Aude Lecrubier

From adolescence onward, the need for sexual health is particularly important. Yet, information and healthcare services are limited, which often leaves patients in distress and subject to misconceptions. What are the specific issues related to sexuality in adolescence, middle age, and beyond? This news organization interviewed Carol Burté, MD, a specialist in sexual medicine from Monaco.

Question: Regarding young individuals, what about sex education in schools?

Dr. Burté: The French law of 2018 specifies that at least three annual sessions must be devoted to sex education in elementary school, middle school, and high school.

In practice, this is not always the case, and interventions are very focused on prevention and rules. Sexuality is almost always absent from the program. Sexuality means: What does it mean to have desire? How does pleasure work? At what age do we have sex? etc. Young people receive prevention advice, but the link with sexuality is not made.

Sexuality remains taboo. You know, like in books: “They got married and had many children ...” End of the story, we don’t know more [laughs].

Question: And outside the school setting, do doctors sufficiently address sexual health issues with adolescents?

Dr. Burté: Rarely. I understand that a general practitioner has little time, but they can still ask the young person if they have any questions. They can refer them to someone or provide reading recommendations. Regarding sex education on the Internet, there are many well-made websites, such as the one by the national education system.

Also, it is important to give young people lifestyle advice to combat overweight, sedentary behavior, etc., by explaining to them that these factors can lead to sexual disorders later as well as infertility.

Another very important point: There is an inequality between boys and girls, but this time, to the disadvantage of boys. We have a sexual health consultation dedicated to young girls for the pill, but no one examines the boys. However, testicular cancer or undescended testicles can occur. I think we really need to change things and establish a clinical examination for boys in adolescence.

Question: More and more young people identify as asexual. What do you think of this?

Dr. Burté: People who identify as asexual represent about 1% of the population. These are individuals who are not attracted to having sexual relationships with someone. This does not prevent them from having a boyfriend, a girlfriend, masturbating, etc. It is sexual intercourse that does not interest them. These young people often say they have done it all. They have seen a lot of images, viewed sexuality as gymnastics with all the positions, tricks. They are jaded. Also, when you are faced with an image that provides a very strong and rapid stimulation, human relationships seem much more difficult because, obviously, you will never reproduce that sensation when you are with your partner with whom you must connect. The relationship is no longer emotional and shared. Yet, sexuality is emotional, relational, intellectual.

I think people go through phases. At a certain point, they feel asexual, but they can change their minds and think differently if they have real encounters, encounters that are increasingly difficult. Today, we are witnessing a loss of confidence. Young people, but also others, want to protect themselves from everything, especially from falling in love, not get back into a relationship because it is constraining. 

Question: Data show that young people are exposed to pornography at an increasingly early age. Is this a problem for their future sexuality?

Dr. Burté: The exposure to pornography at an early age, around 11 years old, has only been a reality for the past decade. It is too early to say how it will impact their sexuality. When examining the literature on this subject, some publications indicate that the consequences can be dramatic for children. Others show that children can distinguish between reality and fantasy.

Whenever I see young people in consultation, I ask them whether they feel pornography has helped or hindered them, whether it is the cause of the issue they are facing. I would say that, other than those who have viewed pornography under duress, which is of the order of violence, pornography does not seem to pose a problem. It can even provide certain knowledge. 

Question: What about sexual violence in children? What are the consequences?

Dr. Burté: In sexual medicine, this is one of the questions we ask systematically because it is very common. It is important to keep in mind that this not only affects girls; boys are also sexually abused. The consequences are dramatic in terms of psychosexual development. Each case is different. 

Question: At the other end of life, is it “normal” to have sexual disorders at a certain age? Should we resign ourselves?

Dr. Burté: When it comes to sexuality, people have many misconceptions and beliefs that are conveyed through media and the Internet. One of them is to believe that because we are aging, we cannot have a proper sexuality. Sexuality slows down with age, as all sensitivities decrease, but desire is something present throughout life. Yet, seniors are rarely questioned about their sexual health by the media.

Note that older people in institutions face an additional obstacle: lack of privacy. Is this normal? Sexuality releases endorphins, oxytocin, it is well-being that costs nothing. It is something that should be prescribed!

Question: Chronic diseases, disabilities with incidence increases with age — are they not inevitable obstacles to a fulfilling sexuality?

Dr. Burté: It is possible to have a sexual life regardless of the disease one has, cancer, diabetes, rheumatic disease — regardless of the disability. 

A collaboration with the National Cancer Institute on the preservation of sexual health after cancer in which I participated shows that people are extremely demanding of care and that this care is still very insufficient, unfortunately, even in the case of prostate cancer, for example, when it should be obvious.

Question: But aging itself brings challenges in terms of sexuality. 

Dr. Burté: Yes, in men, the consequences of low testosterone levels are well known. Therefore, we must stop thinking that men do not have their “menopause.” Men often have a testosterone deficiency after a certain age. This is very annoying because they have many symptoms that are truly unpleasant and yet can be corrected by completely reliable treatments.

Men are very misinformed on this subject. We talk about gender inequality, but in this area, a young woman who has her first period knows very well that one day she will go through menopause, but a boy has no idea that one day he will have hormone problems.

Question: Therefore, is it important to question men past the age of 50 years?

Dr. Burté: Yes. Faced with sexual symptoms or simply fatigue, or among those who are a bit depressed, investigating a testosterone deficiency should be part of the reflexes.

Also, if you ask a man in general, “How is it going from a sexual point of view,” and he answers that everything is going well, this means he has good arteries, good veins, a good nervous system, sufficient hormones, and psychologically, everything is going rather well. Conversely, erectile dysfunction can be one of the first symptoms of cardiovascular pathologies.

After a certain age, there is no test that provides as much information about people’s health as this question about sexual health.

Question: On their side, are women better cared for at menopause?

Dr. Burté: Yes, but women still lack explanations. I work in sexual medicine, and in my consultation, I see women who come simply to get information about menopause.

Women must know that menopause is a turning point in life because they will spend 30%-40% of their lives without hormones.

It is important to explain that indeed, after menopause, without treatment, it is not the same. There are genital and urinary, psychological, sexual, and skin consequences. It is important to provide true data on the influence of hormonal treatments. Today, hormone fear is not over. I think we need to rehabilitate treatments, care for women.

Question: So we must not forget men or women. 

Dr. Burté: Yes. It is also very important to adopt a perspective not only for the individual but also for the couple. If you treat a man with testosterone, after 3 months, he will be in great shape. However, if the couple has long been accustomed to having a limited sexual life, if the woman is not supported on her side, the couple will be unbalanced. The couple is concerned with managing the hormonal changes of both.

Question: Sexual medicine is essential, yet it seems inaccessible. 

Dr. Burté: There are very few specialists in sexual medicine because there is no legal provision for it. These consultations are lengthy but not valued. Who wants to work for that?

If there was reimbursement for sexual medicine consultations at age 15 years, at menopause, and for men around the age of 50 years, it would change mentalities. Sexual medicine must be integrated into medicine. It should also be noted that not all sexologists are physicians.

Some people are very well trained through universities, and others are not. Ideally, someone with a sexual disorder should first have a sexual medicine consultation to understand the situation. Then, the physician can refer the patient to a competent sexologist because we work in a network.

Dr. Burté has no conflicts of interest related to the subject. 

This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. 

A version of this article appeared on Medscape.com.

From adolescence onward, the need for sexual health is particularly important. Yet, information and healthcare services are limited, which often leaves patients in distress and subject to misconceptions. What are the specific issues related to sexuality in adolescence, middle age, and beyond? This news organization interviewed Carol Burté, MD, a specialist in sexual medicine from Monaco.

Question: Regarding young individuals, what about sex education in schools?

Dr. Burté: The French law of 2018 specifies that at least three annual sessions must be devoted to sex education in elementary school, middle school, and high school.

In practice, this is not always the case, and interventions are very focused on prevention and rules. Sexuality is almost always absent from the program. Sexuality means: What does it mean to have desire? How does pleasure work? At what age do we have sex? etc. Young people receive prevention advice, but the link with sexuality is not made.

Sexuality remains taboo. You know, like in books: “They got married and had many children ...” End of the story, we don’t know more [laughs].

Question: And outside the school setting, do doctors sufficiently address sexual health issues with adolescents?

Dr. Burté: Rarely. I understand that a general practitioner has little time, but they can still ask the young person if they have any questions. They can refer them to someone or provide reading recommendations. Regarding sex education on the Internet, there are many well-made websites, such as the one by the national education system.

Also, it is important to give young people lifestyle advice to combat overweight, sedentary behavior, etc., by explaining to them that these factors can lead to sexual disorders later as well as infertility.

Another very important point: There is an inequality between boys and girls, but this time, to the disadvantage of boys. We have a sexual health consultation dedicated to young girls for the pill, but no one examines the boys. However, testicular cancer or undescended testicles can occur. I think we really need to change things and establish a clinical examination for boys in adolescence.

Question: More and more young people identify as asexual. What do you think of this?

Dr. Burté: People who identify as asexual represent about 1% of the population. These are individuals who are not attracted to having sexual relationships with someone. This does not prevent them from having a boyfriend, a girlfriend, masturbating, etc. It is sexual intercourse that does not interest them. These young people often say they have done it all. They have seen a lot of images, viewed sexuality as gymnastics with all the positions, tricks. They are jaded. Also, when you are faced with an image that provides a very strong and rapid stimulation, human relationships seem much more difficult because, obviously, you will never reproduce that sensation when you are with your partner with whom you must connect. The relationship is no longer emotional and shared. Yet, sexuality is emotional, relational, intellectual.

I think people go through phases. At a certain point, they feel asexual, but they can change their minds and think differently if they have real encounters, encounters that are increasingly difficult. Today, we are witnessing a loss of confidence. Young people, but also others, want to protect themselves from everything, especially from falling in love, not get back into a relationship because it is constraining. 

Question: Data show that young people are exposed to pornography at an increasingly early age. Is this a problem for their future sexuality?

Dr. Burté: The exposure to pornography at an early age, around 11 years old, has only been a reality for the past decade. It is too early to say how it will impact their sexuality. When examining the literature on this subject, some publications indicate that the consequences can be dramatic for children. Others show that children can distinguish between reality and fantasy.

Whenever I see young people in consultation, I ask them whether they feel pornography has helped or hindered them, whether it is the cause of the issue they are facing. I would say that, other than those who have viewed pornography under duress, which is of the order of violence, pornography does not seem to pose a problem. It can even provide certain knowledge. 

Question: What about sexual violence in children? What are the consequences?

Dr. Burté: In sexual medicine, this is one of the questions we ask systematically because it is very common. It is important to keep in mind that this not only affects girls; boys are also sexually abused. The consequences are dramatic in terms of psychosexual development. Each case is different. 

Question: At the other end of life, is it “normal” to have sexual disorders at a certain age? Should we resign ourselves?

Dr. Burté: When it comes to sexuality, people have many misconceptions and beliefs that are conveyed through media and the Internet. One of them is to believe that because we are aging, we cannot have a proper sexuality. Sexuality slows down with age, as all sensitivities decrease, but desire is something present throughout life. Yet, seniors are rarely questioned about their sexual health by the media.

