SAN DIEGO – Ibrutinib treatment continued before, during, and after infusion of the CD19-specific chimeric antigen receptor (CAR) T-cell therapy JCAR014 in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) appears to improve patient responses and decrease the risk of severe cytokine release syndrome.

The findings come from a comparison of sequential cohorts from a phase 1/2 study.

At 4 weeks after infusion, the approach was highly efficacious; overall response rates by 2008 International Workshop on CLL (IWCLL) criteria were 83% in 24 patients who received the uninterrupted ibrutinib regimen along with the JCAR014 therapy – a combination of CD4 and CD8 T cells – and 65% in 19 patients from a prior cohort who did not receive continuous ibrutinib, Jordan Gauthier, MD, reported at the annual meeting of the American Society of Hematology.

Concurrent ibrutinib was generally well tolerated, with 13 of 19 patients in the ibrutinib cohort receiving treatment as planned without discontinuation. The rates of grade 1 or higher cytokine release syndrome (CRS) were statistically similar in the ibrutinib and no-ibrutinib cohorts (74% and 92%, respectively). However, the rates of severe CRS (grade 3 or higher) were, strikingly, 0% and 25%, respectively, said Dr. Gauthier, a senior fellow in the Turtle Lab at Fred Hutchinson Cancer Center, Seattle.

Neurotoxicity occurred in 32% and 42% of patients in the groups; severe neurotoxicity occurred in 26% and 29%, respectively.

In the ibrutinib cohort, one patient with grade 2 CRS developed fatal presumed cardiac arrhythmia; in the no-ibrutinib cohort, one patient died from a CAR T cell–related toxicity.

Notably, a trend toward better expansion of CD8 CAR T cells and a significantly greater expansion of CD4 CAR T cells was observed in the ibrutinib cohort, he said.

The study was designed to assess JCAR014, and based on the initial cohort findings published in 2017, established a regimen of cyclophosphamide and fludarabine (Cy/Flu) lymphodepletion followed by JCAR014 infusion at 2 x 10⁶ CAR T cells/kg. The study was not a randomized, head-to-head comparison but the groups were similar with respect to both patient and disease characteristics, Dr. Gauthier noted.

The outcomes in the first cohort were then compared retrospectively with those from the subsequent cohort of patients who received Cy/Flu with 2 x 10⁶ CAR T cells/kg with concurrent ibrutinib administered at 420 mg per day from at least 2 weeks prior to leukapheresis until at least 3 months after JCAR014 infusion.

The rationale for uninterrupted ibrutinib in relapsed/refractory CLL patients receiving JCAR014 included potential prevention of tumor flare, mobilization of CLL cells into the blood from the lymph nodes, improvement of CAR T-cell function, and a decrease in CAR T-cell related toxicity, he said.

The concurrent administration of ibrutinib and JCAR014 was feasible for most patients. “[It] induced high response rates and deep responses early on at 4 weeks, and it was associated with higher in vivo expansion of CD4 CAR T cells and with lower rates of severe toxicity,” Dr. Gauthier said. “The next step is to hopefully validate these findings in a prospective phase 1/2 study.”

Dr. Gauthier reported having no financial disclosures.

[email protected]

SOURCE: Gauthier J et al. ASH 18, Abstract 299.

SAN DIEGO – Ibrutinib treatment continued before, during, and after infusion of the CD19-specific chimeric antigen receptor (CAR) T-cell therapy JCAR014 in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) appears to improve patient responses and decrease the risk of severe cytokine release syndrome.

The findings come from a comparison of sequential cohorts from a phase 1/2 study.

At 4 weeks after infusion, the approach was highly efficacious; overall response rates by 2008 International Workshop on CLL (IWCLL) criteria were 83% in 24 patients who received the uninterrupted ibrutinib regimen along with the JCAR014 therapy – a combination of CD4 and CD8 T cells – and 65% in 19 patients from a prior cohort who did not receive continuous ibrutinib, Jordan Gauthier, MD, reported at the annual meeting of the American Society of Hematology.

Concurrent ibrutinib was generally well tolerated, with 13 of 19 patients in the ibrutinib cohort receiving treatment as planned without discontinuation. The rates of grade 1 or higher cytokine release syndrome (CRS) were statistically similar in the ibrutinib and no-ibrutinib cohorts (74% and 92%, respectively). However, the rates of severe CRS (grade 3 or higher) were, strikingly, 0% and 25%, respectively, said Dr. Gauthier, a senior fellow in the Turtle Lab at Fred Hutchinson Cancer Center, Seattle.

Neurotoxicity occurred in 32% and 42% of patients in the groups; severe neurotoxicity occurred in 26% and 29%, respectively.

In the ibrutinib cohort, one patient with grade 2 CRS developed fatal presumed cardiac arrhythmia; in the no-ibrutinib cohort, one patient died from a CAR T cell–related toxicity.

Notably, a trend toward better expansion of CD8 CAR T cells and a significantly greater expansion of CD4 CAR T cells was observed in the ibrutinib cohort, he said.

The study was designed to assess JCAR014, and based on the initial cohort findings published in 2017, established a regimen of cyclophosphamide and fludarabine (Cy/Flu) lymphodepletion followed by JCAR014 infusion at 2 x 10⁶ CAR T cells/kg. The study was not a randomized, head-to-head comparison but the groups were similar with respect to both patient and disease characteristics, Dr. Gauthier noted.

The outcomes in the first cohort were then compared retrospectively with those from the subsequent cohort of patients who received Cy/Flu with 2 x 10⁶ CAR T cells/kg with concurrent ibrutinib administered at 420 mg per day from at least 2 weeks prior to leukapheresis until at least 3 months after JCAR014 infusion.

The rationale for uninterrupted ibrutinib in relapsed/refractory CLL patients receiving JCAR014 included potential prevention of tumor flare, mobilization of CLL cells into the blood from the lymph nodes, improvement of CAR T-cell function, and a decrease in CAR T-cell related toxicity, he said.

The concurrent administration of ibrutinib and JCAR014 was feasible for most patients. “[It] induced high response rates and deep responses early on at 4 weeks, and it was associated with higher in vivo expansion of CD4 CAR T cells and with lower rates of severe toxicity,” Dr. Gauthier said. “The next step is to hopefully validate these findings in a prospective phase 1/2 study.”

Dr. Gauthier reported having no financial disclosures.

[email protected]

SOURCE: Gauthier J et al. ASH 18, Abstract 299.

SAN DIEGO – Ibrutinib treatment continued before, during, and after infusion of the CD19-specific chimeric antigen receptor (CAR) T-cell therapy JCAR014 in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) appears to improve patient responses and decrease the risk of severe cytokine release syndrome.

The findings come from a comparison of sequential cohorts from a phase 1/2 study.

At 4 weeks after infusion, the approach was highly efficacious; overall response rates by 2008 International Workshop on CLL (IWCLL) criteria were 83% in 24 patients who received the uninterrupted ibrutinib regimen along with the JCAR014 therapy – a combination of CD4 and CD8 T cells – and 65% in 19 patients from a prior cohort who did not receive continuous ibrutinib, Jordan Gauthier, MD, reported at the annual meeting of the American Society of Hematology.

Concurrent ibrutinib was generally well tolerated, with 13 of 19 patients in the ibrutinib cohort receiving treatment as planned without discontinuation. The rates of grade 1 or higher cytokine release syndrome (CRS) were statistically similar in the ibrutinib and no-ibrutinib cohorts (74% and 92%, respectively). However, the rates of severe CRS (grade 3 or higher) were, strikingly, 0% and 25%, respectively, said Dr. Gauthier, a senior fellow in the Turtle Lab at Fred Hutchinson Cancer Center, Seattle.

