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Top US Oncology Regulator Seeks Changes in Drug Studies
Richard Pazdur, MD, who leads the cancer division at the US Food and Drug Administration (FDA), said there’s a need to simplify the paperwork involved in clinical trials. Before joining the FDA in 1999, Dr. Pazdur participated in and published cancer research. He says the informed consent forms used for studies have grown too elaborate over the years, such that they can intimidate even experts.
“When I read informed consents now in clinical trials, folks, it gives me a headache. Okay, I can’t follow them,” Dr. Pazdur said.
Dr. Pazdur said informed consent forms can be “mind-boggling” these days.
“They’re so damn complicated with so many damn questions being answered,” he said. “So our point is what’s the essential question that you need answered and what’s the quickest way of answering that question with the least amount of data that can be collected?”
Dr. Pazdur made these comments during a joint meeting of the FDA and the European Medicines Agency (EMA).
The meeting was a broad discussion about how to build on the successes seen in treatment of blood cancers in the past two decades. No formal recommendations were introduced or considered at the meeting. Instead, the meeting served as a chance for oncologists and patients to discuss ways to more quickly and efficiently address the key questions in drug research: Do medicines deliver a significant benefit to patients?
Dr. Pazdur also said at the meeting that there needs to be a way to attract more people to enroll in clinical trials.
“When I started in oncology, it was about 5%. When I’m sitting here now, 40 years later, it’s 5%. Basically it hasn’t moved,” he said at the discussion, held on February 1.
Ellin Berman, MD, of Memorial Sloan Kettering Cancer Center in New York, spoke at the meeting about the changes she has witnessed in her career in oncology. Until 2001, there were limited drug options, and physicians tried to get patients to transplant teams as possible. Then the FDA in 2001 approved imatinib to treat patients with chronic myelogenous leukemia (CML) that has the Philadelphia chromosome. That set the stage, Dr. Berman said, for a sea change in treatment of CML.
“The fellows now have no idea what it is like to talk to a CML patient about transplant and the question is which among the treasures we have of drugs do we start people on? And that’s always a conversation,” Dr. Berman said.
She noted that advances in treatment have also let some female patients get pregnant and have children.
“We have at least half a dozen women who bring their kids to clinic. And boy, if that doesn’t bring tears to our eyes, our collective eyes, I don’t know what does,” she said.
Dr. Pazdur also recalled his experience treating patients in the 1970s and 1980s for cancers for which “you had nothing so to speak” in terms of effective treatment.
“So then ask yourself the question, what would their stories be now?” with the many options available, Dr. Pazdur said.
Seeking clinician feedback
To try to improve the development and testing of cancer drugs, the FDA is seeking to get more feedback from clinicians about which questions trials should address, Dr. Pazdur said.
The agency is considering a way to poll clinicians on what their most crucial questions are about the medicines, he said. Better design of trial questions might serve to improve enrollment in studies.
“What we’re thinking of doing is taking the common disease areas and asking clinicians what are the five basic questions that you want answered in the next 5 years,” he said.
He cited PD-1 drugs as a possible example of a class where regulators could consider new approaches. There could be a discussion about the safety data collection for this class of drugs, which has been used by millions of patients.
Dr. Pazdur said he has been discussing these kinds of themes with his European and Japanese counterparts, who also are interested in simplifying clinical trials.
The goal is to have trials better represent real-world experiences rather than “artificial” ones created when patients must meet extensive eligibility requirements. Improved use of emerging technologies could aid in the needed streamlining, Dr. Pazdur said.
“As an oncology community, we have made our lives somewhat too complicated and need to draw back and ask the basic questions,” Dr. Pazdur said.
Richard Pazdur, MD, who leads the cancer division at the US Food and Drug Administration (FDA), said there’s a need to simplify the paperwork involved in clinical trials. Before joining the FDA in 1999, Dr. Pazdur participated in and published cancer research. He says the informed consent forms used for studies have grown too elaborate over the years, such that they can intimidate even experts.
“When I read informed consents now in clinical trials, folks, it gives me a headache. Okay, I can’t follow them,” Dr. Pazdur said.
Dr. Pazdur said informed consent forms can be “mind-boggling” these days.
“They’re so damn complicated with so many damn questions being answered,” he said. “So our point is what’s the essential question that you need answered and what’s the quickest way of answering that question with the least amount of data that can be collected?”
Dr. Pazdur made these comments during a joint meeting of the FDA and the European Medicines Agency (EMA).
The meeting was a broad discussion about how to build on the successes seen in treatment of blood cancers in the past two decades. No formal recommendations were introduced or considered at the meeting. Instead, the meeting served as a chance for oncologists and patients to discuss ways to more quickly and efficiently address the key questions in drug research: Do medicines deliver a significant benefit to patients?
Dr. Pazdur also said at the meeting that there needs to be a way to attract more people to enroll in clinical trials.
“When I started in oncology, it was about 5%. When I’m sitting here now, 40 years later, it’s 5%. Basically it hasn’t moved,” he said at the discussion, held on February 1.
Ellin Berman, MD, of Memorial Sloan Kettering Cancer Center in New York, spoke at the meeting about the changes she has witnessed in her career in oncology. Until 2001, there were limited drug options, and physicians tried to get patients to transplant teams as possible. Then the FDA in 2001 approved imatinib to treat patients with chronic myelogenous leukemia (CML) that has the Philadelphia chromosome. That set the stage, Dr. Berman said, for a sea change in treatment of CML.
“The fellows now have no idea what it is like to talk to a CML patient about transplant and the question is which among the treasures we have of drugs do we start people on? And that’s always a conversation,” Dr. Berman said.
She noted that advances in treatment have also let some female patients get pregnant and have children.
“We have at least half a dozen women who bring their kids to clinic. And boy, if that doesn’t bring tears to our eyes, our collective eyes, I don’t know what does,” she said.
Dr. Pazdur also recalled his experience treating patients in the 1970s and 1980s for cancers for which “you had nothing so to speak” in terms of effective treatment.
“So then ask yourself the question, what would their stories be now?” with the many options available, Dr. Pazdur said.
Seeking clinician feedback
To try to improve the development and testing of cancer drugs, the FDA is seeking to get more feedback from clinicians about which questions trials should address, Dr. Pazdur said.
The agency is considering a way to poll clinicians on what their most crucial questions are about the medicines, he said. Better design of trial questions might serve to improve enrollment in studies.
“What we’re thinking of doing is taking the common disease areas and asking clinicians what are the five basic questions that you want answered in the next 5 years,” he said.
He cited PD-1 drugs as a possible example of a class where regulators could consider new approaches. There could be a discussion about the safety data collection for this class of drugs, which has been used by millions of patients.
Dr. Pazdur said he has been discussing these kinds of themes with his European and Japanese counterparts, who also are interested in simplifying clinical trials.
The goal is to have trials better represent real-world experiences rather than “artificial” ones created when patients must meet extensive eligibility requirements. Improved use of emerging technologies could aid in the needed streamlining, Dr. Pazdur said.
“As an oncology community, we have made our lives somewhat too complicated and need to draw back and ask the basic questions,” Dr. Pazdur said.
Richard Pazdur, MD, who leads the cancer division at the US Food and Drug Administration (FDA), said there’s a need to simplify the paperwork involved in clinical trials. Before joining the FDA in 1999, Dr. Pazdur participated in and published cancer research. He says the informed consent forms used for studies have grown too elaborate over the years, such that they can intimidate even experts.
“When I read informed consents now in clinical trials, folks, it gives me a headache. Okay, I can’t follow them,” Dr. Pazdur said.
Dr. Pazdur said informed consent forms can be “mind-boggling” these days.
“They’re so damn complicated with so many damn questions being answered,” he said. “So our point is what’s the essential question that you need answered and what’s the quickest way of answering that question with the least amount of data that can be collected?”
Dr. Pazdur made these comments during a joint meeting of the FDA and the European Medicines Agency (EMA).
The meeting was a broad discussion about how to build on the successes seen in treatment of blood cancers in the past two decades. No formal recommendations were introduced or considered at the meeting. Instead, the meeting served as a chance for oncologists and patients to discuss ways to more quickly and efficiently address the key questions in drug research: Do medicines deliver a significant benefit to patients?
Dr. Pazdur also said at the meeting that there needs to be a way to attract more people to enroll in clinical trials.
“When I started in oncology, it was about 5%. When I’m sitting here now, 40 years later, it’s 5%. Basically it hasn’t moved,” he said at the discussion, held on February 1.
Ellin Berman, MD, of Memorial Sloan Kettering Cancer Center in New York, spoke at the meeting about the changes she has witnessed in her career in oncology. Until 2001, there were limited drug options, and physicians tried to get patients to transplant teams as possible. Then the FDA in 2001 approved imatinib to treat patients with chronic myelogenous leukemia (CML) that has the Philadelphia chromosome. That set the stage, Dr. Berman said, for a sea change in treatment of CML.
“The fellows now have no idea what it is like to talk to a CML patient about transplant and the question is which among the treasures we have of drugs do we start people on? And that’s always a conversation,” Dr. Berman said.
She noted that advances in treatment have also let some female patients get pregnant and have children.
“We have at least half a dozen women who bring their kids to clinic. And boy, if that doesn’t bring tears to our eyes, our collective eyes, I don’t know what does,” she said.
Dr. Pazdur also recalled his experience treating patients in the 1970s and 1980s for cancers for which “you had nothing so to speak” in terms of effective treatment.
“So then ask yourself the question, what would their stories be now?” with the many options available, Dr. Pazdur said.
Seeking clinician feedback
To try to improve the development and testing of cancer drugs, the FDA is seeking to get more feedback from clinicians about which questions trials should address, Dr. Pazdur said.
The agency is considering a way to poll clinicians on what their most crucial questions are about the medicines, he said. Better design of trial questions might serve to improve enrollment in studies.
“What we’re thinking of doing is taking the common disease areas and asking clinicians what are the five basic questions that you want answered in the next 5 years,” he said.
He cited PD-1 drugs as a possible example of a class where regulators could consider new approaches. There could be a discussion about the safety data collection for this class of drugs, which has been used by millions of patients.
Dr. Pazdur said he has been discussing these kinds of themes with his European and Japanese counterparts, who also are interested in simplifying clinical trials.
The goal is to have trials better represent real-world experiences rather than “artificial” ones created when patients must meet extensive eligibility requirements. Improved use of emerging technologies could aid in the needed streamlining, Dr. Pazdur said.
“As an oncology community, we have made our lives somewhat too complicated and need to draw back and ask the basic questions,” Dr. Pazdur said.
Hematology is in the Brodsky family’s blood
In interviews, Robert and Max Brodsky spoke about the appeal of hematology and the threads that unite them with family members who came before. The elder Brodsky also talked about the work that’s made him the proudest during his year-long presidency at ASH.
Robert A. Brodsky is professor of medicine and director of hematology at Johns Hopkins University, Baltimore. He is stepping down as ASH president at its annual meeting in San Diego, December 9-12. Here are excerpts from our conversation:
Q: What drew your dad into medicine?
Dr. Robert A. Brodsky: He was going through his medical training at the University of Pennsylvania, then the Vietnam War came, and he served at the National Institutes of Health in what they referred to as the Yellow Berets. He got very interested in retroviruses and viruses that lead to cancer, which was a foreign idea at the time. This led him into hematology, stem cells, and myeloproliferative disorders.
He had a very successful career in hematology and just loved it. He performed the first bone marrow transplant in the tristate area of Pennsylvania, Delaware, and New Jersey.
Q: What did he like about hematology specifically?
Dr. Robert A. Brodsky: It’s a fascinating field, probably the most scientific area of medicine. It’s so easy to access blood and bone marrow. You can grow it, you can look at it, you can see it. It’s hard to do that with a lung, heart, kidney, or brain. Even back then, they could translate some of the science. What really drew him to hematology — and me, for that matter — was looking at a blood smear or bone marrow and being able to make a diagnosis. The other thing is the personal aspect. Hematologists tend to like the long-term relationships that they develop with their patients over the years.
Q: What were the biggest transformations in hematology during his career?
Dr. Robert A. Brodsky: Bone marrow transplant had the biggest impact, and it’s an area he really pioneered. He was very much involved in some of the early bone marrow transplants and was very close with Dr. George W. Santos, who was at Johns Hopkins and one of the big pioneers in that area as well. To be able to take marrow from related donors, get it to grow without the patient rejecting it, and cure a disease, was really huge. When he started doing this, patients had no other option. To see patients be cured was incredibly satisfying to him.
Q: How did you end up following your father into hematology?
Dr. Robert A. Brodsky: My brother Jeff, who’s a surgeon and older than me, knew he was going into medicine — probably about 3 hours after he was born. I came to it late. I was a political science major as an undergrad and really trying to figure out what I wanted to do. In my sophomore year, I decided I wanted to give this a shot. My dad worked very hard, long hours, but you could tell he loved what he did. And he was never absent, always involved in our lives and still made time for everyone. At some level, that must have had an influence on me.
Q: What has changed in hematology over your 30-plus years in medicine?
A: When I look back at when I was a fellow, it’s just mind-boggling how many lethal or life-threatening diseases are now pretty easy to treat. I studied disorders like aplastic anemia, which was very fatal. Without treatment, patients would die within a year. Now, over 95% are cured. Another classic examples is chronic myeloid leukemia disorder. Back when I was a fellow, the median survival for CML was maybe 4 to 6 years. Now, Kareem Abdul Jabbar has had this[for about 15 years]. Also a lot of hematologic malignancies are being cured with immunotherapy approaches. We’ve figured out the pathophysiology of a lot of diseases, and there are incredible genetic diagnostic assays.
Q: What was your father’s relationship with ASH?
Dr. Robert A. Brodsky: The first ASH meeting was 1958 in Atlantic City, New Jersey. There were 300 hematologists there, and my dad was one of them. We’re going to have over 30,000 people in San Diego, which is a record, and another 5,000 or 6,000 virtually.
Q: As ASH president, what are your biggest accomplishments when it comes to addressing the shortage of hematologists and other issues?
Dr. Robert A. Brodsky: ASH is investing $19 million to develop fellowships with a focus on hematology.* This is going to put lots of new hematologists into the workforce over the next 5 to 10 years. We’ve also been working on the Maintenance of Certification [MOC] process to make it less onerous on physicians. It’s really a bad process, and it’s not just ASH [that’s complaining], it’s all of medicine. We’re hearing this from GI, endocrine, renal and the general internists.
[In a September 2023 letter to the American Board of Internal Medicine’s president and chief officer, Dr. Brodsky wrote that “ASH continues to support the importance of lifelong learning for hematologists via a program that is evidence-based, relevant to one’s practice, and transparent; however, these three basic requirements are not met by the current ABIM MOC program.” ASH is calling for a new and reformed MOC program.]
Q: What convinced ASH to expand its journals by adding Blood Neoplasia and Blood Vessels, Thrombosis & Hemostasis?
Dr. Robert A. Brodsky: ASH has two flagship journals right now, Blood and Blood Advances, and they’re both very competitive, high-impact journals. It turns out there’s not enough room to publish all the new science, and they end up rejecting the majority of the submissions that come to them. We decided to keep these journals in the ASH family because there’s some fantastic clinical trials and science that would be going elsewhere.
