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Tofersen linked to slow, positive effects in ALS
caused by superoxide dismutase 1 (SOD1) gene mutations.
The 1-year results, presented at the European Network for the Cure of Amyotrophic Lateral Sclerosis (ENCALS) 2022 meeting, show a deceleration in functional decline that is similar, but “more pronounced” than the previously reported 6-month results, which were not statistically significant, said lead investigator Timothy Miller, MD, PhD, professor of neurology and director of the ALS Center, Washington University, St. Louis.
“What I thought we saw in the first data cut is confirmed by what we saw in the longer data,” he said in an interview. “There were trends [showing] those treated with tofersen did a bit better, but it was hard to be sure. It was hard to be confident in what we were seeing at that early time point.”
Now, with 6 more months of data, Dr. Miller says he is confident that tofersen is slowing down the neurodegenerative disease process. “I see results that I’m encouraged by,” he said. “As a clinician who treats people with ALS with this mutation I would want this drug to be available to people that I see in my clinic.”
One-year VALOR study results
The primary efficacy objective of the VALOR study was to show the 28-week impact of 100 mg tofersen (three doses given about 2 weeks apart, then five doses given every 4 weeks), versus placebo, on function, measured on the Amyotrophic Lateral Sclerosis Functional Rating Scale–Revised (ALSFRS-R). The open-label extension switched placebo-treated patients to tofersen (delayed-start group) and continued to compare them with the early-start group up to 1 year. This open-label extension phase included 49 patients who had been on early-start tofersen and 18 patients in the delayed-start group.
For the primary endpoint, change from baseline in 48-point ALSFRS-R score, there was a statistically significant benefit for the early-start patients with these patients scoring 3.5 points higher than the delayed-start group (P = .0272, 95% confidence interval [CI], 0.4-6.7). This means that both groups declined in function, which is expected in ALS, but the early-start group declined more slowly.
There was also a benefit associated with early-start tofersen for a number of secondary endpoints, including change from baseline in total SOD1 cerebrospinal fluid concentration (CSF SOD1), plasma neurofilament light chain (NfL) levels, and respiratory function.
“This drug targets the MRNA of SOD1, so it lowers the MRNA and then the SOD1 protein falls,” explained Dr. Miller, adding that these levels dropped 21% in the delayed start group, and 33% in the early-start group. “I think the data pretty clearly show that [tofersen] does what it is supposed to do, and that is the first step.”
Neurofilament light chain, a marker of neurodegeneration, also dropped by 41% in the delayed-start group, and 51% in the early-start group.
Respiratory function, as measured by percent predicted slow vital capacity (SVC), also declined 9.2% more slowly in the early- versus delayed-start group (P = .0159).
Finally, muscle strength, as measured by handheld dynamometry (HHD) score, declined more slowly in the early-start group compared with the late-start group, with an adjusted mean difference in score of 2.8 (P = 0.0186).
Dr. Miller said that the data show that it takes time for tofersen to impact clinical function, but there are signs of benefit before that. “I think what you see is that just starting on the drug, the first thing that happens is SOD1 goes down, the next thing is that neurofilament decreases, but clinical function is not yet changing. It takes time. What I see in these data is that it takes time for us to see that effect on clinical function.”
The bigger picture
While acknowledging that tofersen acts on a genetic mutation found in only about 2% of ALS, Dr. Miller said the study findings carry significance for the wider ALS patient population.
“Assuming we agree there is a clinical effect here, assuming we agree that there is real stabilization of clinical function, I think if we agree on that point then we know that ALS is now a treatable disorder. And that’s a really important point. I’m not sure that we knew that before,” he said. “Yes, there are FDA-approved medications that slow down ALS a bit, but they don’t stabilize it, and if we get the target correct – and we have the correct genetic target here – there can be a substantial influence on slowing down the disease, so that’s one thing to learn for the whole ALS community.”
What lies ahead?
Asked to comment on the study, Richard Bedlack, MD, PhD, who was not involved in the research, said the findings are important and show “clinically meaningful” results. “Based on the new benefit-to-burden ratio, I believe most of my patients with SOD1 mutations will want to try this drug. I would like to be able to offer it to them. But I am curious to see what the FDA will do with these data,” said Dr. Bedlack, professor of neurology at Duke University in Durham, N.C., and director of the Duke ALS Clinic.
“Sometimes that open-label extension gives us time to see differences between patients who initially got drug and those who initially got placebo. That seems to be the case with tofersen here, and it was also the case with AMX0035 [Amylyx Pharmaceuticals Inc.], which did not show a survival benefit in the first 6 months but did in the open-label extension.” A recent FDA advisory board panel concluded there was insufficient evidence of benefit for AMX0035, he noted. “I wonder if the same concern will be raised here, necessitating confirmation in another trial. I hope not, but only time will tell.”
Dr. Miller added that these results “highlight how difficult ALS drug development still is. Among the many uncertainties in setting up a trial (targets, doses, inclusion criteria, outcomes), we still do not know how long we need to treat patients in order to see statistically significant changes in the clinical measures we use (ALSFRS-R, respiratory function, strength, survival, etc.). Most American studies are 6 months long and most European studies are 12 months long. Longer studies may be more likely to show benefits on certain measures (e.g., survival), but they cost more, they are challenged by dropouts as the disease progresses, and the idea of randomizing someone to a placebo for a whole year is psychologically difficult for patients, families, and many clinicians (myself included). So, we are seeing more studies like this one where the first 6 months are randomized, blinded, and placebo controlled, and then there is an open-label extension that lasts many months more.”
The study was sponsored by Biogen. Writing and editorial support was provided by Excel Scientific Solutions. Tofersen was discovered by Ionis Pharmaceuticals Inc. Dr. Miller disclosed ties with Biogen, Ionis Pharmaceuticals Inc., Cytokinetics, C2N, Disarm Therapeutics, and UCB Pharma. Dr. Bedlack disclosed ties with Biogen.
caused by superoxide dismutase 1 (SOD1) gene mutations.
The 1-year results, presented at the European Network for the Cure of Amyotrophic Lateral Sclerosis (ENCALS) 2022 meeting, show a deceleration in functional decline that is similar, but “more pronounced” than the previously reported 6-month results, which were not statistically significant, said lead investigator Timothy Miller, MD, PhD, professor of neurology and director of the ALS Center, Washington University, St. Louis.
“What I thought we saw in the first data cut is confirmed by what we saw in the longer data,” he said in an interview. “There were trends [showing] those treated with tofersen did a bit better, but it was hard to be sure. It was hard to be confident in what we were seeing at that early time point.”
Now, with 6 more months of data, Dr. Miller says he is confident that tofersen is slowing down the neurodegenerative disease process. “I see results that I’m encouraged by,” he said. “As a clinician who treats people with ALS with this mutation I would want this drug to be available to people that I see in my clinic.”
One-year VALOR study results
The primary efficacy objective of the VALOR study was to show the 28-week impact of 100 mg tofersen (three doses given about 2 weeks apart, then five doses given every 4 weeks), versus placebo, on function, measured on the Amyotrophic Lateral Sclerosis Functional Rating Scale–Revised (ALSFRS-R). The open-label extension switched placebo-treated patients to tofersen (delayed-start group) and continued to compare them with the early-start group up to 1 year. This open-label extension phase included 49 patients who had been on early-start tofersen and 18 patients in the delayed-start group.
For the primary endpoint, change from baseline in 48-point ALSFRS-R score, there was a statistically significant benefit for the early-start patients with these patients scoring 3.5 points higher than the delayed-start group (P = .0272, 95% confidence interval [CI], 0.4-6.7). This means that both groups declined in function, which is expected in ALS, but the early-start group declined more slowly.
There was also a benefit associated with early-start tofersen for a number of secondary endpoints, including change from baseline in total SOD1 cerebrospinal fluid concentration (CSF SOD1), plasma neurofilament light chain (NfL) levels, and respiratory function.
“This drug targets the MRNA of SOD1, so it lowers the MRNA and then the SOD1 protein falls,” explained Dr. Miller, adding that these levels dropped 21% in the delayed start group, and 33% in the early-start group. “I think the data pretty clearly show that [tofersen] does what it is supposed to do, and that is the first step.”
Neurofilament light chain, a marker of neurodegeneration, also dropped by 41% in the delayed-start group, and 51% in the early-start group.
Respiratory function, as measured by percent predicted slow vital capacity (SVC), also declined 9.2% more slowly in the early- versus delayed-start group (P = .0159).
Finally, muscle strength, as measured by handheld dynamometry (HHD) score, declined more slowly in the early-start group compared with the late-start group, with an adjusted mean difference in score of 2.8 (P = 0.0186).
Dr. Miller said that the data show that it takes time for tofersen to impact clinical function, but there are signs of benefit before that. “I think what you see is that just starting on the drug, the first thing that happens is SOD1 goes down, the next thing is that neurofilament decreases, but clinical function is not yet changing. It takes time. What I see in these data is that it takes time for us to see that effect on clinical function.”
The bigger picture
While acknowledging that tofersen acts on a genetic mutation found in only about 2% of ALS, Dr. Miller said the study findings carry significance for the wider ALS patient population.
“Assuming we agree there is a clinical effect here, assuming we agree that there is real stabilization of clinical function, I think if we agree on that point then we know that ALS is now a treatable disorder. And that’s a really important point. I’m not sure that we knew that before,” he said. “Yes, there are FDA-approved medications that slow down ALS a bit, but they don’t stabilize it, and if we get the target correct – and we have the correct genetic target here – there can be a substantial influence on slowing down the disease, so that’s one thing to learn for the whole ALS community.”
What lies ahead?
Asked to comment on the study, Richard Bedlack, MD, PhD, who was not involved in the research, said the findings are important and show “clinically meaningful” results. “Based on the new benefit-to-burden ratio, I believe most of my patients with SOD1 mutations will want to try this drug. I would like to be able to offer it to them. But I am curious to see what the FDA will do with these data,” said Dr. Bedlack, professor of neurology at Duke University in Durham, N.C., and director of the Duke ALS Clinic.