Note that older people in institutions face an additional obstacle: lack of privacy. Is this normal? Sexuality releases endorphins, oxytocin, it is well-being that costs nothing. It is something that should be prescribed!

Question: Chronic diseases, disabilities with incidence increases with age — are they not inevitable obstacles to a fulfilling sexuality?

Dr. Burté: It is possible to have a sexual life regardless of the disease one has, cancer, diabetes, rheumatic disease — regardless of the disability. 

A collaboration with the National Cancer Institute on the preservation of sexual health after cancer in which I participated shows that people are extremely demanding of care and that this care is still very insufficient, unfortunately, even in the case of prostate cancer, for example, when it should be obvious.

Question: But aging itself brings challenges in terms of sexuality. 

Dr. Burté: Yes, in men, the consequences of low testosterone levels are well known. Therefore, we must stop thinking that men do not have their “menopause.” Men often have a testosterone deficiency after a certain age. This is very annoying because they have many symptoms that are truly unpleasant and yet can be corrected by completely reliable treatments.

Men are very misinformed on this subject. We talk about gender inequality, but in this area, a young woman who has her first period knows very well that one day she will go through menopause, but a boy has no idea that one day he will have hormone problems.

Question: Therefore, is it important to question men past the age of 50 years?

Dr. Burté: Yes. Faced with sexual symptoms or simply fatigue, or among those who are a bit depressed, investigating a testosterone deficiency should be part of the reflexes.

Also, if you ask a man in general, “How is it going from a sexual point of view,” and he answers that everything is going well, this means he has good arteries, good veins, a good nervous system, sufficient hormones, and psychologically, everything is going rather well. Conversely, erectile dysfunction can be one of the first symptoms of cardiovascular pathologies.

After a certain age, there is no test that provides as much information about people’s health as this question about sexual health.

Question: On their side, are women better cared for at menopause?

Dr. Burté: Yes, but women still lack explanations. I work in sexual medicine, and in my consultation, I see women who come simply to get information about menopause.

Women must know that menopause is a turning point in life because they will spend 30%-40% of their lives without hormones.

It is important to explain that indeed, after menopause, without treatment, it is not the same. There are genital and urinary, psychological, sexual, and skin consequences. It is important to provide true data on the influence of hormonal treatments. Today, hormone fear is not over. I think we need to rehabilitate treatments, care for women.

Question: So we must not forget men or women. 

Dr. Burté: Yes. It is also very important to adopt a perspective not only for the individual but also for the couple. If you treat a man with testosterone, after 3 months, he will be in great shape. However, if the couple has long been accustomed to having a limited sexual life, if the woman is not supported on her side, the couple will be unbalanced. The couple is concerned with managing the hormonal changes of both.

Question: Sexual medicine is essential, yet it seems inaccessible. 

Dr. Burté: There are very few specialists in sexual medicine because there is no legal provision for it. These consultations are lengthy but not valued. Who wants to work for that?

If there was reimbursement for sexual medicine consultations at age 15 years, at menopause, and for men around the age of 50 years, it would change mentalities. Sexual medicine must be integrated into medicine. It should also be noted that not all sexologists are physicians.

Some people are very well trained through universities, and others are not. Ideally, someone with a sexual disorder should first have a sexual medicine consultation to understand the situation. Then, the physician can refer the patient to a competent sexologist because we work in a network.

Dr. Burté has no conflicts of interest related to the subject. 

This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. 

A version of this article appeared on Medscape.com.

From adolescence onward, the need for sexual health is particularly important. Yet, information and healthcare services are limited, which often leaves patients in distress and subject to misconceptions. What are the specific issues related to sexuality in adolescence, middle age, and beyond? This news organization interviewed Carol Burté, MD, a specialist in sexual medicine from Monaco.

Question: Regarding young individuals, what about sex education in schools?

Dr. Burté: The French law of 2018 specifies that at least three annual sessions must be devoted to sex education in elementary school, middle school, and high school.

In practice, this is not always the case, and interventions are very focused on prevention and rules. Sexuality is almost always absent from the program. Sexuality means: What does it mean to have desire? How does pleasure work? At what age do we have sex? etc. Young people receive prevention advice, but the link with sexuality is not made.

Sexuality remains taboo. You know, like in books: “They got married and had many children ...” End of the story, we don’t know more [laughs].

Question: And outside the school setting, do doctors sufficiently address sexual health issues with adolescents?

Dr. Burté: Rarely. I understand that a general practitioner has little time, but they can still ask the young person if they have any questions. They can refer them to someone or provide reading recommendations. Regarding sex education on the Internet, there are many well-made websites, such as the one by the national education system.

Also, it is important to give young people lifestyle advice to combat overweight, sedentary behavior, etc., by explaining to them that these factors can lead to sexual disorders later as well as infertility.

Another very important point: There is an inequality between boys and girls, but this time, to the disadvantage of boys. We have a sexual health consultation dedicated to young girls for the pill, but no one examines the boys. However, testicular cancer or undescended testicles can occur. I think we really need to change things and establish a clinical examination for boys in adolescence.

Question: More and more young people identify as asexual. What do you think of this?

Dr. Burté: People who identify as asexual represent about 1% of the population. These are individuals who are not attracted to having sexual relationships with someone. This does not prevent them from having a boyfriend, a girlfriend, masturbating, etc. It is sexual intercourse that does not interest them. These young people often say they have done it all. They have seen a lot of images, viewed sexuality as gymnastics with all the positions, tricks. They are jaded. Also, when you are faced with an image that provides a very strong and rapid stimulation, human relationships seem much more difficult because, obviously, you will never reproduce that sensation when you are with your partner with whom you must connect. The relationship is no longer emotional and shared. Yet, sexuality is emotional, relational, intellectual.

I think people go through phases. At a certain point, they feel asexual, but they can change their minds and think differently if they have real encounters, encounters that are increasingly difficult. Today, we are witnessing a loss of confidence. Young people, but also others, want to protect themselves from everything, especially from falling in love, not get back into a relationship because it is constraining. 

Question: Data show that young people are exposed to pornography at an increasingly early age. Is this a problem for their future sexuality?

Dr. Burté: The exposure to pornography at an early age, around 11 years old, has only been a reality for the past decade. It is too early to say how it will impact their sexuality. When examining the literature on this subject, some publications indicate that the consequences can be dramatic for children. Others show that children can distinguish between reality and fantasy.

Whenever I see young people in consultation, I ask them whether they feel pornography has helped or hindered them, whether it is the cause of the issue they are facing. I would say that, other than those who have viewed pornography under duress, which is of the order of violence, pornography does not seem to pose a problem. It can even provide certain knowledge. 

Question: What about sexual violence in children? What are the consequences?

Dr. Burté: In sexual medicine, this is one of the questions we ask systematically because it is very common. It is important to keep in mind that this not only affects girls; boys are also sexually abused. The consequences are dramatic in terms of psychosexual development. Each case is different. 

Question: At the other end of life, is it “normal” to have sexual disorders at a certain age? Should we resign ourselves?

Dr. Burté: When it comes to sexuality, people have many misconceptions and beliefs that are conveyed through media and the Internet. One of them is to believe that because we are aging, we cannot have a proper sexuality. Sexuality slows down with age, as all sensitivities decrease, but desire is something present throughout life. Yet, seniors are rarely questioned about their sexual health by the media.

Note that older people in institutions face an additional obstacle: lack of privacy. Is this normal? Sexuality releases endorphins, oxytocin, it is well-being that costs nothing. It is something that should be prescribed!

Question: Chronic diseases, disabilities with incidence increases with age — are they not inevitable obstacles to a fulfilling sexuality?

Dr. Burté: It is possible to have a sexual life regardless of the disease one has, cancer, diabetes, rheumatic disease — regardless of the disability. 

A collaboration with the National Cancer Institute on the preservation of sexual health after cancer in which I participated shows that people are extremely demanding of care and that this care is still very insufficient, unfortunately, even in the case of prostate cancer, for example, when it should be obvious.

Question: But aging itself brings challenges in terms of sexuality. 

Dr. Burté: Yes, in men, the consequences of low testosterone levels are well known. Therefore, we must stop thinking that men do not have their “menopause.” Men often have a testosterone deficiency after a certain age. This is very annoying because they have many symptoms that are truly unpleasant and yet can be corrected by completely reliable treatments.

Men are very misinformed on this subject. We talk about gender inequality, but in this area, a young woman who has her first period knows very well that one day she will go through menopause, but a boy has no idea that one day he will have hormone problems.

Question: Therefore, is it important to question men past the age of 50 years?

Dr. Burté: Yes. Faced with sexual symptoms or simply fatigue, or among those who are a bit depressed, investigating a testosterone deficiency should be part of the reflexes.

Also, if you ask a man in general, “How is it going from a sexual point of view,” and he answers that everything is going well, this means he has good arteries, good veins, a good nervous system, sufficient hormones, and psychologically, everything is going rather well. Conversely, erectile dysfunction can be one of the first symptoms of cardiovascular pathologies.

After a certain age, there is no test that provides as much information about people’s health as this question about sexual health.

Question: On their side, are women better cared for at menopause?

Dr. Burté: Yes, but women still lack explanations. I work in sexual medicine, and in my consultation, I see women who come simply to get information about menopause.

Women must know that menopause is a turning point in life because they will spend 30%-40% of their lives without hormones.

It is important to explain that indeed, after menopause, without treatment, it is not the same. There are genital and urinary, psychological, sexual, and skin consequences. It is important to provide true data on the influence of hormonal treatments. Today, hormone fear is not over. I think we need to rehabilitate treatments, care for women.

Question: So we must not forget men or women. 

Dr. Burté: Yes. It is also very important to adopt a perspective not only for the individual but also for the couple. If you treat a man with testosterone, after 3 months, he will be in great shape. However, if the couple has long been accustomed to having a limited sexual life, if the woman is not supported on her side, the couple will be unbalanced. The couple is concerned with managing the hormonal changes of both.

Question: Sexual medicine is essential, yet it seems inaccessible. 

Dr. Burté: There are very few specialists in sexual medicine because there is no legal provision for it. These consultations are lengthy but not valued. Who wants to work for that?

If there was reimbursement for sexual medicine consultations at age 15 years, at menopause, and for men around the age of 50 years, it would change mentalities. Sexual medicine must be integrated into medicine. It should also be noted that not all sexologists are physicians.

Some people are very well trained through universities, and others are not. Ideally, someone with a sexual disorder should first have a sexual medicine consultation to understand the situation. Then, the physician can refer the patient to a competent sexologist because we work in a network.

Dr. Burté has no conflicts of interest related to the subject. 

This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. 

A version of this article appeared on Medscape.com.

Akira Endo, PhD, the Japanese microbiologist and biochemist known as the father of statins, died at the age of 90 on June 5. His research led to the discovery and rise of a class of drugs that revolutionized the prevention and treatment of cardiovascular diseases. This scientific journey began over half a century ago.

Inspired by Alexander Fleming

Born into a family of farmers in northern Japan, Dr. Endo was fascinated by natural sciences from a young age and showed a particular interest in fungi and molds. At the age of 10, he already knew he wanted to become a scientist.

He studied in Japan and the United States, conducting research at the Albert Einstein College of Medicine in New York City. He was struck by the high number of elderly and overweight individuals in the United States and realized the importance of developing a drug to combat cholesterol. It was upon his return to Japan, when he joined the Sankyo laboratory, that the development of statins began.