Dr. Brodsky’s sons both have medical degrees: Brett Brodsky, DO, is a resident at Virginia Commonwealth University who plans to become a sports medicine specialist, and Max Brodsky, MD, is a second-year fellow in hematology at Johns Hopkins University.
In an interview, Max Brodsky, MD, talked about the roots of his family’s dedication to caring for others.
Q: What drew you to hematology?
Dr. Max Brodsky: I’ve watched both my dad and my grandfather be leaders in the field as both physicians and scientists, and that was very inspirational for me to see. And I went to a medical school [Drexel University College of Medicine] that my dad went to and where my grandfather was on faculty. That was like walking in their footsteps in a major way.
Q: What do you hope to focus on as a hematologist?
Dr. Max Brodsky: I’m still working through that, but I am really interested in thrombotic thrombocytopenic purpura. Patients used to not be able to survive their initial episodes, but now we have good treatments and are able to follow them as outpatients. With this whole cohort of patients that are surviving, we’re seeing that they have more health problems — more heart disease, more strokes and kidney disease. There’s a whole growing field exploring how to treat these patients for their lifespan.
Q: How do you deal with the reality that more of your patients will die than in some other medical fields?
Dr. Max Brodsky: It is challenging, but I also see those moments as opportunities to support patients and families. I’m good at connecting to patients and families who are in scary situations. I’ve always had that skill of putting people at ease, making people feel calm, knowing that they can trust me, and I have their best interests in mind.
Q: Why do you think your family is so committed to medicine?
Dr. Max Brodsky: We’re Jewish, and looking to help the world is one of the main core values of Judaism. The Torah expects us to make this world better. Actually, my great-grandfather Max, whom I’m named after, used to dig tunnels to help people escape Ukraine and get to freedom. He was always looking to help others as well. My great-grandmother was shot crossing the border escaping from Ukraine, and he carried her the whole way to the boat. They lived in very poor West Philadelphia and poured everything into my grandfather. He became a great doctor, and his sons and his grandchildren are in medicine today.
*Correction, 12/11: A previous version of this story misstated the amount of ASH’s $19 million investment in developing fellowships with a focus on hematology.
In interviews, Robert and Max Brodsky spoke about the appeal of hematology and the threads that unite them with family members who came before. The elder Brodsky also talked about the work that’s made him the proudest during his year-long presidency at ASH.
Robert A. Brodsky is professor of medicine and director of hematology at Johns Hopkins University, Baltimore. He is stepping down as ASH president at its annual meeting in San Diego, December 9-12. Here are excerpts from our conversation:
Q: What drew your dad into medicine?
Dr. Robert A. Brodsky: He was going through his medical training at the University of Pennsylvania, then the Vietnam War came, and he served at the National Institutes of Health in what they referred to as the Yellow Berets. He got very interested in retroviruses and viruses that lead to cancer, which was a foreign idea at the time. This led him into hematology, stem cells, and myeloproliferative disorders.
He had a very successful career in hematology and just loved it. He performed the first bone marrow transplant in the tristate area of Pennsylvania, Delaware, and New Jersey.
Q: What did he like about hematology specifically?
Dr. Robert A. Brodsky: It’s a fascinating field, probably the most scientific area of medicine. It’s so easy to access blood and bone marrow. You can grow it, you can look at it, you can see it. It’s hard to do that with a lung, heart, kidney, or brain. Even back then, they could translate some of the science. What really drew him to hematology — and me, for that matter — was looking at a blood smear or bone marrow and being able to make a diagnosis. The other thing is the personal aspect. Hematologists tend to like the long-term relationships that they develop with their patients over the years.
Q: What were the biggest transformations in hematology during his career?
Dr. Robert A. Brodsky: Bone marrow transplant had the biggest impact, and it’s an area he really pioneered. He was very much involved in some of the early bone marrow transplants and was very close with Dr. George W. Santos, who was at Johns Hopkins and one of the big pioneers in that area as well. To be able to take marrow from related donors, get it to grow without the patient rejecting it, and cure a disease, was really huge. When he started doing this, patients had no other option. To see patients be cured was incredibly satisfying to him.
Q: How did you end up following your father into hematology?
Dr. Robert A. Brodsky: My brother Jeff, who’s a surgeon and older than me, knew he was going into medicine — probably about 3 hours after he was born. I came to it late. I was a political science major as an undergrad and really trying to figure out what I wanted to do. In my sophomore year, I decided I wanted to give this a shot. My dad worked very hard, long hours, but you could tell he loved what he did. And he was never absent, always involved in our lives and still made time for everyone. At some level, that must have had an influence on me.
Q: What has changed in hematology over your 30-plus years in medicine?
A: When I look back at when I was a fellow, it’s just mind-boggling how many lethal or life-threatening diseases are now pretty easy to treat. I studied disorders like aplastic anemia, which was very fatal. Without treatment, patients would die within a year. Now, over 95% are cured. Another classic examples is chronic myeloid leukemia disorder. Back when I was a fellow, the median survival for CML was maybe 4 to 6 years. Now, Kareem Abdul Jabbar has had this[for about 15 years]. Also a lot of hematologic malignancies are being cured with immunotherapy approaches. We’ve figured out the pathophysiology of a lot of diseases, and there are incredible genetic diagnostic assays.
Q: What was your father’s relationship with ASH?
Dr. Robert A. Brodsky: The first ASH meeting was 1958 in Atlantic City, New Jersey. There were 300 hematologists there, and my dad was one of them. We’re going to have over 30,000 people in San Diego, which is a record, and another 5,000 or 6,000 virtually.
Q: As ASH president, what are your biggest accomplishments when it comes to addressing the shortage of hematologists and other issues?
Dr. Robert A. Brodsky: ASH is investing $19 million to develop fellowships with a focus on hematology.* This is going to put lots of new hematologists into the workforce over the next 5 to 10 years. We’ve also been working on the Maintenance of Certification [MOC] process to make it less onerous on physicians. It’s really a bad process, and it’s not just ASH [that’s complaining], it’s all of medicine. We’re hearing this from GI, endocrine, renal and the general internists.
[In a September 2023 letter to the American Board of Internal Medicine’s president and chief officer, Dr. Brodsky wrote that “ASH continues to support the importance of lifelong learning for hematologists via a program that is evidence-based, relevant to one’s practice, and transparent; however, these three basic requirements are not met by the current ABIM MOC program.” ASH is calling for a new and reformed MOC program.]
Q: What convinced ASH to expand its journals by adding Blood Neoplasia and Blood Vessels, Thrombosis & Hemostasis?
Dr. Robert A. Brodsky: ASH has two flagship journals right now, Blood and Blood Advances, and they’re both very competitive, high-impact journals. It turns out there’s not enough room to publish all the new science, and they end up rejecting the majority of the submissions that come to them. We decided to keep these journals in the ASH family because there’s some fantastic clinical trials and science that would be going elsewhere.
Dr. Brodsky’s sons both have medical degrees: Brett Brodsky, DO, is a resident at Virginia Commonwealth University who plans to become a sports medicine specialist, and Max Brodsky, MD, is a second-year fellow in hematology at Johns Hopkins University.
In an interview, Max Brodsky, MD, talked about the roots of his family’s dedication to caring for others.
Q: What drew you to hematology?
Dr. Max Brodsky: I’ve watched both my dad and my grandfather be leaders in the field as both physicians and scientists, and that was very inspirational for me to see. And I went to a medical school [Drexel University College of Medicine] that my dad went to and where my grandfather was on faculty. That was like walking in their footsteps in a major way.
Q: What do you hope to focus on as a hematologist?
Dr. Max Brodsky: I’m still working through that, but I am really interested in thrombotic thrombocytopenic purpura. Patients used to not be able to survive their initial episodes, but now we have good treatments and are able to follow them as outpatients. With this whole cohort of patients that are surviving, we’re seeing that they have more health problems — more heart disease, more strokes and kidney disease. There’s a whole growing field exploring how to treat these patients for their lifespan.
Q: How do you deal with the reality that more of your patients will die than in some other medical fields?
Dr. Max Brodsky: It is challenging, but I also see those moments as opportunities to support patients and families. I’m good at connecting to patients and families who are in scary situations. I’ve always had that skill of putting people at ease, making people feel calm, knowing that they can trust me, and I have their best interests in mind.
Q: Why do you think your family is so committed to medicine?
Dr. Max Brodsky: We’re Jewish, and looking to help the world is one of the main core values of Judaism. The Torah expects us to make this world better. Actually, my great-grandfather Max, whom I’m named after, used to dig tunnels to help people escape Ukraine and get to freedom. He was always looking to help others as well. My great-grandmother was shot crossing the border escaping from Ukraine, and he carried her the whole way to the boat. They lived in very poor West Philadelphia and poured everything into my grandfather. He became a great doctor, and his sons and his grandchildren are in medicine today.
*Correction, 12/11: A previous version of this story misstated the amount of ASH’s $19 million investment in developing fellowships with a focus on hematology.
In interviews, Robert and Max Brodsky spoke about the appeal of hematology and the threads that unite them with family members who came before. The elder Brodsky also talked about the work that’s made him the proudest during his year-long presidency at ASH.
Robert A. Brodsky is professor of medicine and director of hematology at Johns Hopkins University, Baltimore. He is stepping down as ASH president at its annual meeting in San Diego, December 9-12. Here are excerpts from our conversation:
Q: What drew your dad into medicine?
Dr. Robert A. Brodsky: He was going through his medical training at the University of Pennsylvania, then the Vietnam War came, and he served at the National Institutes of Health in what they referred to as the Yellow Berets. He got very interested in retroviruses and viruses that lead to cancer, which was a foreign idea at the time. This led him into hematology, stem cells, and myeloproliferative disorders.
He had a very successful career in hematology and just loved it. He performed the first bone marrow transplant in the tristate area of Pennsylvania, Delaware, and New Jersey.
Q: What did he like about hematology specifically?
Dr. Robert A. Brodsky: It’s a fascinating field, probably the most scientific area of medicine. It’s so easy to access blood and bone marrow. You can grow it, you can look at it, you can see it. It’s hard to do that with a lung, heart, kidney, or brain. Even back then, they could translate some of the science. What really drew him to hematology — and me, for that matter — was looking at a blood smear or bone marrow and being able to make a diagnosis. The other thing is the personal aspect. Hematologists tend to like the long-term relationships that they develop with their patients over the years.
Q: What were the biggest transformations in hematology during his career?
Dr. Robert A. Brodsky: Bone marrow transplant had the biggest impact, and it’s an area he really pioneered. He was very much involved in some of the early bone marrow transplants and was very close with Dr. George W. Santos, who was at Johns Hopkins and one of the big pioneers in that area as well. To be able to take marrow from related donors, get it to grow without the patient rejecting it, and cure a disease, was really huge. When he started doing this, patients had no other option. To see patients be cured was incredibly satisfying to him.
Q: How did you end up following your father into hematology?
Dr. Robert A. Brodsky: My brother Jeff, who’s a surgeon and older than me, knew he was going into medicine — probably about 3 hours after he was born. I came to it late. I was a political science major as an undergrad and really trying to figure out what I wanted to do. In my sophomore year, I decided I wanted to give this a shot. My dad worked very hard, long hours, but you could tell he loved what he did. And he was never absent, always involved in our lives and still made time for everyone. At some level, that must have had an influence on me.
Q: What has changed in hematology over your 30-plus years in medicine?
A: When I look back at when I was a fellow, it’s just mind-boggling how many lethal or life-threatening diseases are now pretty easy to treat. I studied disorders like aplastic anemia, which was very fatal. Without treatment, patients would die within a year. Now, over 95% are cured. Another classic examples is chronic myeloid leukemia disorder. Back when I was a fellow, the median survival for CML was maybe 4 to 6 years. Now, Kareem Abdul Jabbar has had this[for about 15 years]. Also a lot of hematologic malignancies are being cured with immunotherapy approaches. We’ve figured out the pathophysiology of a lot of diseases, and there are incredible genetic diagnostic assays.
Q: What was your father’s relationship with ASH?
Dr. Robert A. Brodsky: The first ASH meeting was 1958 in Atlantic City, New Jersey. There were 300 hematologists there, and my dad was one of them. We’re going to have over 30,000 people in San Diego, which is a record, and another 5,000 or 6,000 virtually.
Q: As ASH president, what are your biggest accomplishments when it comes to addressing the shortage of hematologists and other issues?
Dr. Robert A. Brodsky: ASH is investing $19 million to develop fellowships with a focus on hematology.* This is going to put lots of new hematologists into the workforce over the next 5 to 10 years. We’ve also been working on the Maintenance of Certification [MOC] process to make it less onerous on physicians. It’s really a bad process, and it’s not just ASH [that’s complaining], it’s all of medicine. We’re hearing this from GI, endocrine, renal and the general internists.
[In a September 2023 letter to the American Board of Internal Medicine’s president and chief officer, Dr. Brodsky wrote that “ASH continues to support the importance of lifelong learning for hematologists via a program that is evidence-based, relevant to one’s practice, and transparent; however, these three basic requirements are not met by the current ABIM MOC program.” ASH is calling for a new and reformed MOC program.]
Q: What convinced ASH to expand its journals by adding Blood Neoplasia and Blood Vessels, Thrombosis & Hemostasis?
Dr. Robert A. Brodsky: ASH has two flagship journals right now, Blood and Blood Advances, and they’re both very competitive, high-impact journals. It turns out there’s not enough room to publish all the new science, and they end up rejecting the majority of the submissions that come to them. We decided to keep these journals in the ASH family because there’s some fantastic clinical trials and science that would be going elsewhere.
Dr. Brodsky’s sons both have medical degrees: Brett Brodsky, DO, is a resident at Virginia Commonwealth University who plans to become a sports medicine specialist, and Max Brodsky, MD, is a second-year fellow in hematology at Johns Hopkins University.
In an interview, Max Brodsky, MD, talked about the roots of his family’s dedication to caring for others.
Q: What drew you to hematology?
Dr. Max Brodsky: I’ve watched both my dad and my grandfather be leaders in the field as both physicians and scientists, and that was very inspirational for me to see. And I went to a medical school [Drexel University College of Medicine] that my dad went to and where my grandfather was on faculty. That was like walking in their footsteps in a major way.
Q: What do you hope to focus on as a hematologist?
Dr. Max Brodsky: I’m still working through that, but I am really interested in thrombotic thrombocytopenic purpura. Patients used to not be able to survive their initial episodes, but now we have good treatments and are able to follow them as outpatients. With this whole cohort of patients that are surviving, we’re seeing that they have more health problems — more heart disease, more strokes and kidney disease. There’s a whole growing field exploring how to treat these patients for their lifespan.
Q: How do you deal with the reality that more of your patients will die than in some other medical fields?
Dr. Max Brodsky: It is challenging, but I also see those moments as opportunities to support patients and families. I’m good at connecting to patients and families who are in scary situations. I’ve always had that skill of putting people at ease, making people feel calm, knowing that they can trust me, and I have their best interests in mind.
Q: Why do you think your family is so committed to medicine?
