AVAHO

PARIS – What do doctors know about their patients’ sexual health? Not a lot. What about oncologists who treat women with breast cancer? Not much more. Yet sexual dysfunction has a significant impact on the quality of life of patients during and after cancer.

To determine the extent of sexual dysfunction among women with breast cancer, Maria Alice Franzoi, MD, an oncologist at Gustave Roussy Hospital, Villejuif, France, analyzed data concerning sexuality from the CANTO cohort study. She showed that sexual dysfunction often predates the cancer diagnosis and doesn’t improve but rather worsens in the following 2 years. She presented her results at the annual meeting of the European Society for Medical Oncology.
 

Present at diagnosis

Dr. Franzoi, whose research projects have focused on patient monitoring post cancer, drew her conclusions from the data provided by CANTO, a longitudinal, prospective cohort study that monitors women being treated for localized breast cancer. Study participants answered the EORTC-QLQ-BR23 quality-of-life questionnaire at the time of diagnosis (T0), 1 year after diagnosis (T1), and 2 years after diagnosis (T2). Four factors were employed to better define women’s sex-related problems: poor body image, poor sexual functioning (activity and desire), lack of sexual pleasure, and a complete lack of sexual activity.

The analysis focused on the responses of 7,895 patients in the CANTO cohort study on sexual activity; 4,523 of those patients answered questions about sexual pleasure. Female respondents who reported engaging in no sexual activity did not have to answer the questions in this second section.

“Seventy-five percent of patients reported at least one of the four concerns during the study,” noted Dr. Franzoi during her presentation. This finding highlights the fact that “sexual problems are already present at the time of diagnosis in a considerable number of patients,” she said. More than a third of participants complained of at least one of the four items.
 

Developments after diagnosis

The proportion of women who reported no arousal or poor sexual function remained stable at around 30% over time, meaning that the sexual problems were reported in similar numbers at T0, T1, and T2. “However, after cancer, more patients are worried about a lack of sexual pleasure (38.7% at T1 and 38.1% at T2, vs. 29.1% at T0) or report having a negative body image (57.8% at T1 and 52.5% at T2, vs. 32.1% at T0),” said Dr. Franzoi.

She identified the following three variables as being associated with sexual dysfunction 2 years after diagnosis: the existence of this problem at the time of diagnosis, the use of adjuvant hormone therapy, and severe depression or a very high stress level after the first year of treatment.
 

Inadequate specific treatment

“Sexual dysfunction is a major unmet need with a significant impact on quality of life,” said Maryam Lustberg, MD, an oncologist at Yale School of Medicine, New Haven, Conn., who was invited to discuss the results at the conference.

Dr. Franzoi observed that most participants with sexual dysfunction that had continued 2 years after diagnosis had not been referred to a doctor for this problem. “In terms of sexual function, it’s better at T2 than at T1, but only 41% of these women have been seen by a gynecologist, and only 15% have received specific treatment,” she reported, emphasizing the need to assess and treat these issues “proactively” at the time of diagnosis and during and after treatment.

“Now we need to work out what the best treatment approach is,” commented Dr. Lustberg. She said that cancers other than breast and gynecologic cancers should also be taken into consideration. She cited the Sexual Health Assessment in Women With Lung Cancer study, which recently revealed that after being diagnosed with lung cancer, female patients experienced a drop in sexual desire (31% vs. 15% before diagnosis) and an increase in vaginal discomfort or dryness (43% vs. 13% before diagnosis). This study, presented in August to the 2022 International Association for the Study of Lung Cancer World Conference on Lung Cancer, also revealed that different parameters affect satisfaction in one’s sex life, including fatigue, sadness, relationship problems with a partner, and even breathing. Dr. Lustberg concluded from this study that a multidisciplinary approach is needed for cancer survivors.

Dr. Franzoi received research funding from Resilience Care. Dr. Lustberg has links with AstraZeneca, Pfizer, Novartis, Sanofi, and Lilly.

This article was translated from the Medscape French edition.

PARIS – What do doctors know about their patients’ sexual health? Not a lot. What about oncologists who treat women with breast cancer? Not much more. Yet sexual dysfunction has a significant impact on the quality of life of patients during and after cancer.

To determine the extent of sexual dysfunction among women with breast cancer, Maria Alice Franzoi, MD, an oncologist at Gustave Roussy Hospital, Villejuif, France, analyzed data concerning sexuality from the CANTO cohort study. She showed that sexual dysfunction often predates the cancer diagnosis and doesn’t improve but rather worsens in the following 2 years. She presented her results at the annual meeting of the European Society for Medical Oncology.
 

Present at diagnosis

Dr. Franzoi, whose research projects have focused on patient monitoring post cancer, drew her conclusions from the data provided by CANTO, a longitudinal, prospective cohort study that monitors women being treated for localized breast cancer. Study participants answered the EORTC-QLQ-BR23 quality-of-life questionnaire at the time of diagnosis (T0), 1 year after diagnosis (T1), and 2 years after diagnosis (T2). Four factors were employed to better define women’s sex-related problems: poor body image, poor sexual functioning (activity and desire), lack of sexual pleasure, and a complete lack of sexual activity.

The analysis focused on the responses of 7,895 patients in the CANTO cohort study on sexual activity; 4,523 of those patients answered questions about sexual pleasure. Female respondents who reported engaging in no sexual activity did not have to answer the questions in this second section.

“Seventy-five percent of patients reported at least one of the four concerns during the study,” noted Dr. Franzoi during her presentation. This finding highlights the fact that “sexual problems are already present at the time of diagnosis in a considerable number of patients,” she said. More than a third of participants complained of at least one of the four items.
 

Developments after diagnosis

The proportion of women who reported no arousal or poor sexual function remained stable at around 30% over time, meaning that the sexual problems were reported in similar numbers at T0, T1, and T2. “However, after cancer, more patients are worried about a lack of sexual pleasure (38.7% at T1 and 38.1% at T2, vs. 29.1% at T0) or report having a negative body image (57.8% at T1 and 52.5% at T2, vs. 32.1% at T0),” said Dr. Franzoi.

She identified the following three variables as being associated with sexual dysfunction 2 years after diagnosis: the existence of this problem at the time of diagnosis, the use of adjuvant hormone therapy, and severe depression or a very high stress level after the first year of treatment.
 

Inadequate specific treatment

“Sexual dysfunction is a major unmet need with a significant impact on quality of life,” said Maryam Lustberg, MD, an oncologist at Yale School of Medicine, New Haven, Conn., who was invited to discuss the results at the conference.

Dr. Franzoi observed that most participants with sexual dysfunction that had continued 2 years after diagnosis had not been referred to a doctor for this problem. “In terms of sexual function, it’s better at T2 than at T1, but only 41% of these women have been seen by a gynecologist, and only 15% have received specific treatment,” she reported, emphasizing the need to assess and treat these issues “proactively” at the time of diagnosis and during and after treatment.

“Now we need to work out what the best treatment approach is,” commented Dr. Lustberg. She said that cancers other than breast and gynecologic cancers should also be taken into consideration. She cited the Sexual Health Assessment in Women With Lung Cancer study, which recently revealed that after being diagnosed with lung cancer, female patients experienced a drop in sexual desire (31% vs. 15% before diagnosis) and an increase in vaginal discomfort or dryness (43% vs. 13% before diagnosis). This study, presented in August to the 2022 International Association for the Study of Lung Cancer World Conference on Lung Cancer, also revealed that different parameters affect satisfaction in one’s sex life, including fatigue, sadness, relationship problems with a partner, and even breathing. Dr. Lustberg concluded from this study that a multidisciplinary approach is needed for cancer survivors.

Dr. Franzoi received research funding from Resilience Care. Dr. Lustberg has links with AstraZeneca, Pfizer, Novartis, Sanofi, and Lilly.

This article was translated from the Medscape French edition.

PARIS – What do doctors know about their patients’ sexual health? Not a lot. What about oncologists who treat women with breast cancer? Not much more. Yet sexual dysfunction has a significant impact on the quality of life of patients during and after cancer.

To determine the extent of sexual dysfunction among women with breast cancer, Maria Alice Franzoi, MD, an oncologist at Gustave Roussy Hospital, Villejuif, France, analyzed data concerning sexuality from the CANTO cohort study. She showed that sexual dysfunction often predates the cancer diagnosis and doesn’t improve but rather worsens in the following 2 years. She presented her results at the annual meeting of the European Society for Medical Oncology.
 

Present at diagnosis

Dr. Franzoi, whose research projects have focused on patient monitoring post cancer, drew her conclusions from the data provided by CANTO, a longitudinal, prospective cohort study that monitors women being treated for localized breast cancer. Study participants answered the EORTC-QLQ-BR23 quality-of-life questionnaire at the time of diagnosis (T0), 1 year after diagnosis (T1), and 2 years after diagnosis (T2). Four factors were employed to better define women’s sex-related problems: poor body image, poor sexual functioning (activity and desire), lack of sexual pleasure, and a complete lack of sexual activity.

The analysis focused on the responses of 7,895 patients in the CANTO cohort study on sexual activity; 4,523 of those patients answered questions about sexual pleasure. Female respondents who reported engaging in no sexual activity did not have to answer the questions in this second section.

“Seventy-five percent of patients reported at least one of the four concerns during the study,” noted Dr. Franzoi during her presentation. This finding highlights the fact that “sexual problems are already present at the time of diagnosis in a considerable number of patients,” she said. More than a third of participants complained of at least one of the four items.
 

Developments after diagnosis

The proportion of women who reported no arousal or poor sexual function remained stable at around 30% over time, meaning that the sexual problems were reported in similar numbers at T0, T1, and T2. “However, after cancer, more patients are worried about a lack of sexual pleasure (38.7% at T1 and 38.1% at T2, vs. 29.1% at T0) or report having a negative body image (57.8% at T1 and 52.5% at T2, vs. 32.1% at T0),” said Dr. Franzoi.

She identified the following three variables as being associated with sexual dysfunction 2 years after diagnosis: the existence of this problem at the time of diagnosis, the use of adjuvant hormone therapy, and severe depression or a very high stress level after the first year of treatment.
 

Inadequate specific treatment

“Sexual dysfunction is a major unmet need with a significant impact on quality of life,” said Maryam Lustberg, MD, an oncologist at Yale School of Medicine, New Haven, Conn., who was invited to discuss the results at the conference.

Dr. Franzoi observed that most participants with sexual dysfunction that had continued 2 years after diagnosis had not been referred to a doctor for this problem. “In terms of sexual function, it’s better at T2 than at T1, but only 41% of these women have been seen by a gynecologist, and only 15% have received specific treatment,” she reported, emphasizing the need to assess and treat these issues “proactively” at the time of diagnosis and during and after treatment.

“Now we need to work out what the best treatment approach is,” commented Dr. Lustberg. She said that cancers other than breast and gynecologic cancers should also be taken into consideration. She cited the Sexual Health Assessment in Women With Lung Cancer study, which recently revealed that after being diagnosed with lung cancer, female patients experienced a drop in sexual desire (31% vs. 15% before diagnosis) and an increase in vaginal discomfort or dryness (43% vs. 13% before diagnosis). This study, presented in August to the 2022 International Association for the Study of Lung Cancer World Conference on Lung Cancer, also revealed that different parameters affect satisfaction in one’s sex life, including fatigue, sadness, relationship problems with a partner, and even breathing. Dr. Lustberg concluded from this study that a multidisciplinary approach is needed for cancer survivors.

Dr. Franzoi received research funding from Resilience Care. Dr. Lustberg has links with AstraZeneca, Pfizer, Novartis, Sanofi, and Lilly.

This article was translated from the Medscape French edition.

This transcript has been edited for clarity.

John Whyte, MD: Welcome, everyone. I’m Dr John Whyte. I’m the chief medical officer at WebMD, and I’m joined today by Fabrice André. He is the chair of the scientific committee at the European Society for Medical Oncology, where we are today in Paris, France. Bonjour, Fabrice.

So, remind our viewers: What is ESMO? What does it do? And why is it so important?

Fabrice André, MD, PhD: First ESMO, is a scientific society – a member-based organization with around 25,000 members.

Dr. Whyte: Equivalent to ASCO (American Society of Clinical Oncology) in the United States, correct?

Dr. André: It has members worldwide, from all over the world. And it aims at disseminating science, educating. The name is European, so it has some roots in Europe; but it is really a global organization for education, dissemination, and also more and more to generate frameworks for the standards of treatment and the common terminology for healthcare professionals to better care for patients.

Dr. Whyte: What are you most excited by at this conference in terms of the innovations that are being discussed?

Dr. André: Today we are at ESMO 2022 in Paris, with 28,000 people registered and the vast majority on site, and what has been the editorial line – the tagline – for the scientific committee is “understand the disease to better treat the patient.” This is extremely important; all of the educational program is built on this tagline, meaning that we need to understand what are the mechanisms of cancer progression? What are the determinants of outcomes if we want to integrate all the wealth of innovation that is coming?

So, then, what are the new things? In the Presidential Symposium, where we usually have the very new things, we will have very important presentations on the role of pollution on cancer and the biological mechanism that induces cancer. Why is it important? First, it has impact on public health. But also, it’s important because, for us, it’s raising the signal that the oncology community must start to invest in this field of prevention.

Dr. Whyte: I was at your booth, by the way, the ESMO booth here, and you have two bicycles, which impressed me. Nobody was on them, I might point out, but the focus was on prevention. But let’s also address how historically, the academic community, the scientific community hasn’t really been focused on prevention. It’s about treatment. So it’s fascinating that you’re talking about prevention, because usually we talk about precision medicine, right? We talk about checkpoint inhibitors; we talk about immunomodulators. And here you’re saying, “Hey, John, we need to understand how we prevent cancer,” which is really a misnomer in a way, because there are many different diseases. Would you agree with that?

Dr. André: I fully agree with you. But what is the premise we are trying to address here? The premise is that prevention has always been very low in the agenda of international conferences. And we think we want to give the signal that it’s really time now that clinical infrastructure, hospitals, invest in this field, create teams dedicated to prevention, new structures for prevention. Why? Because we are discovering step by step that it could be that some drugs we use for patients with cancer could also be developed in the field of prevention. And for this, we need the oncologists. So, more and more, our conviction is that it is the oncology community that will transform the field of prevention, and we need to invest now. Having said that, we have two very important abstracts on this question. The other one is about early cancer detection. But of course, we have our traditional session on immunotherapeutics, precision medicine, and all the wealth of randomized trials. And so in this field, for patients with cancer, what is the new information?

Dr. Whyte: We have this whole continuum. So you talk about prevention – how much cancer is preventable? Eighty percent? Seventy percent? What do you estimate?

Dr. André: You know, I’m also a scientist. So as a scientist, I will say that there is no limit for this question. No, the only limit is the knowledge.

Dr. Whyte: Well, there is some inherited mutation, so we do know that.

Dr. André: We can just go to the current status – what we know now – but I don’t see why we would put some limit on how much we can prevent cancer. But indeed, so far, what are the risk factors? Genetics, hereditary cancer, all habits, and we know them. It’s about tobacco, alcohol, sun, some sexual behavior, etc., that indeed account. In France, we say that around 40% of cancer could be preventable.

Dr. Whyte: More and more, we learn about the issues of gout, other inflammatory diseases; it can have an association, but then we have early screening as well. So, if we’re on this continuum, how excited are you by what’s happening with liquid biopsies, with other testing? Because if we can get a cancer instead of at 500,000 cells at the time of imaging, at 10 or 50 cells, while there are fragments, that’s revolutionary, isn’t it?

Dr. André: I fully agree with you. We will have an important trial presented during ESMO that is the first prospective trial testing the device called Galleri, a tool for early cancer detection based on ctDNA (circulating tumor DNA) analysis by methylation pattern.

Dr. Whyte: General screening of the population or a more tailored population with certain indications? Because right now, most of those have focused on a limited population or are used for patients who already have a cancer, and testing that way – you think it’s going to be broader?

Dr. André: What this trial is investigating is in participants who do not have cancer, 6,000 participants ...

Dr. Whyte: Pas de tout? No cancer at all?