Inspired by Alexander Fleming, who discovered penicillin in the mold Penicillium, he hypothesized that fungi could produce antibiotics inhibiting 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the enzyme that produces cholesterol precursors.

After a year of research on nearly 3800 strains, his team found a known substance, citrinin, that strongly inhibited HMG-CoA reductase and lowered serum cholesterol levels in rats. The research was halted because of its toxicity to the rodents’ kidneys. “Nevertheless, the experience with citrinin gave us hope and courage to quickly discover much more effective active substances,” said Dr. Endo in an article dedicated to the discovery of statins.
 

First Statin Discovered

In the summer of 1972, researchers discovered a second active culture broth, Penicillium citrinum Pen-51, which was isolated from a sample of rice collected in a grain store in Kyoto.

In July 1973, they isolated three active metabolites from this mold, one of which was compactin, which had structural similarities to HMG-CoA, the substrate of the HMG-CoA reductase reaction.

In 1976, they published two articles reporting the discovery and characterization of compactin (mevastatin), the first statin.
 

Several Setbacks

Unfortunately, when Sankyo biologists assessed the effectiveness of compactin by giving rats a diet supplemented with compactin for 7 days, no reduction in serum cholesterol was observed.

Only later did an unpublished study show that the statin significantly decreased plasma cholesterol after a month of treatment in laying hens. The hypocholesterolemic effects of compactin were then demonstrated in dogs and monkeys.

However, researchers faced a second challenge in April 1977. Microcrystalline structures were detected in the liver cells of rats that had been fed extremely high amounts of compactin (over 500 mg/kg per day for 5 weeks). Initially deemed toxic, the structures were ultimately found to be nontoxic.

A phase 2 trial began in the summer of 1979 with very encouraging preliminary results, but in August 1980, clinical development of compactin was halted, as the drug was suspected of causing lymphomas in dogs given very high doses: 100 or 200 mg/kg per day for 2 years.

This suspicion also led to the termination of trials on another statin, the closely related lovastatin, which was discovered simultaneously from different fungi by the Merck laboratory and Dr. Endo in February 1979.
 

First Statin Marketed

Subsequently, dramatic reductions in cholesterol levels observed in patients prompted Merck to conduct large-scale clinical trials of lovastatin in high-risk patients and long-term toxicity studies in dogs in 1984.

It was confirmed that the drug significantly reduced cholesterol levels and was well tolerated. No tumors were detected.

Lovastatin received approval from the Food and Drug Administration to become the first marketed statin in September 1987.

Dr. Endo received numerous awards for his work, including the Albert Lasker Award for Clinical Medical Research in 2008 and the Outstanding Achievement Award from the International Atherosclerosis Society in 2009.

This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article appeared on Medscape.com.

Akira Endo, PhD, the Japanese microbiologist and biochemist known as the father of statins, died at the age of 90 on June 5. His research led to the discovery and rise of a class of drugs that revolutionized the prevention and treatment of cardiovascular diseases. This scientific journey began over half a century ago.

Inspired by Alexander Fleming

Born into a family of farmers in northern Japan, Dr. Endo was fascinated by natural sciences from a young age and showed a particular interest in fungi and molds. At the age of 10, he already knew he wanted to become a scientist.

He studied in Japan and the United States, conducting research at the Albert Einstein College of Medicine in New York City. He was struck by the high number of elderly and overweight individuals in the United States and realized the importance of developing a drug to combat cholesterol. It was upon his return to Japan, when he joined the Sankyo laboratory, that the development of statins began.

Inspired by Alexander Fleming, who discovered penicillin in the mold Penicillium, he hypothesized that fungi could produce antibiotics inhibiting 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the enzyme that produces cholesterol precursors.

After a year of research on nearly 3800 strains, his team found a known substance, citrinin, that strongly inhibited HMG-CoA reductase and lowered serum cholesterol levels in rats. The research was halted because of its toxicity to the rodents’ kidneys. “Nevertheless, the experience with citrinin gave us hope and courage to quickly discover much more effective active substances,” said Dr. Endo in an article dedicated to the discovery of statins.
 

First Statin Discovered

In the summer of 1972, researchers discovered a second active culture broth, Penicillium citrinum Pen-51, which was isolated from a sample of rice collected in a grain store in Kyoto.

In July 1973, they isolated three active metabolites from this mold, one of which was compactin, which had structural similarities to HMG-CoA, the substrate of the HMG-CoA reductase reaction.

In 1976, they published two articles reporting the discovery and characterization of compactin (mevastatin), the first statin.
 

Several Setbacks

Unfortunately, when Sankyo biologists assessed the effectiveness of compactin by giving rats a diet supplemented with compactin for 7 days, no reduction in serum cholesterol was observed.

Only later did an unpublished study show that the statin significantly decreased plasma cholesterol after a month of treatment in laying hens. The hypocholesterolemic effects of compactin were then demonstrated in dogs and monkeys.

However, researchers faced a second challenge in April 1977. Microcrystalline structures were detected in the liver cells of rats that had been fed extremely high amounts of compactin (over 500 mg/kg per day for 5 weeks). Initially deemed toxic, the structures were ultimately found to be nontoxic.

A phase 2 trial began in the summer of 1979 with very encouraging preliminary results, but in August 1980, clinical development of compactin was halted, as the drug was suspected of causing lymphomas in dogs given very high doses: 100 or 200 mg/kg per day for 2 years.

This suspicion also led to the termination of trials on another statin, the closely related lovastatin, which was discovered simultaneously from different fungi by the Merck laboratory and Dr. Endo in February 1979.
 

First Statin Marketed

Subsequently, dramatic reductions in cholesterol levels observed in patients prompted Merck to conduct large-scale clinical trials of lovastatin in high-risk patients and long-term toxicity studies in dogs in 1984.

It was confirmed that the drug significantly reduced cholesterol levels and was well tolerated. No tumors were detected.

Lovastatin received approval from the Food and Drug Administration to become the first marketed statin in September 1987.

Dr. Endo received numerous awards for his work, including the Albert Lasker Award for Clinical Medical Research in 2008 and the Outstanding Achievement Award from the International Atherosclerosis Society in 2009.

This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article appeared on Medscape.com.

Akira Endo, PhD, the Japanese microbiologist and biochemist known as the father of statins, died at the age of 90 on June 5. His research led to the discovery and rise of a class of drugs that revolutionized the prevention and treatment of cardiovascular diseases. This scientific journey began over half a century ago.

Inspired by Alexander Fleming

Born into a family of farmers in northern Japan, Dr. Endo was fascinated by natural sciences from a young age and showed a particular interest in fungi and molds. At the age of 10, he already knew he wanted to become a scientist.

He studied in Japan and the United States, conducting research at the Albert Einstein College of Medicine in New York City. He was struck by the high number of elderly and overweight individuals in the United States and realized the importance of developing a drug to combat cholesterol. It was upon his return to Japan, when he joined the Sankyo laboratory, that the development of statins began.

Inspired by Alexander Fleming, who discovered penicillin in the mold Penicillium, he hypothesized that fungi could produce antibiotics inhibiting 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the enzyme that produces cholesterol precursors.

After a year of research on nearly 3800 strains, his team found a known substance, citrinin, that strongly inhibited HMG-CoA reductase and lowered serum cholesterol levels in rats. The research was halted because of its toxicity to the rodents’ kidneys. “Nevertheless, the experience with citrinin gave us hope and courage to quickly discover much more effective active substances,” said Dr. Endo in an article dedicated to the discovery of statins.
 

First Statin Discovered

In the summer of 1972, researchers discovered a second active culture broth, Penicillium citrinum Pen-51, which was isolated from a sample of rice collected in a grain store in Kyoto.

In July 1973, they isolated three active metabolites from this mold, one of which was compactin, which had structural similarities to HMG-CoA, the substrate of the HMG-CoA reductase reaction.

In 1976, they published two articles reporting the discovery and characterization of compactin (mevastatin), the first statin.
 

Several Setbacks

Unfortunately, when Sankyo biologists assessed the effectiveness of compactin by giving rats a diet supplemented with compactin for 7 days, no reduction in serum cholesterol was observed.

Only later did an unpublished study show that the statin significantly decreased plasma cholesterol after a month of treatment in laying hens. The hypocholesterolemic effects of compactin were then demonstrated in dogs and monkeys.

However, researchers faced a second challenge in April 1977. Microcrystalline structures were detected in the liver cells of rats that had been fed extremely high amounts of compactin (over 500 mg/kg per day for 5 weeks). Initially deemed toxic, the structures were ultimately found to be nontoxic.

A phase 2 trial began in the summer of 1979 with very encouraging preliminary results, but in August 1980, clinical development of compactin was halted, as the drug was suspected of causing lymphomas in dogs given very high doses: 100 or 200 mg/kg per day for 2 years.

This suspicion also led to the termination of trials on another statin, the closely related lovastatin, which was discovered simultaneously from different fungi by the Merck laboratory and Dr. Endo in February 1979.
 

First Statin Marketed

Subsequently, dramatic reductions in cholesterol levels observed in patients prompted Merck to conduct large-scale clinical trials of lovastatin in high-risk patients and long-term toxicity studies in dogs in 1984.

It was confirmed that the drug significantly reduced cholesterol levels and was well tolerated. No tumors were detected.

Lovastatin received approval from the Food and Drug Administration to become the first marketed statin in September 1987.

Dr. Endo received numerous awards for his work, including the Albert Lasker Award for Clinical Medical Research in 2008 and the Outstanding Achievement Award from the International Atherosclerosis Society in 2009.

This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article appeared on Medscape.com.

Faced with a positive human papillomavirus (HPV) test, patients are quickly overwhelmed by anxiety-inducing questions. It is crucial to provide them with adequate responses to reassure them, emphasized Jean-Louis Mergui, MD, president of the International Federation for Colposcopy, during the press conference of the Congress of the French Society of Colposcopy and Cervico-Vaginal Pathology.

“Do I have cancer? When did I catch this papillomavirus? Is it dangerous for my partner? How do I get rid of it?” “Not everyone is equipped to answer these four questions. However, it is extremely important that healthcare professionals provide correct answers to patients so that they stop worrying,” Dr. Mergui explained.
 

Papillomavirus and Cancer

One of the first instincts of patients who receive a positive HPV test is to turn to the Internet. There, they read about “high-risk HPV, which is potentially oncogenic,” and become completely panicked, said Dr. Mergui.

However, among women, the probability of having a high-grade CIN3 lesion or higher on the cervix when the HPV test is positive is about 7%, according to the ATHENA study. “About 93% of patients do not have a severe lesion on the cervix. That’s why colposcopy is not performed on all patients. They need to be reassured,” said Dr. Mergui. When the papillomavirus persists, there is a risk for a cervical lesion. After 11 years, between 20% and 30% of patients develop a high-grade lesion on the cervix. However, on average, a high-risk HPV is spontaneously eliminated within 1-2 years. “After 14 months, 50% of women will test negative for their papillomavirus,” Dr. Mergui noted.

“High-risk HPV does not mean there is a lesion; it means there is a risk of developing a lesion on the cervix one day. That’s why these patients need to be monitored and explored,” he added.