“Sometimes that open-label extension gives us time to see differences between patients who initially got drug and those who initially got placebo. That seems to be the case with tofersen here, and it was also the case with AMX0035 [Amylyx Pharmaceuticals Inc.], which did not show a survival benefit in the first 6 months but did in the open-label extension.” A recent FDA advisory board panel concluded there was insufficient evidence of benefit for AMX0035, he noted. “I wonder if the same concern will be raised here, necessitating confirmation in another trial. I hope not, but only time will tell.”
Dr. Miller added that these results “highlight how difficult ALS drug development still is. Among the many uncertainties in setting up a trial (targets, doses, inclusion criteria, outcomes), we still do not know how long we need to treat patients in order to see statistically significant changes in the clinical measures we use (ALSFRS-R, respiratory function, strength, survival, etc.). Most American studies are 6 months long and most European studies are 12 months long. Longer studies may be more likely to show benefits on certain measures (e.g., survival), but they cost more, they are challenged by dropouts as the disease progresses, and the idea of randomizing someone to a placebo for a whole year is psychologically difficult for patients, families, and many clinicians (myself included). So, we are seeing more studies like this one where the first 6 months are randomized, blinded, and placebo controlled, and then there is an open-label extension that lasts many months more.”
The study was sponsored by Biogen. Writing and editorial support was provided by Excel Scientific Solutions. Tofersen was discovered by Ionis Pharmaceuticals Inc. Dr. Miller disclosed ties with Biogen, Ionis Pharmaceuticals Inc., Cytokinetics, C2N, Disarm Therapeutics, and UCB Pharma. Dr. Bedlack disclosed ties with Biogen.
caused by superoxide dismutase 1 (SOD1) gene mutations.
The 1-year results, presented at the European Network for the Cure of Amyotrophic Lateral Sclerosis (ENCALS) 2022 meeting, show a deceleration in functional decline that is similar, but “more pronounced” than the previously reported 6-month results, which were not statistically significant, said lead investigator Timothy Miller, MD, PhD, professor of neurology and director of the ALS Center, Washington University, St. Louis.
“What I thought we saw in the first data cut is confirmed by what we saw in the longer data,” he said in an interview. “There were trends [showing] those treated with tofersen did a bit better, but it was hard to be sure. It was hard to be confident in what we were seeing at that early time point.”
Now, with 6 more months of data, Dr. Miller says he is confident that tofersen is slowing down the neurodegenerative disease process. “I see results that I’m encouraged by,” he said. “As a clinician who treats people with ALS with this mutation I would want this drug to be available to people that I see in my clinic.”
One-year VALOR study results
The primary efficacy objective of the VALOR study was to show the 28-week impact of 100 mg tofersen (three doses given about 2 weeks apart, then five doses given every 4 weeks), versus placebo, on function, measured on the Amyotrophic Lateral Sclerosis Functional Rating Scale–Revised (ALSFRS-R). The open-label extension switched placebo-treated patients to tofersen (delayed-start group) and continued to compare them with the early-start group up to 1 year. This open-label extension phase included 49 patients who had been on early-start tofersen and 18 patients in the delayed-start group.
For the primary endpoint, change from baseline in 48-point ALSFRS-R score, there was a statistically significant benefit for the early-start patients with these patients scoring 3.5 points higher than the delayed-start group (P = .0272, 95% confidence interval [CI], 0.4-6.7). This means that both groups declined in function, which is expected in ALS, but the early-start group declined more slowly.
There was also a benefit associated with early-start tofersen for a number of secondary endpoints, including change from baseline in total SOD1 cerebrospinal fluid concentration (CSF SOD1), plasma neurofilament light chain (NfL) levels, and respiratory function.
“This drug targets the MRNA of SOD1, so it lowers the MRNA and then the SOD1 protein falls,” explained Dr. Miller, adding that these levels dropped 21% in the delayed start group, and 33% in the early-start group. “I think the data pretty clearly show that [tofersen] does what it is supposed to do, and that is the first step.”
Neurofilament light chain, a marker of neurodegeneration, also dropped by 41% in the delayed-start group, and 51% in the early-start group.
Respiratory function, as measured by percent predicted slow vital capacity (SVC), also declined 9.2% more slowly in the early- versus delayed-start group (P = .0159).
Finally, muscle strength, as measured by handheld dynamometry (HHD) score, declined more slowly in the early-start group compared with the late-start group, with an adjusted mean difference in score of 2.8 (P = 0.0186).
Dr. Miller said that the data show that it takes time for tofersen to impact clinical function, but there are signs of benefit before that. “I think what you see is that just starting on the drug, the first thing that happens is SOD1 goes down, the next thing is that neurofilament decreases, but clinical function is not yet changing. It takes time. What I see in these data is that it takes time for us to see that effect on clinical function.”
The bigger picture
While acknowledging that tofersen acts on a genetic mutation found in only about 2% of ALS, Dr. Miller said the study findings carry significance for the wider ALS patient population.
“Assuming we agree there is a clinical effect here, assuming we agree that there is real stabilization of clinical function, I think if we agree on that point then we know that ALS is now a treatable disorder. And that’s a really important point. I’m not sure that we knew that before,” he said. “Yes, there are FDA-approved medications that slow down ALS a bit, but they don’t stabilize it, and if we get the target correct – and we have the correct genetic target here – there can be a substantial influence on slowing down the disease, so that’s one thing to learn for the whole ALS community.”
What lies ahead?
Asked to comment on the study, Richard Bedlack, MD, PhD, who was not involved in the research, said the findings are important and show “clinically meaningful” results. “Based on the new benefit-to-burden ratio, I believe most of my patients with SOD1 mutations will want to try this drug. I would like to be able to offer it to them. But I am curious to see what the FDA will do with these data,” said Dr. Bedlack, professor of neurology at Duke University in Durham, N.C., and director of the Duke ALS Clinic.
“Sometimes that open-label extension gives us time to see differences between patients who initially got drug and those who initially got placebo. That seems to be the case with tofersen here, and it was also the case with AMX0035 [Amylyx Pharmaceuticals Inc.], which did not show a survival benefit in the first 6 months but did in the open-label extension.” A recent FDA advisory board panel concluded there was insufficient evidence of benefit for AMX0035, he noted. “I wonder if the same concern will be raised here, necessitating confirmation in another trial. I hope not, but only time will tell.”
Dr. Miller added that these results “highlight how difficult ALS drug development still is. Among the many uncertainties in setting up a trial (targets, doses, inclusion criteria, outcomes), we still do not know how long we need to treat patients in order to see statistically significant changes in the clinical measures we use (ALSFRS-R, respiratory function, strength, survival, etc.). Most American studies are 6 months long and most European studies are 12 months long. Longer studies may be more likely to show benefits on certain measures (e.g., survival), but they cost more, they are challenged by dropouts as the disease progresses, and the idea of randomizing someone to a placebo for a whole year is psychologically difficult for patients, families, and many clinicians (myself included). So, we are seeing more studies like this one where the first 6 months are randomized, blinded, and placebo controlled, and then there is an open-label extension that lasts many months more.”
The study was sponsored by Biogen. Writing and editorial support was provided by Excel Scientific Solutions. Tofersen was discovered by Ionis Pharmaceuticals Inc. Dr. Miller disclosed ties with Biogen, Ionis Pharmaceuticals Inc., Cytokinetics, C2N, Disarm Therapeutics, and UCB Pharma. Dr. Bedlack disclosed ties with Biogen.
FROM THE ENCALS MEETING 2022
Autoimmune disorder drugs top list of meds linked to headache
DENVER – in a federal side effect database that anyone can contribute to, according to a new study presented at the annual meeting of the American Headache Society.
“Surprising findings included the significant number of immunosuppressants and immunomodulators present in the data,” study lead author Brett Musialowicz, a medical student at Robert Wood Johnson Medical School, New Brunswich, N.J., said in an interview. “Additionally, our data provides evidence that suggests that several medications belonging to these drug classes were less likely to be associated with medication-induced headaches,” raising questions about the mechanism.
Drugs most frequently linked to headaches
The researchers launched their study to better understand headache as a side effect of medication use, Mr. Musialowicz said. They analyzed entries from the Food and Drug Administration’s Adverse Event Reporting System for the period from July 2018 to March 2020 and listed the top 30 most commonly reported medications linked to headaches and their reported odds ratio. According to a website devoted to pharmacovigilance training, ROR refers to “the odds of a certain event occurring with your medicinal product, compared with the odds of the same event occurring with all other medicinal products in the database.”
After generic and brand name data was consolidated, the drug most frequently linked to headaches was apremilast with 8,672 reports, followed by adalimumab (5,357), tofacitinib (4,276), fingolimod (4,123), and etanercept (4,111). These drugs treat autoimmune disorders such as psoriasis, multiple sclerosis, and Crohn’s disease.
The other drugs in the top 15 ranked by frequency are treatments for hepatitis C (4 drugs), pulmonary arterial hypertension (4 drugs), arthritis (1 drug), and asthma (1 drug).
Of the top 30 drugs most frequently linked to headaches, the pulmonary hypertension drug epoprostenol – ranked 23rd – had the highest ROR at 12.8. The next highest were the hepatitis C drugs glecaprevir and pibrentasvir, tied at 10th in the frequency analysis and both with an ROR of 9.4.
“Pulmonary arterial dilators and vasodilators are believed to cause headaches by sensitizing extracranial arteries. Clinical evidence suggests there a vascular component to some types of headache,” Mr. Musialowicz said. “Monoclonal antibodies are suggested to cause headache by means of an immune response. Several monoclonal antibodies are in trials targeting [the calcitonin gene-related peptide] receptor, which is believed to be involved in migraine headache. These trials will help further elucidate the mechanisms of headache and potential drugs to treat these conditions.”
Is the data useful?
Stewart Tepper, MD, a neurologist at Geisel School of Medicine at Dartmouth, Hanover, N.H., who’s familiar with the study findings, discounted the new research in an interview. He noted that any member of the public can contribute to the federal database of adverse effects (drug manufacturers are required to contribute to it), and the data says nothing about denominators.
“It’s not a reasonable way to evaluate adverse effects, to just have everyone and their uncle saying ‘This particular drug did this to me.’ It’s not in any way useful,” he said. However, he added that the database sometimes “gives you a bit of a signal so you can go back and try to get scientifically collected data.”