Dr. André: No cancer.

Dr. Whyte: No family history?

Dr. André: They can have family history, but no detectable cancer – can ctDNA analysis detect cancer? And the answer is, indeed, there is around 1% positivity, and around 40% of them, indeed, had cancer. So why is it important? Because it’s really a landmark prospective trial that is telling us that a device based on ctDNA can detect cancer at early stage. Then, how many cancers? What percentage?

Dr. Whyte: Which type of cancer?

Dr. André: And is it going to have an impact on outcome? And for all the questions, we don’t have the answer here. But the answer we have here today is that with this device, done prospectively, you can detect some cancer that would not be detectable without symptoms.

Dr. Whyte: It’s only going to get better, too.

Dr. André: Yeah. So then the next step is improving technology, integrating this technology with other ones we already have, in order to increase the percentage of patients in which we detect cancer at an earlier stage.

Dr. Whyte: What about pancreatic cancer, cancers we can’t detect through screening? People forget that most cancers cannot be detected through screening, so we need better tools. We do know that there are inherited mutations. Those really aren’t preventable in many ways; the goal is to get them early. So then we move to treatments, and you talked about precision medicine. What excites you about what’s going on these days at ESMO right now.

Dr. André: We have many trials on precision medicine. We will have two randomized trials that investigate two new targets; one is gamma secretase inhibitor. So, it’s a first-in-class, first time we even hear about this target at a clinical conference. And the second highly expected trial is a clinical trial in patients with metastatic lung cancer, KRAS mutated, testing sotorasib, which is a KRAS inhibitor, and showing the magnitude of improvement associated with sotorasib. The trial is positive, and it improved PFS [progression-free survival] in these patients. So these are two new targets that are validated at this conference.

Then, if we go on another topic of genomics, there is a question that is extremely important: Can we define patients who present an outlier sensitivity to immunotherapeutics? There will be one trial presented in the Presidential Symposium of immunotherapeutics in patients with colon cancer and microsatellite instability (MSI), showing that a few weeks of immunotherapeutics followed by surgery can cure patients. Why is it important? It’s important because we are all facing a shortage in the healthcare workforce. We have fewer nurses, fewer doctors, and we all have issues of sustainability. So, really now is the time to think about precision medicine, how precision medicine, by identifying outlier responders, can decrease the amount of resources we need to cure a patient. And this trial on immunotherapeutics, guided by genomics, is exactly this point: 8 weeks of treatment to cure a patient.

Dr. Whyte: Do you think there’s going to be a cure for cancer 10 years from now?

Dr. André: What I’m convinced of is that, in the 10 years that are coming, we are going step by step; we’re going to continue to increase the life expectancy of patients with cancer.

Dr. Whyte: And quality of life too, right?

Dr. André: Quality of life is a major issue. We had today a keynote on digital medicine and how ePRO (electronic patient-reported outcomes) can help the patient to really decrease the burden of symptoms. Quality of life is, of course, extremely important because of the very high number of patients who are cured of cancer; we need to decrease the burden of symptom in patients.

Dr. Whyte: And even though cancer rates are going down in most areas of the world, we still globally have millions of deaths from cancer every year. And sometimes people forget that, because they hear about some of the innovations. But I want to end with this: Are we investing enough in cancer care? Because let’s be honest – there are other diseases that we also need to spend time on. Cardiovascular disease is a global burden; infectious disease is a global burden. Are governments, are industries spending enough on cancer research and development?

Dr. André: Well, we can always claim for more, no? This is how everyone is trying to be, I think. But the reality is that we are living in a world where we have limited resources. I think what is more important for me is to be sure that any euro or dollar invested in cancer research is well used and generates an impact for patients. That is the most important, I think.

Dr. Whyte: And that’s why outcomes are so important in this research.

Dr. André: My conviction is that we have the tools, meaning the knowledge, the biotechnology, to really go the next step in terms of improving outcomes for patients. And for this, we now need clinical trials and translational research, but the tools, meaning basic science, basic knowledge, biotechnology – the basement for progress is here. We need now to transform this into direct impact for the patient. But I would not like to finish by saying we need more money in the field; what we need are people who can transform one euro, one dollar into concrete and measurable advances.

Dr. Whyte: We’re going to need more time on another day because I want to ask you about diversity in clinical trials, how important that is. I want to ask you about pediatric cancers; there are a whole bunch of things that I want to talk to you about. So hopefully we’ll find more time when we’re not at a big international conference such as ESMO. So, Dr Fabrice André, I want to thank you for taking time today.

Dr. André: Thank you and have a nice day.

Dr. Whyte: Stay tuned for a future discussion with Dr André on more about where we’re going in terms of cancer research and development. Thanks for watching, everyone.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

John Whyte, MD: Welcome, everyone. I’m Dr John Whyte. I’m the chief medical officer at WebMD, and I’m joined today by Fabrice André. He is the chair of the scientific committee at the European Society for Medical Oncology, where we are today in Paris, France. Bonjour, Fabrice.

So, remind our viewers: What is ESMO? What does it do? And why is it so important?

Fabrice André, MD, PhD: First ESMO, is a scientific society – a member-based organization with around 25,000 members.

Dr. Whyte: Equivalent to ASCO (American Society of Clinical Oncology) in the United States, correct?

Dr. André: It has members worldwide, from all over the world. And it aims at disseminating science, educating. The name is European, so it has some roots in Europe; but it is really a global organization for education, dissemination, and also more and more to generate frameworks for the standards of treatment and the common terminology for healthcare professionals to better care for patients.

Dr. Whyte: What are you most excited by at this conference in terms of the innovations that are being discussed?

Dr. André: Today we are at ESMO 2022 in Paris, with 28,000 people registered and the vast majority on site, and what has been the editorial line – the tagline – for the scientific committee is “understand the disease to better treat the patient.” This is extremely important; all of the educational program is built on this tagline, meaning that we need to understand what are the mechanisms of cancer progression? What are the determinants of outcomes if we want to integrate all the wealth of innovation that is coming?

So, then, what are the new things? In the Presidential Symposium, where we usually have the very new things, we will have very important presentations on the role of pollution on cancer and the biological mechanism that induces cancer. Why is it important? First, it has impact on public health. But also, it’s important because, for us, it’s raising the signal that the oncology community must start to invest in this field of prevention.

Dr. Whyte: I was at your booth, by the way, the ESMO booth here, and you have two bicycles, which impressed me. Nobody was on them, I might point out, but the focus was on prevention. But let’s also address how historically, the academic community, the scientific community hasn’t really been focused on prevention. It’s about treatment. So it’s fascinating that you’re talking about prevention, because usually we talk about precision medicine, right? We talk about checkpoint inhibitors; we talk about immunomodulators. And here you’re saying, “Hey, John, we need to understand how we prevent cancer,” which is really a misnomer in a way, because there are many different diseases. Would you agree with that?

Dr. André: I fully agree with you. But what is the premise we are trying to address here? The premise is that prevention has always been very low in the agenda of international conferences. And we think we want to give the signal that it’s really time now that clinical infrastructure, hospitals, invest in this field, create teams dedicated to prevention, new structures for prevention. Why? Because we are discovering step by step that it could be that some drugs we use for patients with cancer could also be developed in the field of prevention. And for this, we need the oncologists. So, more and more, our conviction is that it is the oncology community that will transform the field of prevention, and we need to invest now. Having said that, we have two very important abstracts on this question. The other one is about early cancer detection. But of course, we have our traditional session on immunotherapeutics, precision medicine, and all the wealth of randomized trials. And so in this field, for patients with cancer, what is the new information?

Dr. Whyte: We have this whole continuum. So you talk about prevention – how much cancer is preventable? Eighty percent? Seventy percent? What do you estimate?

Dr. André: You know, I’m also a scientist. So as a scientist, I will say that there is no limit for this question. No, the only limit is the knowledge.

Dr. Whyte: Well, there is some inherited mutation, so we do know that.

Dr. André: We can just go to the current status – what we know now – but I don’t see why we would put some limit on how much we can prevent cancer. But indeed, so far, what are the risk factors? Genetics, hereditary cancer, all habits, and we know them. It’s about tobacco, alcohol, sun, some sexual behavior, etc., that indeed account. In France, we say that around 40% of cancer could be preventable.

Dr. Whyte: More and more, we learn about the issues of gout, other inflammatory diseases; it can have an association, but then we have early screening as well. So, if we’re on this continuum, how excited are you by what’s happening with liquid biopsies, with other testing? Because if we can get a cancer instead of at 500,000 cells at the time of imaging, at 10 or 50 cells, while there are fragments, that’s revolutionary, isn’t it?

Dr. André: I fully agree with you. We will have an important trial presented during ESMO that is the first prospective trial testing the device called Galleri, a tool for early cancer detection based on ctDNA (circulating tumor DNA) analysis by methylation pattern.

Dr. Whyte: General screening of the population or a more tailored population with certain indications? Because right now, most of those have focused on a limited population or are used for patients who already have a cancer, and testing that way – you think it’s going to be broader?

Dr. André: What this trial is investigating is in participants who do not have cancer, 6,000 participants ...

Dr. Whyte: Pas de tout? No cancer at all?

Dr. André: No cancer.

Dr. Whyte: No family history?

Dr. André: They can have family history, but no detectable cancer – can ctDNA analysis detect cancer? And the answer is, indeed, there is around 1% positivity, and around 40% of them, indeed, had cancer. So why is it important? Because it’s really a landmark prospective trial that is telling us that a device based on ctDNA can detect cancer at early stage. Then, how many cancers? What percentage?

Dr. Whyte: Which type of cancer?

Dr. André: And is it going to have an impact on outcome? And for all the questions, we don’t have the answer here. But the answer we have here today is that with this device, done prospectively, you can detect some cancer that would not be detectable without symptoms.

Dr. Whyte: It’s only going to get better, too.

Dr. André: Yeah. So then the next step is improving technology, integrating this technology with other ones we already have, in order to increase the percentage of patients in which we detect cancer at an earlier stage.

Dr. Whyte: What about pancreatic cancer, cancers we can’t detect through screening? People forget that most cancers cannot be detected through screening, so we need better tools. We do know that there are inherited mutations. Those really aren’t preventable in many ways; the goal is to get them early. So then we move to treatments, and you talked about precision medicine. What excites you about what’s going on these days at ESMO right now.

Dr. André: We have many trials on precision medicine. We will have two randomized trials that investigate two new targets; one is gamma secretase inhibitor. So, it’s a first-in-class, first time we even hear about this target at a clinical conference. And the second highly expected trial is a clinical trial in patients with metastatic lung cancer, KRAS mutated, testing sotorasib, which is a KRAS inhibitor, and showing the magnitude of improvement associated with sotorasib. The trial is positive, and it improved PFS [progression-free survival] in these patients. So these are two new targets that are validated at this conference.

Then, if we go on another topic of genomics, there is a question that is extremely important: Can we define patients who present an outlier sensitivity to immunotherapeutics? There will be one trial presented in the Presidential Symposium of immunotherapeutics in patients with colon cancer and microsatellite instability (MSI), showing that a few weeks of immunotherapeutics followed by surgery can cure patients. Why is it important? It’s important because we are all facing a shortage in the healthcare workforce. We have fewer nurses, fewer doctors, and we all have issues of sustainability. So, really now is the time to think about precision medicine, how precision medicine, by identifying outlier responders, can decrease the amount of resources we need to cure a patient. And this trial on immunotherapeutics, guided by genomics, is exactly this point: 8 weeks of treatment to cure a patient.

Dr. Whyte: Do you think there’s going to be a cure for cancer 10 years from now?

Dr. André: What I’m convinced of is that, in the 10 years that are coming, we are going step by step; we’re going to continue to increase the life expectancy of patients with cancer.

Dr. Whyte: And quality of life too, right?

Dr. André: Quality of life is a major issue. We had today a keynote on digital medicine and how ePRO (electronic patient-reported outcomes) can help the patient to really decrease the burden of symptoms. Quality of life is, of course, extremely important because of the very high number of patients who are cured of cancer; we need to decrease the burden of symptom in patients.

Dr. Whyte: And even though cancer rates are going down in most areas of the world, we still globally have millions of deaths from cancer every year. And sometimes people forget that, because they hear about some of the innovations. But I want to end with this: Are we investing enough in cancer care? Because let’s be honest – there are other diseases that we also need to spend time on. Cardiovascular disease is a global burden; infectious disease is a global burden. Are governments, are industries spending enough on cancer research and development?

Dr. André: Well, we can always claim for more, no? This is how everyone is trying to be, I think. But the reality is that we are living in a world where we have limited resources. I think what is more important for me is to be sure that any euro or dollar invested in cancer research is well used and generates an impact for patients. That is the most important, I think.

Dr. Whyte: And that’s why outcomes are so important in this research.

Dr. André: My conviction is that we have the tools, meaning the knowledge, the biotechnology, to really go the next step in terms of improving outcomes for patients. And for this, we now need clinical trials and translational research, but the tools, meaning basic science, basic knowledge, biotechnology – the basement for progress is here. We need now to transform this into direct impact for the patient. But I would not like to finish by saying we need more money in the field; what we need are people who can transform one euro, one dollar into concrete and measurable advances.

Dr. Whyte: We’re going to need more time on another day because I want to ask you about diversity in clinical trials, how important that is. I want to ask you about pediatric cancers; there are a whole bunch of things that I want to talk to you about. So hopefully we’ll find more time when we’re not at a big international conference such as ESMO. So, Dr Fabrice André, I want to thank you for taking time today.

Dr. André: Thank you and have a nice day.

Dr. Whyte: Stay tuned for a future discussion with Dr André on more about where we’re going in terms of cancer research and development. Thanks for watching, everyone.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

John Whyte, MD: Welcome, everyone. I’m Dr John Whyte. I’m the chief medical officer at WebMD, and I’m joined today by Fabrice André. He is the chair of the scientific committee at the European Society for Medical Oncology, where we are today in Paris, France. Bonjour, Fabrice.

So, remind our viewers: What is ESMO? What does it do? And why is it so important?

Fabrice André, MD, PhD: First ESMO, is a scientific society – a member-based organization with around 25,000 members.

Dr. Whyte: Equivalent to ASCO (American Society of Clinical Oncology) in the United States, correct?

Dr. André: It has members worldwide, from all over the world. And it aims at disseminating science, educating. The name is European, so it has some roots in Europe; but it is really a global organization for education, dissemination, and also more and more to generate frameworks for the standards of treatment and the common terminology for healthcare professionals to better care for patients.

Dr. Whyte: What are you most excited by at this conference in terms of the innovations that are being discussed?

Dr. André: Today we are at ESMO 2022 in Paris, with 28,000 people registered and the vast majority on site, and what has been the editorial line – the tagline – for the scientific committee is “understand the disease to better treat the patient.” This is extremely important; all of the educational program is built on this tagline, meaning that we need to understand what are the mechanisms of cancer progression? What are the determinants of outcomes if we want to integrate all the wealth of innovation that is coming?

So, then, what are the new things? In the Presidential Symposium, where we usually have the very new things, we will have very important presentations on the role of pollution on cancer and the biological mechanism that induces cancer. Why is it important? First, it has impact on public health. But also, it’s important because, for us, it’s raising the signal that the oncology community must start to invest in this field of prevention.

Dr. Whyte: I was at your booth, by the way, the ESMO booth here, and you have two bicycles, which impressed me. Nobody was on them, I might point out, but the focus was on prevention. But let’s also address how historically, the academic community, the scientific community hasn’t really been focused on prevention. It’s about treatment. So it’s fascinating that you’re talking about prevention, because usually we talk about precision medicine, right? We talk about checkpoint inhibitors; we talk about immunomodulators. And here you’re saying, “Hey, John, we need to understand how we prevent cancer,” which is really a misnomer in a way, because there are many different diseases. Would you agree with that?