Neurotoxicity occurred in 32% and 42% of patients in the groups; severe neurotoxicity occurred in 26% and 29%, respectively.

In the ibrutinib cohort, one patient with grade 2 CRS developed fatal presumed cardiac arrhythmia; in the no-ibrutinib cohort, one patient died from a CAR T cell–related toxicity.

Notably, a trend toward better expansion of CD8 CAR T cells and a significantly greater expansion of CD4 CAR T cells was observed in the ibrutinib cohort, he said.

The study was designed to assess JCAR014, and based on the initial cohort findings published in 2017, established a regimen of cyclophosphamide and fludarabine (Cy/Flu) lymphodepletion followed by JCAR014 infusion at 2 x 10⁶ CAR T cells/kg. The study was not a randomized, head-to-head comparison but the groups were similar with respect to both patient and disease characteristics, Dr. Gauthier noted.

The outcomes in the first cohort were then compared retrospectively with those from the subsequent cohort of patients who received Cy/Flu with 2 x 10⁶ CAR T cells/kg with concurrent ibrutinib administered at 420 mg per day from at least 2 weeks prior to leukapheresis until at least 3 months after JCAR014 infusion.

The rationale for uninterrupted ibrutinib in relapsed/refractory CLL patients receiving JCAR014 included potential prevention of tumor flare, mobilization of CLL cells into the blood from the lymph nodes, improvement of CAR T-cell function, and a decrease in CAR T-cell related toxicity, he said.

The concurrent administration of ibrutinib and JCAR014 was feasible for most patients. “[It] induced high response rates and deep responses early on at 4 weeks, and it was associated with higher in vivo expansion of CD4 CAR T cells and with lower rates of severe toxicity,” Dr. Gauthier said. “The next step is to hopefully validate these findings in a prospective phase 1/2 study.”

Dr. Gauthier reported having no financial disclosures.

[email protected]

SOURCE: Gauthier J et al. ASH 18, Abstract 299.

Most of us have a 5-, 10-, or even a necessarily vague 15-year plan for our practices. As you begin your New Year assessments, keep the following overriding considerations in mind to aid in your planning.

1) You are probably never going to be reimbursed better than you are today.

“Wait,” you say, “Don’t we get occasional Medicare updates?”

Yes, but these never keep up with inflation, just as any unlikely increases from private insurers always lag behind the cost of providing the service and have been grinding down toward Medicare rates – or even below them – for years. Any other sweeping insurance proposals, such as Medicare for All, include a hefty cut to physician reimbursement. One exception might be allowing those under age 55 years to buy into the existing Medicare program, which would be beneficial in areas where current private insurers and Medicare Advantage plans pay less than Medicare. It is also possible that you could see some increase if you are on the right side of bundled payments, although this has been more of a threat of penalty rather than a reward so far.

2) Don’t expect an imminent repeal of the ACA

The Affordable Care Act (ACA) favors large groups, and it is still the law, and it’s likely to remain the law for at least the next 5-10 years. Republicans could not repeal it when they held both the Senate and House, as well as the presidency, and certainly Democrats won’t repeal it.

There are myriad regulations and rules that only allow larger groups to reap the benefits from the ACA. Recall President Obama visiting the Cleveland Clinic and touting it and the Geisinger Clinic as examples of the way American medicine should be practiced.

Participation in alternative payment models that bypass many of the onerous requirements of “quality improvement,” and may even allow shared cost savings, are only practical for large groups. A notable exception is the recently proposed “site neutrality of payment” rule proposed by the current administration. This reduces by 50% or so the premium paid to large physician/hospital groups that are not located on the hospital campus to the prevailing rate of pay in the community. No more $3,000echocardiograms that used to cost $300.

Still, this does not increase the overall payments to physicians. Possibly, the proposed new telemedicine reimbursement rules may allow you to more efficiently manage patients without dramatically increasing your overhead.

An estimated 10,000 Baby Boomers are turning age 65 years every day. This ensures an increasing supply of patients, but also strains a federal government that has overpromised on Medicare and Social Security benefits. Recall that on average every Medicare recipient takes out far more than what they put into the program.

It is pay-up time, and the IOUs in the lockbox are unredeemable. This makes inflation and cutting reimbursements the easiest way to cope with older voters and a looming budget crisis.
 

4) Physicians are the weakest leg of the health care chair.

Hospitals, pharma, and insurers all have more powerful lobbying groups, donate more, and are better organized than physician groups. In our system of government, that means they will be favored in health care–related legislation. Physicians are the easiest to cut, although we account for only 15.9% of expenditures, according to 2014 data from the AMA.

The hospitals can close, insurers can refuse to write policies, and pharma can refuse to develop new drugs or manufacture generic ones. Big money (for example, Amazon, Berkshire Hathaway, and JPMorgan Chase) wants to consolidate health care and vertically integrate it. Most physicians cannot even unionize.

So what cheerful conclusions can we draw? If you go to work for a big group, try to negotiate the least restrictive practice covenant possible – or at least one that is not applicable if you are terminated without “cause.” The big group may have to disgorge you someday, and it could be disastrous to have to move or not be able to practice. If you opt for a small group or private practice, keep it small and lean. Build no palaces. There are special small practice situations that will survive or even prosper. Tightly managing your overhead is the key to survival.

Young physicians should recognize that the opportunity costs of an extensive residency after medical school may not be worth it. In fact, considering tuition that results in huge debt, lost income, and lost years of practice, high school graduates aspiring to a career in health care may do better from an economic perspective by pursuing a career as a nurse practitioner or physician assistant than one as a physician. The ACA, with its favoritism to large groups, will not be repealed anytime soon, and the regulations favoring larger groups are not even under discussion. This makes even hospital management more attractive as a career choice.

5. You’ll be doing more with less.

With a projected shortage of more than 100,000 physicians in the next 11 years, prepare for a high volume of patients, less pay for each encounter, and responsibility for multiple extenders. Practice will be much more stressful and difficult than simply managing your own panel of patients. Expect physician networks so narrow that they include only primary care physicians, with all other physicians having moved, died, or retired. It is much easier for insurers to save money by not receiving bills. Start thinking about integrating telemedicine into your practice because this may be a lifeline considering the most recent Medicare final rule that provides for payment for several new telehealth codes.

That all said, I must quote a lawmaker who, when discussing the ACA, told me “Well, you doctors are awfully late to the punch bowl” to which I replied, “Without doctors, there is no punch in the punch bowl.”
 

Dr. Coldiron is in private practice but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. He is a past president of the American Academy of Dermatology. Write to him at [email protected].

Most of us have a 5-, 10-, or even a necessarily vague 15-year plan for our practices. As you begin your New Year assessments, keep the following overriding considerations in mind to aid in your planning.

1) You are probably never going to be reimbursed better than you are today.

“Wait,” you say, “Don’t we get occasional Medicare updates?”

Yes, but these never keep up with inflation, just as any unlikely increases from private insurers always lag behind the cost of providing the service and have been grinding down toward Medicare rates – or even below them – for years. Any other sweeping insurance proposals, such as Medicare for All, include a hefty cut to physician reimbursement. One exception might be allowing those under age 55 years to buy into the existing Medicare program, which would be beneficial in areas where current private insurers and Medicare Advantage plans pay less than Medicare. It is also possible that you could see some increase if you are on the right side of bundled payments, although this has been more of a threat of penalty rather than a reward so far.

2) Don’t expect an imminent repeal of the ACA

The Affordable Care Act (ACA) favors large groups, and it is still the law, and it’s likely to remain the law for at least the next 5-10 years. Republicans could not repeal it when they held both the Senate and House, as well as the presidency, and certainly Democrats won’t repeal it.

