, risk factors included:
- Young recipient age (HR, 0.80; P < .001)
- History of a previous kidney transplant (HR, 1.33; P = .042)
- Dialysis at time of transplantation (HR, 1.54; P < .001)
- Black recipient race (HR, 1.40; P = .006)
- Black donor race (HR, 1.35; P = .038)
- Diabetes as a cause of ESRD (HR, 1.40; P = .002)
- HLA mismatch (HR, 1.27; P < .001)
- Delayed graft function (HR, 2.20; P < .001)
“Over time, DWFG was more common than graft failure,” the authors note.
Modifiable risk factors
As Dr. Bentall acknowledged, not all risk factors contributing to DWFG or graft failure are modifiable. However, diabetes – which stood out as a risk factor for both DWFG and graft failure – is potentially modifiable before patients reach ESRD, as he suggested. Diabetes is currently a cause for up to 40% of all ESRD cases in the United States.
“We can’t necessarily always reverse the diabetes, but there are significant new medications that can be used along with weight loss strategies to improve diabetes control,” he noted.
Similarly, it’s well established that patients who come into transplantation with a body mass index in excess of 30 kg/m2 have more scarring and damage to the kidney 5- and 10-years post-transplantation than healthy weight patients, as Dr. Bentall observed. “Again, this is a key modifiable component, and it fits into diabetes intervention strategies as well,” he emphasized. The use of prednisone as maintenance immunosuppressive therapy similarly emerged as a risk factor for DWFG.
Transplant recipients who receive prednisone may well be a higher risk population to begin with, “but we are also using prednisone in our older patients because we try to use less induction immunosuppression at the time of transplantation. So if we can try and get people off prednisone, that may lessen their risk of infection and subsequent mortality,” Dr. Bentall noted.
A version of this article first appeared on Medscape.com.
FROM TRANSPLANTATION DIRECT
Some U.S. women not getting ET for curable breast cancer
A standard treatment for early breast cancer is endocrine therapy (ET), with drugs such a tamoxifen and aromatase inhibitors.
But the study found that ET was not being used in about half of the eligible patients.
For example, only 13,115 of 26,255 eligible patients (48.8%) initiated ET within 1 year of diagnosis, and only 13,944 (52.1%) continued with ET.
“This is remarkable, considering that ET confers an impressive one-third reduction in the risk of death from breast cancer in the first 15 years after diagnosis,” comment authors Michael J. Hassett, MD, of the Dana-Farber Cancer Institute, Boston, and colleagues.
The findings were published online on Jan. 27 in JAMA Oncology.
This study provides an “important and disturbing” glimpse of the hidden barriers patients face when seeking quality, guideline-concordant care, says Kathy Miller, MD, the Ballve Lantero professor of oncology at Indiana University School of Medicine and associate director of clinical research at the IU Simon Comprehensive Cancer Center, Indianapolis, who was approached for comment.
Geographical variations
In their study, Dr. Hasset and colleagues set out determine the extent to which geospatial variations in early breast cancer care are attributable to health service area versus patient factors. They analyzed Surveillance, Epidemiology, and End Results (SEER) Medicare data for 31,571 patients with newly diagnosed with stage I-II nonmetastatic breast cancer between 2007 and 2013 who were followed for at least 3 years.
The patients had a median age of 71 years, and 61.4% had stage I disease at diagnosis.
Geospatial density maps (heat maps) in the paper highlight regional performance patterns. For initiation of ET within 1 year of diagnosis, the regions that appeared the worst (with less than 50% of patients getting this treatment) were parts of California, Utah, New Mexico, Louisiana, Georgia, Kentucky, Washington, and an isolated patch in Michigan.
In addition to the striking finding that nearly half of all women who are eligible for ET did not receive that therapy, the investigators found that 81.6% of 21,190 eligible patients received radiation therapy and 72.8% of 9,903 eligible patients received chemotherapy.
This also varied across the graphical regions, with the heat maps showing that the areas that were delivering radiation and chemotherapy to 70% to 80% of women were similar to the areas that were not initiating ET in about half of these women.
The authors found that the geographical region and health service area (HSA) explained more observed variation (24% to 48%) than patient factors (1% to 4%).
“While patient characteristics, such as race and ethnicity, were significantly associated with variation in breast cancer care, they explained a relatively small proportion of the total observed geospatial variance,” the authors comment.
“In fact, most of the total observed variance was owing to randomness or unexplained factors,” they add. The largest share of variation – 35% to 45% – was unexplained.
“The ET metrics demonstrated the largest total observed variance, the lowest absolute performance (only 49% of patients had an ET prescription within 1 year of diagnosis), and the strongest association with region/HSA,” they conclude.