Dr. André: I fully agree with you. But what is the premise we are trying to address here? The premise is that prevention has always been very low in the agenda of international conferences. And we think we want to give the signal that it’s really time now that clinical infrastructure, hospitals, invest in this field, create teams dedicated to prevention, new structures for prevention. Why? Because we are discovering step by step that it could be that some drugs we use for patients with cancer could also be developed in the field of prevention. And for this, we need the oncologists. So, more and more, our conviction is that it is the oncology community that will transform the field of prevention, and we need to invest now. Having said that, we have two very important abstracts on this question. The other one is about early cancer detection. But of course, we have our traditional session on immunotherapeutics, precision medicine, and all the wealth of randomized trials. And so in this field, for patients with cancer, what is the new information?

Dr. Whyte: We have this whole continuum. So you talk about prevention – how much cancer is preventable? Eighty percent? Seventy percent? What do you estimate?

Dr. André: You know, I’m also a scientist. So as a scientist, I will say that there is no limit for this question. No, the only limit is the knowledge.

Dr. Whyte: Well, there is some inherited mutation, so we do know that.

Dr. André: We can just go to the current status – what we know now – but I don’t see why we would put some limit on how much we can prevent cancer. But indeed, so far, what are the risk factors? Genetics, hereditary cancer, all habits, and we know them. It’s about tobacco, alcohol, sun, some sexual behavior, etc., that indeed account. In France, we say that around 40% of cancer could be preventable.

Dr. Whyte: More and more, we learn about the issues of gout, other inflammatory diseases; it can have an association, but then we have early screening as well. So, if we’re on this continuum, how excited are you by what’s happening with liquid biopsies, with other testing? Because if we can get a cancer instead of at 500,000 cells at the time of imaging, at 10 or 50 cells, while there are fragments, that’s revolutionary, isn’t it?

Dr. André: I fully agree with you. We will have an important trial presented during ESMO that is the first prospective trial testing the device called Galleri, a tool for early cancer detection based on ctDNA (circulating tumor DNA) analysis by methylation pattern.

Dr. Whyte: General screening of the population or a more tailored population with certain indications? Because right now, most of those have focused on a limited population or are used for patients who already have a cancer, and testing that way – you think it’s going to be broader?

Dr. André: What this trial is investigating is in participants who do not have cancer, 6,000 participants ...

Dr. Whyte: Pas de tout? No cancer at all?

Dr. André: No cancer.

Dr. Whyte: No family history?

Dr. André: They can have family history, but no detectable cancer – can ctDNA analysis detect cancer? And the answer is, indeed, there is around 1% positivity, and around 40% of them, indeed, had cancer. So why is it important? Because it’s really a landmark prospective trial that is telling us that a device based on ctDNA can detect cancer at early stage. Then, how many cancers? What percentage?

Dr. Whyte: Which type of cancer?

Dr. André: And is it going to have an impact on outcome? And for all the questions, we don’t have the answer here. But the answer we have here today is that with this device, done prospectively, you can detect some cancer that would not be detectable without symptoms.

Dr. Whyte: It’s only going to get better, too.

Dr. André: Yeah. So then the next step is improving technology, integrating this technology with other ones we already have, in order to increase the percentage of patients in which we detect cancer at an earlier stage.

Dr. Whyte: What about pancreatic cancer, cancers we can’t detect through screening? People forget that most cancers cannot be detected through screening, so we need better tools. We do know that there are inherited mutations. Those really aren’t preventable in many ways; the goal is to get them early. So then we move to treatments, and you talked about precision medicine. What excites you about what’s going on these days at ESMO right now.

Dr. André: We have many trials on precision medicine. We will have two randomized trials that investigate two new targets; one is gamma secretase inhibitor. So, it’s a first-in-class, first time we even hear about this target at a clinical conference. And the second highly expected trial is a clinical trial in patients with metastatic lung cancer, KRAS mutated, testing sotorasib, which is a KRAS inhibitor, and showing the magnitude of improvement associated with sotorasib. The trial is positive, and it improved PFS [progression-free survival] in these patients. So these are two new targets that are validated at this conference.

Then, if we go on another topic of genomics, there is a question that is extremely important: Can we define patients who present an outlier sensitivity to immunotherapeutics? There will be one trial presented in the Presidential Symposium of immunotherapeutics in patients with colon cancer and microsatellite instability (MSI), showing that a few weeks of immunotherapeutics followed by surgery can cure patients. Why is it important? It’s important because we are all facing a shortage in the healthcare workforce. We have fewer nurses, fewer doctors, and we all have issues of sustainability. So, really now is the time to think about precision medicine, how precision medicine, by identifying outlier responders, can decrease the amount of resources we need to cure a patient. And this trial on immunotherapeutics, guided by genomics, is exactly this point: 8 weeks of treatment to cure a patient.

Dr. Whyte: Do you think there’s going to be a cure for cancer 10 years from now?

Dr. André: What I’m convinced of is that, in the 10 years that are coming, we are going step by step; we’re going to continue to increase the life expectancy of patients with cancer.

Dr. Whyte: And quality of life too, right?

Dr. André: Quality of life is a major issue. We had today a keynote on digital medicine and how ePRO (electronic patient-reported outcomes) can help the patient to really decrease the burden of symptoms. Quality of life is, of course, extremely important because of the very high number of patients who are cured of cancer; we need to decrease the burden of symptom in patients.

Dr. Whyte: And even though cancer rates are going down in most areas of the world, we still globally have millions of deaths from cancer every year. And sometimes people forget that, because they hear about some of the innovations. But I want to end with this: Are we investing enough in cancer care? Because let’s be honest – there are other diseases that we also need to spend time on. Cardiovascular disease is a global burden; infectious disease is a global burden. Are governments, are industries spending enough on cancer research and development?

Dr. André: Well, we can always claim for more, no? This is how everyone is trying to be, I think. But the reality is that we are living in a world where we have limited resources. I think what is more important for me is to be sure that any euro or dollar invested in cancer research is well used and generates an impact for patients. That is the most important, I think.

Dr. Whyte: And that’s why outcomes are so important in this research.

Dr. André: My conviction is that we have the tools, meaning the knowledge, the biotechnology, to really go the next step in terms of improving outcomes for patients. And for this, we now need clinical trials and translational research, but the tools, meaning basic science, basic knowledge, biotechnology – the basement for progress is here. We need now to transform this into direct impact for the patient. But I would not like to finish by saying we need more money in the field; what we need are people who can transform one euro, one dollar into concrete and measurable advances.

Dr. Whyte: We’re going to need more time on another day because I want to ask you about diversity in clinical trials, how important that is. I want to ask you about pediatric cancers; there are a whole bunch of things that I want to talk to you about. So hopefully we’ll find more time when we’re not at a big international conference such as ESMO. So, Dr Fabrice André, I want to thank you for taking time today.

Dr. André: Thank you and have a nice day.

Dr. Whyte: Stay tuned for a future discussion with Dr André on more about where we’re going in terms of cancer research and development. Thanks for watching, everyone.

A version of this article first appeared on Medscape.com.

Early-onset cancer – often defined as cancers diagnosed in adults younger than age 50 years – is an emerging global epidemic, according to a recent review.

While the rising incidence of early-onset colorectal cancer (CRC) is a well-documented problem, the trend appears to extend far beyond CRC. The authors traced patterns of early-onset cancer diagnoses across 14 different cancer types, including breast, prostate, and thyroid, over the past 3 decades and found increases in many countries.

Among the 14 cancers explored, eight relate to the digestive system, which highlights the potential role diet and the oral and gut microbiome may play in cancer risk, the authors noted.

And many of the factors that appear to influence cancer risk – such as diet, exercise, sleep, and vaccination against HPV and other cancer-causing microorganisms – are modifiable.

“[Our] immediate goals should be to raise awareness of the early-onset cancer epidemic and reduce exposure to [these] risk factors,” authors Tomotaka Ugai, MD, PhD, and Shuji Ogino, MD, PhD, with Harvard School of Public Health, Boston, noted in a joint email.

The paper was published in Nature Reviews Clinical Oncology.

While the rise in cancer screenings has contributed to earlier detection of cancers, a genuine increase in the incidence of some early-onset cancers also appears to be happening.

In the current review, Dr. Ugai, Dr. Ogino, and colleagues reviewed the literature and mapped trends in the incidence of 14 cancer types among 20- to 49-year-old adults in 44 countries between 2002 and 2012.

The authors found that, since the 1990s, the incidence of early-onset cancers in the breast, colorectum, endometrium, esophagus, extrahepatic bile duct, gallbladder, head/neck, kidney, liver, bone marrow, pancreas, prostate, stomach, and thyroid, has increased around the world. Looking at the United States, for instance, the average annual percent changes for kidney cancer was 3.6% in women and 4.1% in men and for multiple myeloma was 2% in women and 3% in men for 2002 to 2012.

This overall trend could reflect increased exposures to risk factors in early life and young adulthood, although “specific effects of individual exposures remain largely unknown,” the authors acknowledged.

Since the mid-20th century, substantial changes have occurred in diet, sleep, smoking, obesity, type 2 diabetes, and environmental exposures – all of which may influence the gut microbiome or interact with our genes to increase the incidence of early-onset cancers, the authors explained. For instance, obesity, smoking, and alcohol are all established risk factors for pancreatic cancer and have been linked with early-onset disease risk as well.

“Cancer is a multifactorial disease, and we are aware of the importance of genetics as a risk factor and screening for early detection, but this paper importantly brings to light the importance of correctable lifestyle habits that may slow the rise of early onset cancers,” oncologist Marleen Meyers, MD, director of the survivorship program at NYU Langone Perlmutter Cancer Center, who wasn’t involved in the review, said in an interview.

Although modifiable factors such as diet and exercise may ease the burden of these cancers, such changes are often difficult to implement, Dr. Meyers added. In addition, understanding the impact that certain factors, such as alcohol, obesity, physical activity, and delayed reproduction play in cancer risk requires more research to tease out, but “there is enough reason at this point to address these risk factors for both personal and public health benefits,” Dr. Meyers said.

Support for this research was provided in part by the U.S. National Institutes of Health, Cancer Research UK, Prevent Cancer Foundation, Japan Society for the Promotion of Science, and the Mishima Kaiun Memorial Foundation. Dr. Ugai, Dr. Ogino, and Dr. Meyers have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Early-onset cancer – often defined as cancers diagnosed in adults younger than age 50 years – is an emerging global epidemic, according to a recent review.

While the rising incidence of early-onset colorectal cancer (CRC) is a well-documented problem, the trend appears to extend far beyond CRC. The authors traced patterns of early-onset cancer diagnoses across 14 different cancer types, including breast, prostate, and thyroid, over the past 3 decades and found increases in many countries.

Among the 14 cancers explored, eight relate to the digestive system, which highlights the potential role diet and the oral and gut microbiome may play in cancer risk, the authors noted.

And many of the factors that appear to influence cancer risk – such as diet, exercise, sleep, and vaccination against HPV and other cancer-causing microorganisms – are modifiable.

“[Our] immediate goals should be to raise awareness of the early-onset cancer epidemic and reduce exposure to [these] risk factors,” authors Tomotaka Ugai, MD, PhD, and Shuji Ogino, MD, PhD, with Harvard School of Public Health, Boston, noted in a joint email.

The paper was published in Nature Reviews Clinical Oncology.

While the rise in cancer screenings has contributed to earlier detection of cancers, a genuine increase in the incidence of some early-onset cancers also appears to be happening.

In the current review, Dr. Ugai, Dr. Ogino, and colleagues reviewed the literature and mapped trends in the incidence of 14 cancer types among 20- to 49-year-old adults in 44 countries between 2002 and 2012.

The authors found that, since the 1990s, the incidence of early-onset cancers in the breast, colorectum, endometrium, esophagus, extrahepatic bile duct, gallbladder, head/neck, kidney, liver, bone marrow, pancreas, prostate, stomach, and thyroid, has increased around the world. Looking at the United States, for instance, the average annual percent changes for kidney cancer was 3.6% in women and 4.1% in men and for multiple myeloma was 2% in women and 3% in men for 2002 to 2012.

This overall trend could reflect increased exposures to risk factors in early life and young adulthood, although “specific effects of individual exposures remain largely unknown,” the authors acknowledged.

Since the mid-20th century, substantial changes have occurred in diet, sleep, smoking, obesity, type 2 diabetes, and environmental exposures – all of which may influence the gut microbiome or interact with our genes to increase the incidence of early-onset cancers, the authors explained. For instance, obesity, smoking, and alcohol are all established risk factors for pancreatic cancer and have been linked with early-onset disease risk as well.

“Cancer is a multifactorial disease, and we are aware of the importance of genetics as a risk factor and screening for early detection, but this paper importantly brings to light the importance of correctable lifestyle habits that may slow the rise of early onset cancers,” oncologist Marleen Meyers, MD, director of the survivorship program at NYU Langone Perlmutter Cancer Center, who wasn’t involved in the review, said in an interview.

Although modifiable factors such as diet and exercise may ease the burden of these cancers, such changes are often difficult to implement, Dr. Meyers added. In addition, understanding the impact that certain factors, such as alcohol, obesity, physical activity, and delayed reproduction play in cancer risk requires more research to tease out, but “there is enough reason at this point to address these risk factors for both personal and public health benefits,” Dr. Meyers said.

Support for this research was provided in part by the U.S. National Institutes of Health, Cancer Research UK, Prevent Cancer Foundation, Japan Society for the Promotion of Science, and the Mishima Kaiun Memorial Foundation. Dr. Ugai, Dr. Ogino, and Dr. Meyers have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Early-onset cancer – often defined as cancers diagnosed in adults younger than age 50 years – is an emerging global epidemic, according to a recent review.

While the rising incidence of early-onset colorectal cancer (CRC) is a well-documented problem, the trend appears to extend far beyond CRC. The authors traced patterns of early-onset cancer diagnoses across 14 different cancer types, including breast, prostate, and thyroid, over the past 3 decades and found increases in many countries.

Among the 14 cancers explored, eight relate to the digestive system, which highlights the potential role diet and the oral and gut microbiome may play in cancer risk, the authors noted.

And many of the factors that appear to influence cancer risk – such as diet, exercise, sleep, and vaccination against HPV and other cancer-causing microorganisms – are modifiable.

“[Our] immediate goals should be to raise awareness of the early-onset cancer epidemic and reduce exposure to [these] risk factors,” authors Tomotaka Ugai, MD, PhD, and Shuji Ogino, MD, PhD, with Harvard School of Public Health, Boston, noted in a joint email.

The paper was published in Nature Reviews Clinical Oncology.

While the rise in cancer screenings has contributed to earlier detection of cancers, a genuine increase in the incidence of some early-onset cancers also appears to be happening.

In the current review, Dr. Ugai, Dr. Ogino, and colleagues reviewed the literature and mapped trends in the incidence of 14 cancer types among 20- to 49-year-old adults in 44 countries between 2002 and 2012.

The authors found that, since the 1990s, the incidence of early-onset cancers in the breast, colorectum, endometrium, esophagus, extrahepatic bile duct, gallbladder, head/neck, kidney, liver, bone marrow, pancreas, prostate, stomach, and thyroid, has increased around the world. Looking at the United States, for instance, the average annual percent changes for kidney cancer was 3.6% in women and 4.1% in men and for multiple myeloma was 2% in women and 3% in men for 2002 to 2012.

This overall trend could reflect increased exposures to risk factors in early life and young adulthood, although “specific effects of individual exposures remain largely unknown,” the authors acknowledged.

Since the mid-20th century, substantial changes have occurred in diet, sleep, smoking, obesity, type 2 diabetes, and environmental exposures – all of which may influence the gut microbiome or interact with our genes to increase the incidence of early-onset cancers, the authors explained. For instance, obesity, smoking, and alcohol are all established risk factors for pancreatic cancer and have been linked with early-onset disease risk as well.

“Cancer is a multifactorial disease, and we are aware of the importance of genetics as a risk factor and screening for early detection, but this paper importantly brings to light the importance of correctable lifestyle habits that may slow the rise of early onset cancers,” oncologist Marleen Meyers, MD, director of the survivorship program at NYU Langone Perlmutter Cancer Center, who wasn’t involved in the review, said in an interview.