There are myriad regulations and rules that only allow larger groups to reap the benefits from the ACA. Recall President Obama visiting the Cleveland Clinic and touting it and the Geisinger Clinic as examples of the way American medicine should be practiced.

Participation in alternative payment models that bypass many of the onerous requirements of “quality improvement,” and may even allow shared cost savings, are only practical for large groups. A notable exception is the recently proposed “site neutrality of payment” rule proposed by the current administration. This reduces by 50% or so the premium paid to large physician/hospital groups that are not located on the hospital campus to the prevailing rate of pay in the community. No more $3,000echocardiograms that used to cost $300.

Still, this does not increase the overall payments to physicians. Possibly, the proposed new telemedicine reimbursement rules may allow you to more efficiently manage patients without dramatically increasing your overhead.

An estimated 10,000 Baby Boomers are turning age 65 years every day. This ensures an increasing supply of patients, but also strains a federal government that has overpromised on Medicare and Social Security benefits. Recall that on average every Medicare recipient takes out far more than what they put into the program.

It is pay-up time, and the IOUs in the lockbox are unredeemable. This makes inflation and cutting reimbursements the easiest way to cope with older voters and a looming budget crisis.
 

4) Physicians are the weakest leg of the health care chair.

Hospitals, pharma, and insurers all have more powerful lobbying groups, donate more, and are better organized than physician groups. In our system of government, that means they will be favored in health care–related legislation. Physicians are the easiest to cut, although we account for only 15.9% of expenditures, according to 2014 data from the AMA.

The hospitals can close, insurers can refuse to write policies, and pharma can refuse to develop new drugs or manufacture generic ones. Big money (for example, Amazon, Berkshire Hathaway, and JPMorgan Chase) wants to consolidate health care and vertically integrate it. Most physicians cannot even unionize.

So what cheerful conclusions can we draw? If you go to work for a big group, try to negotiate the least restrictive practice covenant possible – or at least one that is not applicable if you are terminated without “cause.” The big group may have to disgorge you someday, and it could be disastrous to have to move or not be able to practice. If you opt for a small group or private practice, keep it small and lean. Build no palaces. There are special small practice situations that will survive or even prosper. Tightly managing your overhead is the key to survival.

Young physicians should recognize that the opportunity costs of an extensive residency after medical school may not be worth it. In fact, considering tuition that results in huge debt, lost income, and lost years of practice, high school graduates aspiring to a career in health care may do better from an economic perspective by pursuing a career as a nurse practitioner or physician assistant than one as a physician. The ACA, with its favoritism to large groups, will not be repealed anytime soon, and the regulations favoring larger groups are not even under discussion. This makes even hospital management more attractive as a career choice.

5. You’ll be doing more with less.

With a projected shortage of more than 100,000 physicians in the next 11 years, prepare for a high volume of patients, less pay for each encounter, and responsibility for multiple extenders. Practice will be much more stressful and difficult than simply managing your own panel of patients. Expect physician networks so narrow that they include only primary care physicians, with all other physicians having moved, died, or retired. It is much easier for insurers to save money by not receiving bills. Start thinking about integrating telemedicine into your practice because this may be a lifeline considering the most recent Medicare final rule that provides for payment for several new telehealth codes.

That all said, I must quote a lawmaker who, when discussing the ACA, told me “Well, you doctors are awfully late to the punch bowl” to which I replied, “Without doctors, there is no punch in the punch bowl.”
 

Dr. Coldiron is in private practice but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. He is a past president of the American Academy of Dermatology. Write to him at [email protected].

Most of us have a 5-, 10-, or even a necessarily vague 15-year plan for our practices. As you begin your New Year assessments, keep the following overriding considerations in mind to aid in your planning.

1) You are probably never going to be reimbursed better than you are today.

“Wait,” you say, “Don’t we get occasional Medicare updates?”

Yes, but these never keep up with inflation, just as any unlikely increases from private insurers always lag behind the cost of providing the service and have been grinding down toward Medicare rates – or even below them – for years. Any other sweeping insurance proposals, such as Medicare for All, include a hefty cut to physician reimbursement. One exception might be allowing those under age 55 years to buy into the existing Medicare program, which would be beneficial in areas where current private insurers and Medicare Advantage plans pay less than Medicare. It is also possible that you could see some increase if you are on the right side of bundled payments, although this has been more of a threat of penalty rather than a reward so far.

2) Don’t expect an imminent repeal of the ACA

The Affordable Care Act (ACA) favors large groups, and it is still the law, and it’s likely to remain the law for at least the next 5-10 years. Republicans could not repeal it when they held both the Senate and House, as well as the presidency, and certainly Democrats won’t repeal it.

There are myriad regulations and rules that only allow larger groups to reap the benefits from the ACA. Recall President Obama visiting the Cleveland Clinic and touting it and the Geisinger Clinic as examples of the way American medicine should be practiced.

Participation in alternative payment models that bypass many of the onerous requirements of “quality improvement,” and may even allow shared cost savings, are only practical for large groups. A notable exception is the recently proposed “site neutrality of payment” rule proposed by the current administration. This reduces by 50% or so the premium paid to large physician/hospital groups that are not located on the hospital campus to the prevailing rate of pay in the community. No more $3,000echocardiograms that used to cost $300.

Still, this does not increase the overall payments to physicians. Possibly, the proposed new telemedicine reimbursement rules may allow you to more efficiently manage patients without dramatically increasing your overhead.

An estimated 10,000 Baby Boomers are turning age 65 years every day. This ensures an increasing supply of patients, but also strains a federal government that has overpromised on Medicare and Social Security benefits. Recall that on average every Medicare recipient takes out far more than what they put into the program.

It is pay-up time, and the IOUs in the lockbox are unredeemable. This makes inflation and cutting reimbursements the easiest way to cope with older voters and a looming budget crisis.
 

4) Physicians are the weakest leg of the health care chair.

Hospitals, pharma, and insurers all have more powerful lobbying groups, donate more, and are better organized than physician groups. In our system of government, that means they will be favored in health care–related legislation. Physicians are the easiest to cut, although we account for only 15.9% of expenditures, according to 2014 data from the AMA.

The hospitals can close, insurers can refuse to write policies, and pharma can refuse to develop new drugs or manufacture generic ones. Big money (for example, Amazon, Berkshire Hathaway, and JPMorgan Chase) wants to consolidate health care and vertically integrate it. Most physicians cannot even unionize.

So what cheerful conclusions can we draw? If you go to work for a big group, try to negotiate the least restrictive practice covenant possible – or at least one that is not applicable if you are terminated without “cause.” The big group may have to disgorge you someday, and it could be disastrous to have to move or not be able to practice. If you opt for a small group or private practice, keep it small and lean. Build no palaces. There are special small practice situations that will survive or even prosper. Tightly managing your overhead is the key to survival.

Young physicians should recognize that the opportunity costs of an extensive residency after medical school may not be worth it. In fact, considering tuition that results in huge debt, lost income, and lost years of practice, high school graduates aspiring to a career in health care may do better from an economic perspective by pursuing a career as a nurse practitioner or physician assistant than one as a physician. The ACA, with its favoritism to large groups, will not be repealed anytime soon, and the regulations favoring larger groups are not even under discussion. This makes even hospital management more attractive as a career choice.