In practice, when a patient aged between 30 and 65 years has a positive HPV test, cytology is performed to look for lesions. Only in the case of an abnormal smear, ASC-US, is colposcopy recommended. In the absence of a lesion, a control HPV test is conducted 1 year later to monitor virus persistence.

It should be noted that patients who have been treated for a cervical lesion have a five times higher risk of developing invasive cervical, vaginal, or vulvar cancer. Therefore, treated patients must be monitored once every 3 years for life.
 

Time of Infection

Many patients ask, “When did I catch this papillomavirus?” In response, Dr. Mergui first emphasized that HPV infection is common. “Between ages 15 and 30 years, most of us are infected with a high-risk HPV. When we look at the incidence between ages 15 and 25 years, every year, 20% of all young girls are infected with HPV, including 17% with high-risk HPV. The virus is usually caught within the first 5 years of sexual activity, and typically disappears after about a year,” he explained.

However, the most disturbing scenario for patients is when their last examination was negative, and there is no apparent reason for having caught the virus since then. Suspicion often falls on the partner. Once again, the gynecologist seeks to reassure.

It is possible that the last time screening was conducted, the virus was not sought (HPV test), but rather cervical lesions were sought by smear. However, a normal smear does not mean that the papillomavirus is not present. A negative cytology does not mean a negative HPV test. As we have seen, the virus is not always associated with the presence of a lesion, explained Dr. Mergui.

Also, having had a negative HPV test a few years earlier does not mean that one was not already infected. The HPV test determines the quantity of virus. Therefore, it is possible that the virus was present in small quantities that were without clinical significance (hence, a negative test). However, a few years later, the virus may have multiplied, and the HPV test became positive.

“Sometimes, the virus re-emerges 40, 50 years after infection due to age-related immune decline,” said Dr. Mergui. “So, just because the smear was negative or the HPV test was negative at the last examination does not mean that one was infected between the two.” Moreover, only 15% of couples have the same virus present on the penis or vagina, he pointed out.
 

Protecting One’s Partner

Once the diagnosis is made, it is often too late to protect the partner because they have already been infected. “It is certain that the partner will be infected or has already been infected because when the patient comes to you with a positive HPV test, she has already had sexual intercourse. It is worth noting that the virus can be transmitted through digital touching, and condoms are not very effective in preventing virus transmission,” said Dr. Mergui.

The speaker further clarified that the risk for men is much lower than that for women. “In women, about 40,000 lesions linked to high-risk HPV types, precancerous or cancerous, are observed every year. In men, this number is 1900. So, this represents 20 times fewer neoplastic lesions in men. The problem in men is oropharyngeal lesions, which are three times more common than in women. However, there is no screening for oropharyngeal cancer.”

So, when should the partner consult? Dr. Mergui advised consulting when there are clinically visible lesions (small warts, bumps, or ear, nose, and throat symptoms). “I do not recommend systematic examination of male or female partners,” he added.
 

Clearing the Virus

There are treatments for cervical lesions but not for papillomavirus infection.

“The only thing that can be suggested is quitting smoking, which increases viral clearance, thus reducing viral load. Also, the use of condoms helps improve viral clearance, but when women have a stable relationship, it seems unrealistic to think they will constantly use condoms. Finally, the prophylactic vaccine has been proposed, but it does not treat the infection. In fact, the real solution is to tell patients that they need to continue regular monitoring,” said Dr. Mergui.

“It should be noted that an ongoing study at the European level seems to show that when women who have undergone surgical treatment for a high-grade cervical lesion are vaccinated at the time of treatment or just after treatment, it reduces the risk of recurrence by 50%. So, the risk of recurrence is around 7%-8%. This strategy could be interesting, but for now, there is no official recommendation,” Dr. Mergui concluded.
 

This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.

Faced with a positive human papillomavirus (HPV) test, patients are quickly overwhelmed by anxiety-inducing questions. It is crucial to provide them with adequate responses to reassure them, emphasized Jean-Louis Mergui, MD, president of the International Federation for Colposcopy, during the press conference of the Congress of the French Society of Colposcopy and Cervico-Vaginal Pathology.

“Do I have cancer? When did I catch this papillomavirus? Is it dangerous for my partner? How do I get rid of it?” “Not everyone is equipped to answer these four questions. However, it is extremely important that healthcare professionals provide correct answers to patients so that they stop worrying,” Dr. Mergui explained.
 

Papillomavirus and Cancer

One of the first instincts of patients who receive a positive HPV test is to turn to the Internet. There, they read about “high-risk HPV, which is potentially oncogenic,” and become completely panicked, said Dr. Mergui.

However, among women, the probability of having a high-grade CIN3 lesion or higher on the cervix when the HPV test is positive is about 7%, according to the ATHENA study. “About 93% of patients do not have a severe lesion on the cervix. That’s why colposcopy is not performed on all patients. They need to be reassured,” said Dr. Mergui. When the papillomavirus persists, there is a risk for a cervical lesion. After 11 years, between 20% and 30% of patients develop a high-grade lesion on the cervix. However, on average, a high-risk HPV is spontaneously eliminated within 1-2 years. “After 14 months, 50% of women will test negative for their papillomavirus,” Dr. Mergui noted.

“High-risk HPV does not mean there is a lesion; it means there is a risk of developing a lesion on the cervix one day. That’s why these patients need to be monitored and explored,” he added.

In practice, when a patient aged between 30 and 65 years has a positive HPV test, cytology is performed to look for lesions. Only in the case of an abnormal smear, ASC-US, is colposcopy recommended. In the absence of a lesion, a control HPV test is conducted 1 year later to monitor virus persistence.

It should be noted that patients who have been treated for a cervical lesion have a five times higher risk of developing invasive cervical, vaginal, or vulvar cancer. Therefore, treated patients must be monitored once every 3 years for life.
 

Time of Infection

Many patients ask, “When did I catch this papillomavirus?” In response, Dr. Mergui first emphasized that HPV infection is common. “Between ages 15 and 30 years, most of us are infected with a high-risk HPV. When we look at the incidence between ages 15 and 25 years, every year, 20% of all young girls are infected with HPV, including 17% with high-risk HPV. The virus is usually caught within the first 5 years of sexual activity, and typically disappears after about a year,” he explained.

However, the most disturbing scenario for patients is when their last examination was negative, and there is no apparent reason for having caught the virus since then. Suspicion often falls on the partner. Once again, the gynecologist seeks to reassure.

It is possible that the last time screening was conducted, the virus was not sought (HPV test), but rather cervical lesions were sought by smear. However, a normal smear does not mean that the papillomavirus is not present. A negative cytology does not mean a negative HPV test. As we have seen, the virus is not always associated with the presence of a lesion, explained Dr. Mergui.

Also, having had a negative HPV test a few years earlier does not mean that one was not already infected. The HPV test determines the quantity of virus. Therefore, it is possible that the virus was present in small quantities that were without clinical significance (hence, a negative test). However, a few years later, the virus may have multiplied, and the HPV test became positive.

“Sometimes, the virus re-emerges 40, 50 years after infection due to age-related immune decline,” said Dr. Mergui. “So, just because the smear was negative or the HPV test was negative at the last examination does not mean that one was infected between the two.” Moreover, only 15% of couples have the same virus present on the penis or vagina, he pointed out.
 

Protecting One’s Partner

Once the diagnosis is made, it is often too late to protect the partner because they have already been infected. “It is certain that the partner will be infected or has already been infected because when the patient comes to you with a positive HPV test, she has already had sexual intercourse. It is worth noting that the virus can be transmitted through digital touching, and condoms are not very effective in preventing virus transmission,” said Dr. Mergui.

The speaker further clarified that the risk for men is much lower than that for women. “In women, about 40,000 lesions linked to high-risk HPV types, precancerous or cancerous, are observed every year. In men, this number is 1900. So, this represents 20 times fewer neoplastic lesions in men. The problem in men is oropharyngeal lesions, which are three times more common than in women. However, there is no screening for oropharyngeal cancer.”

So, when should the partner consult? Dr. Mergui advised consulting when there are clinically visible lesions (small warts, bumps, or ear, nose, and throat symptoms). “I do not recommend systematic examination of male or female partners,” he added.
 

Clearing the Virus

There are treatments for cervical lesions but not for papillomavirus infection.

“The only thing that can be suggested is quitting smoking, which increases viral clearance, thus reducing viral load. Also, the use of condoms helps improve viral clearance, but when women have a stable relationship, it seems unrealistic to think they will constantly use condoms. Finally, the prophylactic vaccine has been proposed, but it does not treat the infection. In fact, the real solution is to tell patients that they need to continue regular monitoring,” said Dr. Mergui.

“It should be noted that an ongoing study at the European level seems to show that when women who have undergone surgical treatment for a high-grade cervical lesion are vaccinated at the time of treatment or just after treatment, it reduces the risk of recurrence by 50%. So, the risk of recurrence is around 7%-8%. This strategy could be interesting, but for now, there is no official recommendation,” Dr. Mergui concluded.
 

This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.

Faced with a positive human papillomavirus (HPV) test, patients are quickly overwhelmed by anxiety-inducing questions. It is crucial to provide them with adequate responses to reassure them, emphasized Jean-Louis Mergui, MD, president of the International Federation for Colposcopy, during the press conference of the Congress of the French Society of Colposcopy and Cervico-Vaginal Pathology.

“Do I have cancer? When did I catch this papillomavirus? Is it dangerous for my partner? How do I get rid of it?” “Not everyone is equipped to answer these four questions. However, it is extremely important that healthcare professionals provide correct answers to patients so that they stop worrying,” Dr. Mergui explained.
 

Papillomavirus and Cancer

One of the first instincts of patients who receive a positive HPV test is to turn to the Internet. There, they read about “high-risk HPV, which is potentially oncogenic,” and become completely panicked, said Dr. Mergui.

However, among women, the probability of having a high-grade CIN3 lesion or higher on the cervix when the HPV test is positive is about 7%, according to the ATHENA study. “About 93% of patients do not have a severe lesion on the cervix. That’s why colposcopy is not performed on all patients. They need to be reassured,” said Dr. Mergui. When the papillomavirus persists, there is a risk for a cervical lesion. After 11 years, between 20% and 30% of patients develop a high-grade lesion on the cervix. However, on average, a high-risk HPV is spontaneously eliminated within 1-2 years. “After 14 months, 50% of women will test negative for their papillomavirus,” Dr. Mergui noted.

“High-risk HPV does not mean there is a lesion; it means there is a risk of developing a lesion on the cervix one day. That’s why these patients need to be monitored and explored,” he added.

In practice, when a patient aged between 30 and 65 years has a positive HPV test, cytology is performed to look for lesions. Only in the case of an abnormal smear, ASC-US, is colposcopy recommended. In the absence of a lesion, a control HPV test is conducted 1 year later to monitor virus persistence.

It should be noted that patients who have been treated for a cervical lesion have a five times higher risk of developing invasive cervical, vaginal, or vulvar cancer. Therefore, treated patients must be monitored once every 3 years for life.
 