Although modifiable factors such as diet and exercise may ease the burden of these cancers, such changes are often difficult to implement, Dr. Meyers added. In addition, understanding the impact that certain factors, such as alcohol, obesity, physical activity, and delayed reproduction play in cancer risk requires more research to tease out, but “there is enough reason at this point to address these risk factors for both personal and public health benefits,” Dr. Meyers said.

Support for this research was provided in part by the U.S. National Institutes of Health, Cancer Research UK, Prevent Cancer Foundation, Japan Society for the Promotion of Science, and the Mishima Kaiun Memorial Foundation. Dr. Ugai, Dr. Ogino, and Dr. Meyers have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

PARIS – “I thought I was as exhausted, and isolated, and neglected as I could get, and then he came home.”

Those were the words of Kate Washington, PhD, from Sacramento as she gave a moving account of the immense burden she felt as caregiver to her husband with cancer.

She was taking part in the session, “I am FINE: Frustrated * Isolated * Neglected * Emotional,” at the annual meeting of the European Society for Medical Oncology. In that session, speakers assessed the toll of cancer on patients, caregivers, nurses, and doctors.

Dr. Washington, author of “Already Toast: Caregiving and Burnout in America” (Boston: Beacon Press, 2021), explained that she cared for her husband and young family while he was “suffering through two different kinds of lymphoma and really devastating stem cell transplants.”

When her husband was first diagnosed with a rare form of lymphoma in 2015, he was placed on a watch-and-wait protocol. At that point, he seemed fine, Dr. Washington said.

A few months later, he started coughing up blood. After being rushed to the emergency department, doctors found that a slow-growing lung tumor had ruptured.

Three weeks later, he came out of the hospital with a collapsed lung – an effect of his chemotherapy, Dr. Washington said.

But that was hardly the last word. He soon experienced relapse with a “very aggressive” form of his disease, and in 2016, he underwent a stem cell transplant.

“He spent 1½ months in the hospital ... in isolation, not seeing our daughters,” Dr. Washington said. He lost his vision and developed grade 4 graft-versus-host disease, among other problems.

He was alive, just barely, Dr. Washington said.

“As you might imagine, I was pulled between the hospital and the home, taking care of our daughters, who were not seeing him during that time,” she recalled.

But every time someone asked her whether she was okay, she replied: “I am fine.”

“A total lie,” she admitted.

Dr. Washington felt frustrated, not only from the financial strain of out-of-pocket health care costs and lost earnings but also from fast evolving relationships and a feeling of being “unseen and underappreciated.”

Another jarring change: When her husband was discharged from the hospital, Dr. Washington was suddenly thrust into the role of full-time caretaker.

Her husband could not be left alone, his doctor had said. And with two young children, Dr. Washington did not know how she would manage.

The demands of being a full-time caregiver are intense. Caregivers, Dr. Washington explained, can spend 32 hours a week looking after a loved one with cancer.

Like Dr. Washington, most caregivers feel they have no choice but to take on this intense role – one for which they have little or no training or preparation. The nonstop demands leave little time for self-care and can lead to high rates of caregiver injury and illness.

Isolation often creeps in because it can be “hard to ask for help,” she said. About 30% of caregivers report having depression or anxiety, and 21% feel lonely.

“When he was very ill, I found it really difficult to connect with other people and my friends,” Dr. Washington recalled. “I didn’t feel like I could really adequately explain the kind of strain that I was under.”
 

Are patients fine?

Like caregivers, patients often say they are fine when they are not.

The toll cancer takes on patients is immense. Natacha Bolanos Fernandez, from the Lymphoma Coalition Europe, highlighted the physical, mental, and social strain that can affect patients with cancer.

The physical aspects can encompass a host of problems – fatigue, night sweats, weight loss, and the vomiting that accompanies many cancer treatments. Patients may face changes in their mobility and independence as well. The mental side of cancer can include anxiety, depression, and psychological distress, while the social aspects span changing, perhaps strained, relationships with family and friends.

Fatigue, in particular, is an underreported, underdiagnosed, and undertreated problem, Ms. Fernandez noted. According to recent survey data from the Lymphoma Coalition’s Global Patient Survey, 72% of patients reported fatigue. This problem worsened over time, with 59% reporting fatigue after their diagnosis and up to 82% among patients who experienced relapse two or more times.

Fatigue “may be getting worse rather than better over time,” Ms. Fernandez said, and many patients felt that their life had changed completely because of cancer-related fatigue.

To help patients manage, the Lymphoma Coalition has published a report on the impact of cancer-related fatigue and how to improve outcomes. Methods include greater awareness, regular screening, and interventions such as yoga or mindfulness-based cognitive therapy.
 

Are clinicians fine?

Nurses and physicians face challenges caring for patients with cancer.

Although “nurses love their jobs and are extremely committed,” the impact cancer has on a nursing career is often undervalued or “neglected,” said Lena Sharp, RN, PhD, of the Regional Cancer Centre, Stockholm-Gotland.

Burnout, in particular, remains a problem among oncologists and nurses, and it was made worse during the COVID-19 pandemic.

Fatima Cardoso, MD, explained that burnout has an impact on doctors as well as patients because it affects communication with patients and performance. Physicians can, for instance, appear detached, emotional, or tired.

Patients may then feel less inclined to tell their oncologist how they’re feeling, said Dr. Cardoso, director of the breast unit at Champalimaud Clinical Center, Lisbon.

It is important to remember to not just focus on the patient’s disease or treatment but to also ask how they are doing and what is going on in their lives.

Above all, “show that you care,” said Dr. Cardoso.

The Lymphoma Coalition Europe has relationships with Bristol-Myers Squibb, Establishment Labs, Kyowa Kirin, Novartis, Roche, Takeda. Dr. Cardoso has relationships with Amgen, Astellas/Medivation, AstraZeneca, Celgene, Daiichi Sankyo, Eisai, GE Oncology, Genentech, GlaxoSmithKline, and other companies. No other relevant financial relationships were reported.

A version of this article first appeared on Medscape.com.

PARIS – “I thought I was as exhausted, and isolated, and neglected as I could get, and then he came home.”

Those were the words of Kate Washington, PhD, from Sacramento as she gave a moving account of the immense burden she felt as caregiver to her husband with cancer.

She was taking part in the session, “I am FINE: Frustrated * Isolated * Neglected * Emotional,” at the annual meeting of the European Society for Medical Oncology. In that session, speakers assessed the toll of cancer on patients, caregivers, nurses, and doctors.

Dr. Washington, author of “Already Toast: Caregiving and Burnout in America” (Boston: Beacon Press, 2021), explained that she cared for her husband and young family while he was “suffering through two different kinds of lymphoma and really devastating stem cell transplants.”

When her husband was first diagnosed with a rare form of lymphoma in 2015, he was placed on a watch-and-wait protocol. At that point, he seemed fine, Dr. Washington said.

A few months later, he started coughing up blood. After being rushed to the emergency department, doctors found that a slow-growing lung tumor had ruptured.

Three weeks later, he came out of the hospital with a collapsed lung – an effect of his chemotherapy, Dr. Washington said.

But that was hardly the last word. He soon experienced relapse with a “very aggressive” form of his disease, and in 2016, he underwent a stem cell transplant.

“He spent 1½ months in the hospital ... in isolation, not seeing our daughters,” Dr. Washington said. He lost his vision and developed grade 4 graft-versus-host disease, among other problems.

He was alive, just barely, Dr. Washington said.

“As you might imagine, I was pulled between the hospital and the home, taking care of our daughters, who were not seeing him during that time,” she recalled.

But every time someone asked her whether she was okay, she replied: “I am fine.”

“A total lie,” she admitted.

Dr. Washington felt frustrated, not only from the financial strain of out-of-pocket health care costs and lost earnings but also from fast evolving relationships and a feeling of being “unseen and underappreciated.”

Another jarring change: When her husband was discharged from the hospital, Dr. Washington was suddenly thrust into the role of full-time caretaker.

Her husband could not be left alone, his doctor had said. And with two young children, Dr. Washington did not know how she would manage.

The demands of being a full-time caregiver are intense. Caregivers, Dr. Washington explained, can spend 32 hours a week looking after a loved one with cancer.

Like Dr. Washington, most caregivers feel they have no choice but to take on this intense role – one for which they have little or no training or preparation. The nonstop demands leave little time for self-care and can lead to high rates of caregiver injury and illness.

Isolation often creeps in because it can be “hard to ask for help,” she said. About 30% of caregivers report having depression or anxiety, and 21% feel lonely.

“When he was very ill, I found it really difficult to connect with other people and my friends,” Dr. Washington recalled. “I didn’t feel like I could really adequately explain the kind of strain that I was under.”
 

Are patients fine?

Like caregivers, patients often say they are fine when they are not.

The toll cancer takes on patients is immense. Natacha Bolanos Fernandez, from the Lymphoma Coalition Europe, highlighted the physical, mental, and social strain that can affect patients with cancer.

The physical aspects can encompass a host of problems – fatigue, night sweats, weight loss, and the vomiting that accompanies many cancer treatments. Patients may face changes in their mobility and independence as well. The mental side of cancer can include anxiety, depression, and psychological distress, while the social aspects span changing, perhaps strained, relationships with family and friends.

Fatigue, in particular, is an underreported, underdiagnosed, and undertreated problem, Ms. Fernandez noted. According to recent survey data from the Lymphoma Coalition’s Global Patient Survey, 72% of patients reported fatigue. This problem worsened over time, with 59% reporting fatigue after their diagnosis and up to 82% among patients who experienced relapse two or more times.

Fatigue “may be getting worse rather than better over time,” Ms. Fernandez said, and many patients felt that their life had changed completely because of cancer-related fatigue.

To help patients manage, the Lymphoma Coalition has published a report on the impact of cancer-related fatigue and how to improve outcomes. Methods include greater awareness, regular screening, and interventions such as yoga or mindfulness-based cognitive therapy.
 

Are clinicians fine?

Nurses and physicians face challenges caring for patients with cancer.

Although “nurses love their jobs and are extremely committed,” the impact cancer has on a nursing career is often undervalued or “neglected,” said Lena Sharp, RN, PhD, of the Regional Cancer Centre, Stockholm-Gotland.

Burnout, in particular, remains a problem among oncologists and nurses, and it was made worse during the COVID-19 pandemic.

Fatima Cardoso, MD, explained that burnout has an impact on doctors as well as patients because it affects communication with patients and performance. Physicians can, for instance, appear detached, emotional, or tired.

Patients may then feel less inclined to tell their oncologist how they’re feeling, said Dr. Cardoso, director of the breast unit at Champalimaud Clinical Center, Lisbon.

It is important to remember to not just focus on the patient’s disease or treatment but to also ask how they are doing and what is going on in their lives.

Above all, “show that you care,” said Dr. Cardoso.

The Lymphoma Coalition Europe has relationships with Bristol-Myers Squibb, Establishment Labs, Kyowa Kirin, Novartis, Roche, Takeda. Dr. Cardoso has relationships with Amgen, Astellas/Medivation, AstraZeneca, Celgene, Daiichi Sankyo, Eisai, GE Oncology, Genentech, GlaxoSmithKline, and other companies. No other relevant financial relationships were reported.

A version of this article first appeared on Medscape.com.

PARIS – “I thought I was as exhausted, and isolated, and neglected as I could get, and then he came home.”

Those were the words of Kate Washington, PhD, from Sacramento as she gave a moving account of the immense burden she felt as caregiver to her husband with cancer.

She was taking part in the session, “I am FINE: Frustrated * Isolated * Neglected * Emotional,” at the annual meeting of the European Society for Medical Oncology. In that session, speakers assessed the toll of cancer on patients, caregivers, nurses, and doctors.

Dr. Washington, author of “Already Toast: Caregiving and Burnout in America” (Boston: Beacon Press, 2021), explained that she cared for her husband and young family while he was “suffering through two different kinds of lymphoma and really devastating stem cell transplants.”

When her husband was first diagnosed with a rare form of lymphoma in 2015, he was placed on a watch-and-wait protocol. At that point, he seemed fine, Dr. Washington said.

A few months later, he started coughing up blood. After being rushed to the emergency department, doctors found that a slow-growing lung tumor had ruptured.

Three weeks later, he came out of the hospital with a collapsed lung – an effect of his chemotherapy, Dr. Washington said.

But that was hardly the last word. He soon experienced relapse with a “very aggressive” form of his disease, and in 2016, he underwent a stem cell transplant.

“He spent 1½ months in the hospital ... in isolation, not seeing our daughters,” Dr. Washington said. He lost his vision and developed grade 4 graft-versus-host disease, among other problems.

He was alive, just barely, Dr. Washington said.

“As you might imagine, I was pulled between the hospital and the home, taking care of our daughters, who were not seeing him during that time,” she recalled.

But every time someone asked her whether she was okay, she replied: “I am fine.”

“A total lie,” she admitted.

Dr. Washington felt frustrated, not only from the financial strain of out-of-pocket health care costs and lost earnings but also from fast evolving relationships and a feeling of being “unseen and underappreciated.”

Another jarring change: When her husband was discharged from the hospital, Dr. Washington was suddenly thrust into the role of full-time caretaker.

Her husband could not be left alone, his doctor had said. And with two young children, Dr. Washington did not know how she would manage.

The demands of being a full-time caregiver are intense. Caregivers, Dr. Washington explained, can spend 32 hours a week looking after a loved one with cancer.

Like Dr. Washington, most caregivers feel they have no choice but to take on this intense role – one for which they have little or no training or preparation. The nonstop demands leave little time for self-care and can lead to high rates of caregiver injury and illness.

Isolation often creeps in because it can be “hard to ask for help,” she said. About 30% of caregivers report having depression or anxiety, and 21% feel lonely.

“When he was very ill, I found it really difficult to connect with other people and my friends,” Dr. Washington recalled. “I didn’t feel like I could really adequately explain the kind of strain that I was under.”
 

Are patients fine?

Like caregivers, patients often say they are fine when they are not.

The toll cancer takes on patients is immense. Natacha Bolanos Fernandez, from the Lymphoma Coalition Europe, highlighted the physical, mental, and social strain that can affect patients with cancer.

The physical aspects can encompass a host of problems – fatigue, night sweats, weight loss, and the vomiting that accompanies many cancer treatments. Patients may face changes in their mobility and independence as well. The mental side of cancer can include anxiety, depression, and psychological distress, while the social aspects span changing, perhaps strained, relationships with family and friends.

Fatigue, in particular, is an underreported, underdiagnosed, and undertreated problem, Ms. Fernandez noted. According to recent survey data from the Lymphoma Coalition’s Global Patient Survey, 72% of patients reported fatigue. This problem worsened over time, with 59% reporting fatigue after their diagnosis and up to 82% among patients who experienced relapse two or more times.

Fatigue “may be getting worse rather than better over time,” Ms. Fernandez said, and many patients felt that their life had changed completely because of cancer-related fatigue.

To help patients manage, the Lymphoma Coalition has published a report on the impact of cancer-related fatigue and how to improve outcomes. Methods include greater awareness, regular screening, and interventions such as yoga or mindfulness-based cognitive therapy.
 

Are clinicians fine?

Nurses and physicians face challenges caring for patients with cancer.

Although “nurses love their jobs and are extremely committed,” the impact cancer has on a nursing career is often undervalued or “neglected,” said Lena Sharp, RN, PhD, of the Regional Cancer Centre, Stockholm-Gotland.

Burnout, in particular, remains a problem among oncologists and nurses, and it was made worse during the COVID-19 pandemic.

Fatima Cardoso, MD, explained that burnout has an impact on doctors as well as patients because it affects communication with patients and performance. Physicians can, for instance, appear detached, emotional, or tired.

Patients may then feel less inclined to tell their oncologist how they’re feeling, said Dr. Cardoso, director of the breast unit at Champalimaud Clinical Center, Lisbon.

It is important to remember to not just focus on the patient’s disease or treatment but to also ask how they are doing and what is going on in their lives.

Above all, “show that you care,” said Dr. Cardoso.

The Lymphoma Coalition Europe has relationships with Bristol-Myers Squibb, Establishment Labs, Kyowa Kirin, Novartis, Roche, Takeda. Dr. Cardoso has relationships with Amgen, Astellas/Medivation, AstraZeneca, Celgene, Daiichi Sankyo, Eisai, GE Oncology, Genentech, GlaxoSmithKline, and other companies. No other relevant financial relationships were reported.