5. You’ll be doing more with less.

With a projected shortage of more than 100,000 physicians in the next 11 years, prepare for a high volume of patients, less pay for each encounter, and responsibility for multiple extenders. Practice will be much more stressful and difficult than simply managing your own panel of patients. Expect physician networks so narrow that they include only primary care physicians, with all other physicians having moved, died, or retired. It is much easier for insurers to save money by not receiving bills. Start thinking about integrating telemedicine into your practice because this may be a lifeline considering the most recent Medicare final rule that provides for payment for several new telehealth codes.

That all said, I must quote a lawmaker who, when discussing the ACA, told me “Well, you doctors are awfully late to the punch bowl” to which I replied, “Without doctors, there is no punch in the punch bowl.”
 

Dr. Coldiron is in private practice but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. He is a past president of the American Academy of Dermatology. Write to him at [email protected].

Prescribed opioids were associated with an increase in community acquired pneumonia. Also today, evidence of herd immunity with the HPV vaccine, COPD is linked to higher in-hosptial death rates in peripheral arterial disease, and discussions of actinic keratoses need to include the word cancer.

Amazon Alexa

Apple Podcasts

Google Podcasts

Spotify
 

Prescribed opioids were associated with an increase in community acquired pneumonia. Also today, evidence of herd immunity with the HPV vaccine, COPD is linked to higher in-hosptial death rates in peripheral arterial disease, and discussions of actinic keratoses need to include the word cancer.

Amazon Alexa

Apple Podcasts

Google Podcasts

Spotify
 

Prescribed opioids were associated with an increase in community acquired pneumonia. Also today, evidence of herd immunity with the HPV vaccine, COPD is linked to higher in-hosptial death rates in peripheral arterial disease, and discussions of actinic keratoses need to include the word cancer.

Amazon Alexa

Apple Podcasts

Google Podcasts

Spotify
 

This clinical puzzle is based on O’Neil. Diagnosing and classifying anemia in adult primary care. Clinician Reviews. 2017; 27(8):28-35. 

For the best mobile experience, rotate screen to landscape mode.

Have feedback on our new crossword puzzle? Share your thoughts at [email protected].

View Answers

This clinical puzzle is based on O’Neil. Diagnosing and classifying anemia in adult primary care. Clinician Reviews. 2017; 27(8):28-35. 

For the best mobile experience, rotate screen to landscape mode.

Have feedback on our new crossword puzzle? Share your thoughts at [email protected].

View Answers

This clinical puzzle is based on O’Neil. Diagnosing and classifying anemia in adult primary care. Clinician Reviews. 2017; 27(8):28-35. 

For the best mobile experience, rotate screen to landscape mode.

Have feedback on our new crossword puzzle? Share your thoughts at [email protected].

View Answers

The age at which a patient develops migraine with aura may be an important factor in assessing stroke risk, according to a prospective cohort study published in Headache.

DKart/iStockphoto

Patients who had onset of migraine with visual aura after age 50 years had an increased risk of ischemic stroke, compared with patients with no headache, the researchers found. Patients with longer exposure to migraine with visual aura – that is, onset before age 50 years – did not have significantly increased ischemic stroke risk, said X. Michelle Androulakis, MD, of the department of neurology at the University of South Carolina in Columbia, and her colleagues.

“Migraine, especially migraine with aura, is associated with increased risk of ischemic stroke,” but whether age of migraine onset affects the risk of cardiovascular disease has been unclear, the researchers said.

To examine the risk of ischemic stroke in migraineurs with and without aura with onset before and after age 50 years, the investigators conducted a post hoc analysis of data from the ongoing Atherosclerosis Risk in Communities (ARIC) study. The researchers adjusted for potential confounders, including diabetes, body mass index, hypertension, and hyperlipidemia.

In ARIC, participants completed a questionnaire about their migraine history at their third study visit (1993-1995) and were followed for ischemic stroke incidence over 20 years.

Of the 11,592 ARIC participants included in the analysis (mean age, 61 years; 76.5% white; and 55.3% female), 447 had migraine with aura, and 1,128 had migraine without aura. Onset of migraine with aura at age 50 years or older (average duration, 4.75 years) was associated with more than twofold greater risk of ischemic stroke, compared with no headache (multivariable adjusted hazard ratio = 2.17). Onset of migraine with aura before age 50 years (average duration, 28.17 years) was not significantly associated with stroke. A logistic regression model yielded consistent results.

In addition, patients with migraine without aura did not have an increased risk of stroke, regardless of the age of onset. The absolute risk for stroke in migraine with aura was 8.27%, and the absolute risk in migraine without aura was 4.25%.

“We found unexpected results suggesting that the onset of migraine with aura before age 50 is not associated with ischemic stroke. ... These results are specific to first-time ischemic stroke incidents that occurred in mid- to late life; therefore, it cannot be generalized to stroke in younger patients,” the authors wrote.

It could be that migraine with aura symptoms that start at a later age are a red flag for paradoxical emboli from a patent foramen ovale or microemboli, Dr. Androulakis and her colleagues noted. It also is possible that the degree of cortical spreading depression required to induce migraine with aura symptoms is different later in life versus earlier in life.

“This study underscores the importance of MA symptoms onset in evaluation of ischemic stroke risk in late life,” the researchers concluded.

The authors had no relevant conflicts of interest. ARIC has been funded by the National Heart, Lung, and Blood Institute.

[email protected]

SOURCE: Androulakis XM et al. Headache. 2019 Jan 21. doi: 10.1111/head.13468.

The age at which a patient develops migraine with aura may be an important factor in assessing stroke risk, according to a prospective cohort study published in Headache.

DKart/iStockphoto

Patients who had onset of migraine with visual aura after age 50 years had an increased risk of ischemic stroke, compared with patients with no headache, the researchers found. Patients with longer exposure to migraine with visual aura – that is, onset before age 50 years – did not have significantly increased ischemic stroke risk, said X. Michelle Androulakis, MD, of the department of neurology at the University of South Carolina in Columbia, and her colleagues.

“Migraine, especially migraine with aura, is associated with increased risk of ischemic stroke,” but whether age of migraine onset affects the risk of cardiovascular disease has been unclear, the researchers said.

To examine the risk of ischemic stroke in migraineurs with and without aura with onset before and after age 50 years, the investigators conducted a post hoc analysis of data from the ongoing Atherosclerosis Risk in Communities (ARIC) study. The researchers adjusted for potential confounders, including diabetes, body mass index, hypertension, and hyperlipidemia.

In ARIC, participants completed a questionnaire about their migraine history at their third study visit (1993-1995) and were followed for ischemic stroke incidence over 20 years.

Of the 11,592 ARIC participants included in the analysis (mean age, 61 years; 76.5% white; and 55.3% female), 447 had migraine with aura, and 1,128 had migraine without aura. Onset of migraine with aura at age 50 years or older (average duration, 4.75 years) was associated with more than twofold greater risk of ischemic stroke, compared with no headache (multivariable adjusted hazard ratio = 2.17). Onset of migraine with aura before age 50 years (average duration, 28.17 years) was not significantly associated with stroke. A logistic regression model yielded consistent results.

In addition, patients with migraine without aura did not have an increased risk of stroke, regardless of the age of onset. The absolute risk for stroke in migraine with aura was 8.27%, and the absolute risk in migraine without aura was 4.25%.

“We found unexpected results suggesting that the onset of migraine with aura before age 50 is not associated with ischemic stroke. ... These results are specific to first-time ischemic stroke incidents that occurred in mid- to late life; therefore, it cannot be generalized to stroke in younger patients,” the authors wrote.

It could be that migraine with aura symptoms that start at a later age are a red flag for paradoxical emboli from a patent foramen ovale or microemboli, Dr. Androulakis and her colleagues noted. It also is possible that the degree of cortical spreading depression required to induce migraine with aura symptoms is different later in life versus earlier in life.