Time of Infection

Many patients ask, “When did I catch this papillomavirus?” In response, Dr. Mergui first emphasized that HPV infection is common. “Between ages 15 and 30 years, most of us are infected with a high-risk HPV. When we look at the incidence between ages 15 and 25 years, every year, 20% of all young girls are infected with HPV, including 17% with high-risk HPV. The virus is usually caught within the first 5 years of sexual activity, and typically disappears after about a year,” he explained.

However, the most disturbing scenario for patients is when their last examination was negative, and there is no apparent reason for having caught the virus since then. Suspicion often falls on the partner. Once again, the gynecologist seeks to reassure.

It is possible that the last time screening was conducted, the virus was not sought (HPV test), but rather cervical lesions were sought by smear. However, a normal smear does not mean that the papillomavirus is not present. A negative cytology does not mean a negative HPV test. As we have seen, the virus is not always associated with the presence of a lesion, explained Dr. Mergui.

Also, having had a negative HPV test a few years earlier does not mean that one was not already infected. The HPV test determines the quantity of virus. Therefore, it is possible that the virus was present in small quantities that were without clinical significance (hence, a negative test). However, a few years later, the virus may have multiplied, and the HPV test became positive.

“Sometimes, the virus re-emerges 40, 50 years after infection due to age-related immune decline,” said Dr. Mergui. “So, just because the smear was negative or the HPV test was negative at the last examination does not mean that one was infected between the two.” Moreover, only 15% of couples have the same virus present on the penis or vagina, he pointed out.
 

Protecting One’s Partner

Once the diagnosis is made, it is often too late to protect the partner because they have already been infected. “It is certain that the partner will be infected or has already been infected because when the patient comes to you with a positive HPV test, she has already had sexual intercourse. It is worth noting that the virus can be transmitted through digital touching, and condoms are not very effective in preventing virus transmission,” said Dr. Mergui.

The speaker further clarified that the risk for men is much lower than that for women. “In women, about 40,000 lesions linked to high-risk HPV types, precancerous or cancerous, are observed every year. In men, this number is 1900. So, this represents 20 times fewer neoplastic lesions in men. The problem in men is oropharyngeal lesions, which are three times more common than in women. However, there is no screening for oropharyngeal cancer.”

So, when should the partner consult? Dr. Mergui advised consulting when there are clinically visible lesions (small warts, bumps, or ear, nose, and throat symptoms). “I do not recommend systematic examination of male or female partners,” he added.
 

Clearing the Virus

There are treatments for cervical lesions but not for papillomavirus infection.

“The only thing that can be suggested is quitting smoking, which increases viral clearance, thus reducing viral load. Also, the use of condoms helps improve viral clearance, but when women have a stable relationship, it seems unrealistic to think they will constantly use condoms. Finally, the prophylactic vaccine has been proposed, but it does not treat the infection. In fact, the real solution is to tell patients that they need to continue regular monitoring,” said Dr. Mergui.

“It should be noted that an ongoing study at the European level seems to show that when women who have undergone surgical treatment for a high-grade cervical lesion are vaccinated at the time of treatment or just after treatment, it reduces the risk of recurrence by 50%. So, the risk of recurrence is around 7%-8%. This strategy could be interesting, but for now, there is no official recommendation,” Dr. Mergui concluded.
 

This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.

Cases of menstrual disorders, particularly unusually heavy menstrual bleeding, have been reported following RNA vaccination against COVID-19.

In France, this safety signal has been confirmed and added to the product characteristics summaries and vaccine leaflets for mRNA vaccines in October 2022. However, few studies have accurately measured this risk to date.

To address this gap in research, the French scientific interest group in the epidemiology of health products, ANSM-Cnam EPI-PHARE, conducted a study to assess the risk for heavy menstrual bleeding requiring hospitalization after COVID-19 vaccination in France.

“This study provides new evidence supporting the existence of an increased risk for heavy menstrual bleeding following COVID-19 vaccination with mRNA vaccines,” wrote the authors.
 

Study Details

The study included all women aged 15-50 years who were diagnosed with heavy menstrual bleeding in the hospital between May 12, 2021, and August 31, 2022. Participants were identified in the National Health Data System, and the study population totaled 4610 women.

Each participant was randomly matched with as many as 30 women who had not been hospitalized for abnormal genital bleeding and had similar characteristics in terms of age, department of residence, social deprivation index of the commune of residence, and contraceptive method.

Women who had a recent pregnancy, hysterectomy, or coagulation disorder within the specified time frames were excluded.

At the time of the study, 71% of cases and 70% of controls had received at least one dose of the COVID-19 vaccine. Among vaccinated participants, 68% and 66%, respectively, received a vaccination dose (first or second dose). An mRNA vaccine (Comirnaty or Spikevax) was the last vaccine for 99.8% of the population.
 

Increased Risk 

Compared with control women, those hospitalized for heavy menstrual bleeding were more likely to have received their last dose of mRNA vaccine (Comirnaty or Spikevax) in the previous 1-3 months. This association was observed for vaccination doses (odds ratio [OR], 1.20), indicating a 20% increased risk, but it was not found for booster doses (OR, 1.07).

This association was particularly notable for women residing in socially disadvantaged communities (OR, 1.28) and women not using hormonal contraception (OR, 1.28).

The risk did not appear to be increased beyond 3 months after vaccination. Researchers noted that the increased risk may have occurred earlier, considering the likely interval between initial symptoms and hospitalization.

Assuming a causal relationship, the estimated number of cases attributable to vaccination was 8 cases per million vaccinated women, totaling 103 cases among all women aged 15-50 years who were vaccinated in France between May 12, 2021, and August 31, 2022.

As of the study date and in the 3 years before the study, none of the authors had any conflicts of interest with pharmaceutical companies. 
 

This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.

Cases of menstrual disorders, particularly unusually heavy menstrual bleeding, have been reported following RNA vaccination against COVID-19.

In France, this safety signal has been confirmed and added to the product characteristics summaries and vaccine leaflets for mRNA vaccines in October 2022. However, few studies have accurately measured this risk to date.

To address this gap in research, the French scientific interest group in the epidemiology of health products, ANSM-Cnam EPI-PHARE, conducted a study to assess the risk for heavy menstrual bleeding requiring hospitalization after COVID-19 vaccination in France.

“This study provides new evidence supporting the existence of an increased risk for heavy menstrual bleeding following COVID-19 vaccination with mRNA vaccines,” wrote the authors.
 

Study Details

The study included all women aged 15-50 years who were diagnosed with heavy menstrual bleeding in the hospital between May 12, 2021, and August 31, 2022. Participants were identified in the National Health Data System, and the study population totaled 4610 women.

Each participant was randomly matched with as many as 30 women who had not been hospitalized for abnormal genital bleeding and had similar characteristics in terms of age, department of residence, social deprivation index of the commune of residence, and contraceptive method.

Women who had a recent pregnancy, hysterectomy, or coagulation disorder within the specified time frames were excluded.

At the time of the study, 71% of cases and 70% of controls had received at least one dose of the COVID-19 vaccine. Among vaccinated participants, 68% and 66%, respectively, received a vaccination dose (first or second dose). An mRNA vaccine (Comirnaty or Spikevax) was the last vaccine for 99.8% of the population.
 

Increased Risk 

Compared with control women, those hospitalized for heavy menstrual bleeding were more likely to have received their last dose of mRNA vaccine (Comirnaty or Spikevax) in the previous 1-3 months. This association was observed for vaccination doses (odds ratio [OR], 1.20), indicating a 20% increased risk, but it was not found for booster doses (OR, 1.07).

This association was particularly notable for women residing in socially disadvantaged communities (OR, 1.28) and women not using hormonal contraception (OR, 1.28).

The risk did not appear to be increased beyond 3 months after vaccination. Researchers noted that the increased risk may have occurred earlier, considering the likely interval between initial symptoms and hospitalization.

Assuming a causal relationship, the estimated number of cases attributable to vaccination was 8 cases per million vaccinated women, totaling 103 cases among all women aged 15-50 years who were vaccinated in France between May 12, 2021, and August 31, 2022.

As of the study date and in the 3 years before the study, none of the authors had any conflicts of interest with pharmaceutical companies. 
 

This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.

Cases of menstrual disorders, particularly unusually heavy menstrual bleeding, have been reported following RNA vaccination against COVID-19.

In France, this safety signal has been confirmed and added to the product characteristics summaries and vaccine leaflets for mRNA vaccines in October 2022. However, few studies have accurately measured this risk to date.

To address this gap in research, the French scientific interest group in the epidemiology of health products, ANSM-Cnam EPI-PHARE, conducted a study to assess the risk for heavy menstrual bleeding requiring hospitalization after COVID-19 vaccination in France.

“This study provides new evidence supporting the existence of an increased risk for heavy menstrual bleeding following COVID-19 vaccination with mRNA vaccines,” wrote the authors.
 

Study Details

The study included all women aged 15-50 years who were diagnosed with heavy menstrual bleeding in the hospital between May 12, 2021, and August 31, 2022. Participants were identified in the National Health Data System, and the study population totaled 4610 women.

Each participant was randomly matched with as many as 30 women who had not been hospitalized for abnormal genital bleeding and had similar characteristics in terms of age, department of residence, social deprivation index of the commune of residence, and contraceptive method.

Women who had a recent pregnancy, hysterectomy, or coagulation disorder within the specified time frames were excluded.

At the time of the study, 71% of cases and 70% of controls had received at least one dose of the COVID-19 vaccine. Among vaccinated participants, 68% and 66%, respectively, received a vaccination dose (first or second dose). An mRNA vaccine (Comirnaty or Spikevax) was the last vaccine for 99.8% of the population.
 

Increased Risk 

Compared with control women, those hospitalized for heavy menstrual bleeding were more likely to have received their last dose of mRNA vaccine (Comirnaty or Spikevax) in the previous 1-3 months. This association was observed for vaccination doses (odds ratio [OR], 1.20), indicating a 20% increased risk, but it was not found for booster doses (OR, 1.07).

This association was particularly notable for women residing in socially disadvantaged communities (OR, 1.28) and women not using hormonal contraception (OR, 1.28).

The risk did not appear to be increased beyond 3 months after vaccination. Researchers noted that the increased risk may have occurred earlier, considering the likely interval between initial symptoms and hospitalization.

Assuming a causal relationship, the estimated number of cases attributable to vaccination was 8 cases per million vaccinated women, totaling 103 cases among all women aged 15-50 years who were vaccinated in France between May 12, 2021, and August 31, 2022.

As of the study date and in the 3 years before the study, none of the authors had any conflicts of interest with pharmaceutical companies. 
 

This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.

How can we improve the detection, assessment, and treatment of female sexual dysfunction?

Charlotte Methorst, MD, a urologist from Paris, and Carol Burté, MD, a sexologist and andrologist from Nice, dealt with these themes during a session at the French Urology Association’s 2023 conference, emphasizing the need for doctors to be involved in female sexual health.

“There’s currently a real disconnect; doctors talk very little about sexual health, yet it’s a topic that patients would really like to talk about. And this is even truer for women,” said Dr. Methorst.

“We need to spot sexual dysfunction because the topic is rarely broached spontaneously by female patients (19%) and even less so by healthcare workers (9%). Nowadays, it’s a very common problem (40%). Sexual dysfunction affects quality of life and a couple’s relationship. It also can reveal other conditions,” added Dr. Burté.
 