A version of this article first appeared on Medscape.com.

Decades ago I saw a patient with non–small cell lung cancer (NSCLC) whose tumor was sent out for next-generation sequencing only to find a HER2 mutation. What to do? Had my patient come in today, we may have had other options.

Multiple studies have shown that trastuzumab (Herceptin, Genentech), as assessed by HER2 overexpression or amplification, has been shown to have essentially no efficacy benefit in NSCLC alone or in combination with chemotherapy. In fact, a randomized, phase 2 study of gemcitabine-cisplatin with or without trastuzumab in HER2 mutation–positive NSCLC essentially showed no difference between gemcitabine-cisplatin or gemcitabine-cisplatin with trastuzumab.

NSCLC has become the poster child for targeted therapies. After all, NSCLC makes up about 85% of all lung cancer cases, some of which are driven by gene mutations or other genetic abnormalities like translocation, fusion, or amplification. Seven of these genetic alterations have Food and Drug Administration–approved targeted drugs: EGFR, ALK, ROS1, BRAF V6006, RET, KRAS, MET, and NTRK fusions. And, now we have a new one: HER2.

In August, the FDA granted accelerated approval of trastuzumab deruxtecan (T-DXd) (Enhertu, Daiichi Sankyo) for the second-line treatment of NSCLC patients with HER alterations. T-DXd is a humanized anti-HER antibody linked to a topoisomerase 1 inhibitor. When given intravenously, the antibody portion of the molecule binds to cells with a mutated HER2 on the surface. The molecule is taken up by the cancer cell and the linker between the antibody and the chemotherapy drug is broken, so the drug will be delivered very specifically only to cancer cells that have a mutated HER2. In theory, they will only target cells with HER alterations and thus should have less toxicity.

Unlike other driver mutations, HER mutations are relatively rare. Roughly 3% of nonsquamous NSCLC tumors carry mutations in the HER2 gene, and they are associated with female sex, never-smokers, and a poor prognosis. Accelerated approved by the FDA was based on data from the DESTINY-Lung 02 phase 2 trial. An interim efficacy analysis of this trial reported an overall response rate to trastuzumab deruxtecan (at 5.4 mg/kg every 3 weeks) of 57.7% in 52 patients. Median duration of response was 8.7 months. Data are also available from the DESTINY-Lung-01 clinical trial, published in the New England Journal of Medicine, in which 91 patients with metastatic HER2-mutant NSCLC that was refractory to standard treatment were treated with T-DXd (at 6.4 mg/kg every 3 weeks). The investigators reported a 55% objective response rate, a median duration of response of 9.3 months, a median progression-free survival (PFS) of 8.2 months, and a median overall survival of almost 18 months.
 

Companion tests

Biomarker testing is obviously a must in these cases. The FDA-approved companion diagnostic tests to detect HER2 mutations: Life Companion tests, Technologies Corporation’s Oncomine Dx Target Test for use in lung tissue, and Guardant Health’s Guardant360 CDx for use on plasma samples. The agency notes that, if no mutation is detected in a plasma specimen, the tumor tissue should be tested.

Other approvals

T-DXd is also approved for advanced breast and gastric patients who are HER-2 positive. Of note, the majority of HER2-positive NSCLC have HER2 mutations, whereas the majority of HER2-positive breast and gastric cancers have HER2 amplification (increased copy number) or overexpression (increased protein expression).

T-DXd is approved for unresectable or metastatic HER2-positive breast cancer patients who have received a prior anti-HER2–based regimen in the metastatic setting, or in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within 6 months of completing therapy. DESTINY-Breast01 enrolled breast cancer patients who had received two or more prior anti-HER2 therapies in the metastatic setting, and reported a response rate of 60.3% with a median duration of response of 14.8 months.

For patients with locally advanced or metastatic HER2-positive gastric cancer who have received two or more prior therapies, including a trastuzumab-based regimen, approval was based on a randomized, phase 3 study comparing 6.4 mg/kg of T-DXd with physician’s choice – either irinotecan or paclitaxel. Overall survival was 12.5 months in the T-DXd arm, compared with 8.4 months in the irinotecan or paclitaxel arm (hazard ratio, 0.59). Response rates were 40.5% and 11.3%, respectively. Median PFS was 5.6 months in the T-DXd arm, compared with a median PFS of 3.5 months in the chemotherapy arm.
 

Trastuzumab emtansine vs. trastuzumab deruxtecan

Trastuzumab emtansine (T-DM1, ado-trastuzumab emtansine, Kadcyla) is another antibody-drug conjugate consisting of the humanized monoclonal antibody trastuzumab covalently linked to the antimicrotubule agent DM1. It is also approved for advanced breast cancer patients with HER2-positive disease. Although no studies comparing T-DXd with trastuzumab emtansine have been conducted in lung cancer patients, a randomized, phase 3 trial in patients with HER2-positive advanced breast cancer comparing the two reported an overall response rate of 79.7% of the patients who received trastuzumab deruxtecan and 34.2% of those who received trastuzumab emtansine. Drug-related interstitial lung disease (ILD) occurred in 10.5% of the patients in the trastuzumab deruxtecan group and in 1.9% of those in the trastuzumab emtansine group; at 12 months, 75.8% of the patients in the trastuzumab deruxtecan were alive without progression, compared with 34.1% of those receiving trastuzumab emtansine.

ILDs

In DESTINY-Lung01, ILD occurred in 26% of patients and resulted in death in two patients. Increased rates of ILD were more commonly observed at higher dose levels. Of 491 patients with unresectable or metastatic HER2-positive breast cancer treated with 5.4 mg/kg of T-TDx, ILD occurred in 13% of patients. Fatal outcomes caused by ILD and/or pneumonitis occurred in 1.4% of patients. Median time to first onset was 5.5 months (range, 1.1-20.8 months). In DESTINY-Gastric01, of the 125 patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma treated with 6.4 mg/kg, T-DXd ILD occurred in 10% of patients. Median time to first onset was 2.8 months (range, 1.2-21.0 months).

Chemotherapy-like adverse effects

Other adverse events are more typically seen with cytotoxic agents and are presumably related to the release of the topoisomerase inhibitor into the blood stream. Although common (occurring in 97% of patients), these adverse events are generally mild (grade 1 or 2). Nausea was reported in about two-thirds of patients. Other side effects occurring in 20% or more of patients included vomiting, decreased appetite, alopecia, and constipation and diarrhea, musculoskeletal pain, and respiratory infections. Laboratory abnormalities occurred in 20% or more of patients included myelosuppression, increased AST, ALT, alkaline phosphatase, and hypokalemia (28%). Grade 3 or higher drug-related adverse events were observed in 46% of patients, with the most common being neutropenia and anemia which was observed in 19% and 10% of patients in the DESTINY-LUNG-01 trial.

Dr. Schiller is a medical oncologist and founding member of Oncologists United for Climate and Health. She is a former board member of the International Association for the Study of Lung Cancer and a current board member of the Lung Cancer Research Foundation.

Decades ago I saw a patient with non–small cell lung cancer (NSCLC) whose tumor was sent out for next-generation sequencing only to find a HER2 mutation. What to do? Had my patient come in today, we may have had other options.

Multiple studies have shown that trastuzumab (Herceptin, Genentech), as assessed by HER2 overexpression or amplification, has been shown to have essentially no efficacy benefit in NSCLC alone or in combination with chemotherapy. In fact, a randomized, phase 2 study of gemcitabine-cisplatin with or without trastuzumab in HER2 mutation–positive NSCLC essentially showed no difference between gemcitabine-cisplatin or gemcitabine-cisplatin with trastuzumab.

NSCLC has become the poster child for targeted therapies. After all, NSCLC makes up about 85% of all lung cancer cases, some of which are driven by gene mutations or other genetic abnormalities like translocation, fusion, or amplification. Seven of these genetic alterations have Food and Drug Administration–approved targeted drugs: EGFR, ALK, ROS1, BRAF V6006, RET, KRAS, MET, and NTRK fusions. And, now we have a new one: HER2.

In August, the FDA granted accelerated approval of trastuzumab deruxtecan (T-DXd) (Enhertu, Daiichi Sankyo) for the second-line treatment of NSCLC patients with HER alterations. T-DXd is a humanized anti-HER antibody linked to a topoisomerase 1 inhibitor. When given intravenously, the antibody portion of the molecule binds to cells with a mutated HER2 on the surface. The molecule is taken up by the cancer cell and the linker between the antibody and the chemotherapy drug is broken, so the drug will be delivered very specifically only to cancer cells that have a mutated HER2. In theory, they will only target cells with HER alterations and thus should have less toxicity.

Unlike other driver mutations, HER mutations are relatively rare. Roughly 3% of nonsquamous NSCLC tumors carry mutations in the HER2 gene, and they are associated with female sex, never-smokers, and a poor prognosis. Accelerated approved by the FDA was based on data from the DESTINY-Lung 02 phase 2 trial. An interim efficacy analysis of this trial reported an overall response rate to trastuzumab deruxtecan (at 5.4 mg/kg every 3 weeks) of 57.7% in 52 patients. Median duration of response was 8.7 months. Data are also available from the DESTINY-Lung-01 clinical trial, published in the New England Journal of Medicine, in which 91 patients with metastatic HER2-mutant NSCLC that was refractory to standard treatment were treated with T-DXd (at 6.4 mg/kg every 3 weeks). The investigators reported a 55% objective response rate, a median duration of response of 9.3 months, a median progression-free survival (PFS) of 8.2 months, and a median overall survival of almost 18 months.
 

Companion tests

Biomarker testing is obviously a must in these cases. The FDA-approved companion diagnostic tests to detect HER2 mutations: Life Companion tests, Technologies Corporation’s Oncomine Dx Target Test for use in lung tissue, and Guardant Health’s Guardant360 CDx for use on plasma samples. The agency notes that, if no mutation is detected in a plasma specimen, the tumor tissue should be tested.

Other approvals

T-DXd is also approved for advanced breast and gastric patients who are HER-2 positive. Of note, the majority of HER2-positive NSCLC have HER2 mutations, whereas the majority of HER2-positive breast and gastric cancers have HER2 amplification (increased copy number) or overexpression (increased protein expression).

T-DXd is approved for unresectable or metastatic HER2-positive breast cancer patients who have received a prior anti-HER2–based regimen in the metastatic setting, or in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within 6 months of completing therapy. DESTINY-Breast01 enrolled breast cancer patients who had received two or more prior anti-HER2 therapies in the metastatic setting, and reported a response rate of 60.3% with a median duration of response of 14.8 months.

For patients with locally advanced or metastatic HER2-positive gastric cancer who have received two or more prior therapies, including a trastuzumab-based regimen, approval was based on a randomized, phase 3 study comparing 6.4 mg/kg of T-DXd with physician’s choice – either irinotecan or paclitaxel. Overall survival was 12.5 months in the T-DXd arm, compared with 8.4 months in the irinotecan or paclitaxel arm (hazard ratio, 0.59). Response rates were 40.5% and 11.3%, respectively. Median PFS was 5.6 months in the T-DXd arm, compared with a median PFS of 3.5 months in the chemotherapy arm.
 

Trastuzumab emtansine vs. trastuzumab deruxtecan

Trastuzumab emtansine (T-DM1, ado-trastuzumab emtansine, Kadcyla) is another antibody-drug conjugate consisting of the humanized monoclonal antibody trastuzumab covalently linked to the antimicrotubule agent DM1. It is also approved for advanced breast cancer patients with HER2-positive disease. Although no studies comparing T-DXd with trastuzumab emtansine have been conducted in lung cancer patients, a randomized, phase 3 trial in patients with HER2-positive advanced breast cancer comparing the two reported an overall response rate of 79.7% of the patients who received trastuzumab deruxtecan and 34.2% of those who received trastuzumab emtansine. Drug-related interstitial lung disease (ILD) occurred in 10.5% of the patients in the trastuzumab deruxtecan group and in 1.9% of those in the trastuzumab emtansine group; at 12 months, 75.8% of the patients in the trastuzumab deruxtecan were alive without progression, compared with 34.1% of those receiving trastuzumab emtansine.

ILDs

In DESTINY-Lung01, ILD occurred in 26% of patients and resulted in death in two patients. Increased rates of ILD were more commonly observed at higher dose levels. Of 491 patients with unresectable or metastatic HER2-positive breast cancer treated with 5.4 mg/kg of T-TDx, ILD occurred in 13% of patients. Fatal outcomes caused by ILD and/or pneumonitis occurred in 1.4% of patients. Median time to first onset was 5.5 months (range, 1.1-20.8 months). In DESTINY-Gastric01, of the 125 patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma treated with 6.4 mg/kg, T-DXd ILD occurred in 10% of patients. Median time to first onset was 2.8 months (range, 1.2-21.0 months).

Chemotherapy-like adverse effects

Other adverse events are more typically seen with cytotoxic agents and are presumably related to the release of the topoisomerase inhibitor into the blood stream. Although common (occurring in 97% of patients), these adverse events are generally mild (grade 1 or 2). Nausea was reported in about two-thirds of patients. Other side effects occurring in 20% or more of patients included vomiting, decreased appetite, alopecia, and constipation and diarrhea, musculoskeletal pain, and respiratory infections. Laboratory abnormalities occurred in 20% or more of patients included myelosuppression, increased AST, ALT, alkaline phosphatase, and hypokalemia (28%). Grade 3 or higher drug-related adverse events were observed in 46% of patients, with the most common being neutropenia and anemia which was observed in 19% and 10% of patients in the DESTINY-LUNG-01 trial.

Dr. Schiller is a medical oncologist and founding member of Oncologists United for Climate and Health. She is a former board member of the International Association for the Study of Lung Cancer and a current board member of the Lung Cancer Research Foundation.

Decades ago I saw a patient with non–small cell lung cancer (NSCLC) whose tumor was sent out for next-generation sequencing only to find a HER2 mutation. What to do? Had my patient come in today, we may have had other options.

Multiple studies have shown that trastuzumab (Herceptin, Genentech), as assessed by HER2 overexpression or amplification, has been shown to have essentially no efficacy benefit in NSCLC alone or in combination with chemotherapy. In fact, a randomized, phase 2 study of gemcitabine-cisplatin with or without trastuzumab in HER2 mutation–positive NSCLC essentially showed no difference between gemcitabine-cisplatin or gemcitabine-cisplatin with trastuzumab.

NSCLC has become the poster child for targeted therapies. After all, NSCLC makes up about 85% of all lung cancer cases, some of which are driven by gene mutations or other genetic abnormalities like translocation, fusion, or amplification. Seven of these genetic alterations have Food and Drug Administration–approved targeted drugs: EGFR, ALK, ROS1, BRAF V6006, RET, KRAS, MET, and NTRK fusions. And, now we have a new one: HER2.

In August, the FDA granted accelerated approval of trastuzumab deruxtecan (T-DXd) (Enhertu, Daiichi Sankyo) for the second-line treatment of NSCLC patients with HER alterations. T-DXd is a humanized anti-HER antibody linked to a topoisomerase 1 inhibitor. When given intravenously, the antibody portion of the molecule binds to cells with a mutated HER2 on the surface. The molecule is taken up by the cancer cell and the linker between the antibody and the chemotherapy drug is broken, so the drug will be delivered very specifically only to cancer cells that have a mutated HER2. In theory, they will only target cells with HER alterations and thus should have less toxicity.

Unlike other driver mutations, HER mutations are relatively rare. Roughly 3% of nonsquamous NSCLC tumors carry mutations in the HER2 gene, and they are associated with female sex, never-smokers, and a poor prognosis. Accelerated approved by the FDA was based on data from the DESTINY-Lung 02 phase 2 trial. An interim efficacy analysis of this trial reported an overall response rate to trastuzumab deruxtecan (at 5.4 mg/kg every 3 weeks) of 57.7% in 52 patients. Median duration of response was 8.7 months. Data are also available from the DESTINY-Lung-01 clinical trial, published in the New England Journal of Medicine, in which 91 patients with metastatic HER2-mutant NSCLC that was refractory to standard treatment were treated with T-DXd (at 6.4 mg/kg every 3 weeks). The investigators reported a 55% objective response rate, a median duration of response of 9.3 months, a median progression-free survival (PFS) of 8.2 months, and a median overall survival of almost 18 months.
 