“This study underscores the importance of MA symptoms onset in evaluation of ischemic stroke risk in late life,” the researchers concluded.

The authors had no relevant conflicts of interest. ARIC has been funded by the National Heart, Lung, and Blood Institute.

[email protected]

SOURCE: Androulakis XM et al. Headache. 2019 Jan 21. doi: 10.1111/head.13468.

The age at which a patient develops migraine with aura may be an important factor in assessing stroke risk, according to a prospective cohort study published in Headache.

DKart/iStockphoto

Patients who had onset of migraine with visual aura after age 50 years had an increased risk of ischemic stroke, compared with patients with no headache, the researchers found. Patients with longer exposure to migraine with visual aura – that is, onset before age 50 years – did not have significantly increased ischemic stroke risk, said X. Michelle Androulakis, MD, of the department of neurology at the University of South Carolina in Columbia, and her colleagues.

“Migraine, especially migraine with aura, is associated with increased risk of ischemic stroke,” but whether age of migraine onset affects the risk of cardiovascular disease has been unclear, the researchers said.

To examine the risk of ischemic stroke in migraineurs with and without aura with onset before and after age 50 years, the investigators conducted a post hoc analysis of data from the ongoing Atherosclerosis Risk in Communities (ARIC) study. The researchers adjusted for potential confounders, including diabetes, body mass index, hypertension, and hyperlipidemia.

In ARIC, participants completed a questionnaire about their migraine history at their third study visit (1993-1995) and were followed for ischemic stroke incidence over 20 years.

Of the 11,592 ARIC participants included in the analysis (mean age, 61 years; 76.5% white; and 55.3% female), 447 had migraine with aura, and 1,128 had migraine without aura. Onset of migraine with aura at age 50 years or older (average duration, 4.75 years) was associated with more than twofold greater risk of ischemic stroke, compared with no headache (multivariable adjusted hazard ratio = 2.17). Onset of migraine with aura before age 50 years (average duration, 28.17 years) was not significantly associated with stroke. A logistic regression model yielded consistent results.

In addition, patients with migraine without aura did not have an increased risk of stroke, regardless of the age of onset. The absolute risk for stroke in migraine with aura was 8.27%, and the absolute risk in migraine without aura was 4.25%.

“We found unexpected results suggesting that the onset of migraine with aura before age 50 is not associated with ischemic stroke. ... These results are specific to first-time ischemic stroke incidents that occurred in mid- to late life; therefore, it cannot be generalized to stroke in younger patients,” the authors wrote.

It could be that migraine with aura symptoms that start at a later age are a red flag for paradoxical emboli from a patent foramen ovale or microemboli, Dr. Androulakis and her colleagues noted. It also is possible that the degree of cortical spreading depression required to induce migraine with aura symptoms is different later in life versus earlier in life.

“This study underscores the importance of MA symptoms onset in evaluation of ischemic stroke risk in late life,” the researchers concluded.

The authors had no relevant conflicts of interest. ARIC has been funded by the National Heart, Lung, and Blood Institute.

[email protected]

SOURCE: Androulakis XM et al. Headache. 2019 Jan 21. doi: 10.1111/head.13468.

A majority of Americans support the concept of Medicare for all, but “larger majorities favor more incremental changes to the health care system,” according to a new survey by the Kaiser Family Foundation.

Support for a Medicare-for-all health care system came in at 56% (strongly favor, 34%; somewhat favor, 22%) among the 1,190 respondents to the latest KFF Health Tracking Poll, which was conducted Jan. 9-14, 2019. That support came largely from Democrats, 81% of whom favored the plan, compared with only 23% of Republicans, the Kaiser investigators said Jan. 23.

A Medicare buy-in plan for Americans aged 50-64 years also was highly popular, receiving support from 77% of all respondents – 85% of Democrats, 75% of Independents, and 69% of Republicans. Support by party identification was similar for a proposal to enable all those who don’t have employer-based insurance to get coverage through state Medicaid programs, which received 75% support overall, they reported.

Just behind those proposals at 74% support was a federally administered health plan that would be open to anyone but would allow people to keep the coverage they have. It was the most popular proposal among Democrats (91%) but did not garner a majority among Republicans (47%), the investigators said.

Support for the Medicare-for-all plan varied considerably, depending on number of arguments presented to respondents. When told that such a proposal would guarantee insurance as a right for all Americans, 71% favored it, and when they heard that it would eliminate health insurance premiums and reduce out-of-pockets costs, 67% of respondents expressed support. Favorable responses, however, were in the minority when people were told that Medicare-for-all would eliminate private health insurance companies (37%), threaten the current Medicare program (32%), and lead to some delayed medical tests and treatments (26%), according to the Kaiser report.

[email protected]

A majority of Americans support the concept of Medicare for all, but “larger majorities favor more incremental changes to the health care system,” according to a new survey by the Kaiser Family Foundation.

Support for a Medicare-for-all health care system came in at 56% (strongly favor, 34%; somewhat favor, 22%) among the 1,190 respondents to the latest KFF Health Tracking Poll, which was conducted Jan. 9-14, 2019. That support came largely from Democrats, 81% of whom favored the plan, compared with only 23% of Republicans, the Kaiser investigators said Jan. 23.

A Medicare buy-in plan for Americans aged 50-64 years also was highly popular, receiving support from 77% of all respondents – 85% of Democrats, 75% of Independents, and 69% of Republicans. Support by party identification was similar for a proposal to enable all those who don’t have employer-based insurance to get coverage through state Medicaid programs, which received 75% support overall, they reported.

Just behind those proposals at 74% support was a federally administered health plan that would be open to anyone but would allow people to keep the coverage they have. It was the most popular proposal among Democrats (91%) but did not garner a majority among Republicans (47%), the investigators said.

Support for the Medicare-for-all plan varied considerably, depending on number of arguments presented to respondents. When told that such a proposal would guarantee insurance as a right for all Americans, 71% favored it, and when they heard that it would eliminate health insurance premiums and reduce out-of-pockets costs, 67% of respondents expressed support. Favorable responses, however, were in the minority when people were told that Medicare-for-all would eliminate private health insurance companies (37%), threaten the current Medicare program (32%), and lead to some delayed medical tests and treatments (26%), according to the Kaiser report.

[email protected]

A majority of Americans support the concept of Medicare for all, but “larger majorities favor more incremental changes to the health care system,” according to a new survey by the Kaiser Family Foundation.

Support for a Medicare-for-all health care system came in at 56% (strongly favor, 34%; somewhat favor, 22%) among the 1,190 respondents to the latest KFF Health Tracking Poll, which was conducted Jan. 9-14, 2019. That support came largely from Democrats, 81% of whom favored the plan, compared with only 23% of Republicans, the Kaiser investigators said Jan. 23.

A Medicare buy-in plan for Americans aged 50-64 years also was highly popular, receiving support from 77% of all respondents – 85% of Democrats, 75% of Independents, and 69% of Republicans. Support by party identification was similar for a proposal to enable all those who don’t have employer-based insurance to get coverage through state Medicaid programs, which received 75% support overall, they reported.

Just behind those proposals at 74% support was a federally administered health plan that would be open to anyone but would allow people to keep the coverage they have. It was the most popular proposal among Democrats (91%) but did not garner a majority among Republicans (47%), the investigators said.

Support for the Medicare-for-all plan varied considerably, depending on number of arguments presented to respondents. When told that such a proposal would guarantee insurance as a right for all Americans, 71% favored it, and when they heard that it would eliminate health insurance premiums and reduce out-of-pockets costs, 67% of respondents expressed support. Favorable responses, however, were in the minority when people were told that Medicare-for-all would eliminate private health insurance companies (37%), threaten the current Medicare program (32%), and lead to some delayed medical tests and treatments (26%), according to the Kaiser report.