Spot and Assess

In terms of detecting the condition, the reference tool is the self-assessed Female Sexual Function Index, which comprises 19 questions covering six areas of sexual dysfunction: Desire, subjective arousal, lubrication, orgasm, satisfaction, and pain or discomfort.

But it is also possible to use the Sexual Complaints Screener for Women that evaluates sexual health over the past 6 months, explains Dr. Burté. For example, the patient is asked if she has had a lack of or low interest in sex or sexual desire in the past 6 months and if this has been a problem. She is also asked if she has experienced any pain during or after sexual activity.

To understand the root cause of sexual dysfunction, clinicians need to investigate the patient’s sexual health and perform a medical assessment. It’s also essential to ask the patient about her previous sexual, medical, and psychological history and to evaluate the couple and contributory factors, such as stress, fatigue, etc. This approach is known as the biopsychosocial model.

Once the contributory factors have been determined, relevant information can be given to the patient about her specific sexual problem, and the most suitable therapeutic approaches can be discussed with her.
 

Which Treatment Pathway?

Some problems may be improved with simple advice and lifestyle changes, but sex therapy and medication are options in other cases, explained the two doctors. “Since the causes of sexual dysfunction in women are mostly multifactorial, an integrative approach is needed,” said Dr. Burté.

The two main types of therapy that might be proposed for sexual dysfunction are sex therapies with cognitive behavioral therapy (CBT) and certain medicines being used as first-line treatment.

Using CBT in sexology requires patients and therapists to look past prejudices, preconceived ideas, and dysfunctional patterns and learn new behavioral, cognitive, and attentional strategies in terms of sexual health, regardless of whether an individual or couple is being treated.
 

Which Medicines?

Vasoactive drugs such as phosphodiesterase 5 inhibitors and prostaglandin have produced disappointing results. Drugs that act on the central nervous system to stimulate sexual desire, such as bremelanotide and flibanserin, don’t have marketing authorization in France due to their “insufficient” risk-benefit ratio.

However, topical hormone treatments (such as estrogen and dehydroepiandrosterone) are often used, particularly for cases of recurrent cystitis, in postmenopausal women and to treat urinary incontinence. “These topical treatments are very effective and can really change the life of a woman who no longer has a sex life because she is in discomfort and simply has dryness of the vulva and vagina,” said Dr. Burté, who recommends prescribing creams, which are better tolerated than pessaries.

General hormone treatments, hormone replacement therapy (HRT), and tibolone are prescribed to postmenopausal women.

Another option not yet authorized in France is testosterone because sexual desire depends on this hormone. An international consensus (2019, 10 learned societies) and recommendations made by the International Society for the Study of Women’s Sexual Health advise treatment with testosterone in the postmenopausal period, with or without HRT. The dose prescribed is a 10th of the male dose administered subcutaneously (300 µ/d) once a woman›s blood testosterone level has been determined to make sure there is an actual deficiency and to restore her testosterone to near premenopausal levels.

Both doctors indicated that having the chance to work with other doctors as part of a network is essential, especially with a sexual health specialist, if necessary.

Dr. Burté reported no conflicts of interest regarding the content of this article. Dr. Methorst reported relationships with several pharmaceutical laboratories.

This article was translated from the Medscape French edition.

How can we improve the detection, assessment, and treatment of female sexual dysfunction?

Charlotte Methorst, MD, a urologist from Paris, and Carol Burté, MD, a sexologist and andrologist from Nice, dealt with these themes during a session at the French Urology Association’s 2023 conference, emphasizing the need for doctors to be involved in female sexual health.

“There’s currently a real disconnect; doctors talk very little about sexual health, yet it’s a topic that patients would really like to talk about. And this is even truer for women,” said Dr. Methorst.

“We need to spot sexual dysfunction because the topic is rarely broached spontaneously by female patients (19%) and even less so by healthcare workers (9%). Nowadays, it’s a very common problem (40%). Sexual dysfunction affects quality of life and a couple’s relationship. It also can reveal other conditions,” added Dr. Burté.
 

Spot and Assess

In terms of detecting the condition, the reference tool is the self-assessed Female Sexual Function Index, which comprises 19 questions covering six areas of sexual dysfunction: Desire, subjective arousal, lubrication, orgasm, satisfaction, and pain or discomfort.

But it is also possible to use the Sexual Complaints Screener for Women that evaluates sexual health over the past 6 months, explains Dr. Burté. For example, the patient is asked if she has had a lack of or low interest in sex or sexual desire in the past 6 months and if this has been a problem. She is also asked if she has experienced any pain during or after sexual activity.

To understand the root cause of sexual dysfunction, clinicians need to investigate the patient’s sexual health and perform a medical assessment. It’s also essential to ask the patient about her previous sexual, medical, and psychological history and to evaluate the couple and contributory factors, such as stress, fatigue, etc. This approach is known as the biopsychosocial model.

Once the contributory factors have been determined, relevant information can be given to the patient about her specific sexual problem, and the most suitable therapeutic approaches can be discussed with her.
 

Which Treatment Pathway?

Some problems may be improved with simple advice and lifestyle changes, but sex therapy and medication are options in other cases, explained the two doctors. “Since the causes of sexual dysfunction in women are mostly multifactorial, an integrative approach is needed,” said Dr. Burté.

The two main types of therapy that might be proposed for sexual dysfunction are sex therapies with cognitive behavioral therapy (CBT) and certain medicines being used as first-line treatment.

Using CBT in sexology requires patients and therapists to look past prejudices, preconceived ideas, and dysfunctional patterns and learn new behavioral, cognitive, and attentional strategies in terms of sexual health, regardless of whether an individual or couple is being treated.
 

Which Medicines?

Vasoactive drugs such as phosphodiesterase 5 inhibitors and prostaglandin have produced disappointing results. Drugs that act on the central nervous system to stimulate sexual desire, such as bremelanotide and flibanserin, don’t have marketing authorization in France due to their “insufficient” risk-benefit ratio.

However, topical hormone treatments (such as estrogen and dehydroepiandrosterone) are often used, particularly for cases of recurrent cystitis, in postmenopausal women and to treat urinary incontinence. “These topical treatments are very effective and can really change the life of a woman who no longer has a sex life because she is in discomfort and simply has dryness of the vulva and vagina,” said Dr. Burté, who recommends prescribing creams, which are better tolerated than pessaries.

General hormone treatments, hormone replacement therapy (HRT), and tibolone are prescribed to postmenopausal women.

Another option not yet authorized in France is testosterone because sexual desire depends on this hormone. An international consensus (2019, 10 learned societies) and recommendations made by the International Society for the Study of Women’s Sexual Health advise treatment with testosterone in the postmenopausal period, with or without HRT. The dose prescribed is a 10th of the male dose administered subcutaneously (300 µ/d) once a woman›s blood testosterone level has been determined to make sure there is an actual deficiency and to restore her testosterone to near premenopausal levels.

Both doctors indicated that having the chance to work with other doctors as part of a network is essential, especially with a sexual health specialist, if necessary.

Dr. Burté reported no conflicts of interest regarding the content of this article. Dr. Methorst reported relationships with several pharmaceutical laboratories.

This article was translated from the Medscape French edition.

How can we improve the detection, assessment, and treatment of female sexual dysfunction?

Charlotte Methorst, MD, a urologist from Paris, and Carol Burté, MD, a sexologist and andrologist from Nice, dealt with these themes during a session at the French Urology Association’s 2023 conference, emphasizing the need for doctors to be involved in female sexual health.

“There’s currently a real disconnect; doctors talk very little about sexual health, yet it’s a topic that patients would really like to talk about. And this is even truer for women,” said Dr. Methorst.

“We need to spot sexual dysfunction because the topic is rarely broached spontaneously by female patients (19%) and even less so by healthcare workers (9%). Nowadays, it’s a very common problem (40%). Sexual dysfunction affects quality of life and a couple’s relationship. It also can reveal other conditions,” added Dr. Burté.
 

Spot and Assess

In terms of detecting the condition, the reference tool is the self-assessed Female Sexual Function Index, which comprises 19 questions covering six areas of sexual dysfunction: Desire, subjective arousal, lubrication, orgasm, satisfaction, and pain or discomfort.

But it is also possible to use the Sexual Complaints Screener for Women that evaluates sexual health over the past 6 months, explains Dr. Burté. For example, the patient is asked if she has had a lack of or low interest in sex or sexual desire in the past 6 months and if this has been a problem. She is also asked if she has experienced any pain during or after sexual activity.

To understand the root cause of sexual dysfunction, clinicians need to investigate the patient’s sexual health and perform a medical assessment. It’s also essential to ask the patient about her previous sexual, medical, and psychological history and to evaluate the couple and contributory factors, such as stress, fatigue, etc. This approach is known as the biopsychosocial model.

Once the contributory factors have been determined, relevant information can be given to the patient about her specific sexual problem, and the most suitable therapeutic approaches can be discussed with her.
 

Which Treatment Pathway?

Some problems may be improved with simple advice and lifestyle changes, but sex therapy and medication are options in other cases, explained the two doctors. “Since the causes of sexual dysfunction in women are mostly multifactorial, an integrative approach is needed,” said Dr. Burté.

The two main types of therapy that might be proposed for sexual dysfunction are sex therapies with cognitive behavioral therapy (CBT) and certain medicines being used as first-line treatment.

Using CBT in sexology requires patients and therapists to look past prejudices, preconceived ideas, and dysfunctional patterns and learn new behavioral, cognitive, and attentional strategies in terms of sexual health, regardless of whether an individual or couple is being treated.
 

Which Medicines?

Vasoactive drugs such as phosphodiesterase 5 inhibitors and prostaglandin have produced disappointing results. Drugs that act on the central nervous system to stimulate sexual desire, such as bremelanotide and flibanserin, don’t have marketing authorization in France due to their “insufficient” risk-benefit ratio.

However, topical hormone treatments (such as estrogen and dehydroepiandrosterone) are often used, particularly for cases of recurrent cystitis, in postmenopausal women and to treat urinary incontinence. “These topical treatments are very effective and can really change the life of a woman who no longer has a sex life because she is in discomfort and simply has dryness of the vulva and vagina,” said Dr. Burté, who recommends prescribing creams, which are better tolerated than pessaries.

General hormone treatments, hormone replacement therapy (HRT), and tibolone are prescribed to postmenopausal women.

Another option not yet authorized in France is testosterone because sexual desire depends on this hormone. An international consensus (2019, 10 learned societies) and recommendations made by the International Society for the Study of Women’s Sexual Health advise treatment with testosterone in the postmenopausal period, with or without HRT. The dose prescribed is a 10th of the male dose administered subcutaneously (300 µ/d) once a woman›s blood testosterone level has been determined to make sure there is an actual deficiency and to restore her testosterone to near premenopausal levels.

Both doctors indicated that having the chance to work with other doctors as part of a network is essential, especially with a sexual health specialist, if necessary.

Dr. Burté reported no conflicts of interest regarding the content of this article. Dr. Methorst reported relationships with several pharmaceutical laboratories.

This article was translated from the Medscape French edition.

PARIS — Although metabolic liver diseases are mainly seen in patients with obesity or type 2 diabetes, studies have shown that non-alcoholic fatty liver disease, recently renamed metabolic dysfunction-associated steatotic liver disease (MASLD), also affects slim patients. Moreover, the condition could be particularly severe in this population. 