Dr. Max Brodsky: We’re Jewish, and looking to help the world is one of the main core values of Judaism. The Torah expects us to make this world better. Actually, my great-grandfather Max, whom I’m named after, used to dig tunnels to help people escape Ukraine and get to freedom. He was always looking to help others as well. My great-grandmother was shot crossing the border escaping from Ukraine, and he carried her the whole way to the boat. They lived in very poor West Philadelphia and poured everything into my grandfather. He became a great doctor, and his sons and his grandchildren are in medicine today.
*Correction, 12/11: A previous version of this story misstated the amount of ASH’s $19 million investment in developing fellowships with a focus on hematology.
FROM ASH 2023
Study confirms small blood cancer risk from CT scans
The findings, published online in Nature Medicine, are based on more than 1.3 million CT scans in nearly 900,000 people younger than 22 years old when scanned.
This study makes a “significant contribution to the understanding of the effects of ionizing radiation, specifically x-rays, on the human body at the levels of radiation exposure encountered in diagnostic CT procedures,” Peter Marsden, PhD, and Jim Thurston, radiation protection experts at Dorset County (England) Hospital, NHS Foundation Trust, said in a press release from the U.K. nonprofit Science Media Centre.
These findings highlight levels of risk that “align with those currently estimated and do not suggest that the use of CT carries a greater risk than previously thought,” Dr. Marsden and Thurston said.
Exposure to moderate- (≥ 100 mGy) to high-dose (≥ 1 Gy) ionizing radiation is a well-established risk factor for leukemia in both children and adults. However, the risk associated with low-dose exposure (< 100 mGy) typically associated with diagnostic CT exams in children and teens remains unclear.
The current study, coordinated by the International Agency for Research on Cancer, aimed to improve direct estimates of cancer risk from low-dose radiation exposure from CT scans performed in childhood and adolescence. The researchers estimated radiation doses to the active bone marrow based on body part scanned, patient characteristics, time period, and inferred CT technical parameters.
A total of 790 hematologic malignancies, including lymphoid and myeloid malignancies, were identified during follow-up. More than half (51%) of the cases were diagnosed in people under age 20 and 88.5% were diagnosed in people under age 30 years.
Overall, the observational study found a nearly twofold excess risk of all hematologic malignancies per 100 mGy in children, adolescents, and young adults, with similar risk estimates observed for lymphoid and myeloid cancers. The excess relative risk for hematologic malignancies increased as the number of CT exams increased – with risk rising by 43% per exam.
The results of this study “strengthen the findings from previous low-dose studies of a consistent and robust dose-related increased risk of radiation-induced hematological malignancies” and highlight the importance of optimizing doses in this patient population, study author Elisabeth Cardis, PhD, with the Barcelona Institute for Global Health, and colleagues concluded.
Sarah McQuaid, PhD, chair of the nuclear medicine special interest group, Institute of Physics and Engineering in Medicine, York, England, agreed.
“This publication indicates that there could be a small cancer risk from CT scans in young people, but it is important for this to be viewed in the context of the substantial benefit these scans bring, due to the important diagnostic information they provide,” Dr. McQuaid said in the press release. Overall, “the number of patients whose medical care will have been improved from these CT scans will have been very high, and lives undoubtedly saved as a result.”
The study had no commercial funding. The authors and outside experts reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The findings, published online in Nature Medicine, are based on more than 1.3 million CT scans in nearly 900,000 people younger than 22 years old when scanned.
This study makes a “significant contribution to the understanding of the effects of ionizing radiation, specifically x-rays, on the human body at the levels of radiation exposure encountered in diagnostic CT procedures,” Peter Marsden, PhD, and Jim Thurston, radiation protection experts at Dorset County (England) Hospital, NHS Foundation Trust, said in a press release from the U.K. nonprofit Science Media Centre.
These findings highlight levels of risk that “align with those currently estimated and do not suggest that the use of CT carries a greater risk than previously thought,” Dr. Marsden and Thurston said.
Exposure to moderate- (≥ 100 mGy) to high-dose (≥ 1 Gy) ionizing radiation is a well-established risk factor for leukemia in both children and adults. However, the risk associated with low-dose exposure (< 100 mGy) typically associated with diagnostic CT exams in children and teens remains unclear.
The current study, coordinated by the International Agency for Research on Cancer, aimed to improve direct estimates of cancer risk from low-dose radiation exposure from CT scans performed in childhood and adolescence. The researchers estimated radiation doses to the active bone marrow based on body part scanned, patient characteristics, time period, and inferred CT technical parameters.
A total of 790 hematologic malignancies, including lymphoid and myeloid malignancies, were identified during follow-up. More than half (51%) of the cases were diagnosed in people under age 20 and 88.5% were diagnosed in people under age 30 years.
Overall, the observational study found a nearly twofold excess risk of all hematologic malignancies per 100 mGy in children, adolescents, and young adults, with similar risk estimates observed for lymphoid and myeloid cancers. The excess relative risk for hematologic malignancies increased as the number of CT exams increased – with risk rising by 43% per exam.
The results of this study “strengthen the findings from previous low-dose studies of a consistent and robust dose-related increased risk of radiation-induced hematological malignancies” and highlight the importance of optimizing doses in this patient population, study author Elisabeth Cardis, PhD, with the Barcelona Institute for Global Health, and colleagues concluded.
Sarah McQuaid, PhD, chair of the nuclear medicine special interest group, Institute of Physics and Engineering in Medicine, York, England, agreed.
“This publication indicates that there could be a small cancer risk from CT scans in young people, but it is important for this to be viewed in the context of the substantial benefit these scans bring, due to the important diagnostic information they provide,” Dr. McQuaid said in the press release. Overall, “the number of patients whose medical care will have been improved from these CT scans will have been very high, and lives undoubtedly saved as a result.”
The study had no commercial funding. The authors and outside experts reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The findings, published online in Nature Medicine, are based on more than 1.3 million CT scans in nearly 900,000 people younger than 22 years old when scanned.
This study makes a “significant contribution to the understanding of the effects of ionizing radiation, specifically x-rays, on the human body at the levels of radiation exposure encountered in diagnostic CT procedures,” Peter Marsden, PhD, and Jim Thurston, radiation protection experts at Dorset County (England) Hospital, NHS Foundation Trust, said in a press release from the U.K. nonprofit Science Media Centre.
These findings highlight levels of risk that “align with those currently estimated and do not suggest that the use of CT carries a greater risk than previously thought,” Dr. Marsden and Thurston said.
Exposure to moderate- (≥ 100 mGy) to high-dose (≥ 1 Gy) ionizing radiation is a well-established risk factor for leukemia in both children and adults. However, the risk associated with low-dose exposure (< 100 mGy) typically associated with diagnostic CT exams in children and teens remains unclear.
The current study, coordinated by the International Agency for Research on Cancer, aimed to improve direct estimates of cancer risk from low-dose radiation exposure from CT scans performed in childhood and adolescence. The researchers estimated radiation doses to the active bone marrow based on body part scanned, patient characteristics, time period, and inferred CT technical parameters.
A total of 790 hematologic malignancies, including lymphoid and myeloid malignancies, were identified during follow-up. More than half (51%) of the cases were diagnosed in people under age 20 and 88.5% were diagnosed in people under age 30 years.
Overall, the observational study found a nearly twofold excess risk of all hematologic malignancies per 100 mGy in children, adolescents, and young adults, with similar risk estimates observed for lymphoid and myeloid cancers. The excess relative risk for hematologic malignancies increased as the number of CT exams increased – with risk rising by 43% per exam.
The results of this study “strengthen the findings from previous low-dose studies of a consistent and robust dose-related increased risk of radiation-induced hematological malignancies” and highlight the importance of optimizing doses in this patient population, study author Elisabeth Cardis, PhD, with the Barcelona Institute for Global Health, and colleagues concluded.
Sarah McQuaid, PhD, chair of the nuclear medicine special interest group, Institute of Physics and Engineering in Medicine, York, England, agreed.
“This publication indicates that there could be a small cancer risk from CT scans in young people, but it is important for this to be viewed in the context of the substantial benefit these scans bring, due to the important diagnostic information they provide,” Dr. McQuaid said in the press release. Overall, “the number of patients whose medical care will have been improved from these CT scans will have been very high, and lives undoubtedly saved as a result.”
The study had no commercial funding. The authors and outside experts reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM NATURE MEDICINE
FDA’s Project Optimus aims to transform early cancer research
SAN DIEGO –
The goal is “to better identify and characterize optimized doses” in early stages of research and move away from the default of the traditional maximum tolerated dose strategy, hematologist-oncologist Marc R. Theoret, MD, deputy director of the FDA’s Oncology Center of Excellence, said in a presentation at the 2023 Society for Immunotherapy of Cancer annual meeting.
Earlier this year, the FDA released a draft guidance regarding the changes it hopes to see. The agency supported randomized, parallel dose-response trials when feasible, and “strong rationale for choice of dosage should be provided before initiating a registration trial(s) to support a subsequent indication and usage.”
The goal of controlling toxicity is “very highly important” in hematology research since blood cancer drugs can cause significant adverse effects in areas such as the lungs and heart, said Cecilia Yeung, MD, who led the SITC session about Project Optimus. Dr. Yeung is a clinical pathologist who works on investigational trials at Fred Hutchinson Cancer Research Center in Seattle.
In an interview, Dr. Yeung, who has a subspecialty in hematopathology, explained why the foundations of cancer research are changing and what hematologist-oncologists can expect to see on the horizon.
Q: Project Optimus aims to move beyond the traditional dose-escalation approach to the development of cancer drugs. How does that strategy work?
Dr. Yeung: Prior to Project Optimus, they’d use a 3+3 strategy in phase 1 trials: They’d give a dose to three fairly healthy patients, then they’d go up by escalating doses in more patients. They’d keep going up until two-thirds of patients at a specific dose suffered from bad side effects, then they’d back off to the last dose.
Q: This approach, which aims to identify the “maximum tolerated dose,” seemed to work well over decades of research into chemotherapy drugs. But worries arose as targeted therapies appeared in oncology areas such as blood cancer. Why did things change?
Dr. Yeung: With 3+3, you could tell pretty quickly how toxic chemotherapy was. But in targeted therapy, we were finding that these studies are not representative of actual toxicity. You’re not treating these patients for a very long time in phase 1, while patients on targeted therapy may be on these drugs for years. Concerns actually started with the first targeted drugs to treat leukemias and lymphomas. They were shown to have unexpected toxicity. A 2016 study found that drug developers had to reduce the original phase 1 dose in 45% of phase 3 trials [of small molecule and monoclonal antibody targeted agents] approved by the FDA over 12 years because of toxicity.
Q: What is FDA’s goal for Project Optimus?
Dr. Yeung: They want to have a second piece, to balance that maximum tolerated dose with a safe and tolerable dose for most people.
Q: What kind of resistance is the FDA getting from drug companies?
Dr. Yeung: The FDA makes a good argument that the system wasn’t working. But drug companies say this will drive up the cost of clinical trials and won’t allow them to treat patients with the maximal doses they could give them. I see arguments from both sides. There has to be a balance between the two.
Q: How will all this affect drug development?
Dr. Yeung: Drugs may become more expensive because much more testing will happen during clinical trials.
Q: Could this reduce the number of investigational drugs?
Dr. Yeung: Hopefully not, but this is huge endeavor for smaller companies that are strapped for funding.
Q: What do you think the future holds?
Dr. Yeung: Ultimately, this is a good thing because if everything works out, we’ll have fewer toxic side effects. But we’re going to have to go through a period of growing pains.
SAN DIEGO –
The goal is “to better identify and characterize optimized doses” in early stages of research and move away from the default of the traditional maximum tolerated dose strategy, hematologist-oncologist Marc R. Theoret, MD, deputy director of the FDA’s Oncology Center of Excellence, said in a presentation at the 2023 Society for Immunotherapy of Cancer annual meeting.
Earlier this year, the FDA released a draft guidance regarding the changes it hopes to see. The agency supported randomized, parallel dose-response trials when feasible, and “strong rationale for choice of dosage should be provided before initiating a registration trial(s) to support a subsequent indication and usage.”
The goal of controlling toxicity is “very highly important” in hematology research since blood cancer drugs can cause significant adverse effects in areas such as the lungs and heart, said Cecilia Yeung, MD, who led the SITC session about Project Optimus. Dr. Yeung is a clinical pathologist who works on investigational trials at Fred Hutchinson Cancer Research Center in Seattle.
In an interview, Dr. Yeung, who has a subspecialty in hematopathology, explained why the foundations of cancer research are changing and what hematologist-oncologists can expect to see on the horizon.
Q: Project Optimus aims to move beyond the traditional dose-escalation approach to the development of cancer drugs. How does that strategy work?
Dr. Yeung: Prior to Project Optimus, they’d use a 3+3 strategy in phase 1 trials: They’d give a dose to three fairly healthy patients, then they’d go up by escalating doses in more patients. They’d keep going up until two-thirds of patients at a specific dose suffered from bad side effects, then they’d back off to the last dose.
Q: This approach, which aims to identify the “maximum tolerated dose,” seemed to work well over decades of research into chemotherapy drugs. But worries arose as targeted therapies appeared in oncology areas such as blood cancer. Why did things change?
Dr. Yeung: With 3+3, you could tell pretty quickly how toxic chemotherapy was. But in targeted therapy, we were finding that these studies are not representative of actual toxicity. You’re not treating these patients for a very long time in phase 1, while patients on targeted therapy may be on these drugs for years. Concerns actually started with the first targeted drugs to treat leukemias and lymphomas. They were shown to have unexpected toxicity. A 2016 study found that drug developers had to reduce the original phase 1 dose in 45% of phase 3 trials [of small molecule and monoclonal antibody targeted agents] approved by the FDA over 12 years because of toxicity.
Q: What is FDA’s goal for Project Optimus?
Dr. Yeung: They want to have a second piece, to balance that maximum tolerated dose with a safe and tolerable dose for most people.
Q: What kind of resistance is the FDA getting from drug companies?
Dr. Yeung: The FDA makes a good argument that the system wasn’t working. But drug companies say this will drive up the cost of clinical trials and won’t allow them to treat patients with the maximal doses they could give them. I see arguments from both sides. There has to be a balance between the two.
Q: How will all this affect drug development?
Dr. Yeung: Drugs may become more expensive because much more testing will happen during clinical trials.
Q: Could this reduce the number of investigational drugs?
Dr. Yeung: Hopefully not, but this is huge endeavor for smaller companies that are strapped for funding.
Q: What do you think the future holds?
Dr. Yeung: Ultimately, this is a good thing because if everything works out, we’ll have fewer toxic side effects. But we’re going to have to go through a period of growing pains.
SAN DIEGO –
The goal is “to better identify and characterize optimized doses” in early stages of research and move away from the default of the traditional maximum tolerated dose strategy, hematologist-oncologist Marc R. Theoret, MD, deputy director of the FDA’s Oncology Center of Excellence, said in a presentation at the 2023 Society for Immunotherapy of Cancer annual meeting.