When asked to respond, study coauthor and neurologist Pengfei (Phil) Zhang, MD, of Robert Wood Johnson Medical School, noted that the FDA created the database “for a reason.” He also noted that the researchers used a statistical analysis technique – ROR – that was invented to adjust for weaknesses in databases.
No study funding is reported. Mr. Musialowicz reported no disclosures. Dr. Zhang has received honorarium from Alder Biopharmaceuticals, Board Vitals, and Fieve Clinical Research. He collaborates with Headache Science Incorporated without receiving financial support, and he has ownership interest in Cymbeline. Another author reports research grant support from the American Epilepsy Society and the New Jersey Health Foundation. Dr. Tepper reported multiple disclosures.
DENVER – in a federal side effect database that anyone can contribute to, according to a new study presented at the annual meeting of the American Headache Society.
“Surprising findings included the significant number of immunosuppressants and immunomodulators present in the data,” study lead author Brett Musialowicz, a medical student at Robert Wood Johnson Medical School, New Brunswich, N.J., said in an interview. “Additionally, our data provides evidence that suggests that several medications belonging to these drug classes were less likely to be associated with medication-induced headaches,” raising questions about the mechanism.
Drugs most frequently linked to headaches
The researchers launched their study to better understand headache as a side effect of medication use, Mr. Musialowicz said. They analyzed entries from the Food and Drug Administration’s Adverse Event Reporting System for the period from July 2018 to March 2020 and listed the top 30 most commonly reported medications linked to headaches and their reported odds ratio. According to a website devoted to pharmacovigilance training, ROR refers to “the odds of a certain event occurring with your medicinal product, compared with the odds of the same event occurring with all other medicinal products in the database.”
After generic and brand name data was consolidated, the drug most frequently linked to headaches was apremilast with 8,672 reports, followed by adalimumab (5,357), tofacitinib (4,276), fingolimod (4,123), and etanercept (4,111). These drugs treat autoimmune disorders such as psoriasis, multiple sclerosis, and Crohn’s disease.
The other drugs in the top 15 ranked by frequency are treatments for hepatitis C (4 drugs), pulmonary arterial hypertension (4 drugs), arthritis (1 drug), and asthma (1 drug).
Of the top 30 drugs most frequently linked to headaches, the pulmonary hypertension drug epoprostenol – ranked 23rd – had the highest ROR at 12.8. The next highest were the hepatitis C drugs glecaprevir and pibrentasvir, tied at 10th in the frequency analysis and both with an ROR of 9.4.
“Pulmonary arterial dilators and vasodilators are believed to cause headaches by sensitizing extracranial arteries. Clinical evidence suggests there a vascular component to some types of headache,” Mr. Musialowicz said. “Monoclonal antibodies are suggested to cause headache by means of an immune response. Several monoclonal antibodies are in trials targeting [the calcitonin gene-related peptide] receptor, which is believed to be involved in migraine headache. These trials will help further elucidate the mechanisms of headache and potential drugs to treat these conditions.”
Is the data useful?
Stewart Tepper, MD, a neurologist at Geisel School of Medicine at Dartmouth, Hanover, N.H., who’s familiar with the study findings, discounted the new research in an interview. He noted that any member of the public can contribute to the federal database of adverse effects (drug manufacturers are required to contribute to it), and the data says nothing about denominators.
“It’s not a reasonable way to evaluate adverse effects, to just have everyone and their uncle saying ‘This particular drug did this to me.’ It’s not in any way useful,” he said. However, he added that the database sometimes “gives you a bit of a signal so you can go back and try to get scientifically collected data.”
When asked to respond, study coauthor and neurologist Pengfei (Phil) Zhang, MD, of Robert Wood Johnson Medical School, noted that the FDA created the database “for a reason.” He also noted that the researchers used a statistical analysis technique – ROR – that was invented to adjust for weaknesses in databases.
No study funding is reported. Mr. Musialowicz reported no disclosures. Dr. Zhang has received honorarium from Alder Biopharmaceuticals, Board Vitals, and Fieve Clinical Research. He collaborates with Headache Science Incorporated without receiving financial support, and he has ownership interest in Cymbeline. Another author reports research grant support from the American Epilepsy Society and the New Jersey Health Foundation. Dr. Tepper reported multiple disclosures.
DENVER – in a federal side effect database that anyone can contribute to, according to a new study presented at the annual meeting of the American Headache Society.
“Surprising findings included the significant number of immunosuppressants and immunomodulators present in the data,” study lead author Brett Musialowicz, a medical student at Robert Wood Johnson Medical School, New Brunswich, N.J., said in an interview. “Additionally, our data provides evidence that suggests that several medications belonging to these drug classes were less likely to be associated with medication-induced headaches,” raising questions about the mechanism.
Drugs most frequently linked to headaches
The researchers launched their study to better understand headache as a side effect of medication use, Mr. Musialowicz said. They analyzed entries from the Food and Drug Administration’s Adverse Event Reporting System for the period from July 2018 to March 2020 and listed the top 30 most commonly reported medications linked to headaches and their reported odds ratio. According to a website devoted to pharmacovigilance training, ROR refers to “the odds of a certain event occurring with your medicinal product, compared with the odds of the same event occurring with all other medicinal products in the database.”
After generic and brand name data was consolidated, the drug most frequently linked to headaches was apremilast with 8,672 reports, followed by adalimumab (5,357), tofacitinib (4,276), fingolimod (4,123), and etanercept (4,111). These drugs treat autoimmune disorders such as psoriasis, multiple sclerosis, and Crohn’s disease.
The other drugs in the top 15 ranked by frequency are treatments for hepatitis C (4 drugs), pulmonary arterial hypertension (4 drugs), arthritis (1 drug), and asthma (1 drug).
Of the top 30 drugs most frequently linked to headaches, the pulmonary hypertension drug epoprostenol – ranked 23rd – had the highest ROR at 12.8. The next highest were the hepatitis C drugs glecaprevir and pibrentasvir, tied at 10th in the frequency analysis and both with an ROR of 9.4.
“Pulmonary arterial dilators and vasodilators are believed to cause headaches by sensitizing extracranial arteries. Clinical evidence suggests there a vascular component to some types of headache,” Mr. Musialowicz said. “Monoclonal antibodies are suggested to cause headache by means of an immune response. Several monoclonal antibodies are in trials targeting [the calcitonin gene-related peptide] receptor, which is believed to be involved in migraine headache. These trials will help further elucidate the mechanisms of headache and potential drugs to treat these conditions.”
Is the data useful?
Stewart Tepper, MD, a neurologist at Geisel School of Medicine at Dartmouth, Hanover, N.H., who’s familiar with the study findings, discounted the new research in an interview. He noted that any member of the public can contribute to the federal database of adverse effects (drug manufacturers are required to contribute to it), and the data says nothing about denominators.
“It’s not a reasonable way to evaluate adverse effects, to just have everyone and their uncle saying ‘This particular drug did this to me.’ It’s not in any way useful,” he said. However, he added that the database sometimes “gives you a bit of a signal so you can go back and try to get scientifically collected data.”
When asked to respond, study coauthor and neurologist Pengfei (Phil) Zhang, MD, of Robert Wood Johnson Medical School, noted that the FDA created the database “for a reason.” He also noted that the researchers used a statistical analysis technique – ROR – that was invented to adjust for weaknesses in databases.
No study funding is reported. Mr. Musialowicz reported no disclosures. Dr. Zhang has received honorarium from Alder Biopharmaceuticals, Board Vitals, and Fieve Clinical Research. He collaborates with Headache Science Incorporated without receiving financial support, and he has ownership interest in Cymbeline. Another author reports research grant support from the American Epilepsy Society and the New Jersey Health Foundation. Dr. Tepper reported multiple disclosures.
AT AHS 2022
Recommended headache treatments get mixed reception in EDs
DENVER – a new study finds. But the use of diphenhydramine (Benadryl) more than doubled even though guidelines caution against it, while recommended drugs such triptans and corticosteroids were rarely prescribed.
From 2007-2010 to 2015-2018, researchers reported at the annual meeting of the American Headache Society, a database reveals that opioid use in headache cases at EDs fell from 54% to 28%. Diphenhydramine use grew from 17% to 36% (both (P < .001). The percentage of cases in which EDs sought neuroimaging stayed stable at about 36%, a number that the study authors described as too high.
“Future studies are warranted to identify strategies to promote evidence-based treatments for headaches and appropriate outpatient referrals for follow-up and to reduce unnecessary neuroimaging orders in EDs,” lead author Seonkyeong Yang, MS, of the University of Florida, Gainesville, said in an interview.
Ms. Yang said researchers launched the study to update previous data in light of changes in opioid prescribing and the 2016 release of American Headache Society guidelines for the treatment of acute migraines in the ED setting. The research was published in the Journal of Clinical Medicine.
Headache treatment in the ED
For the study, researchers analyzed data from the U.S. National Hospital Ambulatory Medical Care survey and focused on adults who had a primary discharge diagnosis of headache.
For the 2015-2018 period, per weighted numbers, the survey encompassed 10.2 million headaches mostly among people younger than 50 (71%), female (73%), and White (73%). Migraines made up 33% of the total, with nonspecified headache accounting for almost all of the remainder (63%).
In 68% of cases, two or more medications were administered in the ED. This number rose to 83% among patients with migraine. But most of the time (54%), no medications were prescribed at discharge.
Among recommended medications, antiemetics – the most commonly used class of drugs in these patients – were prescribed 59% of the time in both 2007-2010 and 2015-2018 (P = .88). Usage of acetaminophens and NSAIDs grew from 37% to 52% over that time period.
Despite recommendations, the use of ergot alkaloids/triptans and corticosteroids remained low (less than 6% of the time).
“Several factors may contribute to the underuse of triptans in EDs, including their cardiovascular contraindications, ED physicians’ unfamiliarity with injectable triptans, higher costs, and treatment failures with triptans before ED visits,” Ms. Yang said. “We observed an upward trend in dexamethasone use over time. However, it was still underutilized. [The corticosteroid was only used 3.5% of the time from 2015-2018.] The 2016 AHS guideline strongly recommends dexamethasone use to prevent migraine recurrence after ED discharge. Identifying patients at high risk of headache recurrence for dexamethasone use may further improve patient outcomes of acute headache management in ED settings.”