A recent study carried out using data from the French Constance cohort showed that of the 25,753 patients with MASLD, 16.3% were lean (BMI of less than 25 kg/m²). In addition, 50% of these patients had no metabolic risk factors. 

These slim patients with MASLD were most often young patients, for the most part female, and less likely to present with symptoms of metabolic syndrome. Asian patients were overrepresented in this group. 

“These patients probably have genetic and/or environmental risk factors,” commented senior author Lawrence Serfaty, MD, PhD, head of the metabolic liver unit at the new Strasbourg public hospital, during a press conference at the Paris NASH meeting. 

The disease was more severe in slim subjects. Overall, 3.6% of the slim subjects had advanced fibrosis (Forns index > 6.9) vs 1.7% of patients with overweight or obesity (P < .001), regardless of demographic variables, metabolic risk factors, and lifestyle. They also had higher alanine aminotransferase levels. 

In addition, over the course of a mean follow-up of 3.8 years, liver events (eg, cirrhosis, decompensated cirrhosis, and liver cancer), chronic kidney diseases, and all-cause mortality were much more common in these patients than in patients with overweight or obesity (adjusted hazard ratios of 5.84, 2.49, and 3.01, respectively). It should be noted that these clinical results were linked to fibrosis severity in both slim and overweight subjects with MASLD. 

Nonetheless, cardiovascular events remained more common in patients with overweight or obesity, suggesting that obesity itself is a major risk factor for cardiovascular diseases, regardless of MASLD. 

“Armed with these results, which confirm those obtained from other studies, we must seek to understand the pathogenesis of the disease in slim patients and study the role of the microbiota, genetics, and diet, as well as determining the effects of alcohol and tobacco, consumption of which was slightly more common in this subpopulation,” said Dr. Serfaty. 

According to the study authors, sarcopenia and bile acids could also be involved in the pathogenesis of MASLD in slim patients. The researchers concluded that “due to the relatively low rate of MASLD in slim subjects, screening should target patients presenting with metabolic anomalies and/or unexplained cytolysis.”
 

This article was translated from the Medscape French edition.

PARIS — Although metabolic liver diseases are mainly seen in patients with obesity or type 2 diabetes, studies have shown that non-alcoholic fatty liver disease, recently renamed metabolic dysfunction-associated steatotic liver disease (MASLD), also affects slim patients. Moreover, the condition could be particularly severe in this population. 

A recent study carried out using data from the French Constance cohort showed that of the 25,753 patients with MASLD, 16.3% were lean (BMI of less than 25 kg/m²). In addition, 50% of these patients had no metabolic risk factors. 

These slim patients with MASLD were most often young patients, for the most part female, and less likely to present with symptoms of metabolic syndrome. Asian patients were overrepresented in this group. 

“These patients probably have genetic and/or environmental risk factors,” commented senior author Lawrence Serfaty, MD, PhD, head of the metabolic liver unit at the new Strasbourg public hospital, during a press conference at the Paris NASH meeting. 

The disease was more severe in slim subjects. Overall, 3.6% of the slim subjects had advanced fibrosis (Forns index > 6.9) vs 1.7% of patients with overweight or obesity (P < .001), regardless of demographic variables, metabolic risk factors, and lifestyle. They also had higher alanine aminotransferase levels. 

In addition, over the course of a mean follow-up of 3.8 years, liver events (eg, cirrhosis, decompensated cirrhosis, and liver cancer), chronic kidney diseases, and all-cause mortality were much more common in these patients than in patients with overweight or obesity (adjusted hazard ratios of 5.84, 2.49, and 3.01, respectively). It should be noted that these clinical results were linked to fibrosis severity in both slim and overweight subjects with MASLD. 

Nonetheless, cardiovascular events remained more common in patients with overweight or obesity, suggesting that obesity itself is a major risk factor for cardiovascular diseases, regardless of MASLD. 

“Armed with these results, which confirm those obtained from other studies, we must seek to understand the pathogenesis of the disease in slim patients and study the role of the microbiota, genetics, and diet, as well as determining the effects of alcohol and tobacco, consumption of which was slightly more common in this subpopulation,” said Dr. Serfaty. 

According to the study authors, sarcopenia and bile acids could also be involved in the pathogenesis of MASLD in slim patients. The researchers concluded that “due to the relatively low rate of MASLD in slim subjects, screening should target patients presenting with metabolic anomalies and/or unexplained cytolysis.”
 

This article was translated from the Medscape French edition.

PARIS — Although metabolic liver diseases are mainly seen in patients with obesity or type 2 diabetes, studies have shown that non-alcoholic fatty liver disease, recently renamed metabolic dysfunction-associated steatotic liver disease (MASLD), also affects slim patients. Moreover, the condition could be particularly severe in this population. 

A recent study carried out using data from the French Constance cohort showed that of the 25,753 patients with MASLD, 16.3% were lean (BMI of less than 25 kg/m²). In addition, 50% of these patients had no metabolic risk factors. 

These slim patients with MASLD were most often young patients, for the most part female, and less likely to present with symptoms of metabolic syndrome. Asian patients were overrepresented in this group. 

“These patients probably have genetic and/or environmental risk factors,” commented senior author Lawrence Serfaty, MD, PhD, head of the metabolic liver unit at the new Strasbourg public hospital, during a press conference at the Paris NASH meeting. 

The disease was more severe in slim subjects. Overall, 3.6% of the slim subjects had advanced fibrosis (Forns index > 6.9) vs 1.7% of patients with overweight or obesity (P < .001), regardless of demographic variables, metabolic risk factors, and lifestyle. They also had higher alanine aminotransferase levels. 

In addition, over the course of a mean follow-up of 3.8 years, liver events (eg, cirrhosis, decompensated cirrhosis, and liver cancer), chronic kidney diseases, and all-cause mortality were much more common in these patients than in patients with overweight or obesity (adjusted hazard ratios of 5.84, 2.49, and 3.01, respectively). It should be noted that these clinical results were linked to fibrosis severity in both slim and overweight subjects with MASLD. 

Nonetheless, cardiovascular events remained more common in patients with overweight or obesity, suggesting that obesity itself is a major risk factor for cardiovascular diseases, regardless of MASLD. 

“Armed with these results, which confirm those obtained from other studies, we must seek to understand the pathogenesis of the disease in slim patients and study the role of the microbiota, genetics, and diet, as well as determining the effects of alcohol and tobacco, consumption of which was slightly more common in this subpopulation,” said Dr. Serfaty. 

According to the study authors, sarcopenia and bile acids could also be involved in the pathogenesis of MASLD in slim patients. The researchers concluded that “due to the relatively low rate of MASLD in slim subjects, screening should target patients presenting with metabolic anomalies and/or unexplained cytolysis.”
 

This article was translated from the Medscape French edition.

MADRID – Fine particulate matter pollution in the atmosphere around homes and workplaces increases the risk for breast cancer, according to a new analysis of the XENAIR study presented at the European Society of Medical Oncology (ESMO) Congress 2023. Béatrice Fervers, MD, PhD, head of the environmental cancer prevention department at the Léon Bérard Center, Lyon, France, presented her findings.

“To our knowledge, this study is the first to examine the risk of breast cancer associated with long-term exposure of subjects to atmospheric pollution both at home and in the workplace, estimated using a very small spatial resolution [statistical] model,” said the researchers.

“Our data showed a statistically significant association between long-term exposure to fine particulate matter air pollution, at home and at work, and risk of breast cancer. This [finding] contrasts with previous research that looked only at fine particulate exposure where women were living and showed small or no effects on breast cancer risk,” said Dr. Fervers in a press release issued before the Congress.

The XENAIR study carried out on the prospective, longitudinal E3N cohort a year ago showed an increased risk for breast cancer after exposure to five atmospheric pollutants. Notably, it showed an increased risk in women exposed to BaP and PCB153, two pollutants classed as endocrine-disrupting chemicals, during perimenopause.
 

Increased linear risk

In this new analysis, exposure to PM2.5, PM10, and NO2 pollution at home and in the workplace of 2,419 women with breast cancer was compared with that of 2,984 women without breast cancer during the period from 1990 to 2011.

This was a case-control study in which participants were matched by department of residence in France, age (± 1 year), date (± 3 months), and menopausal status at the time of the blood draw.

Breast cancer risk increased by 28% when exposure to fine particulate (PM2.5) air pollution increased by 10 mcg/m3. The increment is approximately equivalent to the difference in PM2.5 particulate concentration typically seen in rural versus urban areas of Europe.

Smaller increases in breast cancer risk were also recorded in women exposed to high levels of larger particulate air pollution (PM10 and NO2).

No change in effect was seen according to menopausal status. Analyses that examined hormone receptor status showed a positive but not significant association for PM2.5 in cases of estrogen receptor positive breast cancer.

Dr. Fervers and colleagues plan to investigate the effects of pollution exposure during the commute to get a complete picture of effects on breast cancer risk.
 

Regulators respond

Charles Swanton, PhD, a clinician scientist at the Francis Crick Institute, London, emphasized the importance of these new results for breast cancer. At last year’s ESMO Congress, he explained how particulate matter air pollution caused tumor proliferation in patients with a certain type of genetic mutation.

“Fine particle pollutants can penetrate deep into the lungs, enter the bloodstream, and be absorbed into breast and other tissue. There is already evidence that air pollutants can change the architecture of the breast. It will be important to test if pollutants allow cells in breast tissue with pre-existing mutations to expand and drive tumor promotion, possibly through inflammatory processes, similar to our observations in nonsmokers with lung cancer,” said Dr. Swanton in the ESMO press release.

“It is very concerning that small pollutant particles in the air and indeed microplastic particles of similar size are getting into the environment when we don’t yet understand their potential to promote cancer. There is an urgent need to set up laboratory studies to investigate the effects of these small air pollutant particles on the latency, grade, aggression, and progression of breast tumors,” he added.

“There is now strong epidemiological and biological evidence for the link between PM2.5 particulate exposure and cancer, and there are good clinical and economic reasons for reducing pollution to prevent cancers,” said Jean-Yves Blay, MD, PhD, director of public policy for ESMO.

Following a proposal from the European Commission in October 2022 to reduce the limit for PM2.5 particulates in the air from the current 25 mcg/m3 to 10 mcg/m3 by 2030, ESMO urged a further reduction in the PM2.5 limit to 5 mcg/m3, in line with the World Health Organization’s air quality guidance, according to the press release.

“Reducing PM2.5 particles in the air to the WHO recommended level is critical because of their association with a variety of tumor types, including breast cancer,” Dr. Blay added.

In September 2023, the European Parliament adopted in a plenary session its report on the ongoing revision of the EU Ambient Air Quality Directives, which reflects ESMO’s recommendations to set the annual limit value for PM2.5 at 5 mcg/m³. This adoption opens interinstitutional negotiations between the legislators (the European Parliament, European Commission, and EU Council) to agree on the final text of the directive.

“By supporting our requests with solid scientific evidence, we are offering a new dimension to health public policy. The work is not over, and change will not happen overnight, but we are moving in the right direction,” concluded Dr. Blay.