Earlier this year, the FDA released a draft guidance regarding the changes it hopes to see. The agency supported randomized, parallel dose-response trials when feasible, and “strong rationale for choice of dosage should be provided before initiating a registration trial(s) to support a subsequent indication and usage.”
The goal of controlling toxicity is “very highly important” in hematology research since blood cancer drugs can cause significant adverse effects in areas such as the lungs and heart, said Cecilia Yeung, MD, who led the SITC session about Project Optimus. Dr. Yeung is a clinical pathologist who works on investigational trials at Fred Hutchinson Cancer Research Center in Seattle.
In an interview, Dr. Yeung, who has a subspecialty in hematopathology, explained why the foundations of cancer research are changing and what hematologist-oncologists can expect to see on the horizon.
Q: Project Optimus aims to move beyond the traditional dose-escalation approach to the development of cancer drugs. How does that strategy work?
Dr. Yeung: Prior to Project Optimus, they’d use a 3+3 strategy in phase 1 trials: They’d give a dose to three fairly healthy patients, then they’d go up by escalating doses in more patients. They’d keep going up until two-thirds of patients at a specific dose suffered from bad side effects, then they’d back off to the last dose.
Q: This approach, which aims to identify the “maximum tolerated dose,” seemed to work well over decades of research into chemotherapy drugs. But worries arose as targeted therapies appeared in oncology areas such as blood cancer. Why did things change?
Dr. Yeung: With 3+3, you could tell pretty quickly how toxic chemotherapy was. But in targeted therapy, we were finding that these studies are not representative of actual toxicity. You’re not treating these patients for a very long time in phase 1, while patients on targeted therapy may be on these drugs for years. Concerns actually started with the first targeted drugs to treat leukemias and lymphomas. They were shown to have unexpected toxicity. A 2016 study found that drug developers had to reduce the original phase 1 dose in 45% of phase 3 trials [of small molecule and monoclonal antibody targeted agents] approved by the FDA over 12 years because of toxicity.
Q: What is FDA’s goal for Project Optimus?
Dr. Yeung: They want to have a second piece, to balance that maximum tolerated dose with a safe and tolerable dose for most people.
Q: What kind of resistance is the FDA getting from drug companies?
Dr. Yeung: The FDA makes a good argument that the system wasn’t working. But drug companies say this will drive up the cost of clinical trials and won’t allow them to treat patients with the maximal doses they could give them. I see arguments from both sides. There has to be a balance between the two.
Q: How will all this affect drug development?
Dr. Yeung: Drugs may become more expensive because much more testing will happen during clinical trials.
Q: Could this reduce the number of investigational drugs?
Dr. Yeung: Hopefully not, but this is huge endeavor for smaller companies that are strapped for funding.
Q: What do you think the future holds?
Dr. Yeung: Ultimately, this is a good thing because if everything works out, we’ll have fewer toxic side effects. But we’re going to have to go through a period of growing pains.
AT SITC 2023
FDA approves bosutinib for children with CML
The agency also approved new 50-mg and 100-mg capsules to help treat children.
For newly diagnosed disease, the dose is 300 mg/m2 once daily with food. For resistant/intolerant disease, the dose is 400 mg/m2 once daily. For children who cannot swallow capsules, the contents can be mixed into applesauce or yogurt, the FDA said in a press release announcing the approval.
The tyrosine kinase inhibitor (TKI) was previously approved for adults. Three other TKIs were previously approved for pediatric CML.
The approval was based on the BCHILD trial, a pediatric dose-finding study involving patients aged 1 year or older. Among the 21 children with newly diagnosed chronic phase, Ph+ CML treated with 300 mg/m2, the rate of major cytogenetic response was 76.2%, the rate of complete cytogenetic response was 71.4%, and the rate of major molecular response rate was 28.6% over a median duration of 14.2 months.
Among the 28 children with relapsed/intolerant disease treated with up to 400 mg/m2, the rate of major cytogenetic response was 82.1%, the rate of complete cytogenetic response was 78.6%, and the rate of major molecular response was 50% over a median duration of 23.2 months. Among the 14 patients who had a major molecular response, two lost it – one after 13.6 months of treatment, and the other after 24.7 months of treatment.
Adverse events that occurred in 20% or more of children included diarrhea, abdominal pain, vomiting, nausea, rash, fatigue, hepatic dysfunction, headache, pyrexia, decreased appetite, and constipation. Overall, 45% or more of patients experienced an increase in creatinine, alanine aminotransferase, or aspartate aminotransferase levels, or a decrease in white blood cell count or platelet count.
The full labeling information is available online.
A version of this article first appeared on Medscape.com.
The agency also approved new 50-mg and 100-mg capsules to help treat children.
For newly diagnosed disease, the dose is 300 mg/m2 once daily with food. For resistant/intolerant disease, the dose is 400 mg/m2 once daily. For children who cannot swallow capsules, the contents can be mixed into applesauce or yogurt, the FDA said in a press release announcing the approval.
The tyrosine kinase inhibitor (TKI) was previously approved for adults. Three other TKIs were previously approved for pediatric CML.
The approval was based on the BCHILD trial, a pediatric dose-finding study involving patients aged 1 year or older. Among the 21 children with newly diagnosed chronic phase, Ph+ CML treated with 300 mg/m2, the rate of major cytogenetic response was 76.2%, the rate of complete cytogenetic response was 71.4%, and the rate of major molecular response rate was 28.6% over a median duration of 14.2 months.
Among the 28 children with relapsed/intolerant disease treated with up to 400 mg/m2, the rate of major cytogenetic response was 82.1%, the rate of complete cytogenetic response was 78.6%, and the rate of major molecular response was 50% over a median duration of 23.2 months. Among the 14 patients who had a major molecular response, two lost it – one after 13.6 months of treatment, and the other after 24.7 months of treatment.
Adverse events that occurred in 20% or more of children included diarrhea, abdominal pain, vomiting, nausea, rash, fatigue, hepatic dysfunction, headache, pyrexia, decreased appetite, and constipation. Overall, 45% or more of patients experienced an increase in creatinine, alanine aminotransferase, or aspartate aminotransferase levels, or a decrease in white blood cell count or platelet count.
The full labeling information is available online.
A version of this article first appeared on Medscape.com.
The agency also approved new 50-mg and 100-mg capsules to help treat children.
For newly diagnosed disease, the dose is 300 mg/m2 once daily with food. For resistant/intolerant disease, the dose is 400 mg/m2 once daily. For children who cannot swallow capsules, the contents can be mixed into applesauce or yogurt, the FDA said in a press release announcing the approval.
The tyrosine kinase inhibitor (TKI) was previously approved for adults. Three other TKIs were previously approved for pediatric CML.
The approval was based on the BCHILD trial, a pediatric dose-finding study involving patients aged 1 year or older. Among the 21 children with newly diagnosed chronic phase, Ph+ CML treated with 300 mg/m2, the rate of major cytogenetic response was 76.2%, the rate of complete cytogenetic response was 71.4%, and the rate of major molecular response rate was 28.6% over a median duration of 14.2 months.
Among the 28 children with relapsed/intolerant disease treated with up to 400 mg/m2, the rate of major cytogenetic response was 82.1%, the rate of complete cytogenetic response was 78.6%, and the rate of major molecular response was 50% over a median duration of 23.2 months. Among the 14 patients who had a major molecular response, two lost it – one after 13.6 months of treatment, and the other after 24.7 months of treatment.
Adverse events that occurred in 20% or more of children included diarrhea, abdominal pain, vomiting, nausea, rash, fatigue, hepatic dysfunction, headache, pyrexia, decreased appetite, and constipation. Overall, 45% or more of patients experienced an increase in creatinine, alanine aminotransferase, or aspartate aminotransferase levels, or a decrease in white blood cell count or platelet count.
The full labeling information is available online.
A version of this article first appeared on Medscape.com.
Antibody shows promise in preventing GVHD
Early, intriguing research suggests that preventing acute graft-versus-host disease (GVHD) in the gut – a potentially life-threatening complication of allogeneic hematopoietic cell transplantation (allo-HCT) – could be accomplished by the administration of a single antibody that targets the anti-DLL4 Notch signaling pathway, without compromising the stem cell transplant.
“The major surprise was that none of the anti–DLL4-treated animals developed acute gastrointestinal GVHD for the entire duration of the study. This was a remarkable finding, given that intestinal GVHD is otherwise seen in the vast majority of nonhuman primate transplant recipients that receive either no prophylaxis, or prophylaxis with agents other than anti-DLL4 antibodies,” co–senior author Ivan Maillard, MD, PhD, a professor of medicine and vice chief for research in hematology-oncology at the University of Pennsylvania, Philadelphia, said in an interview.
“The timing was critical,” the authors noted in the study, recently published in Science Translational Medicine. “Intervening before any symptoms of GvHD appear made the long-term protection possible.”
While GVHD may be mild to moderate in chronic forms, acute cases can be serious, if not fatal, and nearly all severe acute GVHD prominently involves the gastrointestinal tract, which can drive activation of pathogenic T cells and potentially lead to tissue damage following allo-HCT.
Systemic corticosteroids are standard first-line treatment for acute GVHD. However, response rates generally range only from 40% to 60%, and there are concerns of side effects. Meanwhile, second-line treatments are of inconsistent benefit.
With previous studies on mice showing benefits of targeting Notch pathway inhibition, particularly DLL4, Dr. Maillard and colleagues further investigated the effects in nonhuman primates that were allo-HCT recipients, using the anti-DLL4 antibody REGN421, which has pharmacokinetic and toxicity information available from previous studies.
The nonhuman primates were treated with one of two dosing regimens: a single dose of REGN421 3 mg/kg at baseline, post HCT, (n = 7) or three weekly doses at days 0, 7 and 14, post transplant (n = 4). Those primates were compared with 11 primates receiving allo-HCT transplants that received supportive care only.
Primates receiving three weekly doses of REGN421 showed antibody concentrations of greater than 2 mcg/mL for more than 30 days post HCT. A single dose of REGN421 was associated with protection from acute GVHD at day 0, while three weekly doses showed protection at day 0, 7, and 14, consistent with an impact of REGN421 during the early phases of T-cell activation.
Compared with animals receiving only supportive care, prophylaxis with REGN421 was associated with delayed acute GVHD onset and lengthened survival.
Of the 11 primates treated with REGN421, none developed clinical signs of gastrointestinal acute GVHD, whereas the majority of those receiving standard care or other preventive interventions did.
“Detailed analysis of acute GVHD clinical presentations in REGN421-treated animals in comparison to no treatment controls revealed near complete protection from GI-acute GvHD with REGN421,” the authors reported.
Furthermore, pathology scores in the gastrointestinal tract were lower with REGN421 treatment, compared with the no-treatment cohort, and the scores matched those of healthy nontransplanted nonhuman primates.
The primates treated with REGN421 did ultimately develop other clinical and pathologic signs of skin, hepatic or pulmonary acute GVHD, but without gastrointestinal disease.
The treatment was not associated with any adverse effects on the allo-HCT, with primates receiving either a single dose or three weekly doses of REGN421 showing rapid donor engraftment after allo-HCT, including high bone marrow, whole blood, and T-cell donor chimerism.
“Reassuringly, short-term systemic DLL4 blockade with REGN421 did not trigger unexpected side effects in our nonhuman primate model, while preserving rapid engraftment as well hematopoietic and immune reconstitution.”
The mechanism preserving the engraftment, described as a “major surprise,” specifically involved DLL4 inhibition blocking the homing of pathogenic T cells to the gut while preserving homing of regulatory T cells that dampen the immune response, Dr. Maillard explained.
“This effect turned out to be at least in part through a posttranslational effect of DLL4/Notch blockade on integrin pairing at the T-cell surface,” he explained. “This was a novel and quite unexpected mechanism of action conserved from mice to nonhuman primates.”
The results are encouraging in terms of translating to humans because of their closer similarities in various physiological factors, Dr. Maillard said.
“The nonhuman primate model of transplantation [offers] a transplantation model very close to what is being performed in humans, as well as the opportunity to study an immune system very similar to that of humans in nonhuman primates,” he said.
Dr. Maillard noted that, while trials in humans are not underway yet, “we are in active discussions about it,” and the team is indeed interested in testing REGN421 itself, with the effects likely to be as a prophylactic strategy.
There are currently no approved anti-DLL4 antibody drugs for use in humans.
“Our approach is mostly promising as a preventive treatment, rather than as a secondary treatment for GVHD, because DLL4/Notch blockade seems most active when applied early after transplantation during the time of initial seeding of the gut by T cells (in mice, we had observed the critical time window for a successful intervention to be within 48 hours of transplantation),” Dr. Maillard said.“There remain questions about which other prophylactic treatments we should ideally combine anti-DLL4 antibodies with.”
Dr. Maillard has received research funding from Regeneron and Genentech and is a member of Garuda Therapeutics’s scientific advisory board.
Early, intriguing research suggests that preventing acute graft-versus-host disease (GVHD) in the gut – a potentially life-threatening complication of allogeneic hematopoietic cell transplantation (allo-HCT) – could be accomplished by the administration of a single antibody that targets the anti-DLL4 Notch signaling pathway, without compromising the stem cell transplant.
“The major surprise was that none of the anti–DLL4-treated animals developed acute gastrointestinal GVHD for the entire duration of the study. This was a remarkable finding, given that intestinal GVHD is otherwise seen in the vast majority of nonhuman primate transplant recipients that receive either no prophylaxis, or prophylaxis with agents other than anti-DLL4 antibodies,” co–senior author Ivan Maillard, MD, PhD, a professor of medicine and vice chief for research in hematology-oncology at the University of Pennsylvania, Philadelphia, said in an interview.
“The timing was critical,” the authors noted in the study, recently published in Science Translational Medicine. “Intervening before any symptoms of GvHD appear made the long-term protection possible.”
While GVHD may be mild to moderate in chronic forms, acute cases can be serious, if not fatal, and nearly all severe acute GVHD prominently involves the gastrointestinal tract, which can drive activation of pathogenic T cells and potentially lead to tissue damage following allo-HCT.
Systemic corticosteroids are standard first-line treatment for acute GVHD. However, response rates generally range only from 40% to 60%, and there are concerns of side effects. Meanwhile, second-line treatments are of inconsistent benefit.
With previous studies on mice showing benefits of targeting Notch pathway inhibition, particularly DLL4, Dr. Maillard and colleagues further investigated the effects in nonhuman primates that were allo-HCT recipients, using the anti-DLL4 antibody REGN421, which has pharmacokinetic and toxicity information available from previous studies.
The nonhuman primates were treated with one of two dosing regimens: a single dose of REGN421 3 mg/kg at baseline, post HCT, (n = 7) or three weekly doses at days 0, 7 and 14, post transplant (n = 4). Those primates were compared with 11 primates receiving allo-HCT transplants that received supportive care only.
Primates receiving three weekly doses of REGN421 showed antibody concentrations of greater than 2 mcg/mL for more than 30 days post HCT. A single dose of REGN421 was associated with protection from acute GVHD at day 0, while three weekly doses showed protection at day 0, 7, and 14, consistent with an impact of REGN421 during the early phases of T-cell activation.
Compared with animals receiving only supportive care, prophylaxis with REGN421 was associated with delayed acute GVHD onset and lengthened survival.