Companion tests

Biomarker testing is obviously a must in these cases. The FDA-approved companion diagnostic tests to detect HER2 mutations: Life Companion tests, Technologies Corporation’s Oncomine Dx Target Test for use in lung tissue, and Guardant Health’s Guardant360 CDx for use on plasma samples. The agency notes that, if no mutation is detected in a plasma specimen, the tumor tissue should be tested.

Other approvals

T-DXd is also approved for advanced breast and gastric patients who are HER-2 positive. Of note, the majority of HER2-positive NSCLC have HER2 mutations, whereas the majority of HER2-positive breast and gastric cancers have HER2 amplification (increased copy number) or overexpression (increased protein expression).

T-DXd is approved for unresectable or metastatic HER2-positive breast cancer patients who have received a prior anti-HER2–based regimen in the metastatic setting, or in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within 6 months of completing therapy. DESTINY-Breast01 enrolled breast cancer patients who had received two or more prior anti-HER2 therapies in the metastatic setting, and reported a response rate of 60.3% with a median duration of response of 14.8 months.

For patients with locally advanced or metastatic HER2-positive gastric cancer who have received two or more prior therapies, including a trastuzumab-based regimen, approval was based on a randomized, phase 3 study comparing 6.4 mg/kg of T-DXd with physician’s choice – either irinotecan or paclitaxel. Overall survival was 12.5 months in the T-DXd arm, compared with 8.4 months in the irinotecan or paclitaxel arm (hazard ratio, 0.59). Response rates were 40.5% and 11.3%, respectively. Median PFS was 5.6 months in the T-DXd arm, compared with a median PFS of 3.5 months in the chemotherapy arm.
 

Trastuzumab emtansine vs. trastuzumab deruxtecan

Trastuzumab emtansine (T-DM1, ado-trastuzumab emtansine, Kadcyla) is another antibody-drug conjugate consisting of the humanized monoclonal antibody trastuzumab covalently linked to the antimicrotubule agent DM1. It is also approved for advanced breast cancer patients with HER2-positive disease. Although no studies comparing T-DXd with trastuzumab emtansine have been conducted in lung cancer patients, a randomized, phase 3 trial in patients with HER2-positive advanced breast cancer comparing the two reported an overall response rate of 79.7% of the patients who received trastuzumab deruxtecan and 34.2% of those who received trastuzumab emtansine. Drug-related interstitial lung disease (ILD) occurred in 10.5% of the patients in the trastuzumab deruxtecan group and in 1.9% of those in the trastuzumab emtansine group; at 12 months, 75.8% of the patients in the trastuzumab deruxtecan were alive without progression, compared with 34.1% of those receiving trastuzumab emtansine.

ILDs

In DESTINY-Lung01, ILD occurred in 26% of patients and resulted in death in two patients. Increased rates of ILD were more commonly observed at higher dose levels. Of 491 patients with unresectable or metastatic HER2-positive breast cancer treated with 5.4 mg/kg of T-TDx, ILD occurred in 13% of patients. Fatal outcomes caused by ILD and/or pneumonitis occurred in 1.4% of patients. Median time to first onset was 5.5 months (range, 1.1-20.8 months). In DESTINY-Gastric01, of the 125 patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma treated with 6.4 mg/kg, T-DXd ILD occurred in 10% of patients. Median time to first onset was 2.8 months (range, 1.2-21.0 months).

Chemotherapy-like adverse effects

Other adverse events are more typically seen with cytotoxic agents and are presumably related to the release of the topoisomerase inhibitor into the blood stream. Although common (occurring in 97% of patients), these adverse events are generally mild (grade 1 or 2). Nausea was reported in about two-thirds of patients. Other side effects occurring in 20% or more of patients included vomiting, decreased appetite, alopecia, and constipation and diarrhea, musculoskeletal pain, and respiratory infections. Laboratory abnormalities occurred in 20% or more of patients included myelosuppression, increased AST, ALT, alkaline phosphatase, and hypokalemia (28%). Grade 3 or higher drug-related adverse events were observed in 46% of patients, with the most common being neutropenia and anemia which was observed in 19% and 10% of patients in the DESTINY-LUNG-01 trial.

Dr. Schiller is a medical oncologist and founding member of Oncologists United for Climate and Health. She is a former board member of the International Association for the Study of Lung Cancer and a current board member of the Lung Cancer Research Foundation.

The Centers for Disease Control has changed its position on mandatory masking in health care settings, no longer recommending that it be universal.

It’s a “major departure” from the CDC’s previous recommendation of universal masking to fight the COVID-19 pandemic, The Hill says.

“Updates were made to reflect the high levels of vaccine-and infection-induced immunity and the availability of effective treatments and prevention tools,” the CDC’s new guidance says.

The agency now says that facilities in areas without high transmission can decide for themselves whether to require everyone – doctors, patients, and visitors – to wear masks.

Community transmission “is the metric currently recommended to guide select practices in healthcare settings to allow for earlier intervention, before there is strain on the health care system and to better protect the individuals seeking care in these settings,” the CDC said.

About 73% of the country is having “high” rates of transmission, The Hill said.

“Community transmission” is different from the “community level” metric that’s used for non–health care settings. 

Community transmission refers to measures of the presence and spread of SARS-CoV-2, the CDC said. “Community levels place an emphasis on measures of the impact of COVID-19 in terms of hospitalizations and health care system strain, while accounting for transmission in the community.”

Just 7% of counties are considered high risk, while nearly 62 percent are low.

The new guidance applies wherever health care is delivered, including nursing homes and home health, the CDC said.

A version of this article first appeared on WebMD.com.

The Centers for Disease Control has changed its position on mandatory masking in health care settings, no longer recommending that it be universal.

It’s a “major departure” from the CDC’s previous recommendation of universal masking to fight the COVID-19 pandemic, The Hill says.

“Updates were made to reflect the high levels of vaccine-and infection-induced immunity and the availability of effective treatments and prevention tools,” the CDC’s new guidance says.

The agency now says that facilities in areas without high transmission can decide for themselves whether to require everyone – doctors, patients, and visitors – to wear masks.

Community transmission “is the metric currently recommended to guide select practices in healthcare settings to allow for earlier intervention, before there is strain on the health care system and to better protect the individuals seeking care in these settings,” the CDC said.

About 73% of the country is having “high” rates of transmission, The Hill said.

“Community transmission” is different from the “community level” metric that’s used for non–health care settings. 

Community transmission refers to measures of the presence and spread of SARS-CoV-2, the CDC said. “Community levels place an emphasis on measures of the impact of COVID-19 in terms of hospitalizations and health care system strain, while accounting for transmission in the community.”

Just 7% of counties are considered high risk, while nearly 62 percent are low.

The new guidance applies wherever health care is delivered, including nursing homes and home health, the CDC said.

A version of this article first appeared on WebMD.com.

The Centers for Disease Control has changed its position on mandatory masking in health care settings, no longer recommending that it be universal.

It’s a “major departure” from the CDC’s previous recommendation of universal masking to fight the COVID-19 pandemic, The Hill says.

“Updates were made to reflect the high levels of vaccine-and infection-induced immunity and the availability of effective treatments and prevention tools,” the CDC’s new guidance says.

The agency now says that facilities in areas without high transmission can decide for themselves whether to require everyone – doctors, patients, and visitors – to wear masks.

Community transmission “is the metric currently recommended to guide select practices in healthcare settings to allow for earlier intervention, before there is strain on the health care system and to better protect the individuals seeking care in these settings,” the CDC said.

About 73% of the country is having “high” rates of transmission, The Hill said.

“Community transmission” is different from the “community level” metric that’s used for non–health care settings. 

Community transmission refers to measures of the presence and spread of SARS-CoV-2, the CDC said. “Community levels place an emphasis on measures of the impact of COVID-19 in terms of hospitalizations and health care system strain, while accounting for transmission in the community.”

Just 7% of counties are considered high risk, while nearly 62 percent are low.

The new guidance applies wherever health care is delivered, including nursing homes and home health, the CDC said.

A version of this article first appeared on WebMD.com.

The study covered in this summary was published on medRxiv.org as a preprint and has not yet been peer reviewed.

Key takeaway

• Absolute lesion control rate with image-guided superficial radiation therapy (IGSRT) for early-stage nonmelanoma skin cancer was achieved in nearly all patients.

Why this matters

• IGSRT is a newer radiation technique for skin cancer, an alternative to Mohs micrographic surgery and other surgical options.
• The ultrasound imaging used during IGSRT allows for precise targeting of cancer cells while sparing surrounding tissue.
• IGSRT is currently recommended for early-stage nonmelanoma skin cancer among patients who refuse or cannot tolerate surgery.
• Given the safety, lack of surgical disfigurement, cost-effectiveness, and high cure rate, IGSRT should be considered more broadly as a first-line option for early-stage nonmelanoma skin cancer, the researchers concluded.

Study design

• The investigators reviewed 1,899 early-stage nonmelanoma skin cancer lesions in 1,243 patients treated with IGSRT at an outpatient dermatology clinic in Dallas.
• Energies ranged from 50 to 100 kV, with a mean treatment dose of 5,364.4 cGy over an average of 20.2 fractions.
• Treatment duration was a mean of 7.5 weeks and followed for a mean of 65.5 weeks.

Key results

• Absolute lesion control was achieved in 99.7% of patients, with a stable control rate of 99.6% past 12 months.
• At a 5-year follow-up, local control was 99.4%.
• Local control for both basal and squamous cell carcinoma at 5 years was 99%; local control for squamous cell carcinoma in situ was 100% at 5 years.
• The most common side effects were erythema, dryness, and dry desquamation. Some patients had ulceration and moist desquamation, but it did not affect lesion control.
• The procedure was well tolerated, with a grade 1 Radiation Treatment Oncology Group toxicity score in 72% of lesions.
• The results compare favorably with Mohs surgery.

Limitations

• No study limitations were noted.

Disclosures

• No funding source was reported.
• Senior investigator Lio Yu, MD, reported research, speaking and/or consulting for SkinCure Oncology, a developer of IGSRT technology.

This is a summary of a preprint research study, “Analysis of Image-Guided Superficial Radiation Therapy (IGSRT) on the Treatment of Early Stage Non-Melanoma Skin Cancer (NMSC) in the Outpatient Dermatology Setting,” led by Alison Tran, MD, of Baylor University Medical Center, Dallas. The study has not been peer reviewed. The full text can be found at medRxiv.org.

A version of this article first appeared on Medscape.com.

The study covered in this summary was published on medRxiv.org as a preprint and has not yet been peer reviewed.

Key takeaway

• Absolute lesion control rate with image-guided superficial radiation therapy (IGSRT) for early-stage nonmelanoma skin cancer was achieved in nearly all patients.

Why this matters

• IGSRT is a newer radiation technique for skin cancer, an alternative to Mohs micrographic surgery and other surgical options.
• The ultrasound imaging used during IGSRT allows for precise targeting of cancer cells while sparing surrounding tissue.
• IGSRT is currently recommended for early-stage nonmelanoma skin cancer among patients who refuse or cannot tolerate surgery.
• Given the safety, lack of surgical disfigurement, cost-effectiveness, and high cure rate, IGSRT should be considered more broadly as a first-line option for early-stage nonmelanoma skin cancer, the researchers concluded.

Study design

• The investigators reviewed 1,899 early-stage nonmelanoma skin cancer lesions in 1,243 patients treated with IGSRT at an outpatient dermatology clinic in Dallas.
• Energies ranged from 50 to 100 kV, with a mean treatment dose of 5,364.4 cGy over an average of 20.2 fractions.
• Treatment duration was a mean of 7.5 weeks and followed for a mean of 65.5 weeks.

Key results

• Absolute lesion control was achieved in 99.7% of patients, with a stable control rate of 99.6% past 12 months.
• At a 5-year follow-up, local control was 99.4%.
• Local control for both basal and squamous cell carcinoma at 5 years was 99%; local control for squamous cell carcinoma in situ was 100% at 5 years.
• The most common side effects were erythema, dryness, and dry desquamation. Some patients had ulceration and moist desquamation, but it did not affect lesion control.
• The procedure was well tolerated, with a grade 1 Radiation Treatment Oncology Group toxicity score in 72% of lesions.
• The results compare favorably with Mohs surgery.

Limitations

• No study limitations were noted.

Disclosures

• No funding source was reported.
• Senior investigator Lio Yu, MD, reported research, speaking and/or consulting for SkinCure Oncology, a developer of IGSRT technology.

This is a summary of a preprint research study, “Analysis of Image-Guided Superficial Radiation Therapy (IGSRT) on the Treatment of Early Stage Non-Melanoma Skin Cancer (NMSC) in the Outpatient Dermatology Setting,” led by Alison Tran, MD, of Baylor University Medical Center, Dallas. The study has not been peer reviewed. The full text can be found at medRxiv.org.

A version of this article first appeared on Medscape.com.

The study covered in this summary was published on medRxiv.org as a preprint and has not yet been peer reviewed.

Key takeaway

• Absolute lesion control rate with image-guided superficial radiation therapy (IGSRT) for early-stage nonmelanoma skin cancer was achieved in nearly all patients.

Why this matters

• IGSRT is a newer radiation technique for skin cancer, an alternative to Mohs micrographic surgery and other surgical options.
• The ultrasound imaging used during IGSRT allows for precise targeting of cancer cells while sparing surrounding tissue.
• IGSRT is currently recommended for early-stage nonmelanoma skin cancer among patients who refuse or cannot tolerate surgery.
• Given the safety, lack of surgical disfigurement, cost-effectiveness, and high cure rate, IGSRT should be considered more broadly as a first-line option for early-stage nonmelanoma skin cancer, the researchers concluded.

Study design

• The investigators reviewed 1,899 early-stage nonmelanoma skin cancer lesions in 1,243 patients treated with IGSRT at an outpatient dermatology clinic in Dallas.
• Energies ranged from 50 to 100 kV, with a mean treatment dose of 5,364.4 cGy over an average of 20.2 fractions.
• Treatment duration was a mean of 7.5 weeks and followed for a mean of 65.5 weeks.

Key results

• Absolute lesion control was achieved in 99.7% of patients, with a stable control rate of 99.6% past 12 months.
• At a 5-year follow-up, local control was 99.4%.
• Local control for both basal and squamous cell carcinoma at 5 years was 99%; local control for squamous cell carcinoma in situ was 100% at 5 years.
• The most common side effects were erythema, dryness, and dry desquamation. Some patients had ulceration and moist desquamation, but it did not affect lesion control.
• The procedure was well tolerated, with a grade 1 Radiation Treatment Oncology Group toxicity score in 72% of lesions.
• The results compare favorably with Mohs surgery.

Limitations

• No study limitations were noted.

Disclosures

• No funding source was reported.
• Senior investigator Lio Yu, MD, reported research, speaking and/or consulting for SkinCure Oncology, a developer of IGSRT technology.

This is a summary of a preprint research study, “Analysis of Image-Guided Superficial Radiation Therapy (IGSRT) on the Treatment of Early Stage Non-Melanoma Skin Cancer (NMSC) in the Outpatient Dermatology Setting,” led by Alison Tran, MD, of Baylor University Medical Center, Dallas. The study has not been peer reviewed. The full text can be found at medRxiv.org.

A version of this article first appeared on Medscape.com.

The Asia-Pacific Colorectal Screening (APCS) scoring system, combined with a stool DNA test, could improve the detection of advanced colorectal neoplasms and limit colonoscopy use, according to a new study published in Clinical Gastroenterology and Hepatology.

Although a colonoscopy can detect both colorectal cancer and precancerous lesions, using it as the primary screening tool can cause barriers due to high costs, limited resources, and low compliance, wrote Junfeng Xu of the gastroenterology department at the First Medical Center of Chinese PLA General Hospital, Beijing, and colleagues.