Ms. Yang also reported that the use of diphenhydramine grew even though it’s not recommended. “Diphenhydramine is more likely to be used to prevent akathisia, a side effect of some antiemetics [that is, dopamine receptor antagonists] in headache-related ED visits,” she said. “However, the 2016 AHS guideline recommends against diphenhydramine use due to its limited efficacy in relieving headache pain. In addition, there is also conflicting evidence on diphenhydramine’s efficacy in preventing akathisia when coadministered with antiemetics. Diphenhydramine use requires caution due to its sedative effect and abuse potential.”
As for medication combinations, Ms. Yang said “the most broadly used therapy among headache-related ED visits in 2007-2010 was an opioid with an antiemetic (21.0%), which decreased to 6.6% in 2015-2018. Meanwhile, the combined use of acetaminophen/NSAIDs with antiemetic and diphenhydramine increased substantially from 3.9% to 15.7% and became the most prevalent therapy in 2015-2018. Opioid monotherapy use gradually decreased during the study period [from 8.8% to 1.9%].”
Evidence-based treatments underutilized
Commenting on the findings, New York University Langone neurologist and headache researcher Mia Tova Minen, MD, MPH, noted in an interview that AHS guidelines do not indicate acetaminophen/NSAIDs, diphenhydramine, and corticosteroids for the acute treatment of migraine. “The recommended treatments are sumatriptan subcutaneous, IV metoclopramide, and IV prochlorperazine. Steroids can be helpful in the prevention of migraine recurrence but not for the acute treatment of the migraine itself,” she said. “We need to ensure that patients with migraine get the top evidence-based treatments for migraine.”
As for diphenhydramine, she said it “is not a treatment for headache disorders. It does not have proven efficacy. It is sometimes given to reduce side effects of more acute treatments of headache, but it can make patients fatigued and keep them in the ED longer.”
Overuse of neuroimaging
Ms. Yang also highlighted study data about the frequency of neuroimaging. “Understandably, ED physicians do not want to miss any life-threatening secondary headaches like stroke,” she said. “However, other factors also contribute to the overuse of neuroimaging in headache-related ED visits: patient demands, financial incentives, a busy ED practice where clinical evaluation is replaced by tests, and ED physicians’ unfamiliarity with ICHD-3 diagnostic criteria for primary headache disorders. There is still much room for improvement in neuroimaging use for headaches in ED settings.”
For her part, Dr. Minen said scans are often performed reflexively and can be overused. “A CT scan is really only good in the case of acute trauma to rule out a fracture or a bleed or if there are signs of an emergent neurologic emergency like herniation or if a MRI is contraindicated. An MRI of the brain is typically the best test to examine brain tissue, though sometimes vessel imaging is also warranted. In the case of no red flags and a normal neurologic exam, the use of neuroimaging is low yield.”
The research has no funding. Ms. Yang and two other authors disclosed research funding from Merck. Dr. Minen reports no disclosures.
DENVER – a new study finds. But the use of diphenhydramine (Benadryl) more than doubled even though guidelines caution against it, while recommended drugs such triptans and corticosteroids were rarely prescribed.
From 2007-2010 to 2015-2018, researchers reported at the annual meeting of the American Headache Society, a database reveals that opioid use in headache cases at EDs fell from 54% to 28%. Diphenhydramine use grew from 17% to 36% (both (P < .001). The percentage of cases in which EDs sought neuroimaging stayed stable at about 36%, a number that the study authors described as too high.
“Future studies are warranted to identify strategies to promote evidence-based treatments for headaches and appropriate outpatient referrals for follow-up and to reduce unnecessary neuroimaging orders in EDs,” lead author Seonkyeong Yang, MS, of the University of Florida, Gainesville, said in an interview.
Ms. Yang said researchers launched the study to update previous data in light of changes in opioid prescribing and the 2016 release of American Headache Society guidelines for the treatment of acute migraines in the ED setting. The research was published in the Journal of Clinical Medicine.
Headache treatment in the ED
For the study, researchers analyzed data from the U.S. National Hospital Ambulatory Medical Care survey and focused on adults who had a primary discharge diagnosis of headache.
For the 2015-2018 period, per weighted numbers, the survey encompassed 10.2 million headaches mostly among people younger than 50 (71%), female (73%), and White (73%). Migraines made up 33% of the total, with nonspecified headache accounting for almost all of the remainder (63%).
In 68% of cases, two or more medications were administered in the ED. This number rose to 83% among patients with migraine. But most of the time (54%), no medications were prescribed at discharge.
Among recommended medications, antiemetics – the most commonly used class of drugs in these patients – were prescribed 59% of the time in both 2007-2010 and 2015-2018 (P = .88). Usage of acetaminophens and NSAIDs grew from 37% to 52% over that time period.
Despite recommendations, the use of ergot alkaloids/triptans and corticosteroids remained low (less than 6% of the time).
“Several factors may contribute to the underuse of triptans in EDs, including their cardiovascular contraindications, ED physicians’ unfamiliarity with injectable triptans, higher costs, and treatment failures with triptans before ED visits,” Ms. Yang said. “We observed an upward trend in dexamethasone use over time. However, it was still underutilized. [The corticosteroid was only used 3.5% of the time from 2015-2018.] The 2016 AHS guideline strongly recommends dexamethasone use to prevent migraine recurrence after ED discharge. Identifying patients at high risk of headache recurrence for dexamethasone use may further improve patient outcomes of acute headache management in ED settings.”
Ms. Yang also reported that the use of diphenhydramine grew even though it’s not recommended. “Diphenhydramine is more likely to be used to prevent akathisia, a side effect of some antiemetics [that is, dopamine receptor antagonists] in headache-related ED visits,” she said. “However, the 2016 AHS guideline recommends against diphenhydramine use due to its limited efficacy in relieving headache pain. In addition, there is also conflicting evidence on diphenhydramine’s efficacy in preventing akathisia when coadministered with antiemetics. Diphenhydramine use requires caution due to its sedative effect and abuse potential.”
As for medication combinations, Ms. Yang said “the most broadly used therapy among headache-related ED visits in 2007-2010 was an opioid with an antiemetic (21.0%), which decreased to 6.6% in 2015-2018. Meanwhile, the combined use of acetaminophen/NSAIDs with antiemetic and diphenhydramine increased substantially from 3.9% to 15.7% and became the most prevalent therapy in 2015-2018. Opioid monotherapy use gradually decreased during the study period [from 8.8% to 1.9%].”
Evidence-based treatments underutilized
Commenting on the findings, New York University Langone neurologist and headache researcher Mia Tova Minen, MD, MPH, noted in an interview that AHS guidelines do not indicate acetaminophen/NSAIDs, diphenhydramine, and corticosteroids for the acute treatment of migraine. “The recommended treatments are sumatriptan subcutaneous, IV metoclopramide, and IV prochlorperazine. Steroids can be helpful in the prevention of migraine recurrence but not for the acute treatment of the migraine itself,” she said. “We need to ensure that patients with migraine get the top evidence-based treatments for migraine.”
As for diphenhydramine, she said it “is not a treatment for headache disorders. It does not have proven efficacy. It is sometimes given to reduce side effects of more acute treatments of headache, but it can make patients fatigued and keep them in the ED longer.”
Overuse of neuroimaging
Ms. Yang also highlighted study data about the frequency of neuroimaging. “Understandably, ED physicians do not want to miss any life-threatening secondary headaches like stroke,” she said. “However, other factors also contribute to the overuse of neuroimaging in headache-related ED visits: patient demands, financial incentives, a busy ED practice where clinical evaluation is replaced by tests, and ED physicians’ unfamiliarity with ICHD-3 diagnostic criteria for primary headache disorders. There is still much room for improvement in neuroimaging use for headaches in ED settings.”
For her part, Dr. Minen said scans are often performed reflexively and can be overused. “A CT scan is really only good in the case of acute trauma to rule out a fracture or a bleed or if there are signs of an emergent neurologic emergency like herniation or if a MRI is contraindicated. An MRI of the brain is typically the best test to examine brain tissue, though sometimes vessel imaging is also warranted. In the case of no red flags and a normal neurologic exam, the use of neuroimaging is low yield.”
The research has no funding. Ms. Yang and two other authors disclosed research funding from Merck. Dr. Minen reports no disclosures.
DENVER – a new study finds. But the use of diphenhydramine (Benadryl) more than doubled even though guidelines caution against it, while recommended drugs such triptans and corticosteroids were rarely prescribed.
From 2007-2010 to 2015-2018, researchers reported at the annual meeting of the American Headache Society, a database reveals that opioid use in headache cases at EDs fell from 54% to 28%. Diphenhydramine use grew from 17% to 36% (both (P < .001). The percentage of cases in which EDs sought neuroimaging stayed stable at about 36%, a number that the study authors described as too high.
“Future studies are warranted to identify strategies to promote evidence-based treatments for headaches and appropriate outpatient referrals for follow-up and to reduce unnecessary neuroimaging orders in EDs,” lead author Seonkyeong Yang, MS, of the University of Florida, Gainesville, said in an interview.
Ms. Yang said researchers launched the study to update previous data in light of changes in opioid prescribing and the 2016 release of American Headache Society guidelines for the treatment of acute migraines in the ED setting. The research was published in the Journal of Clinical Medicine.
Headache treatment in the ED
For the study, researchers analyzed data from the U.S. National Hospital Ambulatory Medical Care survey and focused on adults who had a primary discharge diagnosis of headache.
For the 2015-2018 period, per weighted numbers, the survey encompassed 10.2 million headaches mostly among people younger than 50 (71%), female (73%), and White (73%). Migraines made up 33% of the total, with nonspecified headache accounting for almost all of the remainder (63%).
In 68% of cases, two or more medications were administered in the ED. This number rose to 83% among patients with migraine. But most of the time (54%), no medications were prescribed at discharge.