Of the 11 primates treated with REGN421, none developed clinical signs of gastrointestinal acute GVHD, whereas the majority of those receiving standard care or other preventive interventions did.
“Detailed analysis of acute GVHD clinical presentations in REGN421-treated animals in comparison to no treatment controls revealed near complete protection from GI-acute GvHD with REGN421,” the authors reported.
Furthermore, pathology scores in the gastrointestinal tract were lower with REGN421 treatment, compared with the no-treatment cohort, and the scores matched those of healthy nontransplanted nonhuman primates.
The primates treated with REGN421 did ultimately develop other clinical and pathologic signs of skin, hepatic or pulmonary acute GVHD, but without gastrointestinal disease.
The treatment was not associated with any adverse effects on the allo-HCT, with primates receiving either a single dose or three weekly doses of REGN421 showing rapid donor engraftment after allo-HCT, including high bone marrow, whole blood, and T-cell donor chimerism.
“Reassuringly, short-term systemic DLL4 blockade with REGN421 did not trigger unexpected side effects in our nonhuman primate model, while preserving rapid engraftment as well hematopoietic and immune reconstitution.”
The mechanism preserving the engraftment, described as a “major surprise,” specifically involved DLL4 inhibition blocking the homing of pathogenic T cells to the gut while preserving homing of regulatory T cells that dampen the immune response, Dr. Maillard explained.
“This effect turned out to be at least in part through a posttranslational effect of DLL4/Notch blockade on integrin pairing at the T-cell surface,” he explained. “This was a novel and quite unexpected mechanism of action conserved from mice to nonhuman primates.”
The results are encouraging in terms of translating to humans because of their closer similarities in various physiological factors, Dr. Maillard said.
“The nonhuman primate model of transplantation [offers] a transplantation model very close to what is being performed in humans, as well as the opportunity to study an immune system very similar to that of humans in nonhuman primates,” he said.
Dr. Maillard noted that, while trials in humans are not underway yet, “we are in active discussions about it,” and the team is indeed interested in testing REGN421 itself, with the effects likely to be as a prophylactic strategy.
There are currently no approved anti-DLL4 antibody drugs for use in humans.
“Our approach is mostly promising as a preventive treatment, rather than as a secondary treatment for GVHD, because DLL4/Notch blockade seems most active when applied early after transplantation during the time of initial seeding of the gut by T cells (in mice, we had observed the critical time window for a successful intervention to be within 48 hours of transplantation),” Dr. Maillard said.“There remain questions about which other prophylactic treatments we should ideally combine anti-DLL4 antibodies with.”
Dr. Maillard has received research funding from Regeneron and Genentech and is a member of Garuda Therapeutics’s scientific advisory board.
Early, intriguing research suggests that preventing acute graft-versus-host disease (GVHD) in the gut – a potentially life-threatening complication of allogeneic hematopoietic cell transplantation (allo-HCT) – could be accomplished by the administration of a single antibody that targets the anti-DLL4 Notch signaling pathway, without compromising the stem cell transplant.
“The major surprise was that none of the anti–DLL4-treated animals developed acute gastrointestinal GVHD for the entire duration of the study. This was a remarkable finding, given that intestinal GVHD is otherwise seen in the vast majority of nonhuman primate transplant recipients that receive either no prophylaxis, or prophylaxis with agents other than anti-DLL4 antibodies,” co–senior author Ivan Maillard, MD, PhD, a professor of medicine and vice chief for research in hematology-oncology at the University of Pennsylvania, Philadelphia, said in an interview.
“The timing was critical,” the authors noted in the study, recently published in Science Translational Medicine. “Intervening before any symptoms of GvHD appear made the long-term protection possible.”
While GVHD may be mild to moderate in chronic forms, acute cases can be serious, if not fatal, and nearly all severe acute GVHD prominently involves the gastrointestinal tract, which can drive activation of pathogenic T cells and potentially lead to tissue damage following allo-HCT.
Systemic corticosteroids are standard first-line treatment for acute GVHD. However, response rates generally range only from 40% to 60%, and there are concerns of side effects. Meanwhile, second-line treatments are of inconsistent benefit.
With previous studies on mice showing benefits of targeting Notch pathway inhibition, particularly DLL4, Dr. Maillard and colleagues further investigated the effects in nonhuman primates that were allo-HCT recipients, using the anti-DLL4 antibody REGN421, which has pharmacokinetic and toxicity information available from previous studies.
The nonhuman primates were treated with one of two dosing regimens: a single dose of REGN421 3 mg/kg at baseline, post HCT, (n = 7) or three weekly doses at days 0, 7 and 14, post transplant (n = 4). Those primates were compared with 11 primates receiving allo-HCT transplants that received supportive care only.
Primates receiving three weekly doses of REGN421 showed antibody concentrations of greater than 2 mcg/mL for more than 30 days post HCT. A single dose of REGN421 was associated with protection from acute GVHD at day 0, while three weekly doses showed protection at day 0, 7, and 14, consistent with an impact of REGN421 during the early phases of T-cell activation.
Compared with animals receiving only supportive care, prophylaxis with REGN421 was associated with delayed acute GVHD onset and lengthened survival.
Of the 11 primates treated with REGN421, none developed clinical signs of gastrointestinal acute GVHD, whereas the majority of those receiving standard care or other preventive interventions did.
“Detailed analysis of acute GVHD clinical presentations in REGN421-treated animals in comparison to no treatment controls revealed near complete protection from GI-acute GvHD with REGN421,” the authors reported.
Furthermore, pathology scores in the gastrointestinal tract were lower with REGN421 treatment, compared with the no-treatment cohort, and the scores matched those of healthy nontransplanted nonhuman primates.
The primates treated with REGN421 did ultimately develop other clinical and pathologic signs of skin, hepatic or pulmonary acute GVHD, but without gastrointestinal disease.
The treatment was not associated with any adverse effects on the allo-HCT, with primates receiving either a single dose or three weekly doses of REGN421 showing rapid donor engraftment after allo-HCT, including high bone marrow, whole blood, and T-cell donor chimerism.
“Reassuringly, short-term systemic DLL4 blockade with REGN421 did not trigger unexpected side effects in our nonhuman primate model, while preserving rapid engraftment as well hematopoietic and immune reconstitution.”
The mechanism preserving the engraftment, described as a “major surprise,” specifically involved DLL4 inhibition blocking the homing of pathogenic T cells to the gut while preserving homing of regulatory T cells that dampen the immune response, Dr. Maillard explained.
“This effect turned out to be at least in part through a posttranslational effect of DLL4/Notch blockade on integrin pairing at the T-cell surface,” he explained. “This was a novel and quite unexpected mechanism of action conserved from mice to nonhuman primates.”
The results are encouraging in terms of translating to humans because of their closer similarities in various physiological factors, Dr. Maillard said.
“The nonhuman primate model of transplantation [offers] a transplantation model very close to what is being performed in humans, as well as the opportunity to study an immune system very similar to that of humans in nonhuman primates,” he said.
Dr. Maillard noted that, while trials in humans are not underway yet, “we are in active discussions about it,” and the team is indeed interested in testing REGN421 itself, with the effects likely to be as a prophylactic strategy.
There are currently no approved anti-DLL4 antibody drugs for use in humans.
“Our approach is mostly promising as a preventive treatment, rather than as a secondary treatment for GVHD, because DLL4/Notch blockade seems most active when applied early after transplantation during the time of initial seeding of the gut by T cells (in mice, we had observed the critical time window for a successful intervention to be within 48 hours of transplantation),” Dr. Maillard said.“There remain questions about which other prophylactic treatments we should ideally combine anti-DLL4 antibodies with.”
Dr. Maillard has received research funding from Regeneron and Genentech and is a member of Garuda Therapeutics’s scientific advisory board.
FROM SCIENCE TRANSLATIONAL MEDICINE
ESMO helps hematologists assess new cancer drugs
It consists of 11 2- to 3-page forms with checklists to grade treatment trials on the extent to which they meet efficacy and safety thresholds. Each of the 11 forms covers a specific trial scenario, such as a randomized controlled trial with curative intent or a trial of a therapy that is not likely to be curative with a primary endpoint of overall survival.
Treatments with curative intent are graded A, B, or C, while treatments in the noncurative setting are graded on a descending scale from 5 to 1. Scores of A and B in the curative setting and 5 and 4 in the noncurative setting represent substantial benefit.
On the form for RCTs with curative intent, for instance, a survival improvement of 5% or more garners an A but an improvement of less than 3% gets a C. Scores are also annotated for serious acute and/or persistent toxicity if present.
The tool, dubbed the ESMO-MCBS:H (European Society for Medical Oncology Magnitude of Clinical Benefit Scale: Hematology), is explained in an article published in Annals of Oncology. The evaluation forms are available online.
The idea behind the work is to help health care professionals and others to more “accurately assess the value of and prioritise therapies for patients with blood cancers. For clinicians, ESMO-MCBS:H will aid in their clinical decision-making and in the development of evidence-based practice and guidelines,” ESMO said in a press release.
To develop ESMO-MCBS:H, the group tailored its tool for evaluating solid tumor therapies, the ESMO-MCBS, to account for the sometimes different endpoints used in hematologic malignancy trials and the very indolent nature of some blood cancers, such as follicular lymphoma, which hampers development of mature data.
Specific changes include adding a new evaluation form to grade single-arm trials with curative intent, such as those used for CAR-T-cell therapies; incorporating molecular surrogate endpoints used in CML trials; and adding a way to grade outcomes for indolent cancers, among others.
The development process included applying the solid tumor tool to 80 blood cancer studies to identify shortcomings and improve its applicability. The final tool was field tested with 51 international experts from EHA and ESMO who largely agreed on the reasonableness of the trial scores.
ESMO said it expects ESMO-MCBS:H will be useful. The solid tumor tool, first published in 2015, is used by the World Health Organization to screen medications for its essential medicines list as well as by ESMO to generate guidelines and oncology centers across Europe to help with resource allocation decisions.
It consists of 11 2- to 3-page forms with checklists to grade treatment trials on the extent to which they meet efficacy and safety thresholds. Each of the 11 forms covers a specific trial scenario, such as a randomized controlled trial with curative intent or a trial of a therapy that is not likely to be curative with a primary endpoint of overall survival.
Treatments with curative intent are graded A, B, or C, while treatments in the noncurative setting are graded on a descending scale from 5 to 1. Scores of A and B in the curative setting and 5 and 4 in the noncurative setting represent substantial benefit.
On the form for RCTs with curative intent, for instance, a survival improvement of 5% or more garners an A but an improvement of less than 3% gets a C. Scores are also annotated for serious acute and/or persistent toxicity if present.
The tool, dubbed the ESMO-MCBS:H (European Society for Medical Oncology Magnitude of Clinical Benefit Scale: Hematology), is explained in an article published in Annals of Oncology. The evaluation forms are available online.
The idea behind the work is to help health care professionals and others to more “accurately assess the value of and prioritise therapies for patients with blood cancers. For clinicians, ESMO-MCBS:H will aid in their clinical decision-making and in the development of evidence-based practice and guidelines,” ESMO said in a press release.
To develop ESMO-MCBS:H, the group tailored its tool for evaluating solid tumor therapies, the ESMO-MCBS, to account for the sometimes different endpoints used in hematologic malignancy trials and the very indolent nature of some blood cancers, such as follicular lymphoma, which hampers development of mature data.
Specific changes include adding a new evaluation form to grade single-arm trials with curative intent, such as those used for CAR-T-cell therapies; incorporating molecular surrogate endpoints used in CML trials; and adding a way to grade outcomes for indolent cancers, among others.
The development process included applying the solid tumor tool to 80 blood cancer studies to identify shortcomings and improve its applicability. The final tool was field tested with 51 international experts from EHA and ESMO who largely agreed on the reasonableness of the trial scores.
ESMO said it expects ESMO-MCBS:H will be useful. The solid tumor tool, first published in 2015, is used by the World Health Organization to screen medications for its essential medicines list as well as by ESMO to generate guidelines and oncology centers across Europe to help with resource allocation decisions.
It consists of 11 2- to 3-page forms with checklists to grade treatment trials on the extent to which they meet efficacy and safety thresholds. Each of the 11 forms covers a specific trial scenario, such as a randomized controlled trial with curative intent or a trial of a therapy that is not likely to be curative with a primary endpoint of overall survival.
Treatments with curative intent are graded A, B, or C, while treatments in the noncurative setting are graded on a descending scale from 5 to 1. Scores of A and B in the curative setting and 5 and 4 in the noncurative setting represent substantial benefit.
On the form for RCTs with curative intent, for instance, a survival improvement of 5% or more garners an A but an improvement of less than 3% gets a C. Scores are also annotated for serious acute and/or persistent toxicity if present.
The tool, dubbed the ESMO-MCBS:H (European Society for Medical Oncology Magnitude of Clinical Benefit Scale: Hematology), is explained in an article published in Annals of Oncology. The evaluation forms are available online.
The idea behind the work is to help health care professionals and others to more “accurately assess the value of and prioritise therapies for patients with blood cancers. For clinicians, ESMO-MCBS:H will aid in their clinical decision-making and in the development of evidence-based practice and guidelines,” ESMO said in a press release.
To develop ESMO-MCBS:H, the group tailored its tool for evaluating solid tumor therapies, the ESMO-MCBS, to account for the sometimes different endpoints used in hematologic malignancy trials and the very indolent nature of some blood cancers, such as follicular lymphoma, which hampers development of mature data.
Specific changes include adding a new evaluation form to grade single-arm trials with curative intent, such as those used for CAR-T-cell therapies; incorporating molecular surrogate endpoints used in CML trials; and adding a way to grade outcomes for indolent cancers, among others.
The development process included applying the solid tumor tool to 80 blood cancer studies to identify shortcomings and improve its applicability. The final tool was field tested with 51 international experts from EHA and ESMO who largely agreed on the reasonableness of the trial scores.
ESMO said it expects ESMO-MCBS:H will be useful. The solid tumor tool, first published in 2015, is used by the World Health Organization to screen medications for its essential medicines list as well as by ESMO to generate guidelines and oncology centers across Europe to help with resource allocation decisions.
FROM ANNALS OF ONCOLOGY
Multiprong strategy makes clinical trials less White
CHICAGO – Clinical trials are so White. Only a small percentage of eligible patients participate in clinical trials in the first place, and very few come from racial and ethnic minority groups.
For example, according to the Food and Drug Administration, in trials that resulted in drug approvals from 2017 to 2020, only 2%-5% of participants were Black patients.
When clinical trials lack diverse patient populations, those who are left out have fewer opportunities to get new therapies. Moreover, the scope of the research is limited by smaller phenotypic and genotypic samples, and the trial results are applicable only to more homogeneous patient groups.
There has been a push to include more underrepresented patients in clinical trials. One group reported its success in doing so here at the annual meeting of the American Society of Clinical Oncology.
a period that included a pandemic-induced hiatus in clinical trials in general.
Alliance member Electra D. Paskett, PhD, from the College of Public Health at the Ohio State University in Columbus, presented accrual data from 117 trials led by the Alliance from 2014 to 2022.