Though limited by factors inherent in a retrospective review of SEER-Medicare data, the “unexplained nature of most geospatial variation in initial breast cancer care is not likely to change,” they comment.
Future quality improvement efforts should focus on reducing this unwarranted geospatial variation, particularly through the use of ET in eligible patients and with strategies that work across health care delivery systems, they suggest.
Approached for comment on the new findings, Dr. Miller posits that “many factors may be at play.”
“Unfortunately, the SEER database doesn’t allow us to sort out the impact of poverty/cost of care, distance to medical care, availability of specialty and subspecialty care, and payer/provider networks that may limit choices and options for second opinions,” Dr. Miller told this news organization.
She said that patients should be encouraged to consult reliable patient-focused information, such as that provided by the American Society of Clinical Oncology through its disease-specific sites, and to seek a second opinion from a university center. In many cases, major centers have become more accessible through virtual visits made available in the wake of the COVID-19 pandemic, she noted.
This study was supported by Dana-Farber Cancer Institute and the American Cancer Society. The authors and Dr. Miller have disclosed no relevant financial relationships. Dr. Miller is a regular contributor to Medscape with her Miller on Oncology column.
A version of this article first appeared on Medscape.com.
A standard treatment for early breast cancer is endocrine therapy (ET), with drugs such a tamoxifen and aromatase inhibitors.
But the study found that ET was not being used in about half of the eligible patients.
For example, only 13,115 of 26,255 eligible patients (48.8%) initiated ET within 1 year of diagnosis, and only 13,944 (52.1%) continued with ET.
“This is remarkable, considering that ET confers an impressive one-third reduction in the risk of death from breast cancer in the first 15 years after diagnosis,” comment authors Michael J. Hassett, MD, of the Dana-Farber Cancer Institute, Boston, and colleagues.
The findings were published online on Jan. 27 in JAMA Oncology.
This study provides an “important and disturbing” glimpse of the hidden barriers patients face when seeking quality, guideline-concordant care, says Kathy Miller, MD, the Ballve Lantero professor of oncology at Indiana University School of Medicine and associate director of clinical research at the IU Simon Comprehensive Cancer Center, Indianapolis, who was approached for comment.
Geographical variations
In their study, Dr. Hasset and colleagues set out determine the extent to which geospatial variations in early breast cancer care are attributable to health service area versus patient factors. They analyzed Surveillance, Epidemiology, and End Results (SEER) Medicare data for 31,571 patients with newly diagnosed with stage I-II nonmetastatic breast cancer between 2007 and 2013 who were followed for at least 3 years.
The patients had a median age of 71 years, and 61.4% had stage I disease at diagnosis.
Geospatial density maps (heat maps) in the paper highlight regional performance patterns. For initiation of ET within 1 year of diagnosis, the regions that appeared the worst (with less than 50% of patients getting this treatment) were parts of California, Utah, New Mexico, Louisiana, Georgia, Kentucky, Washington, and an isolated patch in Michigan.
In addition to the striking finding that nearly half of all women who are eligible for ET did not receive that therapy, the investigators found that 81.6% of 21,190 eligible patients received radiation therapy and 72.8% of 9,903 eligible patients received chemotherapy.
This also varied across the graphical regions, with the heat maps showing that the areas that were delivering radiation and chemotherapy to 70% to 80% of women were similar to the areas that were not initiating ET in about half of these women.
The authors found that the geographical region and health service area (HSA) explained more observed variation (24% to 48%) than patient factors (1% to 4%).
“While patient characteristics, such as race and ethnicity, were significantly associated with variation in breast cancer care, they explained a relatively small proportion of the total observed geospatial variance,” the authors comment.
“In fact, most of the total observed variance was owing to randomness or unexplained factors,” they add. The largest share of variation – 35% to 45% – was unexplained.
“The ET metrics demonstrated the largest total observed variance, the lowest absolute performance (only 49% of patients had an ET prescription within 1 year of diagnosis), and the strongest association with region/HSA,” they conclude.
Though limited by factors inherent in a retrospective review of SEER-Medicare data, the “unexplained nature of most geospatial variation in initial breast cancer care is not likely to change,” they comment.
Future quality improvement efforts should focus on reducing this unwarranted geospatial variation, particularly through the use of ET in eligible patients and with strategies that work across health care delivery systems, they suggest.
Approached for comment on the new findings, Dr. Miller posits that “many factors may be at play.”
“Unfortunately, the SEER database doesn’t allow us to sort out the impact of poverty/cost of care, distance to medical care, availability of specialty and subspecialty care, and payer/provider networks that may limit choices and options for second opinions,” Dr. Miller told this news organization.