Among recommended medications, antiemetics – the most commonly used class of drugs in these patients – were prescribed 59% of the time in both 2007-2010 and 2015-2018 (P = .88). Usage of acetaminophens and NSAIDs grew from 37% to 52% over that time period.
Despite recommendations, the use of ergot alkaloids/triptans and corticosteroids remained low (less than 6% of the time).
“Several factors may contribute to the underuse of triptans in EDs, including their cardiovascular contraindications, ED physicians’ unfamiliarity with injectable triptans, higher costs, and treatment failures with triptans before ED visits,” Ms. Yang said. “We observed an upward trend in dexamethasone use over time. However, it was still underutilized. [The corticosteroid was only used 3.5% of the time from 2015-2018.] The 2016 AHS guideline strongly recommends dexamethasone use to prevent migraine recurrence after ED discharge. Identifying patients at high risk of headache recurrence for dexamethasone use may further improve patient outcomes of acute headache management in ED settings.”
Ms. Yang also reported that the use of diphenhydramine grew even though it’s not recommended. “Diphenhydramine is more likely to be used to prevent akathisia, a side effect of some antiemetics [that is, dopamine receptor antagonists] in headache-related ED visits,” she said. “However, the 2016 AHS guideline recommends against diphenhydramine use due to its limited efficacy in relieving headache pain. In addition, there is also conflicting evidence on diphenhydramine’s efficacy in preventing akathisia when coadministered with antiemetics. Diphenhydramine use requires caution due to its sedative effect and abuse potential.”
As for medication combinations, Ms. Yang said “the most broadly used therapy among headache-related ED visits in 2007-2010 was an opioid with an antiemetic (21.0%), which decreased to 6.6% in 2015-2018. Meanwhile, the combined use of acetaminophen/NSAIDs with antiemetic and diphenhydramine increased substantially from 3.9% to 15.7% and became the most prevalent therapy in 2015-2018. Opioid monotherapy use gradually decreased during the study period [from 8.8% to 1.9%].”
Evidence-based treatments underutilized
Commenting on the findings, New York University Langone neurologist and headache researcher Mia Tova Minen, MD, MPH, noted in an interview that AHS guidelines do not indicate acetaminophen/NSAIDs, diphenhydramine, and corticosteroids for the acute treatment of migraine. “The recommended treatments are sumatriptan subcutaneous, IV metoclopramide, and IV prochlorperazine. Steroids can be helpful in the prevention of migraine recurrence but not for the acute treatment of the migraine itself,” she said. “We need to ensure that patients with migraine get the top evidence-based treatments for migraine.”
As for diphenhydramine, she said it “is not a treatment for headache disorders. It does not have proven efficacy. It is sometimes given to reduce side effects of more acute treatments of headache, but it can make patients fatigued and keep them in the ED longer.”
Overuse of neuroimaging
Ms. Yang also highlighted study data about the frequency of neuroimaging. “Understandably, ED physicians do not want to miss any life-threatening secondary headaches like stroke,” she said. “However, other factors also contribute to the overuse of neuroimaging in headache-related ED visits: patient demands, financial incentives, a busy ED practice where clinical evaluation is replaced by tests, and ED physicians’ unfamiliarity with ICHD-3 diagnostic criteria for primary headache disorders. There is still much room for improvement in neuroimaging use for headaches in ED settings.”
For her part, Dr. Minen said scans are often performed reflexively and can be overused. “A CT scan is really only good in the case of acute trauma to rule out a fracture or a bleed or if there are signs of an emergent neurologic emergency like herniation or if a MRI is contraindicated. An MRI of the brain is typically the best test to examine brain tissue, though sometimes vessel imaging is also warranted. In the case of no red flags and a normal neurologic exam, the use of neuroimaging is low yield.”
The research has no funding. Ms. Yang and two other authors disclosed research funding from Merck. Dr. Minen reports no disclosures.
AT AHS 2022
Patients with blood cancers underutilize palliative care
I used to attend the Supportive Care in Oncology Symposium every year, but to my dismay, the American Society for Clinical Oncology stopped hosting the symposium a few years ago. Instead, ASCO now incorporates palliative care research fully into its annual meeting which was held in early June in Chicago. Being integrated into the annual meeting means greater exposure to a broader audience that may not otherwise see this work. In this column, I highlight some presentations that stood out to me.
Palliative care studies for patients with hematologic malignancies
There continues to be low uptake of outpatient palliative care services among patients with hematologic malignancies. Fortunately, there are efforts underway to study the impact of integrating early palliative care into the routine care of hematology patients. In a study presented by Mazie Tsang, MD, a clinical fellow at the University of California, San Francisco, researchers embedded a palliative care nurse practitioner in a hematology clinic and studied the impact this single NP had over 4 years of integration. They found that patients were less likely to be hospitalized or visit the emergency department after integrating the NP. They also found that advance directives were more likely to be completed following NP integration. The results were limited by small sample size and lack of a true control group, but generally trended toward significance when compared with historical controls.
Other studies highlighted the relatively high symptom burden among patients with hematologic malignancies, such as myeloma, leukemia, and lymphoma. In a study presented by Sarah E. Monick, MD, of the University of Chicago, researchers found that, among adolescents and young adults with hematologic malignancies seen in a clinic where a palliative care provider was embedded, symptom burden was high across the board regardless of where patients were in their disease trajectory or their demographic characteristics. Due to the presence of high symptom burden among adolescents and young adults, the authors suggest that patients undergo screening at every visit and that supportive care be incorporated throughout the patient’s journey.
Kyle Fitzgibbon of the Princess Margaret Cancer Centre in Toronto shared details of an ongoing multicenter, randomized, controlled, phase 3 trial designed to evaluate the effect of a novel psychosocial/palliative care intervention for patients with acute leukemia hospitalized for induction chemotherapy. The intervention will consist of 8 weeks of psychological support as well as access to palliative care for physical symptoms. Participants will be randomized to receive either intervention or standard of care at the beginning of their hospitalization. Researchers plan to study the impact of the intervention on physical and psychological symptom severity, quality of life, and patient satisfaction at multiple time points. It will be exciting to see the results of this study given that there are very few research clinical trials examining early palliative care with patients who have hematologic malignancies.
Trends in palliative care integration with oncology care
One key trend that I am elated to see is the integration of palliative care throughout the entire patient journey. A secondary analysis of oncology practice data from the National Cancer Institute Community Oncology Research Program found that more than three-quarters of outpatient oncology practices surveyed in 2015 have integrated palliative care inpatient and outpatient services. 36% said they had an outpatient palliative care clinic. More availability of services typically translates to better access to care and improved outcomes for patients, so it is always nice to see these quality metrics continue to move in a positive direction. The analysis was presented by Tiffany M. Statler, PA, of Atrium Health Wake Forest Baptist, Winston Salem, N.C.
It turns out that patients are also advocating for integrated palliative care. A unique qualitative project brought together patient advocates from several countries to hold a moderated discussion about quality of life and treatment side effects. The advocates focused on the importance of maintaining independence with activities of daily living as a significant quality of life goal, particularly as treatments tend to cause cumulative mental and physical fatigue. They highlighted the importance of palliative care for helping achieve quality of life goals, especially in latter part of the disease trajectory. The project was presented by Paul Wheatley-Price, MD, of the Ottawa Hospital Cancer Centre, University of Ottawa.
In 2010, a study by Temel and colleagues was published, finding that patients with metastatic non–small cell lung cancer who received palliative care early had significant improvements in quality of life and mood as compared with patients who received standard care. It was a landmark study and is frequently cited. The Temel group reports on the planning process for a new randomized controlled trial of palliative care with metastatic lung cancer patients who have targetable mutations. With next generation sequencing of tumor tissue, many patients with metastatic lung cancer are identified at diagnosis as having a targetable mutation. As such, they may receive a targeted therapy as first-line treatment instead of traditional chemotherapy. This has lengthened survival considerably, but the disease remains incurable and ultimately fatal, and the trajectory can resemble a roller-coaster ride.
In this new randomized controlled trial, patients in the experimental arm will receive four monthly visits with a palliative care clinician who is specially trained to help patients manage the uncertainties of prolonged illness. The researchers plan to evaluate patients’ distress levels and prognostic awareness, as well as evidence of advance care planning in the chart.
And, a study presented by Roberto Enrique Ochoa Planchart, MD, of Chen Medical Centers, Miami, found that when primary care providers used declines in functional status as a trigger for referring advanced cancer patients to palliative care, those patients were less likely to be admitted to the hospital near the end of life, translating to an 86% cost savings. This study reiterated the importance of partnering with a patient’s nononcologic providers, that is, primary care and palliative care clinicians to improve outcomes at the end of life.
Use of technology in palliative care
Numerous studies were reported on innovative uses of technology for various functions relevant to palliative care. They included everything from capturing patient-reported outcomes through patient-facing smartphone apps, to using artificial intelligence and/or machine learning to build prognostication tools and to generate earlier referrals to palliative care. There were presentations on the use of online tools to assist with and document goals of care conversations.
As a clinician who is always looking for new ways to capture patient symptom information and motivate patients to engage in advance care planning, I am excited about the prospect of using some of these tools in real time.
Ms. D’Ambruoso is a hospice and palliative care nurse practitioner for UCLA Health Cancer Care, Santa Monica, Calif.
I used to attend the Supportive Care in Oncology Symposium every year, but to my dismay, the American Society for Clinical Oncology stopped hosting the symposium a few years ago. Instead, ASCO now incorporates palliative care research fully into its annual meeting which was held in early June in Chicago. Being integrated into the annual meeting means greater exposure to a broader audience that may not otherwise see this work. In this column, I highlight some presentations that stood out to me.
Palliative care studies for patients with hematologic malignancies
There continues to be low uptake of outpatient palliative care services among patients with hematologic malignancies. Fortunately, there are efforts underway to study the impact of integrating early palliative care into the routine care of hematology patients. In a study presented by Mazie Tsang, MD, a clinical fellow at the University of California, San Francisco, researchers embedded a palliative care nurse practitioner in a hematology clinic and studied the impact this single NP had over 4 years of integration. They found that patients were less likely to be hospitalized or visit the emergency department after integrating the NP. They also found that advance directives were more likely to be completed following NP integration. The results were limited by small sample size and lack of a true control group, but generally trended toward significance when compared with historical controls.