[email protected]

The ideas and opinions expressed in Best of 2018 – The RA Report: Top News Highlights do not necessarily reflect those of the publisher. Frontline Medical Communications will not assume responsibility for damages, loss, or claims of any kind arising from or related to the information contained in this publication, including any claims related to the products, drugs, or services mentioned herein.

The ideas and opinions expressed in Best of 2018 – The RA Report: Top News Highlights do not necessarily reflect those of the publisher. Frontline Medical Communications will not assume responsibility for damages, loss, or claims of any kind arising from or related to the information contained in this publication, including any claims related to the products, drugs, or services mentioned herein.

The ideas and opinions expressed in Best of 2018 – The RA Report: Top News Highlights do not necessarily reflect those of the publisher. Frontline Medical Communications will not assume responsibility for damages, loss, or claims of any kind arising from or related to the information contained in this publication, including any claims related to the products, drugs, or services mentioned herein.

This week, the FDA weighs in on concerning reports about paclitaxel-coated stents, and it approves a device to treat patent ductus arteriosus in infants weighing as little as 2 pounds. Also, a treat-to-target approach for CVD risk factors decreased atherosclerosis in rheumatoid arthritis patients, and ezetimibe was effective for primary prevention in elderly patients.

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This week, the FDA weighs in on concerning reports about paclitaxel-coated stents, and it approves a device to treat patent ductus arteriosus in infants weighing as little as 2 pounds. Also, a treat-to-target approach for CVD risk factors decreased atherosclerosis in rheumatoid arthritis patients, and ezetimibe was effective for primary prevention in elderly patients.

Subscribe to Cardiocast wherever you get your podcasts.
Amazon Alexa
Apple Podcasts






 

This week, the FDA weighs in on concerning reports about paclitaxel-coated stents, and it approves a device to treat patent ductus arteriosus in infants weighing as little as 2 pounds. Also, a treat-to-target approach for CVD risk factors decreased atherosclerosis in rheumatoid arthritis patients, and ezetimibe was effective for primary prevention in elderly patients.

Subscribe to Cardiocast wherever you get your podcasts.
Amazon Alexa
Apple Podcasts






 

Aspirin use is associated with a reduced risk of cardiovascular events among adults without cardiovascular disease, but this protection comes with a similarly increased risk for bleeding, according to data from a meta-analysis that included more than 1 million participant-years of follow-up.

©David Sucsy/iStockphoto

“The uncertain role of aspirin in primary prevention of cardiovascular events is reflected in contrasting recommendations offered by guideline bodies,” and has led to a decline in prescribing aspirin for primary prevention of such events, wrote Sean L. Zheng, MRCP, of Imperial College London (England) and his colleagues.

In a systematic review and meta-analysis published in JAMA, the researchers examined 13 randomized trials altogether including 164,225 participants and 1,050,511 participant-years of follow-up.

Overall, aspirin use significantly reduced a composite of cardiovascular outcomes, compared with no aspirin (hazard ratio, 0.89). The composite outcome included cardiovascular mortality, nonfatal myocardial infarction, and nonfatal stroke, and it occurred in 57.1 per 10,000 participant-years in aspirin users versus 61.4 per 10,000 participant-years among individuals who did not use aspirin. The absolute risk reduction was 0.38%.

The median age of the study participants was 62 years, and roughly half (47%) were male.

However, the risk of major bleeding events was significantly higher among aspirin users, compared with nonusers (23.1 per 10,000 participant-years and 16.4 per 10,000 participant-years, respectively), with a HR of 1.43 and an absolute risk increase of 0.47%.

Aspirin use was not associated with several secondary outcomes, including reductions in all-cause mortality or cardiovascular mortality, compared with no aspirin, but it was associated with a reduced risk specifically of myocardial infarction and ischemic stroke. Few deaths related to bleeding were reported.

The number needed to treat (265) and the number needed to harm (210) were similar, which emphasizes the need for an individual approach to treatment, the researchers noted.

“Consequently, the decision to use aspirin for primary prevention may need to be made on an individual basis, accounting for the patient’s risk of bleeding and their views on the balance of risk vs. benefit,” they concluded.

The researchers had no financial conflicts to disclose.

SOURCE: Zheng SL et al. JAMA. 2019;321(3):277-87.

Aspirin use is associated with a reduced risk of cardiovascular events among adults without cardiovascular disease, but this protection comes with a similarly increased risk for bleeding, according to data from a meta-analysis that included more than 1 million participant-years of follow-up.

©David Sucsy/iStockphoto

“The uncertain role of aspirin in primary prevention of cardiovascular events is reflected in contrasting recommendations offered by guideline bodies,” and has led to a decline in prescribing aspirin for primary prevention of such events, wrote Sean L. Zheng, MRCP, of Imperial College London (England) and his colleagues.

In a systematic review and meta-analysis published in JAMA, the researchers examined 13 randomized trials altogether including 164,225 participants and 1,050,511 participant-years of follow-up.

Overall, aspirin use significantly reduced a composite of cardiovascular outcomes, compared with no aspirin (hazard ratio, 0.89). The composite outcome included cardiovascular mortality, nonfatal myocardial infarction, and nonfatal stroke, and it occurred in 57.1 per 10,000 participant-years in aspirin users versus 61.4 per 10,000 participant-years among individuals who did not use aspirin. The absolute risk reduction was 0.38%.

The median age of the study participants was 62 years, and roughly half (47%) were male.

However, the risk of major bleeding events was significantly higher among aspirin users, compared with nonusers (23.1 per 10,000 participant-years and 16.4 per 10,000 participant-years, respectively), with a HR of 1.43 and an absolute risk increase of 0.47%.

Aspirin use was not associated with several secondary outcomes, including reductions in all-cause mortality or cardiovascular mortality, compared with no aspirin, but it was associated with a reduced risk specifically of myocardial infarction and ischemic stroke. Few deaths related to bleeding were reported.

The number needed to treat (265) and the number needed to harm (210) were similar, which emphasizes the need for an individual approach to treatment, the researchers noted.

“Consequently, the decision to use aspirin for primary prevention may need to be made on an individual basis, accounting for the patient’s risk of bleeding and their views on the balance of risk vs. benefit,” they concluded.

The researchers had no financial conflicts to disclose.

SOURCE: Zheng SL et al. JAMA. 2019;321(3):277-87.

Aspirin use is associated with a reduced risk of cardiovascular events among adults without cardiovascular disease, but this protection comes with a similarly increased risk for bleeding, according to data from a meta-analysis that included more than 1 million participant-years of follow-up.

©David Sucsy/iStockphoto

“The uncertain role of aspirin in primary prevention of cardiovascular events is reflected in contrasting recommendations offered by guideline bodies,” and has led to a decline in prescribing aspirin for primary prevention of such events, wrote Sean L. Zheng, MRCP, of Imperial College London (England) and his colleagues.

In a systematic review and meta-analysis published in JAMA, the researchers examined 13 randomized trials altogether including 164,225 participants and 1,050,511 participant-years of follow-up.

Overall, aspirin use significantly reduced a composite of cardiovascular outcomes, compared with no aspirin (hazard ratio, 0.89). The composite outcome included cardiovascular mortality, nonfatal myocardial infarction, and nonfatal stroke, and it occurred in 57.1 per 10,000 participant-years in aspirin users versus 61.4 per 10,000 participant-years among individuals who did not use aspirin. The absolute risk reduction was 0.38%.

The median age of the study participants was 62 years, and roughly half (47%) were male.