During this period, accrual of racial and ethnic minority patients increased from 13.6% to 25.3% for cancer treatment trials and from 13% to 21.5% for cancer control trials.
Overall, the recruitment program resulted in an absolute increase from 13.5 % to 23.6% of underrepresented populations, which translated into a relative 74.8% improvement.
“We’re focusing now on monitoring accrual of women, rural populations, younger AYAs [adolescents and young adults] and older patients, and we’ll see what strategies we need to implement,” Dr. Packett told this news organization.
The Alliance has implemented a real-time accrual dashboard on its website that allows individual sites to review accrual by trial and overall for all of the identified underrepresented populations, she noted.
Program to increase underrepresented patient accrual
The impetus for the program to increase enrollment of underrepresented patients came from the goal set by Monica M. Bertagnolli, MD, group chair of the Alliance from 2011 to 2022 and currently the director of the U.S. National Cancer Institute.
“Our leader, Dr. Bertagnolli, set out a group-wide goal for accrual of underrepresented minorities to our trials of 20%, and that gave us permission to implement a whole host of new strategies,” Dr. Paskett said in an interview.
“These strategies follow the Accrual of Clinical Trials framework, which essentially says that the interaction between the patient and the provider for going on a clinical trial is not just an interaction between the patient and provider but recognizes, for example, that the provider has coworkers and they have norms and beliefs and attitudes, and the patient comes from a family with their own values. And then there are system-level barriers, and there are community barriers that all relate to this interaction about going on a trial,” Dr. Packett said.
What works?
The study was presented as a poster at the meeting. During the poster discussion session, comoderator Victoria S. Blinder, MD, from Memorial Sloan Kettering Cancer Center in New York, asked Dr. Paskett, “If you had a certain amount of money and you really wanted to use that resource to focus on one area, where would you put that resource?”
“I’m going to violate the rules of your question,” Dr. Paskett replied.
“You cannot change this problem by focusing on one thing, and that’s what we showed in our Alliance poster, and what I’ve said is based on over 30 years of work in this area,” she said.
She cited what she considered as the two most important components for improving accrual of underrepresented populations: a commitment by leadership to a recruitment goal, and the development of protocols with specific accrual goals for minority populations.
Still, those are only two components of a comprehensive program that includes the aforementioned accrual goal set by Dr. Bertagnolli, as well as the following:
- Funding of minority junior investigators and research that focuses on issues of concern to underrepresented populations.
- Establishment of work groups that focus on specific populations with the Alliance health disparities committee.
- Translation of informational materials for patients.
- Opening studies at National Cancer Institute Community. Oncology Research Program–designated minority underserved sites.
- Real-time monitoring of accrual demographics by the Alliance and at the trial site.
- Closing protocol enrollment to majority populations.
- Increasing the study sample sizes to enroll additional minority participants and to allow for subgroup analyses.
The study was funded by the National Institutes of Health. Dr. Packett and Dr. Blinder reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
CHICAGO – Clinical trials are so White. Only a small percentage of eligible patients participate in clinical trials in the first place, and very few come from racial and ethnic minority groups.
For example, according to the Food and Drug Administration, in trials that resulted in drug approvals from 2017 to 2020, only 2%-5% of participants were Black patients.
When clinical trials lack diverse patient populations, those who are left out have fewer opportunities to get new therapies. Moreover, the scope of the research is limited by smaller phenotypic and genotypic samples, and the trial results are applicable only to more homogeneous patient groups.
There has been a push to include more underrepresented patients in clinical trials. One group reported its success in doing so here at the annual meeting of the American Society of Clinical Oncology.
a period that included a pandemic-induced hiatus in clinical trials in general.
Alliance member Electra D. Paskett, PhD, from the College of Public Health at the Ohio State University in Columbus, presented accrual data from 117 trials led by the Alliance from 2014 to 2022.
During this period, accrual of racial and ethnic minority patients increased from 13.6% to 25.3% for cancer treatment trials and from 13% to 21.5% for cancer control trials.
Overall, the recruitment program resulted in an absolute increase from 13.5 % to 23.6% of underrepresented populations, which translated into a relative 74.8% improvement.
“We’re focusing now on monitoring accrual of women, rural populations, younger AYAs [adolescents and young adults] and older patients, and we’ll see what strategies we need to implement,” Dr. Packett told this news organization.
The Alliance has implemented a real-time accrual dashboard on its website that allows individual sites to review accrual by trial and overall for all of the identified underrepresented populations, she noted.
Program to increase underrepresented patient accrual
The impetus for the program to increase enrollment of underrepresented patients came from the goal set by Monica M. Bertagnolli, MD, group chair of the Alliance from 2011 to 2022 and currently the director of the U.S. National Cancer Institute.
“Our leader, Dr. Bertagnolli, set out a group-wide goal for accrual of underrepresented minorities to our trials of 20%, and that gave us permission to implement a whole host of new strategies,” Dr. Paskett said in an interview.
“These strategies follow the Accrual of Clinical Trials framework, which essentially says that the interaction between the patient and the provider for going on a clinical trial is not just an interaction between the patient and provider but recognizes, for example, that the provider has coworkers and they have norms and beliefs and attitudes, and the patient comes from a family with their own values. And then there are system-level barriers, and there are community barriers that all relate to this interaction about going on a trial,” Dr. Packett said.
What works?
The study was presented as a poster at the meeting. During the poster discussion session, comoderator Victoria S. Blinder, MD, from Memorial Sloan Kettering Cancer Center in New York, asked Dr. Paskett, “If you had a certain amount of money and you really wanted to use that resource to focus on one area, where would you put that resource?”
“I’m going to violate the rules of your question,” Dr. Paskett replied.
“You cannot change this problem by focusing on one thing, and that’s what we showed in our Alliance poster, and what I’ve said is based on over 30 years of work in this area,” she said.
She cited what she considered as the two most important components for improving accrual of underrepresented populations: a commitment by leadership to a recruitment goal, and the development of protocols with specific accrual goals for minority populations.
Still, those are only two components of a comprehensive program that includes the aforementioned accrual goal set by Dr. Bertagnolli, as well as the following:
- Funding of minority junior investigators and research that focuses on issues of concern to underrepresented populations.
- Establishment of work groups that focus on specific populations with the Alliance health disparities committee.
- Translation of informational materials for patients.
- Opening studies at National Cancer Institute Community. Oncology Research Program–designated minority underserved sites.
- Real-time monitoring of accrual demographics by the Alliance and at the trial site.
- Closing protocol enrollment to majority populations.
- Increasing the study sample sizes to enroll additional minority participants and to allow for subgroup analyses.
The study was funded by the National Institutes of Health. Dr. Packett and Dr. Blinder reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
CHICAGO – Clinical trials are so White. Only a small percentage of eligible patients participate in clinical trials in the first place, and very few come from racial and ethnic minority groups.
For example, according to the Food and Drug Administration, in trials that resulted in drug approvals from 2017 to 2020, only 2%-5% of participants were Black patients.
When clinical trials lack diverse patient populations, those who are left out have fewer opportunities to get new therapies. Moreover, the scope of the research is limited by smaller phenotypic and genotypic samples, and the trial results are applicable only to more homogeneous patient groups.
There has been a push to include more underrepresented patients in clinical trials. One group reported its success in doing so here at the annual meeting of the American Society of Clinical Oncology.
a period that included a pandemic-induced hiatus in clinical trials in general.
Alliance member Electra D. Paskett, PhD, from the College of Public Health at the Ohio State University in Columbus, presented accrual data from 117 trials led by the Alliance from 2014 to 2022.
During this period, accrual of racial and ethnic minority patients increased from 13.6% to 25.3% for cancer treatment trials and from 13% to 21.5% for cancer control trials.
Overall, the recruitment program resulted in an absolute increase from 13.5 % to 23.6% of underrepresented populations, which translated into a relative 74.8% improvement.
“We’re focusing now on monitoring accrual of women, rural populations, younger AYAs [adolescents and young adults] and older patients, and we’ll see what strategies we need to implement,” Dr. Packett told this news organization.
The Alliance has implemented a real-time accrual dashboard on its website that allows individual sites to review accrual by trial and overall for all of the identified underrepresented populations, she noted.
Program to increase underrepresented patient accrual
The impetus for the program to increase enrollment of underrepresented patients came from the goal set by Monica M. Bertagnolli, MD, group chair of the Alliance from 2011 to 2022 and currently the director of the U.S. National Cancer Institute.
“Our leader, Dr. Bertagnolli, set out a group-wide goal for accrual of underrepresented minorities to our trials of 20%, and that gave us permission to implement a whole host of new strategies,” Dr. Paskett said in an interview.
“These strategies follow the Accrual of Clinical Trials framework, which essentially says that the interaction between the patient and the provider for going on a clinical trial is not just an interaction between the patient and provider but recognizes, for example, that the provider has coworkers and they have norms and beliefs and attitudes, and the patient comes from a family with their own values. And then there are system-level barriers, and there are community barriers that all relate to this interaction about going on a trial,” Dr. Packett said.
What works?
The study was presented as a poster at the meeting. During the poster discussion session, comoderator Victoria S. Blinder, MD, from Memorial Sloan Kettering Cancer Center in New York, asked Dr. Paskett, “If you had a certain amount of money and you really wanted to use that resource to focus on one area, where would you put that resource?”
“I’m going to violate the rules of your question,” Dr. Paskett replied.
“You cannot change this problem by focusing on one thing, and that’s what we showed in our Alliance poster, and what I’ve said is based on over 30 years of work in this area,” she said.
She cited what she considered as the two most important components for improving accrual of underrepresented populations: a commitment by leadership to a recruitment goal, and the development of protocols with specific accrual goals for minority populations.
Still, those are only two components of a comprehensive program that includes the aforementioned accrual goal set by Dr. Bertagnolli, as well as the following:
- Funding of minority junior investigators and research that focuses on issues of concern to underrepresented populations.
- Establishment of work groups that focus on specific populations with the Alliance health disparities committee.
- Translation of informational materials for patients.
- Opening studies at National Cancer Institute Community. Oncology Research Program–designated minority underserved sites.
- Real-time monitoring of accrual demographics by the Alliance and at the trial site.
- Closing protocol enrollment to majority populations.
- Increasing the study sample sizes to enroll additional minority participants and to allow for subgroup analyses.
The study was funded by the National Institutes of Health. Dr. Packett and Dr. Blinder reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
AT ASCO 2023
CBSM phone app eases anxiety, depression in cancer patients
CHICAGO – One-third of patients with cancer also experience anxiety or depression, and an estimated 70% of the 18 million patients with cancer and cancer survivors in the US experience emotional symptoms, including fear of recurrence.
Despite many having these symptoms, few patients with cancer have access to psycho-oncologic support.
A digital cognitive-behavioral stress management (CBSM) application may help to ease some of the burden, reported Allison Ramiller, MPH, of Blue Note Therapeutics in San Francisco, which developed the app version of the program.
In addition, patients assigned to the CBSM app were twice as likely as control persons to report that their symptoms were “much” or “very much” improved after using the app for 12 weeks, Ms. Ramiller reported at an oral abstract session at the annual meeting of the American Society of Clinical Oncology (ASCO).
However, the investigators did not report baseline characteristics of patients in each of the study arms, which might have helped to clarify the depth of the effects they saw.
The CBSM program was developed by Michael H. Antoni, PhD, and colleagues in the University of Miami Health System. It is based on cognitive-behavioral therapy but also includes stress management and relaxation techniques to help patients cope with cancer-specific stress.
“”It has been clinically validated and shown to benefit patients with cancer,” Ms. Ramiller said. “However, access is a problem,” she said.
“There aren’t enough qualified, trained providers for the need, and patients with cancer encounter barriers to in-person participation, including things like transportation or financial barriers. So to overcome this, we developed a digitized version of CBSM,” she explained.
Impressive and elegant
“Everything about [the study] I thought was very impressive, very elegant, very nicely done,” said invited discussant Raymond U. Osarogiagbon, MBBS, FACP, chief scientist at Baptist Memorial Health Care Corp in Memphis, Tenn.
“They showed efficacy, they showed safety – very nice – user friendliness – very good. Certainly they look like they’re trying to address a highly important, unmet need in a very elegant way. Certainly, they pointed out it needs longer follow-up to see sustainability. We need to see will this work in other settings. Will this be cost-effective? You’ve gotta believe it probably will be,” he said.
CBSM has previously been shown to help patients with cancer reduce stress, improve general and cancer-specific quality of life at various stages of treatment, reduce symptom burden, and improve coping skills, Ms. Ramiller said.
To see whether these benefits could be conveyed digitally rather than in face-to-face encounters, Ms. Ramiller and colleagues worked with Dr. Antoni to develop the CBSM app.
Patients using the app received therapeutic content over 10 sessions with audio, video, and interactive tools that mimicked the sessions they would have received during in-person interventions.
They then compared the app against the control educational app in the randomized, decentralized RESTORE study.
High-quality control
Ms. Ramiller said that the control app set “a high bar.”
“The control also offered 10 interactive self-guided sessions. Both treatment apps were professionally designed and visually similar in styling, and they were presented as digital therapeutic-specific for cancer patients. And they were also in a match condition, meaning they received the same attention from study staff and cadence of reminders, but importantly, only the intervention app was based on CBSM,” she explained.
A total of 449 patients with cancers of stage I–III who were undergoing active systemic treatment or were planning to undergo such treatment within 6 months were randomly assigned to the CBSM app or the control app.
The CBSM app was superior to the control app for the primary outcome of anxiety reduction over baseline, as measured at 4, 8 and 12 weeks by the Patient-Reported Outcomes Measurement Information System Anxiety Scale (PROMIS-A) (beta = -.03; P = .019).
CBSM was also significantly better than the control app for the secondary endpoints of reducing symptoms of depression, as measured by the PROMIS-D scale (beta = -.02, P = .042), and also at increasing the percentage of patients who reported improvement in anxiety and depression symptoms on the Patient Global Impression of Change instrument (P < .001)
An extension study of the durability of the effects at 3 and 6 months is underway.
The investigators noted that the incremental cost of management of anxiety or depression is greater than $17,000 per patient per year.
“One of the big promises of a digital therapeutic like this is that it could potentially reduce costs,” Ms. Ramiller told the audience, but she acknowledged, “More work is really needed, however, to directly test the potential savings.”
The RESTORE study is funded by Blue Note Therapeutics. Dr. Osarogiagbon owns stock in Gilead, Lilly, and Pfizer, has received honoraria from Biodesix and Medscape, and has a consulting or advisory role for the American Cancer Society AstraZeneca, Genentech/Roche, LUNGevity, National Cancer Institute, and Triptych Health Partners.
A version of this article originally appeared on Medscape.com.
CHICAGO – One-third of patients with cancer also experience anxiety or depression, and an estimated 70% of the 18 million patients with cancer and cancer survivors in the US experience emotional symptoms, including fear of recurrence.
Despite many having these symptoms, few patients with cancer have access to psycho-oncologic support.
A digital cognitive-behavioral stress management (CBSM) application may help to ease some of the burden, reported Allison Ramiller, MPH, of Blue Note Therapeutics in San Francisco, which developed the app version of the program.