Other studies highlighted the relatively high symptom burden among patients with hematologic malignancies, such as myeloma, leukemia, and lymphoma. In a study presented by Sarah E. Monick, MD, of the University of Chicago, researchers found that, among adolescents and young adults with hematologic malignancies seen in a clinic where a palliative care provider was embedded, symptom burden was high across the board regardless of where patients were in their disease trajectory or their demographic characteristics. Due to the presence of high symptom burden among adolescents and young adults, the authors suggest that patients undergo screening at every visit and that supportive care be incorporated throughout the patient’s journey.
Kyle Fitzgibbon of the Princess Margaret Cancer Centre in Toronto shared details of an ongoing multicenter, randomized, controlled, phase 3 trial designed to evaluate the effect of a novel psychosocial/palliative care intervention for patients with acute leukemia hospitalized for induction chemotherapy. The intervention will consist of 8 weeks of psychological support as well as access to palliative care for physical symptoms. Participants will be randomized to receive either intervention or standard of care at the beginning of their hospitalization. Researchers plan to study the impact of the intervention on physical and psychological symptom severity, quality of life, and patient satisfaction at multiple time points. It will be exciting to see the results of this study given that there are very few research clinical trials examining early palliative care with patients who have hematologic malignancies.
Trends in palliative care integration with oncology care
One key trend that I am elated to see is the integration of palliative care throughout the entire patient journey. A secondary analysis of oncology practice data from the National Cancer Institute Community Oncology Research Program found that more than three-quarters of outpatient oncology practices surveyed in 2015 have integrated palliative care inpatient and outpatient services. 36% said they had an outpatient palliative care clinic. More availability of services typically translates to better access to care and improved outcomes for patients, so it is always nice to see these quality metrics continue to move in a positive direction. The analysis was presented by Tiffany M. Statler, PA, of Atrium Health Wake Forest Baptist, Winston Salem, N.C.
It turns out that patients are also advocating for integrated palliative care. A unique qualitative project brought together patient advocates from several countries to hold a moderated discussion about quality of life and treatment side effects. The advocates focused on the importance of maintaining independence with activities of daily living as a significant quality of life goal, particularly as treatments tend to cause cumulative mental and physical fatigue. They highlighted the importance of palliative care for helping achieve quality of life goals, especially in latter part of the disease trajectory. The project was presented by Paul Wheatley-Price, MD, of the Ottawa Hospital Cancer Centre, University of Ottawa.
In 2010, a study by Temel and colleagues was published, finding that patients with metastatic non–small cell lung cancer who received palliative care early had significant improvements in quality of life and mood as compared with patients who received standard care. It was a landmark study and is frequently cited. The Temel group reports on the planning process for a new randomized controlled trial of palliative care with metastatic lung cancer patients who have targetable mutations. With next generation sequencing of tumor tissue, many patients with metastatic lung cancer are identified at diagnosis as having a targetable mutation. As such, they may receive a targeted therapy as first-line treatment instead of traditional chemotherapy. This has lengthened survival considerably, but the disease remains incurable and ultimately fatal, and the trajectory can resemble a roller-coaster ride.
In this new randomized controlled trial, patients in the experimental arm will receive four monthly visits with a palliative care clinician who is specially trained to help patients manage the uncertainties of prolonged illness. The researchers plan to evaluate patients’ distress levels and prognostic awareness, as well as evidence of advance care planning in the chart.
And, a study presented by Roberto Enrique Ochoa Planchart, MD, of Chen Medical Centers, Miami, found that when primary care providers used declines in functional status as a trigger for referring advanced cancer patients to palliative care, those patients were less likely to be admitted to the hospital near the end of life, translating to an 86% cost savings. This study reiterated the importance of partnering with a patient’s nononcologic providers, that is, primary care and palliative care clinicians to improve outcomes at the end of life.
Use of technology in palliative care
Numerous studies were reported on innovative uses of technology for various functions relevant to palliative care. They included everything from capturing patient-reported outcomes through patient-facing smartphone apps, to using artificial intelligence and/or machine learning to build prognostication tools and to generate earlier referrals to palliative care. There were presentations on the use of online tools to assist with and document goals of care conversations.
As a clinician who is always looking for new ways to capture patient symptom information and motivate patients to engage in advance care planning, I am excited about the prospect of using some of these tools in real time.
Ms. D’Ambruoso is a hospice and palliative care nurse practitioner for UCLA Health Cancer Care, Santa Monica, Calif.
I used to attend the Supportive Care in Oncology Symposium every year, but to my dismay, the American Society for Clinical Oncology stopped hosting the symposium a few years ago. Instead, ASCO now incorporates palliative care research fully into its annual meeting which was held in early June in Chicago. Being integrated into the annual meeting means greater exposure to a broader audience that may not otherwise see this work. In this column, I highlight some presentations that stood out to me.
Palliative care studies for patients with hematologic malignancies
There continues to be low uptake of outpatient palliative care services among patients with hematologic malignancies. Fortunately, there are efforts underway to study the impact of integrating early palliative care into the routine care of hematology patients. In a study presented by Mazie Tsang, MD, a clinical fellow at the University of California, San Francisco, researchers embedded a palliative care nurse practitioner in a hematology clinic and studied the impact this single NP had over 4 years of integration. They found that patients were less likely to be hospitalized or visit the emergency department after integrating the NP. They also found that advance directives were more likely to be completed following NP integration. The results were limited by small sample size and lack of a true control group, but generally trended toward significance when compared with historical controls.
Other studies highlighted the relatively high symptom burden among patients with hematologic malignancies, such as myeloma, leukemia, and lymphoma. In a study presented by Sarah E. Monick, MD, of the University of Chicago, researchers found that, among adolescents and young adults with hematologic malignancies seen in a clinic where a palliative care provider was embedded, symptom burden was high across the board regardless of where patients were in their disease trajectory or their demographic characteristics. Due to the presence of high symptom burden among adolescents and young adults, the authors suggest that patients undergo screening at every visit and that supportive care be incorporated throughout the patient’s journey.
Kyle Fitzgibbon of the Princess Margaret Cancer Centre in Toronto shared details of an ongoing multicenter, randomized, controlled, phase 3 trial designed to evaluate the effect of a novel psychosocial/palliative care intervention for patients with acute leukemia hospitalized for induction chemotherapy. The intervention will consist of 8 weeks of psychological support as well as access to palliative care for physical symptoms. Participants will be randomized to receive either intervention or standard of care at the beginning of their hospitalization. Researchers plan to study the impact of the intervention on physical and psychological symptom severity, quality of life, and patient satisfaction at multiple time points. It will be exciting to see the results of this study given that there are very few research clinical trials examining early palliative care with patients who have hematologic malignancies.
Trends in palliative care integration with oncology care
One key trend that I am elated to see is the integration of palliative care throughout the entire patient journey. A secondary analysis of oncology practice data from the National Cancer Institute Community Oncology Research Program found that more than three-quarters of outpatient oncology practices surveyed in 2015 have integrated palliative care inpatient and outpatient services. 36% said they had an outpatient palliative care clinic. More availability of services typically translates to better access to care and improved outcomes for patients, so it is always nice to see these quality metrics continue to move in a positive direction. The analysis was presented by Tiffany M. Statler, PA, of Atrium Health Wake Forest Baptist, Winston Salem, N.C.
It turns out that patients are also advocating for integrated palliative care. A unique qualitative project brought together patient advocates from several countries to hold a moderated discussion about quality of life and treatment side effects. The advocates focused on the importance of maintaining independence with activities of daily living as a significant quality of life goal, particularly as treatments tend to cause cumulative mental and physical fatigue. They highlighted the importance of palliative care for helping achieve quality of life goals, especially in latter part of the disease trajectory. The project was presented by Paul Wheatley-Price, MD, of the Ottawa Hospital Cancer Centre, University of Ottawa.
In 2010, a study by Temel and colleagues was published, finding that patients with metastatic non–small cell lung cancer who received palliative care early had significant improvements in quality of life and mood as compared with patients who received standard care. It was a landmark study and is frequently cited. The Temel group reports on the planning process for a new randomized controlled trial of palliative care with metastatic lung cancer patients who have targetable mutations. With next generation sequencing of tumor tissue, many patients with metastatic lung cancer are identified at diagnosis as having a targetable mutation. As such, they may receive a targeted therapy as first-line treatment instead of traditional chemotherapy. This has lengthened survival considerably, but the disease remains incurable and ultimately fatal, and the trajectory can resemble a roller-coaster ride.
In this new randomized controlled trial, patients in the experimental arm will receive four monthly visits with a palliative care clinician who is specially trained to help patients manage the uncertainties of prolonged illness. The researchers plan to evaluate patients’ distress levels and prognostic awareness, as well as evidence of advance care planning in the chart.
And, a study presented by Roberto Enrique Ochoa Planchart, MD, of Chen Medical Centers, Miami, found that when primary care providers used declines in functional status as a trigger for referring advanced cancer patients to palliative care, those patients were less likely to be admitted to the hospital near the end of life, translating to an 86% cost savings. This study reiterated the importance of partnering with a patient’s nononcologic providers, that is, primary care and palliative care clinicians to improve outcomes at the end of life.
Use of technology in palliative care
Numerous studies were reported on innovative uses of technology for various functions relevant to palliative care. They included everything from capturing patient-reported outcomes through patient-facing smartphone apps, to using artificial intelligence and/or machine learning to build prognostication tools and to generate earlier referrals to palliative care. There were presentations on the use of online tools to assist with and document goals of care conversations.
As a clinician who is always looking for new ways to capture patient symptom information and motivate patients to engage in advance care planning, I am excited about the prospect of using some of these tools in real time.
Ms. D’Ambruoso is a hospice and palliative care nurse practitioner for UCLA Health Cancer Care, Santa Monica, Calif.
FROM ASCO 2022
SBRT plus TACE better than monotherapy in HCC with portal vein tumor thrombus
Key clinical point: Stereotactic body radiotherapy (SBRT) plus transcatheter arterial chemoembolization (TACE) may be safe and more effective than either of the procedures alone (monotherapy) for treating inoperable hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT).