However, the risk of major bleeding events was significantly higher among aspirin users, compared with nonusers (23.1 per 10,000 participant-years and 16.4 per 10,000 participant-years, respectively), with a HR of 1.43 and an absolute risk increase of 0.47%.

Aspirin use was not associated with several secondary outcomes, including reductions in all-cause mortality or cardiovascular mortality, compared with no aspirin, but it was associated with a reduced risk specifically of myocardial infarction and ischemic stroke. Few deaths related to bleeding were reported.

The number needed to treat (265) and the number needed to harm (210) were similar, which emphasizes the need for an individual approach to treatment, the researchers noted.

“Consequently, the decision to use aspirin for primary prevention may need to be made on an individual basis, accounting for the patient’s risk of bleeding and their views on the balance of risk vs. benefit,” they concluded.

The researchers had no financial conflicts to disclose.

SOURCE: Zheng SL et al. JAMA. 2019;321(3):277-87.

SAN FRANCISCO – Simultaneously targeting two components of the same signaling pathway in BRAF V600E–mutated biliary tract cancer is a winning strategy, suggests an analysis of the multicenter phase 2 ROAR basket trial.

Susan London/MDedge News

“Recently, a number of genetic targets have been identified with distinct rates of frequency in intrahepatic, extrahepatic, and gallbladder cancer that are the subject of a number of ongoing clinical trials. In retrospective studies, mutations in BRAF have been identified in about 5%-7% of patients, predominantly in the intrahepatic cohort,” lead investigator Zev A. Wainberg, MD, noted at the 2019 GI Cancers Symposium. Previous research has shown combined inhibition of BRAF and MEK – two sequential proteins on the MAP kinase signaling pathway – to be efficacious in BRAF V600E–mutated melanoma, non–small cell lung cancer, and anaplastic thyroid cancer.

In the ROAR trial, 178 patients with advanced or metastatic BRAF V600E–mutated rare cancers who had exhausted standard treatment options were treated with the combination of the BRAF inhibitor dabrafenib (Tafinlar) and the MEK inhibitor trametinib (Mekinist). Dr. Wainberg reported results for the 35 patients having biliary tract cancer, most of whom were heavily pretreated.

With a median duration of follow-up of 8 months, the overall response rate was 42% as assessed by investigators and 36% as assessed by independent reviewers. More than half of patients had a grade 3 or 4 adverse event, but just one had to permanently stop treatment because of toxicity.

“These results represent the first prospectively analyzed cohort of patients with BRAF V600E–mutated biliary tract cancers treated with the combination of BRAF and MEK inhibition. Efficacy in this patient population with advanced disease was comparable to that of first-line chemotherapy with gemcitabine and cisplatin,” pointed out Dr. Wainberg, codirector of the GI oncology program and an assistant professor of medicine at the University of California, Los Angeles.

“Dabrafenib and trametinib demonstrated clinical benefit in patients with BRAF-mutant biliary tract cancers and should be considered a meaningful therapeutic option for these patients,” he contended. “BRAF V600E is one of several actionable driver mutations in this disease and should be considered for routine testing in patients with biliary tract cancers. In addition, among all the other data [that are] emerging in molecular analysis of this malignancy, perhaps among all the GI malignancies, this has the potential to undergo multiple studies of other targeted therapies.”
 

Why stop there?

“I don’t think there is anything needed to convince you that this treatment is very effective. It’s incredibly impressive,” commented invited discussant Heinz-Josef Lenz, MD, associate director for adult oncology and coleader of the gastrointestinal cancers program, University of Southern California Norris Comprehensive Cancer Center in Los Angeles.

Susan London/MDedge News

But experience with other BRAF-mutant malignancies, such as BRAF-mutant colorectal cancer, suggests that further benefit can accrue from hitting additional molecular targets, he said. For example, rationally selected triplet combinations can suppress emergence of resistant clones up front.

“How can we do even better? I think we need to be smart in how we inhibit downstream signaling of BRAF-mutant disease,” Dr. Lenz maintained, as downstream targeting is potentially more effective. Therefore, a logical candidate for improving on the combination of BRAF and MEK inhibitors in biliary tract cancer is an ERK inhibitor. Alternatively, the combination may be synergistic when used with immune checkpoint inhibitors that target programmed death-1 or programmed death–ligand 1.

Oncologists should perform next-generation sequencing for all patients with biliary tract cancer, in Dr. Lenz’s opinion. “Biliary cancer is one of these cancers where we have many potentially actionable mutations. I know there is no drug approved, but many trials are ongoing,” he elaborated. “So I just encourage you to do that in order to identify potential trials or treatment options.”
 

Study details

In the ROAR trial, patients received open-label dabrafenib (150 mg, twice daily) plus trametinib (2 mg, once daily) until unacceptable toxicity, disease progression, or death.

All 35 patients with biliary cancer had received gemcitabine, and 80% had received at least two lines of prior systemic therapy.

The median treatment duration was 6 months, Dr. Wainberg reported at the symposium, sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology. Fully 86% of patients were on treatment for longer than 3 months.

In addition to the impressive response rates, the patients had a median progression-free survival of 9.2 months, and a median overall survival of 11.7 months.

Adverse events were as expected based on previous experience with these targeted therapies, according to Dr. Wainberg. The rate of grade 3 or 4 adverse events was 57%. “These were predominantly pyrexia, a known side effect of BRAF inhibitors, which is managed with antipyretic therapy and dexamethasone,” he noted. Rash and gastrointestinal toxicity were also common.

Although adverse events often led to dose reductions and dose interruptions, only a single patient (3% of the cohort) had to stop treatment early because of an event (cholangitis).
 

SOURCE: Wainberg ZA et al. 2019 GI Cancers Symposium, Abstract 187.

SAN FRANCISCO – Simultaneously targeting two components of the same signaling pathway in BRAF V600E–mutated biliary tract cancer is a winning strategy, suggests an analysis of the multicenter phase 2 ROAR basket trial.

Susan London/MDedge News

“Recently, a number of genetic targets have been identified with distinct rates of frequency in intrahepatic, extrahepatic, and gallbladder cancer that are the subject of a number of ongoing clinical trials. In retrospective studies, mutations in BRAF have been identified in about 5%-7% of patients, predominantly in the intrahepatic cohort,” lead investigator Zev A. Wainberg, MD, noted at the 2019 GI Cancers Symposium. Previous research has shown combined inhibition of BRAF and MEK – two sequential proteins on the MAP kinase signaling pathway – to be efficacious in BRAF V600E–mutated melanoma, non–small cell lung cancer, and anaplastic thyroid cancer.

In the ROAR trial, 178 patients with advanced or metastatic BRAF V600E–mutated rare cancers who had exhausted standard treatment options were treated with the combination of the BRAF inhibitor dabrafenib (Tafinlar) and the MEK inhibitor trametinib (Mekinist). Dr. Wainberg reported results for the 35 patients having biliary tract cancer, most of whom were heavily pretreated.

With a median duration of follow-up of 8 months, the overall response rate was 42% as assessed by investigators and 36% as assessed by independent reviewers. More than half of patients had a grade 3 or 4 adverse event, but just one had to permanently stop treatment because of toxicity.

“These results represent the first prospectively analyzed cohort of patients with BRAF V600E–mutated biliary tract cancers treated with the combination of BRAF and MEK inhibition. Efficacy in this patient population with advanced disease was comparable to that of first-line chemotherapy with gemcitabine and cisplatin,” pointed out Dr. Wainberg, codirector of the GI oncology program and an assistant professor of medicine at the University of California, Los Angeles.