In addition, patients assigned to the CBSM app were twice as likely as control persons to report that their symptoms were “much” or “very much” improved after using the app for 12 weeks, Ms. Ramiller reported at an oral abstract session at the annual meeting of the American Society of Clinical Oncology (ASCO).
However, the investigators did not report baseline characteristics of patients in each of the study arms, which might have helped to clarify the depth of the effects they saw.
The CBSM program was developed by Michael H. Antoni, PhD, and colleagues in the University of Miami Health System. It is based on cognitive-behavioral therapy but also includes stress management and relaxation techniques to help patients cope with cancer-specific stress.
“”It has been clinically validated and shown to benefit patients with cancer,” Ms. Ramiller said. “However, access is a problem,” she said.
“There aren’t enough qualified, trained providers for the need, and patients with cancer encounter barriers to in-person participation, including things like transportation or financial barriers. So to overcome this, we developed a digitized version of CBSM,” she explained.
Impressive and elegant
“Everything about [the study] I thought was very impressive, very elegant, very nicely done,” said invited discussant Raymond U. Osarogiagbon, MBBS, FACP, chief scientist at Baptist Memorial Health Care Corp in Memphis, Tenn.
“They showed efficacy, they showed safety – very nice – user friendliness – very good. Certainly they look like they’re trying to address a highly important, unmet need in a very elegant way. Certainly, they pointed out it needs longer follow-up to see sustainability. We need to see will this work in other settings. Will this be cost-effective? You’ve gotta believe it probably will be,” he said.
CBSM has previously been shown to help patients with cancer reduce stress, improve general and cancer-specific quality of life at various stages of treatment, reduce symptom burden, and improve coping skills, Ms. Ramiller said.
To see whether these benefits could be conveyed digitally rather than in face-to-face encounters, Ms. Ramiller and colleagues worked with Dr. Antoni to develop the CBSM app.
Patients using the app received therapeutic content over 10 sessions with audio, video, and interactive tools that mimicked the sessions they would have received during in-person interventions.
They then compared the app against the control educational app in the randomized, decentralized RESTORE study.
High-quality control
Ms. Ramiller said that the control app set “a high bar.”
“The control also offered 10 interactive self-guided sessions. Both treatment apps were professionally designed and visually similar in styling, and they were presented as digital therapeutic-specific for cancer patients. And they were also in a match condition, meaning they received the same attention from study staff and cadence of reminders, but importantly, only the intervention app was based on CBSM,” she explained.
A total of 449 patients with cancers of stage I–III who were undergoing active systemic treatment or were planning to undergo such treatment within 6 months were randomly assigned to the CBSM app or the control app.
The CBSM app was superior to the control app for the primary outcome of anxiety reduction over baseline, as measured at 4, 8 and 12 weeks by the Patient-Reported Outcomes Measurement Information System Anxiety Scale (PROMIS-A) (beta = -.03; P = .019).
CBSM was also significantly better than the control app for the secondary endpoints of reducing symptoms of depression, as measured by the PROMIS-D scale (beta = -.02, P = .042), and also at increasing the percentage of patients who reported improvement in anxiety and depression symptoms on the Patient Global Impression of Change instrument (P < .001)
An extension study of the durability of the effects at 3 and 6 months is underway.
The investigators noted that the incremental cost of management of anxiety or depression is greater than $17,000 per patient per year.
“One of the big promises of a digital therapeutic like this is that it could potentially reduce costs,” Ms. Ramiller told the audience, but she acknowledged, “More work is really needed, however, to directly test the potential savings.”
The RESTORE study is funded by Blue Note Therapeutics. Dr. Osarogiagbon owns stock in Gilead, Lilly, and Pfizer, has received honoraria from Biodesix and Medscape, and has a consulting or advisory role for the American Cancer Society AstraZeneca, Genentech/Roche, LUNGevity, National Cancer Institute, and Triptych Health Partners.
A version of this article originally appeared on Medscape.com.
CHICAGO – One-third of patients with cancer also experience anxiety or depression, and an estimated 70% of the 18 million patients with cancer and cancer survivors in the US experience emotional symptoms, including fear of recurrence.
Despite many having these symptoms, few patients with cancer have access to psycho-oncologic support.
A digital cognitive-behavioral stress management (CBSM) application may help to ease some of the burden, reported Allison Ramiller, MPH, of Blue Note Therapeutics in San Francisco, which developed the app version of the program.
In addition, patients assigned to the CBSM app were twice as likely as control persons to report that their symptoms were “much” or “very much” improved after using the app for 12 weeks, Ms. Ramiller reported at an oral abstract session at the annual meeting of the American Society of Clinical Oncology (ASCO).
However, the investigators did not report baseline characteristics of patients in each of the study arms, which might have helped to clarify the depth of the effects they saw.
The CBSM program was developed by Michael H. Antoni, PhD, and colleagues in the University of Miami Health System. It is based on cognitive-behavioral therapy but also includes stress management and relaxation techniques to help patients cope with cancer-specific stress.
“”It has been clinically validated and shown to benefit patients with cancer,” Ms. Ramiller said. “However, access is a problem,” she said.
“There aren’t enough qualified, trained providers for the need, and patients with cancer encounter barriers to in-person participation, including things like transportation or financial barriers. So to overcome this, we developed a digitized version of CBSM,” she explained.
Impressive and elegant
“Everything about [the study] I thought was very impressive, very elegant, very nicely done,” said invited discussant Raymond U. Osarogiagbon, MBBS, FACP, chief scientist at Baptist Memorial Health Care Corp in Memphis, Tenn.
“They showed efficacy, they showed safety – very nice – user friendliness – very good. Certainly they look like they’re trying to address a highly important, unmet need in a very elegant way. Certainly, they pointed out it needs longer follow-up to see sustainability. We need to see will this work in other settings. Will this be cost-effective? You’ve gotta believe it probably will be,” he said.
CBSM has previously been shown to help patients with cancer reduce stress, improve general and cancer-specific quality of life at various stages of treatment, reduce symptom burden, and improve coping skills, Ms. Ramiller said.
To see whether these benefits could be conveyed digitally rather than in face-to-face encounters, Ms. Ramiller and colleagues worked with Dr. Antoni to develop the CBSM app.
Patients using the app received therapeutic content over 10 sessions with audio, video, and interactive tools that mimicked the sessions they would have received during in-person interventions.
They then compared the app against the control educational app in the randomized, decentralized RESTORE study.
High-quality control
Ms. Ramiller said that the control app set “a high bar.”
“The control also offered 10 interactive self-guided sessions. Both treatment apps were professionally designed and visually similar in styling, and they were presented as digital therapeutic-specific for cancer patients. And they were also in a match condition, meaning they received the same attention from study staff and cadence of reminders, but importantly, only the intervention app was based on CBSM,” she explained.
A total of 449 patients with cancers of stage I–III who were undergoing active systemic treatment or were planning to undergo such treatment within 6 months were randomly assigned to the CBSM app or the control app.
The CBSM app was superior to the control app for the primary outcome of anxiety reduction over baseline, as measured at 4, 8 and 12 weeks by the Patient-Reported Outcomes Measurement Information System Anxiety Scale (PROMIS-A) (beta = -.03; P = .019).
CBSM was also significantly better than the control app for the secondary endpoints of reducing symptoms of depression, as measured by the PROMIS-D scale (beta = -.02, P = .042), and also at increasing the percentage of patients who reported improvement in anxiety and depression symptoms on the Patient Global Impression of Change instrument (P < .001)
An extension study of the durability of the effects at 3 and 6 months is underway.
The investigators noted that the incremental cost of management of anxiety or depression is greater than $17,000 per patient per year.
“One of the big promises of a digital therapeutic like this is that it could potentially reduce costs,” Ms. Ramiller told the audience, but she acknowledged, “More work is really needed, however, to directly test the potential savings.”
The RESTORE study is funded by Blue Note Therapeutics. Dr. Osarogiagbon owns stock in Gilead, Lilly, and Pfizer, has received honoraria from Biodesix and Medscape, and has a consulting or advisory role for the American Cancer Society AstraZeneca, Genentech/Roche, LUNGevity, National Cancer Institute, and Triptych Health Partners.
A version of this article originally appeared on Medscape.com.
AT ASCO 2023
Huge underuse of germline testing for cancer patients
Information from germline genetic testing could affect a patient’s cancer care. For example, such testing could indicate that targeted therapies would be beneficial, and it would have implications for close relatives who may carry the same genes.
The finding that so few patients with newly diagnosed cancer were tested comes from an analysis of data on more than 1.3 million individuals across two U.S. states. The data were taken from the Surveillance, Epidemiology, and End Results (SEER) registry.
The rate is “well below guideline recommendations,” said study presenter Allison W. Kurian, MD, department of medicine, Stanford (Calif.) University.
“Innovative care delivery” is needed to tackle the problem, including the streamlining of pretest counseling, making posttest counseling more widely available, and employing long-term follow-up to track patient outcomes, she suggested.
“I do think this is a time for creative solutions of a number of different kinds,” she said. She suggested that lessons could be learned from the use of telemedicine during the COVID-19 pandemic. She also noted that “there have been some interesting studies on embedding genetic counselors in oncology clinics.”
Dr. Kurian presented the study at the annual meeting of the American Society of Clinical Oncology (ASCO). The study was simultaneously published in the Journal of the American Medical Association.
The current results represent a “missed opportunity for decrease the population-level burden of cancer,” experts noted in an accompanying editorial.
“Clinicians should recommend testing to their patients and provide them with the information necessary to make informed decisions about whether to undergo testing,” Zsofia K. Stadler, MD, and Deborah Schrag, MD, MPH, of Memorial Sloan Kettering Cancer Center, New York, wrote in their editorial.
They suggested novel approaches to widen access, such as use of point-of-care testing, telecounseling, and, in the future, chatbots to respond to patient questions.
“With greater emphasis on overcoming both health system and patient-level barriers to genetic cancer susceptibility testing for patients with cancer, treatment outcomes will improve and cancer diagnoses and related deaths in family members will be prevented,” they concluded.
At the meeting, invited discussant Erin Frances Cobain, MD, assistant professor of medical oncology, University of Michigan Health, Ann Arbor, referring to breast cancer as an example, said that progress has “stagnated” in recent years.
The study found a higher rate of gene testing among patients with newly diagnosed breast cancer, at just over 20%.
Dr. Cobain argued that this was still too low. She pointed out that “a recent study suggested that over 60% of individuals with an incident cancer diagnosis would meet criteria for genetic testing by National Comprehensive Cancer Network guidelines.
“This may be because testing is not offered, there may be poor access to genetic counseling resources, or patients may be offered testing but decline it,” she suggested.
One compelling reason to conduct genetic testing for patients newly diagnosed with breast cancer is that it may show that they are candidates for treatment with PARP (poly[ADP]-ribose polymerase) inhibitors, which “may have a direct impact on cancer-related mortality,” she pointed out.
“We need increased awareness and access to genetic testing resources for patients with breast cancer, particularly for racial and ethnic minorities,” she said.
Dr. Cobain also noted that finding variants of uncertain significance (VUS) was more likely among patients from racial and ethnic minorities than among White patients. She said such a finding “increases patient and physician anxiety,” and there may be “unclear optimal management recommendations for these patients.”
Details of the study
Germline genetic testing is “increasingly essential for cancer care,” Dr. Kurian said.
It is central to risk-adapted screening and secondary prevention, the use of targeted therapies, including PARP and checkpoint inhibitors, and cascade testing to identify at-risk relatives.
She pointed out that in clinical practice, testing has “evolved rapidly.” Panels include more and more genes. In addition, the cost of these tests is falling, and guidelines have become “more expansive.”
However, “little is known about genetic testing use and results,” Dr. Kurian noted.
The team therefore undertook the SEER-GeneLINK initiative, which involved patients aged ≥ 20 years who were diagnosed with cancer between Jan. 1, 2013, and March 31, 2019, and who were reported to statewide SEER registries in California and Georgia.
The team looked for patients for whom germline genetic test results had been reported by the four laboratories that performed the majority of patient testing in the two states. Results were categorized as pathogenic, benign, or VUS.
The results were classified on the basis of current guidelines for testing and/or management as related to breast/ovarian cancer, gastrointestinal cancer, other hereditary cancers, or those with no guidelines for testing or management.
Dr. Kurian reported that from an overall population of 1,412,388 patients diagnosed with cancer, 1,369,660 were eligible for inclusion. Of those, about half (51.9%) were women, and the majority (86.3%) were aged 50 years or older.
Many of these patients (61.4%) were non-Hispanic White persons, and slightly fewer than half (49.8%) were deemed to be in medium or high poverty, as determined using U.S. Census tract levels.
Overall, germline genetic testing was performed in 93,052 (6.8%) of patients over the study period.
Women were more likely to have undergone germline mutation testing than men, at 13.9% vs. 2.2%, as were patients aged 20-49 years, at 22.1% vs. 8.2% for those aged 50-69 years, and 3.3% for those aged 70 years and older.
The number of genes for which testing was conducted increased from a median of 2 in 2013 to 34 in 2019. Rates of VUS increased more than that for pathologic variants and substantially more so in non-White patients.
By 2019, the ratio of VUS to pathologic variants stood at 1.7 among White patients, vs. 3.9 among Asian patients, 3.6 among Black patients, and 2.2 among Hispanic patients.
The majority of identified pathologic variants that were related to the diagnosed cancer and genes with testing and/or management guidelines accounted for 67.5% to 94.9% of such variants.
Regarding specific cancer diagnoses, Dr. Kurian said that over the course of the study period, testing rates consistently exceeded 50% only among male breast cancer patients.
There were rapid increases in testing for ovarian cancer, from 28.0% of cases in 2013 to 54.0% in 2019. For pancreatic cancer, rates increased from 1.0% to 19.0% over the same period, and for prostate cancer, rates increased from 0.1% to 4.0%. She suggested that these increases in rates may be related to the approval of PARP inhibitors for use in these indications.
However, there was little change in the rates of germline mutation testing for lung cancer patients, from 01% in 2013 to 0.8% in 2019, and for other cancers, from 0.3% to 2.0%.
The results also revealed racial and ethnic differences in testing after controlling for age, cancer type, and year. Over the course of the study period, 8.0% of White patients underwent genetic testing, compared with 6.0% each for Asian, Black, and Hispanic patients and 5.0% for other patients (P < .001).
With regard specifically to male and female breast cancer and ovarian cancer, testing rates were 31% among White patients, 22% for Asian patients, 25% for Black patients, and 23% for Hispanic patients (P < .001).
Dr. Kurian acknowledged that the study is limited by a lack of testing from other laboratories and direct-to-consumer test data, although a recent survey suggested that this represents fewer than 5% of all germline genetic tests.
She also noted that the SEER registries do not collect data on family history or tumor sequencing.