Major finding: SBRT plus TACE vs. monotherapy led to significantly higher overall survival (1-year: risk ratio [RR] 1.52; 95% CI 1.33-1.74; 2-year: RR 2.00; 95% CI 1.48-2.70) and objective response (RR 1.22; 95% CI 1.08-1.37) rates, a significantly lower disease progression rate (RR 0.45; 95% CI 0.26-0.79), and a similar adverse event incidence (RR 1.03; 95% CI 0.82-1.31).
Study details: This was a meta-analysis of nine studies involving 938 patients with inoperable HCC and PVTT who received SBRT plus TACE (n = 455) or monotherapy (n = 483).
Disclosures: The study was sponsored by Chinese Medical Hand in Hand Project Committee & Beijing Medical Award Foundation, among others. The authors declared no conflicts of interest.
Source: Zhang X-F et al. Stereotactic body radiotherapy plus transcatheter arterial chemoembolization for inoperable hepatocellular carcinoma patients with portal vein tumour thrombus: A meta-analysis. PLoS One. 2022;17(5): e0268779 (May 20). Doi: 10.1371/journal.pone.0268779
Key clinical point: Stereotactic body radiotherapy (SBRT) plus transcatheter arterial chemoembolization (TACE) may be safe and more effective than either of the procedures alone (monotherapy) for treating inoperable hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT).
Major finding: SBRT plus TACE vs. monotherapy led to significantly higher overall survival (1-year: risk ratio [RR] 1.52; 95% CI 1.33-1.74; 2-year: RR 2.00; 95% CI 1.48-2.70) and objective response (RR 1.22; 95% CI 1.08-1.37) rates, a significantly lower disease progression rate (RR 0.45; 95% CI 0.26-0.79), and a similar adverse event incidence (RR 1.03; 95% CI 0.82-1.31).
Study details: This was a meta-analysis of nine studies involving 938 patients with inoperable HCC and PVTT who received SBRT plus TACE (n = 455) or monotherapy (n = 483).
Disclosures: The study was sponsored by Chinese Medical Hand in Hand Project Committee & Beijing Medical Award Foundation, among others. The authors declared no conflicts of interest.
Source: Zhang X-F et al. Stereotactic body radiotherapy plus transcatheter arterial chemoembolization for inoperable hepatocellular carcinoma patients with portal vein tumour thrombus: A meta-analysis. PLoS One. 2022;17(5): e0268779 (May 20). Doi: 10.1371/journal.pone.0268779
Key clinical point: Stereotactic body radiotherapy (SBRT) plus transcatheter arterial chemoembolization (TACE) may be safe and more effective than either of the procedures alone (monotherapy) for treating inoperable hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT).
Major finding: SBRT plus TACE vs. monotherapy led to significantly higher overall survival (1-year: risk ratio [RR] 1.52; 95% CI 1.33-1.74; 2-year: RR 2.00; 95% CI 1.48-2.70) and objective response (RR 1.22; 95% CI 1.08-1.37) rates, a significantly lower disease progression rate (RR 0.45; 95% CI 0.26-0.79), and a similar adverse event incidence (RR 1.03; 95% CI 0.82-1.31).
Study details: This was a meta-analysis of nine studies involving 938 patients with inoperable HCC and PVTT who received SBRT plus TACE (n = 455) or monotherapy (n = 483).
Disclosures: The study was sponsored by Chinese Medical Hand in Hand Project Committee & Beijing Medical Award Foundation, among others. The authors declared no conflicts of interest.
Source: Zhang X-F et al. Stereotactic body radiotherapy plus transcatheter arterial chemoembolization for inoperable hepatocellular carcinoma patients with portal vein tumour thrombus: A meta-analysis. PLoS One. 2022;17(5): e0268779 (May 20). Doi: 10.1371/journal.pone.0268779
Unresectable HCC: Differential efficacy of atezolizumab plus bevacizumab according to hepatic function grade
Key clinical point: Atezolizumab plus bevacizumab (Atez/Bev) shows potent therapeutic efficacy against unresectable hepatocellular carcinoma (uHCC) in patients with a good hepatic function, classified as Child-Pugh A (CP-A), but has decreased efficacy in those with CP-B.
Major finding: Patients with CP-A vs. CP-B showed better 6-, 12-, and 18-month progression-free (58.2%, 36.1%, and 27.8% vs. 49.6%, 8.7%, and non-estimable, respectively; P < .001) and overall (89.9%, 71.7%, and 51.4% vs. 63.6%, 18.4%, and non-estimable, respectively; P < .001) survival rates.
Study details: This retrospective study included 457 patients with uHCC and CP-A (n = 427) or CP-B (n = 30) who received Atez/Bev.
Disclosures: This study received no financial support. Some authors declared serving as advisors for and receiving lecture fees or research funds from various sources. Two authors declared serving as editors/editorial board members of Liver Cancer.
Source: Tanaka T et al. Therapeutic efficacy of atezolizumab plus bevacizumab treatment for unresectable hepatocellular carcinoma in patients with Child-Pugh class A or B liver function in real-world clinical practice. Hepatol Res. 2022 (May 28). Doi: 10.1111/hepr.13797
Key clinical point: Atezolizumab plus bevacizumab (Atez/Bev) shows potent therapeutic efficacy against unresectable hepatocellular carcinoma (uHCC) in patients with a good hepatic function, classified as Child-Pugh A (CP-A), but has decreased efficacy in those with CP-B.
Major finding: Patients with CP-A vs. CP-B showed better 6-, 12-, and 18-month progression-free (58.2%, 36.1%, and 27.8% vs. 49.6%, 8.7%, and non-estimable, respectively; P < .001) and overall (89.9%, 71.7%, and 51.4% vs. 63.6%, 18.4%, and non-estimable, respectively; P < .001) survival rates.
Study details: This retrospective study included 457 patients with uHCC and CP-A (n = 427) or CP-B (n = 30) who received Atez/Bev.
Disclosures: This study received no financial support. Some authors declared serving as advisors for and receiving lecture fees or research funds from various sources. Two authors declared serving as editors/editorial board members of Liver Cancer.
Source: Tanaka T et al. Therapeutic efficacy of atezolizumab plus bevacizumab treatment for unresectable hepatocellular carcinoma in patients with Child-Pugh class A or B liver function in real-world clinical practice. Hepatol Res. 2022 (May 28). Doi: 10.1111/hepr.13797
Key clinical point: Atezolizumab plus bevacizumab (Atez/Bev) shows potent therapeutic efficacy against unresectable hepatocellular carcinoma (uHCC) in patients with a good hepatic function, classified as Child-Pugh A (CP-A), but has decreased efficacy in those with CP-B.
Major finding: Patients with CP-A vs. CP-B showed better 6-, 12-, and 18-month progression-free (58.2%, 36.1%, and 27.8% vs. 49.6%, 8.7%, and non-estimable, respectively; P < .001) and overall (89.9%, 71.7%, and 51.4% vs. 63.6%, 18.4%, and non-estimable, respectively; P < .001) survival rates.
Study details: This retrospective study included 457 patients with uHCC and CP-A (n = 427) or CP-B (n = 30) who received Atez/Bev.
Disclosures: This study received no financial support. Some authors declared serving as advisors for and receiving lecture fees or research funds from various sources. Two authors declared serving as editors/editorial board members of Liver Cancer.
Source: Tanaka T et al. Therapeutic efficacy of atezolizumab plus bevacizumab treatment for unresectable hepatocellular carcinoma in patients with Child-Pugh class A or B liver function in real-world clinical practice. Hepatol Res. 2022 (May 28). Doi: 10.1111/hepr.13797
Atezolizumab plus bevacizumab offers a better prognosis than lenvatinib in unresectable HCC
Key clinical point: Therapy with atezolizumab plus bevacizumab (Atez/Bev) vs. lenvatinib in the first-line setting may confer a survival benefit in patients with unresectable hepatocellular carcinoma (uHCC).
Major finding: Patients receiving Atez/Bev vs. lenvatinib showed better overall survival (1 year: 67.2% vs. 66.2%; 1.5 years: 58.1% vs. 52.7%; P = .002) and progression-free survival (1 year: 31.6% vs. 20.4%; 1.5 years: non-estimable vs. 11.2%; P < .0001) rates.
Study details: This retrospective study included 251 systemic treatment-naive patients with uHCC who received standard-dose Atez/Bev (n = 194) or lenvatinib (n = 57).
Disclosures: The study did not receive any funding. Some authors declared serving as advisors or receiving lecture fees or research funding from various sources.
Source: Hiraoka A et al. Does first-line treatment have prognostic impact for unresectable HCC?—Atezolizumab plus bevacizumab versus lenvatinib .Cancer Med. 2022 (Jun 3). Doi: 10.1002/cam4.4854
Key clinical point: Therapy with atezolizumab plus bevacizumab (Atez/Bev) vs. lenvatinib in the first-line setting may confer a survival benefit in patients with unresectable hepatocellular carcinoma (uHCC).
Major finding: Patients receiving Atez/Bev vs. lenvatinib showed better overall survival (1 year: 67.2% vs. 66.2%; 1.5 years: 58.1% vs. 52.7%; P = .002) and progression-free survival (1 year: 31.6% vs. 20.4%; 1.5 years: non-estimable vs. 11.2%; P < .0001) rates.
Study details: This retrospective study included 251 systemic treatment-naive patients with uHCC who received standard-dose Atez/Bev (n = 194) or lenvatinib (n = 57).
Disclosures: The study did not receive any funding. Some authors declared serving as advisors or receiving lecture fees or research funding from various sources.
Source: Hiraoka A et al. Does first-line treatment have prognostic impact for unresectable HCC?—Atezolizumab plus bevacizumab versus lenvatinib .Cancer Med. 2022 (Jun 3). Doi: 10.1002/cam4.4854
Key clinical point: Therapy with atezolizumab plus bevacizumab (Atez/Bev) vs. lenvatinib in the first-line setting may confer a survival benefit in patients with unresectable hepatocellular carcinoma (uHCC).