ChrisChrisW/iStock/Getty Images

Avoiding complications

“Colonoscopy is expensive and time consuming for both the patient and the health care system. Colonoscopy is also not without risk since bowel perforation, post-procedural bleeding, and sedation-related complications all occur at low but measurable rates,” said Reid Ness, MD, associate professor of medicine and gastroenterologist at Vanderbilt University Medical Center, Nashville, Tenn.

“The primary strength of the study was that all patients eventually received colonoscopy, allowing for the best estimate of strategy sensitivity for advanced colorectal neoplasia,” he said.

At the same time, the cross-sectional study was unable to estimate the benefit of using this type of screening strategy over time, Dr. Ness said. With limited endoscopic resources available in many countries, however, clinicians need better modalities and strategies for noninvasive identification of advanced colorectal neoplasia, he added.

“Since less than 5% of the population will eventually develop colorectal cancer, the overwhelming majority can only be discomfited and possibly injured through colonoscopy screening,” he said. “For these reasons, the use of a CRC screening strategy that minimizes the use of colonoscopy without compromising the identification rate for advanced colorectal neoplasia is best for both the patient and the health care system.”

The study was supported by grants from the Beijing Municipal Science and Technology Commission. The authors declared no conflicts of interest. Dr. Ness reported no relevant disclosures.

This article was updated Oct. 4, 2022.

The Asia-Pacific Colorectal Screening (APCS) scoring system, combined with a stool DNA test, could improve the detection of advanced colorectal neoplasms and limit colonoscopy use, according to a new study published in Clinical Gastroenterology and Hepatology.

Although a colonoscopy can detect both colorectal cancer and precancerous lesions, using it as the primary screening tool can cause barriers due to high costs, limited resources, and low compliance, wrote Junfeng Xu of the gastroenterology department at the First Medical Center of Chinese PLA General Hospital, Beijing, and colleagues.

ChrisChrisW/iStock/Getty Images

Avoiding complications

“Colonoscopy is expensive and time consuming for both the patient and the health care system. Colonoscopy is also not without risk since bowel perforation, post-procedural bleeding, and sedation-related complications all occur at low but measurable rates,” said Reid Ness, MD, associate professor of medicine and gastroenterologist at Vanderbilt University Medical Center, Nashville, Tenn.

“The primary strength of the study was that all patients eventually received colonoscopy, allowing for the best estimate of strategy sensitivity for advanced colorectal neoplasia,” he said.

At the same time, the cross-sectional study was unable to estimate the benefit of using this type of screening strategy over time, Dr. Ness said. With limited endoscopic resources available in many countries, however, clinicians need better modalities and strategies for noninvasive identification of advanced colorectal neoplasia, he added.

“Since less than 5% of the population will eventually develop colorectal cancer, the overwhelming majority can only be discomfited and possibly injured through colonoscopy screening,” he said. “For these reasons, the use of a CRC screening strategy that minimizes the use of colonoscopy without compromising the identification rate for advanced colorectal neoplasia is best for both the patient and the health care system.”

The study was supported by grants from the Beijing Municipal Science and Technology Commission. The authors declared no conflicts of interest. Dr. Ness reported no relevant disclosures.

This article was updated Oct. 4, 2022.

The Asia-Pacific Colorectal Screening (APCS) scoring system, combined with a stool DNA test, could improve the detection of advanced colorectal neoplasms and limit colonoscopy use, according to a new study published in Clinical Gastroenterology and Hepatology.

Although a colonoscopy can detect both colorectal cancer and precancerous lesions, using it as the primary screening tool can cause barriers due to high costs, limited resources, and low compliance, wrote Junfeng Xu of the gastroenterology department at the First Medical Center of Chinese PLA General Hospital, Beijing, and colleagues.

ChrisChrisW/iStock/Getty Images

Avoiding complications

“Colonoscopy is expensive and time consuming for both the patient and the health care system. Colonoscopy is also not without risk since bowel perforation, post-procedural bleeding, and sedation-related complications all occur at low but measurable rates,” said Reid Ness, MD, associate professor of medicine and gastroenterologist at Vanderbilt University Medical Center, Nashville, Tenn.

“The primary strength of the study was that all patients eventually received colonoscopy, allowing for the best estimate of strategy sensitivity for advanced colorectal neoplasia,” he said.

At the same time, the cross-sectional study was unable to estimate the benefit of using this type of screening strategy over time, Dr. Ness said. With limited endoscopic resources available in many countries, however, clinicians need better modalities and strategies for noninvasive identification of advanced colorectal neoplasia, he added.

“Since less than 5% of the population will eventually develop colorectal cancer, the overwhelming majority can only be discomfited and possibly injured through colonoscopy screening,” he said. “For these reasons, the use of a CRC screening strategy that minimizes the use of colonoscopy without compromising the identification rate for advanced colorectal neoplasia is best for both the patient and the health care system.”

The study was supported by grants from the Beijing Municipal Science and Technology Commission. The authors declared no conflicts of interest. Dr. Ness reported no relevant disclosures.

This article was updated Oct. 4, 2022.

Patients undergoing chimeric antigen receptor (CAR) T-cell therapy who develop potentially serious neurotoxicity from the therapy show elevated plasma levels of neurofilament light chain (NfL) prior to the treatment, suggesting a possibly important predictor of risk for the side effect.

“This is the first study to show NfL levels are elevated even before CAR T treatment is given,” first author Omar H. Butt, MD, PhD, of the Siteman Cancer Center at Barnes-Jewish Hospital and Washington University in St. Louis, said in an interview.

“While unlikely to be the sole driver of [the neurotoxicity], neural injury reflected by NfL may aid in identifying a high-risk subset of patients undergoing cellular therapy,” the authors concluded in the study, published in JAMA Oncology.

CAR T-cell therapy has gained favor for virtually revolutionizing the treatment of some leukemias and lymphomas, however, as many as 40%-60% of patients develop the neurotoxicity side effect, called immune effector cell–associated neurotoxicity syndrome (ICANS), which, though usually low grade, in more severe cases can cause substantial morbidity and even mortality.

Hence, “the early identification of patients at risk for ICANS is critical for preemptive management,” the authors noted.

NfL, an established marker of neuroaxonal injury in neurodegenerative diseases including multiple sclerosis and Alzheimer’s disease, has been shown in previous studies to be elevated following the development of ICANS and up to 5 days prior to its peak symptoms.

To further evaluate NfL elevations in relation to ICANS, Dr. Butt and colleagues identified 30 patients undergoing CD19 CART-cell therapy, including 77% for diffuse large B-cell lymphoma, at two U.S. centers: Washington University in St. Louis and Case Western Reserve University, Cleveland.

The patients had a median age of 64 and were 40% female.

Among them, four developed low-grade ICANS grade 1-2, and 7 developed ICANS grade 3 or higher.

Of those developing any-grade ICANS, baseline elevations of NfL prior to the CAR T-cell treatment, were significantly higher, compared with those who did not develop ICANs (mean 87.6 pg/mL vs. 29.4 pg/mL, P < .001), with no significant differences between the low-grade (1 and 2) and higher-grade (3 or higher) ICANS groups.

A receiver operating characteristic analysis showed baseline NfL levels significantly predicted the development of ICANS with high accuracy (area under the ROC curve, 0.96), as well as sensitivity (AUROC, 0.91) and specificity (AUROC, 0.95).

Notably, baseline NfL levels were associated with ICANS severity, but did not correlate with other factors including demographic, oncologic history, nononcologic neurologic history, or history of exposure to neurotoxic therapies.

However, Dr. Butt added, “it is important to note that our study was insufficiently powered to examine those relationships in earnest. Therefore, [a correlation between NfL and those factors] remains possible,” he said.

The elevated NfL levels observed prior to the development of ICANS remained high across the study’s seven time points, up to day 30 post infusion.
 

Interest in NfL levels on the rise

NfL assessment is currently only clinically validated in amyotrophic lateral sclerosis, where it is used to assess neuroaxonal health and integrity. However, testing is available as interest and evidence of NfL’s potential role in other settings grows.

Meanwhile, Dr. Butt and associates are themselves developing an assay to predict the development of ICANS, which will likely include NfL, if the role is validated in further studies.

“Future studies will explore validating NfL for ICANS and additional indications,” he said.

ICANS symptoms can range from headaches and confusion to seizures or strokes in more severe cases.

The current gold standard for treatment includes early intervention with high-dose steroids and careful monitoring, but there is reluctance to use such therapies because of concerns about their blunting the anticancer effects of the CAR T cells.

Importantly, if validated, elevations in NfL could signal the need for more precautionary measures with CAR T-cell therapy, Dr. Butt noted.

“Our data suggests patients with high NfL levels at baseline would benefit most from perhaps closer monitoring with frequent checks and possible early intervention at the first sign of symptoms, a period of time when it may be hard to distinguish ICANS from other causes of confusion, such as delirium,” he explained.
 

Limitations: Validation, preventive measures needed

Commenting on the study, Sattva S. Neelapu, MD, a professor and deputy chair of the department of lymphoma and myeloma at the University of Texas MD Anderson Cancer Center, Houston, agreed that the findings have potentially important implications.

“I think this is a very intriguing and novel finding that needs to be investigated further prospectively in a larger cohort and across different CAR T products in patients with lymphoma, leukemia, and myeloma,” Dr. Neelapu said in an interview.

The NfL elevations observed even before CAR T-cell therapy among those who went on to develop ICANS are notable, he added.

“This is the surprising finding in the study,” Dr. Neelapu said. “It raises the question whether neurologic injury is caused by prior therapies that these patients received or whether it is an age-related phenomenon, as we do see higher incidence and severity of ICANS in older patients or some other mechanisms.”

A key caveat, however, is that even if a risk is identified, options to prevent ICANS are currently limited, Dr. Neelapu noted.

“I think it is too early to implement this into clinical practice,” he said. In addition to needing further validation, “assessing NfL levels would be useful when there is an effective prophylactic or therapeutic strategy – both of which also need to be investigated.”

Dr. Butt and colleagues are developing a clinical assay for ICANS and reported a provisional patent pending on the use of plasma NfL as a predictive biomarker for ICANS. The study received support from the Washington University in St. Louis, the Paula and Rodger O. Riney Fund, the Daniel J. Brennan MD Fund, the Fred Simmons and Olga Mohan Fund; the National Cancer Institute, the National Multiple Sclerosis Society, and the National Institute of Neurological Disorders and Stroke. Dr. Neelapu reported conflicts of interest with numerous pharmaceutical companies.

Patients undergoing chimeric antigen receptor (CAR) T-cell therapy who develop potentially serious neurotoxicity from the therapy show elevated plasma levels of neurofilament light chain (NfL) prior to the treatment, suggesting a possibly important predictor of risk for the side effect.

“This is the first study to show NfL levels are elevated even before CAR T treatment is given,” first author Omar H. Butt, MD, PhD, of the Siteman Cancer Center at Barnes-Jewish Hospital and Washington University in St. Louis, said in an interview.

“While unlikely to be the sole driver of [the neurotoxicity], neural injury reflected by NfL may aid in identifying a high-risk subset of patients undergoing cellular therapy,” the authors concluded in the study, published in JAMA Oncology.

CAR T-cell therapy has gained favor for virtually revolutionizing the treatment of some leukemias and lymphomas, however, as many as 40%-60% of patients develop the neurotoxicity side effect, called immune effector cell–associated neurotoxicity syndrome (ICANS), which, though usually low grade, in more severe cases can cause substantial morbidity and even mortality.

Hence, “the early identification of patients at risk for ICANS is critical for preemptive management,” the authors noted.

NfL, an established marker of neuroaxonal injury in neurodegenerative diseases including multiple sclerosis and Alzheimer’s disease, has been shown in previous studies to be elevated following the development of ICANS and up to 5 days prior to its peak symptoms.

To further evaluate NfL elevations in relation to ICANS, Dr. Butt and colleagues identified 30 patients undergoing CD19 CART-cell therapy, including 77% for diffuse large B-cell lymphoma, at two U.S. centers: Washington University in St. Louis and Case Western Reserve University, Cleveland.

The patients had a median age of 64 and were 40% female.

Among them, four developed low-grade ICANS grade 1-2, and 7 developed ICANS grade 3 or higher.

Of those developing any-grade ICANS, baseline elevations of NfL prior to the CAR T-cell treatment, were significantly higher, compared with those who did not develop ICANs (mean 87.6 pg/mL vs. 29.4 pg/mL, P < .001), with no significant differences between the low-grade (1 and 2) and higher-grade (3 or higher) ICANS groups.

A receiver operating characteristic analysis showed baseline NfL levels significantly predicted the development of ICANS with high accuracy (area under the ROC curve, 0.96), as well as sensitivity (AUROC, 0.91) and specificity (AUROC, 0.95).

Notably, baseline NfL levels were associated with ICANS severity, but did not correlate with other factors including demographic, oncologic history, nononcologic neurologic history, or history of exposure to neurotoxic therapies.

However, Dr. Butt added, “it is important to note that our study was insufficiently powered to examine those relationships in earnest. Therefore, [a correlation between NfL and those factors] remains possible,” he said.

The elevated NfL levels observed prior to the development of ICANS remained high across the study’s seven time points, up to day 30 post infusion.
 

Interest in NfL levels on the rise

NfL assessment is currently only clinically validated in amyotrophic lateral sclerosis, where it is used to assess neuroaxonal health and integrity. However, testing is available as interest and evidence of NfL’s potential role in other settings grows.

Meanwhile, Dr. Butt and associates are themselves developing an assay to predict the development of ICANS, which will likely include NfL, if the role is validated in further studies.

“Future studies will explore validating NfL for ICANS and additional indications,” he said.

ICANS symptoms can range from headaches and confusion to seizures or strokes in more severe cases.

The current gold standard for treatment includes early intervention with high-dose steroids and careful monitoring, but there is reluctance to use such therapies because of concerns about their blunting the anticancer effects of the CAR T cells.

Importantly, if validated, elevations in NfL could signal the need for more precautionary measures with CAR T-cell therapy, Dr. Butt noted.

“Our data suggests patients with high NfL levels at baseline would benefit most from perhaps closer monitoring with frequent checks and possible early intervention at the first sign of symptoms, a period of time when it may be hard to distinguish ICANS from other causes of confusion, such as delirium,” he explained.
 

Limitations: Validation, preventive measures needed

Commenting on the study, Sattva S. Neelapu, MD, a professor and deputy chair of the department of lymphoma and myeloma at the University of Texas MD Anderson Cancer Center, Houston, agreed that the findings have potentially important implications.

“I think this is a very intriguing and novel finding that needs to be investigated further prospectively in a larger cohort and across different CAR T products in patients with lymphoma, leukemia, and myeloma,” Dr. Neelapu said in an interview.

The NfL elevations observed even before CAR T-cell therapy among those who went on to develop ICANS are notable, he added.

“This is the surprising finding in the study,” Dr. Neelapu said. “It raises the question whether neurologic injury is caused by prior therapies that these patients received or whether it is an age-related phenomenon, as we do see higher incidence and severity of ICANS in older patients or some other mechanisms.”

A key caveat, however, is that even if a risk is identified, options to prevent ICANS are currently limited, Dr. Neelapu noted.

“I think it is too early to implement this into clinical practice,” he said. In addition to needing further validation, “assessing NfL levels would be useful when there is an effective prophylactic or therapeutic strategy – both of which also need to be investigated.”

Dr. Butt and colleagues are developing a clinical assay for ICANS and reported a provisional patent pending on the use of plasma NfL as a predictive biomarker for ICANS. The study received support from the Washington University in St. Louis, the Paula and Rodger O. Riney Fund, the Daniel J. Brennan MD Fund, the Fred Simmons and Olga Mohan Fund; the National Cancer Institute, the National Multiple Sclerosis Society, and the National Institute of Neurological Disorders and Stroke. Dr. Neelapu reported conflicts of interest with numerous pharmaceutical companies.