“Dabrafenib and trametinib demonstrated clinical benefit in patients with BRAF-mutant biliary tract cancers and should be considered a meaningful therapeutic option for these patients,” he contended. “BRAF V600E is one of several actionable driver mutations in this disease and should be considered for routine testing in patients with biliary tract cancers. In addition, among all the other data [that are] emerging in molecular analysis of this malignancy, perhaps among all the GI malignancies, this has the potential to undergo multiple studies of other targeted therapies.”
 

Why stop there?

“I don’t think there is anything needed to convince you that this treatment is very effective. It’s incredibly impressive,” commented invited discussant Heinz-Josef Lenz, MD, associate director for adult oncology and coleader of the gastrointestinal cancers program, University of Southern California Norris Comprehensive Cancer Center in Los Angeles.

Susan London/MDedge News

But experience with other BRAF-mutant malignancies, such as BRAF-mutant colorectal cancer, suggests that further benefit can accrue from hitting additional molecular targets, he said. For example, rationally selected triplet combinations can suppress emergence of resistant clones up front.

“How can we do even better? I think we need to be smart in how we inhibit downstream signaling of BRAF-mutant disease,” Dr. Lenz maintained, as downstream targeting is potentially more effective. Therefore, a logical candidate for improving on the combination of BRAF and MEK inhibitors in biliary tract cancer is an ERK inhibitor. Alternatively, the combination may be synergistic when used with immune checkpoint inhibitors that target programmed death-1 or programmed death–ligand 1.

Oncologists should perform next-generation sequencing for all patients with biliary tract cancer, in Dr. Lenz’s opinion. “Biliary cancer is one of these cancers where we have many potentially actionable mutations. I know there is no drug approved, but many trials are ongoing,” he elaborated. “So I just encourage you to do that in order to identify potential trials or treatment options.”
 

Study details

In the ROAR trial, patients received open-label dabrafenib (150 mg, twice daily) plus trametinib (2 mg, once daily) until unacceptable toxicity, disease progression, or death.

All 35 patients with biliary cancer had received gemcitabine, and 80% had received at least two lines of prior systemic therapy.

The median treatment duration was 6 months, Dr. Wainberg reported at the symposium, sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology. Fully 86% of patients were on treatment for longer than 3 months.

In addition to the impressive response rates, the patients had a median progression-free survival of 9.2 months, and a median overall survival of 11.7 months.

Adverse events were as expected based on previous experience with these targeted therapies, according to Dr. Wainberg. The rate of grade 3 or 4 adverse events was 57%. “These were predominantly pyrexia, a known side effect of BRAF inhibitors, which is managed with antipyretic therapy and dexamethasone,” he noted. Rash and gastrointestinal toxicity were also common.

Although adverse events often led to dose reductions and dose interruptions, only a single patient (3% of the cohort) had to stop treatment early because of an event (cholangitis).
 

SOURCE: Wainberg ZA et al. 2019 GI Cancers Symposium, Abstract 187.

SAN FRANCISCO – Simultaneously targeting two components of the same signaling pathway in BRAF V600E–mutated biliary tract cancer is a winning strategy, suggests an analysis of the multicenter phase 2 ROAR basket trial.

Susan London/MDedge News

“Recently, a number of genetic targets have been identified with distinct rates of frequency in intrahepatic, extrahepatic, and gallbladder cancer that are the subject of a number of ongoing clinical trials. In retrospective studies, mutations in BRAF have been identified in about 5%-7% of patients, predominantly in the intrahepatic cohort,” lead investigator Zev A. Wainberg, MD, noted at the 2019 GI Cancers Symposium. Previous research has shown combined inhibition of BRAF and MEK – two sequential proteins on the MAP kinase signaling pathway – to be efficacious in BRAF V600E–mutated melanoma, non–small cell lung cancer, and anaplastic thyroid cancer.

In the ROAR trial, 178 patients with advanced or metastatic BRAF V600E–mutated rare cancers who had exhausted standard treatment options were treated with the combination of the BRAF inhibitor dabrafenib (Tafinlar) and the MEK inhibitor trametinib (Mekinist). Dr. Wainberg reported results for the 35 patients having biliary tract cancer, most of whom were heavily pretreated.

With a median duration of follow-up of 8 months, the overall response rate was 42% as assessed by investigators and 36% as assessed by independent reviewers. More than half of patients had a grade 3 or 4 adverse event, but just one had to permanently stop treatment because of toxicity.

“These results represent the first prospectively analyzed cohort of patients with BRAF V600E–mutated biliary tract cancers treated with the combination of BRAF and MEK inhibition. Efficacy in this patient population with advanced disease was comparable to that of first-line chemotherapy with gemcitabine and cisplatin,” pointed out Dr. Wainberg, codirector of the GI oncology program and an assistant professor of medicine at the University of California, Los Angeles.

“Dabrafenib and trametinib demonstrated clinical benefit in patients with BRAF-mutant biliary tract cancers and should be considered a meaningful therapeutic option for these patients,” he contended. “BRAF V600E is one of several actionable driver mutations in this disease and should be considered for routine testing in patients with biliary tract cancers. In addition, among all the other data [that are] emerging in molecular analysis of this malignancy, perhaps among all the GI malignancies, this has the potential to undergo multiple studies of other targeted therapies.”
 

Why stop there?

“I don’t think there is anything needed to convince you that this treatment is very effective. It’s incredibly impressive,” commented invited discussant Heinz-Josef Lenz, MD, associate director for adult oncology and coleader of the gastrointestinal cancers program, University of Southern California Norris Comprehensive Cancer Center in Los Angeles.

Susan London/MDedge News

But experience with other BRAF-mutant malignancies, such as BRAF-mutant colorectal cancer, suggests that further benefit can accrue from hitting additional molecular targets, he said. For example, rationally selected triplet combinations can suppress emergence of resistant clones up front.

“How can we do even better? I think we need to be smart in how we inhibit downstream signaling of BRAF-mutant disease,” Dr. Lenz maintained, as downstream targeting is potentially more effective. Therefore, a logical candidate for improving on the combination of BRAF and MEK inhibitors in biliary tract cancer is an ERK inhibitor. Alternatively, the combination may be synergistic when used with immune checkpoint inhibitors that target programmed death-1 or programmed death–ligand 1.

Oncologists should perform next-generation sequencing for all patients with biliary tract cancer, in Dr. Lenz’s opinion. “Biliary cancer is one of these cancers where we have many potentially actionable mutations. I know there is no drug approved, but many trials are ongoing,” he elaborated. “So I just encourage you to do that in order to identify potential trials or treatment options.”
 

Study details

In the ROAR trial, patients received open-label dabrafenib (150 mg, twice daily) plus trametinib (2 mg, once daily) until unacceptable toxicity, disease progression, or death.

All 35 patients with biliary cancer had received gemcitabine, and 80% had received at least two lines of prior systemic therapy.

The median treatment duration was 6 months, Dr. Wainberg reported at the symposium, sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology. Fully 86% of patients were on treatment for longer than 3 months.

In addition to the impressive response rates, the patients had a median progression-free survival of 9.2 months, and a median overall survival of 11.7 months.

Adverse events were as expected based on previous experience with these targeted therapies, according to Dr. Wainberg. The rate of grade 3 or 4 adverse events was 57%. “These were predominantly pyrexia, a known side effect of BRAF inhibitors, which is managed with antipyretic therapy and dexamethasone,” he noted. Rash and gastrointestinal toxicity were also common.

Although adverse events often led to dose reductions and dose interruptions, only a single patient (3% of the cohort) had to stop treatment early because of an event (cholangitis).
 

SOURCE: Wainberg ZA et al. 2019 GI Cancers Symposium, Abstract 187.