The study was funded by the National Institutes of Health, and the Centers for Disease Control and Prevention. Dr. Kurian has relationships with Adela, Ambry Genetics, Color Genomics, GeneDx/BioReference, Genentech, InVitae, and Myriad Genetics. Other authors report numerous relationships with industry. Dr. Cobain has ties with AstraZeneca, Daiichi Sankyo, Athenex, Ayala Pharmaceuticals, bioTheranostics, and Immunomedics. Dr. Schrag has relationships with Merck, JAMA, AACR, and Grail. Dr. Stadler has ties with Adverum Biotechnologies, Genentech, Neurogene, Novartis, Optos Plc, Outlook Therapeutics, and Regeneron Pharmaceuticals.
A version of this article first appeared on Medscape.com.
Information from germline genetic testing could affect a patient’s cancer care. For example, such testing could indicate that targeted therapies would be beneficial, and it would have implications for close relatives who may carry the same genes.
The finding that so few patients with newly diagnosed cancer were tested comes from an analysis of data on more than 1.3 million individuals across two U.S. states. The data were taken from the Surveillance, Epidemiology, and End Results (SEER) registry.
The rate is “well below guideline recommendations,” said study presenter Allison W. Kurian, MD, department of medicine, Stanford (Calif.) University.
“Innovative care delivery” is needed to tackle the problem, including the streamlining of pretest counseling, making posttest counseling more widely available, and employing long-term follow-up to track patient outcomes, she suggested.
“I do think this is a time for creative solutions of a number of different kinds,” she said. She suggested that lessons could be learned from the use of telemedicine during the COVID-19 pandemic. She also noted that “there have been some interesting studies on embedding genetic counselors in oncology clinics.”
Dr. Kurian presented the study at the annual meeting of the American Society of Clinical Oncology (ASCO). The study was simultaneously published in the Journal of the American Medical Association.
The current results represent a “missed opportunity for decrease the population-level burden of cancer,” experts noted in an accompanying editorial.
“Clinicians should recommend testing to their patients and provide them with the information necessary to make informed decisions about whether to undergo testing,” Zsofia K. Stadler, MD, and Deborah Schrag, MD, MPH, of Memorial Sloan Kettering Cancer Center, New York, wrote in their editorial.
They suggested novel approaches to widen access, such as use of point-of-care testing, telecounseling, and, in the future, chatbots to respond to patient questions.
“With greater emphasis on overcoming both health system and patient-level barriers to genetic cancer susceptibility testing for patients with cancer, treatment outcomes will improve and cancer diagnoses and related deaths in family members will be prevented,” they concluded.
At the meeting, invited discussant Erin Frances Cobain, MD, assistant professor of medical oncology, University of Michigan Health, Ann Arbor, referring to breast cancer as an example, said that progress has “stagnated” in recent years.
The study found a higher rate of gene testing among patients with newly diagnosed breast cancer, at just over 20%.
Dr. Cobain argued that this was still too low. She pointed out that “a recent study suggested that over 60% of individuals with an incident cancer diagnosis would meet criteria for genetic testing by National Comprehensive Cancer Network guidelines.
“This may be because testing is not offered, there may be poor access to genetic counseling resources, or patients may be offered testing but decline it,” she suggested.
One compelling reason to conduct genetic testing for patients newly diagnosed with breast cancer is that it may show that they are candidates for treatment with PARP (poly[ADP]-ribose polymerase) inhibitors, which “may have a direct impact on cancer-related mortality,” she pointed out.
“We need increased awareness and access to genetic testing resources for patients with breast cancer, particularly for racial and ethnic minorities,” she said.
Dr. Cobain also noted that finding variants of uncertain significance (VUS) was more likely among patients from racial and ethnic minorities than among White patients. She said such a finding “increases patient and physician anxiety,” and there may be “unclear optimal management recommendations for these patients.”
Details of the study
Germline genetic testing is “increasingly essential for cancer care,” Dr. Kurian said.
It is central to risk-adapted screening and secondary prevention, the use of targeted therapies, including PARP and checkpoint inhibitors, and cascade testing to identify at-risk relatives.
She pointed out that in clinical practice, testing has “evolved rapidly.” Panels include more and more genes. In addition, the cost of these tests is falling, and guidelines have become “more expansive.”
However, “little is known about genetic testing use and results,” Dr. Kurian noted.
The team therefore undertook the SEER-GeneLINK initiative, which involved patients aged ≥ 20 years who were diagnosed with cancer between Jan. 1, 2013, and March 31, 2019, and who were reported to statewide SEER registries in California and Georgia.
The team looked for patients for whom germline genetic test results had been reported by the four laboratories that performed the majority of patient testing in the two states. Results were categorized as pathogenic, benign, or VUS.
The results were classified on the basis of current guidelines for testing and/or management as related to breast/ovarian cancer, gastrointestinal cancer, other hereditary cancers, or those with no guidelines for testing or management.
Dr. Kurian reported that from an overall population of 1,412,388 patients diagnosed with cancer, 1,369,660 were eligible for inclusion. Of those, about half (51.9%) were women, and the majority (86.3%) were aged 50 years or older.
Many of these patients (61.4%) were non-Hispanic White persons, and slightly fewer than half (49.8%) were deemed to be in medium or high poverty, as determined using U.S. Census tract levels.
Overall, germline genetic testing was performed in 93,052 (6.8%) of patients over the study period.
Women were more likely to have undergone germline mutation testing than men, at 13.9% vs. 2.2%, as were patients aged 20-49 years, at 22.1% vs. 8.2% for those aged 50-69 years, and 3.3% for those aged 70 years and older.
The number of genes for which testing was conducted increased from a median of 2 in 2013 to 34 in 2019. Rates of VUS increased more than that for pathologic variants and substantially more so in non-White patients.
By 2019, the ratio of VUS to pathologic variants stood at 1.7 among White patients, vs. 3.9 among Asian patients, 3.6 among Black patients, and 2.2 among Hispanic patients.
The majority of identified pathologic variants that were related to the diagnosed cancer and genes with testing and/or management guidelines accounted for 67.5% to 94.9% of such variants.
Regarding specific cancer diagnoses, Dr. Kurian said that over the course of the study period, testing rates consistently exceeded 50% only among male breast cancer patients.
There were rapid increases in testing for ovarian cancer, from 28.0% of cases in 2013 to 54.0% in 2019. For pancreatic cancer, rates increased from 1.0% to 19.0% over the same period, and for prostate cancer, rates increased from 0.1% to 4.0%. She suggested that these increases in rates may be related to the approval of PARP inhibitors for use in these indications.
However, there was little change in the rates of germline mutation testing for lung cancer patients, from 01% in 2013 to 0.8% in 2019, and for other cancers, from 0.3% to 2.0%.
The results also revealed racial and ethnic differences in testing after controlling for age, cancer type, and year. Over the course of the study period, 8.0% of White patients underwent genetic testing, compared with 6.0% each for Asian, Black, and Hispanic patients and 5.0% for other patients (P < .001).
With regard specifically to male and female breast cancer and ovarian cancer, testing rates were 31% among White patients, 22% for Asian patients, 25% for Black patients, and 23% for Hispanic patients (P < .001).
Dr. Kurian acknowledged that the study is limited by a lack of testing from other laboratories and direct-to-consumer test data, although a recent survey suggested that this represents fewer than 5% of all germline genetic tests.
She also noted that the SEER registries do not collect data on family history or tumor sequencing.
The study was funded by the National Institutes of Health, and the Centers for Disease Control and Prevention. Dr. Kurian has relationships with Adela, Ambry Genetics, Color Genomics, GeneDx/BioReference, Genentech, InVitae, and Myriad Genetics. Other authors report numerous relationships with industry. Dr. Cobain has ties with AstraZeneca, Daiichi Sankyo, Athenex, Ayala Pharmaceuticals, bioTheranostics, and Immunomedics. Dr. Schrag has relationships with Merck, JAMA, AACR, and Grail. Dr. Stadler has ties with Adverum Biotechnologies, Genentech, Neurogene, Novartis, Optos Plc, Outlook Therapeutics, and Regeneron Pharmaceuticals.
A version of this article first appeared on Medscape.com.
Information from germline genetic testing could affect a patient’s cancer care. For example, such testing could indicate that targeted therapies would be beneficial, and it would have implications for close relatives who may carry the same genes.
The finding that so few patients with newly diagnosed cancer were tested comes from an analysis of data on more than 1.3 million individuals across two U.S. states. The data were taken from the Surveillance, Epidemiology, and End Results (SEER) registry.
The rate is “well below guideline recommendations,” said study presenter Allison W. Kurian, MD, department of medicine, Stanford (Calif.) University.
“Innovative care delivery” is needed to tackle the problem, including the streamlining of pretest counseling, making posttest counseling more widely available, and employing long-term follow-up to track patient outcomes, she suggested.
“I do think this is a time for creative solutions of a number of different kinds,” she said. She suggested that lessons could be learned from the use of telemedicine during the COVID-19 pandemic. She also noted that “there have been some interesting studies on embedding genetic counselors in oncology clinics.”
Dr. Kurian presented the study at the annual meeting of the American Society of Clinical Oncology (ASCO). The study was simultaneously published in the Journal of the American Medical Association.
The current results represent a “missed opportunity for decrease the population-level burden of cancer,” experts noted in an accompanying editorial.
“Clinicians should recommend testing to their patients and provide them with the information necessary to make informed decisions about whether to undergo testing,” Zsofia K. Stadler, MD, and Deborah Schrag, MD, MPH, of Memorial Sloan Kettering Cancer Center, New York, wrote in their editorial.
They suggested novel approaches to widen access, such as use of point-of-care testing, telecounseling, and, in the future, chatbots to respond to patient questions.
“With greater emphasis on overcoming both health system and patient-level barriers to genetic cancer susceptibility testing for patients with cancer, treatment outcomes will improve and cancer diagnoses and related deaths in family members will be prevented,” they concluded.
At the meeting, invited discussant Erin Frances Cobain, MD, assistant professor of medical oncology, University of Michigan Health, Ann Arbor, referring to breast cancer as an example, said that progress has “stagnated” in recent years.
The study found a higher rate of gene testing among patients with newly diagnosed breast cancer, at just over 20%.
Dr. Cobain argued that this was still too low. She pointed out that “a recent study suggested that over 60% of individuals with an incident cancer diagnosis would meet criteria for genetic testing by National Comprehensive Cancer Network guidelines.
“This may be because testing is not offered, there may be poor access to genetic counseling resources, or patients may be offered testing but decline it,” she suggested.
One compelling reason to conduct genetic testing for patients newly diagnosed with breast cancer is that it may show that they are candidates for treatment with PARP (poly[ADP]-ribose polymerase) inhibitors, which “may have a direct impact on cancer-related mortality,” she pointed out.
“We need increased awareness and access to genetic testing resources for patients with breast cancer, particularly for racial and ethnic minorities,” she said.
Dr. Cobain also noted that finding variants of uncertain significance (VUS) was more likely among patients from racial and ethnic minorities than among White patients. She said such a finding “increases patient and physician anxiety,” and there may be “unclear optimal management recommendations for these patients.”
Details of the study
Germline genetic testing is “increasingly essential for cancer care,” Dr. Kurian said.
It is central to risk-adapted screening and secondary prevention, the use of targeted therapies, including PARP and checkpoint inhibitors, and cascade testing to identify at-risk relatives.
She pointed out that in clinical practice, testing has “evolved rapidly.” Panels include more and more genes. In addition, the cost of these tests is falling, and guidelines have become “more expansive.”
However, “little is known about genetic testing use and results,” Dr. Kurian noted.
The team therefore undertook the SEER-GeneLINK initiative, which involved patients aged ≥ 20 years who were diagnosed with cancer between Jan. 1, 2013, and March 31, 2019, and who were reported to statewide SEER registries in California and Georgia.
The team looked for patients for whom germline genetic test results had been reported by the four laboratories that performed the majority of patient testing in the two states. Results were categorized as pathogenic, benign, or VUS.
The results were classified on the basis of current guidelines for testing and/or management as related to breast/ovarian cancer, gastrointestinal cancer, other hereditary cancers, or those with no guidelines for testing or management.
Dr. Kurian reported that from an overall population of 1,412,388 patients diagnosed with cancer, 1,369,660 were eligible for inclusion. Of those, about half (51.9%) were women, and the majority (86.3%) were aged 50 years or older.
Many of these patients (61.4%) were non-Hispanic White persons, and slightly fewer than half (49.8%) were deemed to be in medium or high poverty, as determined using U.S. Census tract levels.
Overall, germline genetic testing was performed in 93,052 (6.8%) of patients over the study period.
Women were more likely to have undergone germline mutation testing than men, at 13.9% vs. 2.2%, as were patients aged 20-49 years, at 22.1% vs. 8.2% for those aged 50-69 years, and 3.3% for those aged 70 years and older.
The number of genes for which testing was conducted increased from a median of 2 in 2013 to 34 in 2019. Rates of VUS increased more than that for pathologic variants and substantially more so in non-White patients.
By 2019, the ratio of VUS to pathologic variants stood at 1.7 among White patients, vs. 3.9 among Asian patients, 3.6 among Black patients, and 2.2 among Hispanic patients.
The majority of identified pathologic variants that were related to the diagnosed cancer and genes with testing and/or management guidelines accounted for 67.5% to 94.9% of such variants.
Regarding specific cancer diagnoses, Dr. Kurian said that over the course of the study period, testing rates consistently exceeded 50% only among male breast cancer patients.
There were rapid increases in testing for ovarian cancer, from 28.0% of cases in 2013 to 54.0% in 2019. For pancreatic cancer, rates increased from 1.0% to 19.0% over the same period, and for prostate cancer, rates increased from 0.1% to 4.0%. She suggested that these increases in rates may be related to the approval of PARP inhibitors for use in these indications.
However, there was little change in the rates of germline mutation testing for lung cancer patients, from 01% in 2013 to 0.8% in 2019, and for other cancers, from 0.3% to 2.0%.
The results also revealed racial and ethnic differences in testing after controlling for age, cancer type, and year. Over the course of the study period, 8.0% of White patients underwent genetic testing, compared with 6.0% each for Asian, Black, and Hispanic patients and 5.0% for other patients (P < .001).
With regard specifically to male and female breast cancer and ovarian cancer, testing rates were 31% among White patients, 22% for Asian patients, 25% for Black patients, and 23% for Hispanic patients (P < .001).
Dr. Kurian acknowledged that the study is limited by a lack of testing from other laboratories and direct-to-consumer test data, although a recent survey suggested that this represents fewer than 5% of all germline genetic tests.
She also noted that the SEER registries do not collect data on family history or tumor sequencing.
The study was funded by the National Institutes of Health, and the Centers for Disease Control and Prevention. Dr. Kurian has relationships with Adela, Ambry Genetics, Color Genomics, GeneDx/BioReference, Genentech, InVitae, and Myriad Genetics. Other authors report numerous relationships with industry. Dr. Cobain has ties with AstraZeneca, Daiichi Sankyo, Athenex, Ayala Pharmaceuticals, bioTheranostics, and Immunomedics. Dr. Schrag has relationships with Merck, JAMA, AACR, and Grail. Dr. Stadler has ties with Adverum Biotechnologies, Genentech, Neurogene, Novartis, Optos Plc, Outlook Therapeutics, and Regeneron Pharmaceuticals.
A version of this article first appeared on Medscape.com.
AT ASCO 2023