Patients undergoing chimeric antigen receptor (CAR) T-cell therapy who develop potentially serious neurotoxicity from the therapy show elevated plasma levels of neurofilament light chain (NfL) prior to the treatment, suggesting a possibly important predictor of risk for the side effect.

“This is the first study to show NfL levels are elevated even before CAR T treatment is given,” first author Omar H. Butt, MD, PhD, of the Siteman Cancer Center at Barnes-Jewish Hospital and Washington University in St. Louis, said in an interview.

“While unlikely to be the sole driver of [the neurotoxicity], neural injury reflected by NfL may aid in identifying a high-risk subset of patients undergoing cellular therapy,” the authors concluded in the study, published in JAMA Oncology.

CAR T-cell therapy has gained favor for virtually revolutionizing the treatment of some leukemias and lymphomas, however, as many as 40%-60% of patients develop the neurotoxicity side effect, called immune effector cell–associated neurotoxicity syndrome (ICANS), which, though usually low grade, in more severe cases can cause substantial morbidity and even mortality.

Hence, “the early identification of patients at risk for ICANS is critical for preemptive management,” the authors noted.

NfL, an established marker of neuroaxonal injury in neurodegenerative diseases including multiple sclerosis and Alzheimer’s disease, has been shown in previous studies to be elevated following the development of ICANS and up to 5 days prior to its peak symptoms.

To further evaluate NfL elevations in relation to ICANS, Dr. Butt and colleagues identified 30 patients undergoing CD19 CART-cell therapy, including 77% for diffuse large B-cell lymphoma, at two U.S. centers: Washington University in St. Louis and Case Western Reserve University, Cleveland.

The patients had a median age of 64 and were 40% female.

Among them, four developed low-grade ICANS grade 1-2, and 7 developed ICANS grade 3 or higher.

Of those developing any-grade ICANS, baseline elevations of NfL prior to the CAR T-cell treatment, were significantly higher, compared with those who did not develop ICANs (mean 87.6 pg/mL vs. 29.4 pg/mL, P < .001), with no significant differences between the low-grade (1 and 2) and higher-grade (3 or higher) ICANS groups.

A receiver operating characteristic analysis showed baseline NfL levels significantly predicted the development of ICANS with high accuracy (area under the ROC curve, 0.96), as well as sensitivity (AUROC, 0.91) and specificity (AUROC, 0.95).

Notably, baseline NfL levels were associated with ICANS severity, but did not correlate with other factors including demographic, oncologic history, nononcologic neurologic history, or history of exposure to neurotoxic therapies.

However, Dr. Butt added, “it is important to note that our study was insufficiently powered to examine those relationships in earnest. Therefore, [a correlation between NfL and those factors] remains possible,” he said.

The elevated NfL levels observed prior to the development of ICANS remained high across the study’s seven time points, up to day 30 post infusion.
 

Interest in NfL levels on the rise

NfL assessment is currently only clinically validated in amyotrophic lateral sclerosis, where it is used to assess neuroaxonal health and integrity. However, testing is available as interest and evidence of NfL’s potential role in other settings grows.

Meanwhile, Dr. Butt and associates are themselves developing an assay to predict the development of ICANS, which will likely include NfL, if the role is validated in further studies.

“Future studies will explore validating NfL for ICANS and additional indications,” he said.

ICANS symptoms can range from headaches and confusion to seizures or strokes in more severe cases.

The current gold standard for treatment includes early intervention with high-dose steroids and careful monitoring, but there is reluctance to use such therapies because of concerns about their blunting the anticancer effects of the CAR T cells.

Importantly, if validated, elevations in NfL could signal the need for more precautionary measures with CAR T-cell therapy, Dr. Butt noted.

“Our data suggests patients with high NfL levels at baseline would benefit most from perhaps closer monitoring with frequent checks and possible early intervention at the first sign of symptoms, a period of time when it may be hard to distinguish ICANS from other causes of confusion, such as delirium,” he explained.
 

Limitations: Validation, preventive measures needed

Commenting on the study, Sattva S. Neelapu, MD, a professor and deputy chair of the department of lymphoma and myeloma at the University of Texas MD Anderson Cancer Center, Houston, agreed that the findings have potentially important implications.

“I think this is a very intriguing and novel finding that needs to be investigated further prospectively in a larger cohort and across different CAR T products in patients with lymphoma, leukemia, and myeloma,” Dr. Neelapu said in an interview.

The NfL elevations observed even before CAR T-cell therapy among those who went on to develop ICANS are notable, he added.

“This is the surprising finding in the study,” Dr. Neelapu said. “It raises the question whether neurologic injury is caused by prior therapies that these patients received or whether it is an age-related phenomenon, as we do see higher incidence and severity of ICANS in older patients or some other mechanisms.”

A key caveat, however, is that even if a risk is identified, options to prevent ICANS are currently limited, Dr. Neelapu noted.

“I think it is too early to implement this into clinical practice,” he said. In addition to needing further validation, “assessing NfL levels would be useful when there is an effective prophylactic or therapeutic strategy – both of which also need to be investigated.”

Dr. Butt and colleagues are developing a clinical assay for ICANS and reported a provisional patent pending on the use of plasma NfL as a predictive biomarker for ICANS. The study received support from the Washington University in St. Louis, the Paula and Rodger O. Riney Fund, the Daniel J. Brennan MD Fund, the Fred Simmons and Olga Mohan Fund; the National Cancer Institute, the National Multiple Sclerosis Society, and the National Institute of Neurological Disorders and Stroke. Dr. Neelapu reported conflicts of interest with numerous pharmaceutical companies.

Adding venetoclax (Venclexta) to a gilteritinib (Xospata) regimen appeared to improve outcomes in refractory/relapsed FLT3-mutated acute myeloid leukemia (AML), a new industry-funded phase 1b study reported.

“The combination of venetoclax and gilteritinib is a highly active and tolerable oral combination regimen that potentially improves response frequency and depth over existing standards in a high-risk, mutation-defined group of patients with AML,” wrote the authors of the study, which appeared in the Journal of Clinical Oncology.

Outcomes in AML are poor. As the study notes, most patients relapse and face a median overall survival of 4-7 months even with standard chemotherapy. Gilteritinib, a selective oral FLT3 inhibitor, is Food and Drug Administration–approved for the 30% of relapsed/refractory patients with AML who have FLT3 mutations.

“The general sentiment is that, although some patients have great benefit from gilteritinib monotherapy, there is room to improve the quality, frequency, and duration of responses with combinations,” said hematologist Andrew Brunner, MD, of Massachusetts General Hospital in Boston, in an interview. He was not involved with the study research.

For the new open-label, dose-escalation/dose-expansion study, led by hematologist Naval Daver, MD, of the University of Texas MD Anderson Cancer Center, Houston, researchers enrolled 61 patients (56 with FLT3 mutations) from 2018 to 2020. The median age was 63 years (range 21-85).

The subjects were assigned to get a recommended phase 2 dose of 400 mg venetoclax once daily and 120 mg gilteritinib once daily.

Over a median follow-up of 17.5 months, the median remission time was 4.9 months (95% confidence interval, 3.4-6.6), and the patients with FLT3 mutations survived a median of 10 months.

“The combination of venetoclax and gilteritinib was tolerable at standard doses of each drug, generated remarkably high response rates, and markedly reduced FLT3-internal tandem duplications mutation burden. … Early mortality was similar to gilteritinib monotherapy,” the authors wrote.

Eighty percent of patients experienced cytopenias, and “adverse events prompted venetoclax and gilteritinib dose interruptions in 51% and 48%, respectively.”

About 60% of patients who went on to receive allogeneic hematopoietic stem cell transplantation were alive at the end of follow-up, “suggesting that VenGilt [the combo treatment] could be an effective bridge to transplant in young/fit patients with relapsed FLT3mut AML,” the researchers wrote.

All patients withdrew from the study by November 2021 for several reasons such as death (n=42), adverse events (n=10), and disease progression (29); some had multiple reasons.

Dr. Brunner said the study is “an important step toward evaluating a new potential regimen.”

The remission duration, FLT3 molecular response, and median overall survival “seem quite encouraging for a severe disease like AML in relapse,” he said. However, he added that the drug combo “would need to be evaluated in a randomized and, ideally, placebo-controlled setting to know if this is a significant improvement.”

He also highlighted the high number of severe cyptopenias with associated complications such as death. “Whether this is acceptable depends on the patient and circumstances,” he said. “But it does suggest that this regimen would potentially be for more robust patients, particularly since the group that did best were those who went to transplant later.”

Pending more research, Dr. Brunner said, “I am not sure I would use [the combination treatment] over gilteritinib monotherapy, for instance. But there may be settings where no other options are available, and this could be considered, particularly if a transplant option is a next step.”

The study was funded by AbbVie, Genentech, and Astellas. The study authors report multiple disclosures; some are employed by Astellas, AbbVie, and Genentech/Roche.

Dr. Bronner reports running clinical trials, advisory board service and/or consultation for Acceleron, Agios, Abbvie, BMS/Celgene, Keros Therapeutics, Novartis, Takeda, GSK, AstraZeneca, Janssen, and Gilead.

Adding venetoclax (Venclexta) to a gilteritinib (Xospata) regimen appeared to improve outcomes in refractory/relapsed FLT3-mutated acute myeloid leukemia (AML), a new industry-funded phase 1b study reported.

“The combination of venetoclax and gilteritinib is a highly active and tolerable oral combination regimen that potentially improves response frequency and depth over existing standards in a high-risk, mutation-defined group of patients with AML,” wrote the authors of the study, which appeared in the Journal of Clinical Oncology.

Outcomes in AML are poor. As the study notes, most patients relapse and face a median overall survival of 4-7 months even with standard chemotherapy. Gilteritinib, a selective oral FLT3 inhibitor, is Food and Drug Administration–approved for the 30% of relapsed/refractory patients with AML who have FLT3 mutations.

“The general sentiment is that, although some patients have great benefit from gilteritinib monotherapy, there is room to improve the quality, frequency, and duration of responses with combinations,” said hematologist Andrew Brunner, MD, of Massachusetts General Hospital in Boston, in an interview. He was not involved with the study research.

For the new open-label, dose-escalation/dose-expansion study, led by hematologist Naval Daver, MD, of the University of Texas MD Anderson Cancer Center, Houston, researchers enrolled 61 patients (56 with FLT3 mutations) from 2018 to 2020. The median age was 63 years (range 21-85).

The subjects were assigned to get a recommended phase 2 dose of 400 mg venetoclax once daily and 120 mg gilteritinib once daily.

Over a median follow-up of 17.5 months, the median remission time was 4.9 months (95% confidence interval, 3.4-6.6), and the patients with FLT3 mutations survived a median of 10 months.

“The combination of venetoclax and gilteritinib was tolerable at standard doses of each drug, generated remarkably high response rates, and markedly reduced FLT3-internal tandem duplications mutation burden. … Early mortality was similar to gilteritinib monotherapy,” the authors wrote.

Eighty percent of patients experienced cytopenias, and “adverse events prompted venetoclax and gilteritinib dose interruptions in 51% and 48%, respectively.”

About 60% of patients who went on to receive allogeneic hematopoietic stem cell transplantation were alive at the end of follow-up, “suggesting that VenGilt [the combo treatment] could be an effective bridge to transplant in young/fit patients with relapsed FLT3mut AML,” the researchers wrote.

All patients withdrew from the study by November 2021 for several reasons such as death (n=42), adverse events (n=10), and disease progression (29); some had multiple reasons.

Dr. Brunner said the study is “an important step toward evaluating a new potential regimen.”

The remission duration, FLT3 molecular response, and median overall survival “seem quite encouraging for a severe disease like AML in relapse,” he said. However, he added that the drug combo “would need to be evaluated in a randomized and, ideally, placebo-controlled setting to know if this is a significant improvement.”

He also highlighted the high number of severe cyptopenias with associated complications such as death. “Whether this is acceptable depends on the patient and circumstances,” he said. “But it does suggest that this regimen would potentially be for more robust patients, particularly since the group that did best were those who went to transplant later.”

Pending more research, Dr. Brunner said, “I am not sure I would use [the combination treatment] over gilteritinib monotherapy, for instance. But there may be settings where no other options are available, and this could be considered, particularly if a transplant option is a next step.”

The study was funded by AbbVie, Genentech, and Astellas. The study authors report multiple disclosures; some are employed by Astellas, AbbVie, and Genentech/Roche.

Dr. Bronner reports running clinical trials, advisory board service and/or consultation for Acceleron, Agios, Abbvie, BMS/Celgene, Keros Therapeutics, Novartis, Takeda, GSK, AstraZeneca, Janssen, and Gilead.

Adding venetoclax (Venclexta) to a gilteritinib (Xospata) regimen appeared to improve outcomes in refractory/relapsed FLT3-mutated acute myeloid leukemia (AML), a new industry-funded phase 1b study reported.

“The combination of venetoclax and gilteritinib is a highly active and tolerable oral combination regimen that potentially improves response frequency and depth over existing standards in a high-risk, mutation-defined group of patients with AML,” wrote the authors of the study, which appeared in the Journal of Clinical Oncology.

Outcomes in AML are poor. As the study notes, most patients relapse and face a median overall survival of 4-7 months even with standard chemotherapy. Gilteritinib, a selective oral FLT3 inhibitor, is Food and Drug Administration–approved for the 30% of relapsed/refractory patients with AML who have FLT3 mutations.

“The general sentiment is that, although some patients have great benefit from gilteritinib monotherapy, there is room to improve the quality, frequency, and duration of responses with combinations,” said hematologist Andrew Brunner, MD, of Massachusetts General Hospital in Boston, in an interview. He was not involved with the study research.

For the new open-label, dose-escalation/dose-expansion study, led by hematologist Naval Daver, MD, of the University of Texas MD Anderson Cancer Center, Houston, researchers enrolled 61 patients (56 with FLT3 mutations) from 2018 to 2020. The median age was 63 years (range 21-85).

The subjects were assigned to get a recommended phase 2 dose of 400 mg venetoclax once daily and 120 mg gilteritinib once daily.

Over a median follow-up of 17.5 months, the median remission time was 4.9 months (95% confidence interval, 3.4-6.6), and the patients with FLT3 mutations survived a median of 10 months.

“The combination of venetoclax and gilteritinib was tolerable at standard doses of each drug, generated remarkably high response rates, and markedly reduced FLT3-internal tandem duplications mutation burden. … Early mortality was similar to gilteritinib monotherapy,” the authors wrote.

Eighty percent of patients experienced cytopenias, and “adverse events prompted venetoclax and gilteritinib dose interruptions in 51% and 48%, respectively.”

About 60% of patients who went on to receive allogeneic hematopoietic stem cell transplantation were alive at the end of follow-up, “suggesting that VenGilt [the combo treatment] could be an effective bridge to transplant in young/fit patients with relapsed FLT3mut AML,” the researchers wrote.

All patients withdrew from the study by November 2021 for several reasons such as death (n=42), adverse events (n=10), and disease progression (29); some had multiple reasons.

Dr. Brunner said the study is “an important step toward evaluating a new potential regimen.”

The remission duration, FLT3 molecular response, and median overall survival “seem quite encouraging for a severe disease like AML in relapse,” he said. However, he added that the drug combo “would need to be evaluated in a randomized and, ideally, placebo-controlled setting to know if this is a significant improvement.”

He also highlighted the high number of severe cyptopenias with associated complications such as death. “Whether this is acceptable depends on the patient and circumstances,” he said. “But it does suggest that this regimen would potentially be for more robust patients, particularly since the group that did best were those who went to transplant later.”

Pending more research, Dr. Brunner said, “I am not sure I would use [the combination treatment] over gilteritinib monotherapy, for instance. But there may be settings where no other options are available, and this could be considered, particularly if a transplant option is a next step.”

The study was funded by AbbVie, Genentech, and Astellas. The study authors report multiple disclosures; some are employed by Astellas, AbbVie, and Genentech/Roche.

Dr. Bronner reports running clinical trials, advisory board service and/or consultation for Acceleron, Agios, Abbvie, BMS/Celgene, Keros Therapeutics, Novartis, Takeda, GSK, AstraZeneca, Janssen, and Gilead.