She said that patients should be encouraged to consult reliable patient-focused information, such as that provided by the American Society of Clinical Oncology through its disease-specific sites, and to seek a second opinion from a university center. In many cases, major centers have become more accessible through virtual visits made available in the wake of the COVID-19 pandemic, she noted.
This study was supported by Dana-Farber Cancer Institute and the American Cancer Society. The authors and Dr. Miller have disclosed no relevant financial relationships. Dr. Miller is a regular contributor to Medscape with her Miller on Oncology column.
A version of this article first appeared on Medscape.com.
A standard treatment for early breast cancer is endocrine therapy (ET), with drugs such a tamoxifen and aromatase inhibitors.
But the study found that ET was not being used in about half of the eligible patients.
For example, only 13,115 of 26,255 eligible patients (48.8%) initiated ET within 1 year of diagnosis, and only 13,944 (52.1%) continued with ET.
“This is remarkable, considering that ET confers an impressive one-third reduction in the risk of death from breast cancer in the first 15 years after diagnosis,” comment authors Michael J. Hassett, MD, of the Dana-Farber Cancer Institute, Boston, and colleagues.
The findings were published online on Jan. 27 in JAMA Oncology.
This study provides an “important and disturbing” glimpse of the hidden barriers patients face when seeking quality, guideline-concordant care, says Kathy Miller, MD, the Ballve Lantero professor of oncology at Indiana University School of Medicine and associate director of clinical research at the IU Simon Comprehensive Cancer Center, Indianapolis, who was approached for comment.
Geographical variations
In their study, Dr. Hasset and colleagues set out determine the extent to which geospatial variations in early breast cancer care are attributable to health service area versus patient factors. They analyzed Surveillance, Epidemiology, and End Results (SEER) Medicare data for 31,571 patients with newly diagnosed with stage I-II nonmetastatic breast cancer between 2007 and 2013 who were followed for at least 3 years.
The patients had a median age of 71 years, and 61.4% had stage I disease at diagnosis.
Geospatial density maps (heat maps) in the paper highlight regional performance patterns. For initiation of ET within 1 year of diagnosis, the regions that appeared the worst (with less than 50% of patients getting this treatment) were parts of California, Utah, New Mexico, Louisiana, Georgia, Kentucky, Washington, and an isolated patch in Michigan.
In addition to the striking finding that nearly half of all women who are eligible for ET did not receive that therapy, the investigators found that 81.6% of 21,190 eligible patients received radiation therapy and 72.8% of 9,903 eligible patients received chemotherapy.
This also varied across the graphical regions, with the heat maps showing that the areas that were delivering radiation and chemotherapy to 70% to 80% of women were similar to the areas that were not initiating ET in about half of these women.
The authors found that the geographical region and health service area (HSA) explained more observed variation (24% to 48%) than patient factors (1% to 4%).
“While patient characteristics, such as race and ethnicity, were significantly associated with variation in breast cancer care, they explained a relatively small proportion of the total observed geospatial variance,” the authors comment.
“In fact, most of the total observed variance was owing to randomness or unexplained factors,” they add. The largest share of variation – 35% to 45% – was unexplained.
“The ET metrics demonstrated the largest total observed variance, the lowest absolute performance (only 49% of patients had an ET prescription within 1 year of diagnosis), and the strongest association with region/HSA,” they conclude.
Though limited by factors inherent in a retrospective review of SEER-Medicare data, the “unexplained nature of most geospatial variation in initial breast cancer care is not likely to change,” they comment.
Future quality improvement efforts should focus on reducing this unwarranted geospatial variation, particularly through the use of ET in eligible patients and with strategies that work across health care delivery systems, they suggest.
Approached for comment on the new findings, Dr. Miller posits that “many factors may be at play.”
“Unfortunately, the SEER database doesn’t allow us to sort out the impact of poverty/cost of care, distance to medical care, availability of specialty and subspecialty care, and payer/provider networks that may limit choices and options for second opinions,” Dr. Miller told this news organization.
She said that patients should be encouraged to consult reliable patient-focused information, such as that provided by the American Society of Clinical Oncology through its disease-specific sites, and to seek a second opinion from a university center. In many cases, major centers have become more accessible through virtual visits made available in the wake of the COVID-19 pandemic, she noted.
This study was supported by Dana-Farber Cancer Institute and the American Cancer Society. The authors and Dr. Miller have disclosed no relevant financial relationships. Dr. Miller is a regular contributor to Medscape with her Miller on Oncology column.
A version of this article first appeared on Medscape.com.
FROM JAMA ONCOLOGY