Major finding: Patients receiving Atez/Bev vs. lenvatinib showed better overall survival (1 year: 67.2% vs. 66.2%; 1.5 years: 58.1% vs. 52.7%; P = .002) and progression-free survival (1 year: 31.6% vs. 20.4%; 1.5 years: non-estimable vs. 11.2%; P < .0001) rates.
Study details: This retrospective study included 251 systemic treatment-naive patients with uHCC who received standard-dose Atez/Bev (n = 194) or lenvatinib (n = 57).
Disclosures: The study did not receive any funding. Some authors declared serving as advisors or receiving lecture fees or research funding from various sources.
Source: Hiraoka A et al. Does first-line treatment have prognostic impact for unresectable HCC?—Atezolizumab plus bevacizumab versus lenvatinib .Cancer Med. 2022 (Jun 3). Doi: 10.1002/cam4.4854
HCC with Child-Pugh B cirrhosis: Nivolumab a promising first-line systemic treatment option
Key clinical point: Nivolumab may serve as a first-line systemic treatment option in patients with hepatocellular carcinoma (HCC) and Child-Pugh B (CP-B) cirrhosis.
Major finding: Patients receiving nivolumab vs. sorafenib had a 31% reduced hazard of death (adjusted hazard ratio 0.69; P = .008) and were less likely to discontinue treatment due to toxicity (12% vs. 36%; P = .001).
Study details: The data come from a retrospective real-world cohort study that included patients with HCC and CP-B cirrhosis who received nivolumab (n = 79) or sorafenib (n = 431) as the first-line systemic treatment.
Disclosures: The study was funded by the US National Institutes of Health. Some authors declared serving on the advisory boards of or receiving honoraria or research grants from various sources.
Source: Chapin WJ et al. Comparison of nivolumab and sorafenib for first systemic therapy in patients with hepatocellular carcinoma and Child-Pugh B cirrhosis. Cancer Med. 2022 (Jun 2). Doi: 10.1002/cam4.4906
Key clinical point: Nivolumab may serve as a first-line systemic treatment option in patients with hepatocellular carcinoma (HCC) and Child-Pugh B (CP-B) cirrhosis.
Major finding: Patients receiving nivolumab vs. sorafenib had a 31% reduced hazard of death (adjusted hazard ratio 0.69; P = .008) and were less likely to discontinue treatment due to toxicity (12% vs. 36%; P = .001).
Study details: The data come from a retrospective real-world cohort study that included patients with HCC and CP-B cirrhosis who received nivolumab (n = 79) or sorafenib (n = 431) as the first-line systemic treatment.
Disclosures: The study was funded by the US National Institutes of Health. Some authors declared serving on the advisory boards of or receiving honoraria or research grants from various sources.
Source: Chapin WJ et al. Comparison of nivolumab and sorafenib for first systemic therapy in patients with hepatocellular carcinoma and Child-Pugh B cirrhosis. Cancer Med. 2022 (Jun 2). Doi: 10.1002/cam4.4906
Key clinical point: Nivolumab may serve as a first-line systemic treatment option in patients with hepatocellular carcinoma (HCC) and Child-Pugh B (CP-B) cirrhosis.
Major finding: Patients receiving nivolumab vs. sorafenib had a 31% reduced hazard of death (adjusted hazard ratio 0.69; P = .008) and were less likely to discontinue treatment due to toxicity (12% vs. 36%; P = .001).
Study details: The data come from a retrospective real-world cohort study that included patients with HCC and CP-B cirrhosis who received nivolumab (n = 79) or sorafenib (n = 431) as the first-line systemic treatment.
Disclosures: The study was funded by the US National Institutes of Health. Some authors declared serving on the advisory boards of or receiving honoraria or research grants from various sources.
Source: Chapin WJ et al. Comparison of nivolumab and sorafenib for first systemic therapy in patients with hepatocellular carcinoma and Child-Pugh B cirrhosis. Cancer Med. 2022 (Jun 2). Doi: 10.1002/cam4.4906
Preoperative ratio of creatinine and cystatin C estimated glomerular filtration rates predicts survival outcomes after hepatic resection for HCC
Key clinical point: The preoperative ratio of creatinine and cystatin C estimated glomerular filtration rates (eGFRcre/eGFRcys) can predict overall survival (OS) and recurrence-free survival (RFS) in patients with hepatocellular carcinoma (HCC) undergoing hepatic resection.
Major finding: High eGFRcre/eGFRcys (>1.0025) was significantly associated with worse OS (adjusted hazard ratio [aHR] 4.07; P = .03) and RFS (aHR 2.12; P = .04).
Study details: The data come from a retrospective study that included 157 patients with HCC who underwent curative hepatic resection.
Disclosures: The study was sponsored by Grants-in-Aid for Scientific Research, Japan Society for the Promotion of Science. The authors reported no conflicts of interest.
Source: Harimoto N et al. The ratio of creatinine and cystatin C estimated glomerular filtration rates as a surrogate marker in patients with hepatocellular carcinoma undergoing hepatic resection. J Hepatobiliary Pancreat Sci. 2022 (May 11). Doi: 10.1002/jhbp.1164
Key clinical point: The preoperative ratio of creatinine and cystatin C estimated glomerular filtration rates (eGFRcre/eGFRcys) can predict overall survival (OS) and recurrence-free survival (RFS) in patients with hepatocellular carcinoma (HCC) undergoing hepatic resection.
Major finding: High eGFRcre/eGFRcys (>1.0025) was significantly associated with worse OS (adjusted hazard ratio [aHR] 4.07; P = .03) and RFS (aHR 2.12; P = .04).
Study details: The data come from a retrospective study that included 157 patients with HCC who underwent curative hepatic resection.
Disclosures: The study was sponsored by Grants-in-Aid for Scientific Research, Japan Society for the Promotion of Science. The authors reported no conflicts of interest.
Source: Harimoto N et al. The ratio of creatinine and cystatin C estimated glomerular filtration rates as a surrogate marker in patients with hepatocellular carcinoma undergoing hepatic resection. J Hepatobiliary Pancreat Sci. 2022 (May 11). Doi: 10.1002/jhbp.1164
Key clinical point: The preoperative ratio of creatinine and cystatin C estimated glomerular filtration rates (eGFRcre/eGFRcys) can predict overall survival (OS) and recurrence-free survival (RFS) in patients with hepatocellular carcinoma (HCC) undergoing hepatic resection.
Major finding: High eGFRcre/eGFRcys (>1.0025) was significantly associated with worse OS (adjusted hazard ratio [aHR] 4.07; P = .03) and RFS (aHR 2.12; P = .04).
Study details: The data come from a retrospective study that included 157 patients with HCC who underwent curative hepatic resection.
Disclosures: The study was sponsored by Grants-in-Aid for Scientific Research, Japan Society for the Promotion of Science. The authors reported no conflicts of interest.
Source: Harimoto N et al. The ratio of creatinine and cystatin C estimated glomerular filtration rates as a surrogate marker in patients with hepatocellular carcinoma undergoing hepatic resection. J Hepatobiliary Pancreat Sci. 2022 (May 11). Doi: 10.1002/jhbp.1164
C reactive protein to albumin ratio predicts survival outcomes in lenvatinib-treated patients with unresectable HCC
Key clinical point: C-reactive protein to albumin ratio (CAR) can predict overall survival (OS) and progression-free survival (PFS) in patients treated with lenvatinib for unresectable hepatocellular carcinoma (uHCC).
Major finding: High CAR (≥0.108) was independently associated with OS (adjusted hazard ratio [aHR] 1.915; P < .001) and PFS (aHR 1.644; P < .001). Patients with low vs. high CAR showed significantly better cumulative OS and PFS (both P < .001).
Study details: This retrospective, multicenter study included 522 patients with uHCC who were treated with lenvatinib for >2 weeks, followed-up for >4 weeks, and had CAR data available at the beginning of follow-up.
Disclosures: This study did not receive any funding. Some authors reported serving as advisors for or receiving research funds or lecture fees from various sources.
Source: Tada T et al. C-reactive protein to albumin ratio predicts survival in patients with unresectable hepatocellular carcinoma treated with Lenvatinib. Sci Rep. 2022;12:8421 (May 19). Doi: 10.1038/s41598-022-12058-y
Key clinical point: C-reactive protein to albumin ratio (CAR) can predict overall survival (OS) and progression-free survival (PFS) in patients treated with lenvatinib for unresectable hepatocellular carcinoma (uHCC).
Major finding: High CAR (≥0.108) was independently associated with OS (adjusted hazard ratio [aHR] 1.915; P < .001) and PFS (aHR 1.644; P < .001). Patients with low vs. high CAR showed significantly better cumulative OS and PFS (both P < .001).
Study details: This retrospective, multicenter study included 522 patients with uHCC who were treated with lenvatinib for >2 weeks, followed-up for >4 weeks, and had CAR data available at the beginning of follow-up.
Disclosures: This study did not receive any funding. Some authors reported serving as advisors for or receiving research funds or lecture fees from various sources.
Source: Tada T et al. C-reactive protein to albumin ratio predicts survival in patients with unresectable hepatocellular carcinoma treated with Lenvatinib. Sci Rep. 2022;12:8421 (May 19). Doi: 10.1038/s41598-022-12058-y
Key clinical point: C-reactive protein to albumin ratio (CAR) can predict overall survival (OS) and progression-free survival (PFS) in patients treated with lenvatinib for unresectable hepatocellular carcinoma (uHCC).
Major finding: High CAR (≥0.108) was independently associated with OS (adjusted hazard ratio [aHR] 1.915; P < .001) and PFS (aHR 1.644; P < .001). Patients with low vs. high CAR showed significantly better cumulative OS and PFS (both P < .001).
Study details: This retrospective, multicenter study included 522 patients with uHCC who were treated with lenvatinib for >2 weeks, followed-up for >4 weeks, and had CAR data available at the beginning of follow-up.
Disclosures: This study did not receive any funding. Some authors reported serving as advisors for or receiving research funds or lecture fees from various sources.
Source: Tada T et al. C-reactive protein to albumin ratio predicts survival in patients with unresectable hepatocellular carcinoma treated with Lenvatinib. Sci Rep. 2022;12:8421 (May 19). Doi: 10.1038/s41598-022-12058-y