The new analysis of the XENAIR study was funded by ARC Foundation for cancer research; the French Agency for Food, Environmental, and Occupational Health and Safety; French National League against Cancer; and Fondation de France, an independent administrative agency. The authors report no relevant financial relationships.

This article was translated from the Medscape French edition and a version appeared on Medscape.com.

MADRID – Fine particulate matter pollution in the atmosphere around homes and workplaces increases the risk for breast cancer, according to a new analysis of the XENAIR study presented at the European Society of Medical Oncology (ESMO) Congress 2023. Béatrice Fervers, MD, PhD, head of the environmental cancer prevention department at the Léon Bérard Center, Lyon, France, presented her findings.

“To our knowledge, this study is the first to examine the risk of breast cancer associated with long-term exposure of subjects to atmospheric pollution both at home and in the workplace, estimated using a very small spatial resolution [statistical] model,” said the researchers.

“Our data showed a statistically significant association between long-term exposure to fine particulate matter air pollution, at home and at work, and risk of breast cancer. This [finding] contrasts with previous research that looked only at fine particulate exposure where women were living and showed small or no effects on breast cancer risk,” said Dr. Fervers in a press release issued before the Congress.

The XENAIR study carried out on the prospective, longitudinal E3N cohort a year ago showed an increased risk for breast cancer after exposure to five atmospheric pollutants. Notably, it showed an increased risk in women exposed to BaP and PCB153, two pollutants classed as endocrine-disrupting chemicals, during perimenopause.
 

Increased linear risk

In this new analysis, exposure to PM2.5, PM10, and NO2 pollution at home and in the workplace of 2,419 women with breast cancer was compared with that of 2,984 women without breast cancer during the period from 1990 to 2011.

This was a case-control study in which participants were matched by department of residence in France, age (± 1 year), date (± 3 months), and menopausal status at the time of the blood draw.

Breast cancer risk increased by 28% when exposure to fine particulate (PM2.5) air pollution increased by 10 mcg/m3. The increment is approximately equivalent to the difference in PM2.5 particulate concentration typically seen in rural versus urban areas of Europe.

Smaller increases in breast cancer risk were also recorded in women exposed to high levels of larger particulate air pollution (PM10 and NO2).

No change in effect was seen according to menopausal status. Analyses that examined hormone receptor status showed a positive but not significant association for PM2.5 in cases of estrogen receptor positive breast cancer.

Dr. Fervers and colleagues plan to investigate the effects of pollution exposure during the commute to get a complete picture of effects on breast cancer risk.
 

Regulators respond

Charles Swanton, PhD, a clinician scientist at the Francis Crick Institute, London, emphasized the importance of these new results for breast cancer. At last year’s ESMO Congress, he explained how particulate matter air pollution caused tumor proliferation in patients with a certain type of genetic mutation.

“Fine particle pollutants can penetrate deep into the lungs, enter the bloodstream, and be absorbed into breast and other tissue. There is already evidence that air pollutants can change the architecture of the breast. It will be important to test if pollutants allow cells in breast tissue with pre-existing mutations to expand and drive tumor promotion, possibly through inflammatory processes, similar to our observations in nonsmokers with lung cancer,” said Dr. Swanton in the ESMO press release.

“It is very concerning that small pollutant particles in the air and indeed microplastic particles of similar size are getting into the environment when we don’t yet understand their potential to promote cancer. There is an urgent need to set up laboratory studies to investigate the effects of these small air pollutant particles on the latency, grade, aggression, and progression of breast tumors,” he added.

“There is now strong epidemiological and biological evidence for the link between PM2.5 particulate exposure and cancer, and there are good clinical and economic reasons for reducing pollution to prevent cancers,” said Jean-Yves Blay, MD, PhD, director of public policy for ESMO.

Following a proposal from the European Commission in October 2022 to reduce the limit for PM2.5 particulates in the air from the current 25 mcg/m3 to 10 mcg/m3 by 2030, ESMO urged a further reduction in the PM2.5 limit to 5 mcg/m3, in line with the World Health Organization’s air quality guidance, according to the press release.

“Reducing PM2.5 particles in the air to the WHO recommended level is critical because of their association with a variety of tumor types, including breast cancer,” Dr. Blay added.

In September 2023, the European Parliament adopted in a plenary session its report on the ongoing revision of the EU Ambient Air Quality Directives, which reflects ESMO’s recommendations to set the annual limit value for PM2.5 at 5 mcg/m³. This adoption opens interinstitutional negotiations between the legislators (the European Parliament, European Commission, and EU Council) to agree on the final text of the directive.

“By supporting our requests with solid scientific evidence, we are offering a new dimension to health public policy. The work is not over, and change will not happen overnight, but we are moving in the right direction,” concluded Dr. Blay.

The new analysis of the XENAIR study was funded by ARC Foundation for cancer research; the French Agency for Food, Environmental, and Occupational Health and Safety; French National League against Cancer; and Fondation de France, an independent administrative agency. The authors report no relevant financial relationships.

This article was translated from the Medscape French edition and a version appeared on Medscape.com.

MADRID – Fine particulate matter pollution in the atmosphere around homes and workplaces increases the risk for breast cancer, according to a new analysis of the XENAIR study presented at the European Society of Medical Oncology (ESMO) Congress 2023. Béatrice Fervers, MD, PhD, head of the environmental cancer prevention department at the Léon Bérard Center, Lyon, France, presented her findings.

“To our knowledge, this study is the first to examine the risk of breast cancer associated with long-term exposure of subjects to atmospheric pollution both at home and in the workplace, estimated using a very small spatial resolution [statistical] model,” said the researchers.

“Our data showed a statistically significant association between long-term exposure to fine particulate matter air pollution, at home and at work, and risk of breast cancer. This [finding] contrasts with previous research that looked only at fine particulate exposure where women were living and showed small or no effects on breast cancer risk,” said Dr. Fervers in a press release issued before the Congress.

The XENAIR study carried out on the prospective, longitudinal E3N cohort a year ago showed an increased risk for breast cancer after exposure to five atmospheric pollutants. Notably, it showed an increased risk in women exposed to BaP and PCB153, two pollutants classed as endocrine-disrupting chemicals, during perimenopause.
 

Increased linear risk

In this new analysis, exposure to PM2.5, PM10, and NO2 pollution at home and in the workplace of 2,419 women with breast cancer was compared with that of 2,984 women without breast cancer during the period from 1990 to 2011.

This was a case-control study in which participants were matched by department of residence in France, age (± 1 year), date (± 3 months), and menopausal status at the time of the blood draw.

Breast cancer risk increased by 28% when exposure to fine particulate (PM2.5) air pollution increased by 10 mcg/m3. The increment is approximately equivalent to the difference in PM2.5 particulate concentration typically seen in rural versus urban areas of Europe.

Smaller increases in breast cancer risk were also recorded in women exposed to high levels of larger particulate air pollution (PM10 and NO2).

No change in effect was seen according to menopausal status. Analyses that examined hormone receptor status showed a positive but not significant association for PM2.5 in cases of estrogen receptor positive breast cancer.

Dr. Fervers and colleagues plan to investigate the effects of pollution exposure during the commute to get a complete picture of effects on breast cancer risk.
 

Regulators respond

Charles Swanton, PhD, a clinician scientist at the Francis Crick Institute, London, emphasized the importance of these new results for breast cancer. At last year’s ESMO Congress, he explained how particulate matter air pollution caused tumor proliferation in patients with a certain type of genetic mutation.

“Fine particle pollutants can penetrate deep into the lungs, enter the bloodstream, and be absorbed into breast and other tissue. There is already evidence that air pollutants can change the architecture of the breast. It will be important to test if pollutants allow cells in breast tissue with pre-existing mutations to expand and drive tumor promotion, possibly through inflammatory processes, similar to our observations in nonsmokers with lung cancer,” said Dr. Swanton in the ESMO press release.

“It is very concerning that small pollutant particles in the air and indeed microplastic particles of similar size are getting into the environment when we don’t yet understand their potential to promote cancer. There is an urgent need to set up laboratory studies to investigate the effects of these small air pollutant particles on the latency, grade, aggression, and progression of breast tumors,” he added.

“There is now strong epidemiological and biological evidence for the link between PM2.5 particulate exposure and cancer, and there are good clinical and economic reasons for reducing pollution to prevent cancers,” said Jean-Yves Blay, MD, PhD, director of public policy for ESMO.

Following a proposal from the European Commission in October 2022 to reduce the limit for PM2.5 particulates in the air from the current 25 mcg/m3 to 10 mcg/m3 by 2030, ESMO urged a further reduction in the PM2.5 limit to 5 mcg/m3, in line with the World Health Organization’s air quality guidance, according to the press release.

“Reducing PM2.5 particles in the air to the WHO recommended level is critical because of their association with a variety of tumor types, including breast cancer,” Dr. Blay added.

In September 2023, the European Parliament adopted in a plenary session its report on the ongoing revision of the EU Ambient Air Quality Directives, which reflects ESMO’s recommendations to set the annual limit value for PM2.5 at 5 mcg/m³. This adoption opens interinstitutional negotiations between the legislators (the European Parliament, European Commission, and EU Council) to agree on the final text of the directive.

“By supporting our requests with solid scientific evidence, we are offering a new dimension to health public policy. The work is not over, and change will not happen overnight, but we are moving in the right direction,” concluded Dr. Blay.

The new analysis of the XENAIR study was funded by ARC Foundation for cancer research; the French Agency for Food, Environmental, and Occupational Health and Safety; French National League against Cancer; and Fondation de France, an independent administrative agency. The authors report no relevant financial relationships.

This article was translated from the Medscape French edition and a version appeared on Medscape.com.

MADRID – Cancer-related fatigue is common but often undertreated. Similarly, its impact is underestimated. These were the messages delivered by speakers at the annual meeting of the European Society for Medical Oncology during a session titled “The Multiple Faces of Fatigue in the Cancer Ecosystem.”

Cancer-related fatigue is said to affect 40% of patients at the time of cancer diagnosis, 65% of patients during active or maintenance treatment, 21%-52% of patients in the 5 years following cancer diagnosis, and even one quarter of patients who are between 5 and 30 years post diagnosis, said Florian Scotté, MD, PhD, head of the interdisciplinary department for the Organization of Patient Pathways at Gustave Roussy Institute in Villejuif, France.

However, he underlines that “up to 50% of cancer survivors report never having discussed their cancer-related fatigue or received advice or support on how to manage it.”

What exactly is this fatigue? According to the definition set out in the ESMO 2020 recommendations and repeated word for word in the latest recommendations issued by the National Comprehensive Cancer Network published on Oct. 6, cancer-related fatigue is “a distressing, persistent, subjective sense of physical, emotional, and/or cognitive tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and interferes with usual functioning.”
 

Mechanisms at play

The mechanisms at play in cancer-related fatigue are clinical, molecular, and psychological, stated Dr. Scotté.

In terms of the clinical factors responsible for patients’ fatigue, comorbidities such as anemia, diabetes, heart disease, and even psychological conditions are significant elements. In addition, taking medicinal products such as antidepressants or beta-blockers can also cause fatigue. Furthermore, cancer treatment itself has many possible side effects, such as anemia, hypothyroidism, insomnia, pain, and hypopituitarism.

In terms of molecular and physiologic factors, central nervous system dysfunction (inflammation, hypothalamic-pituitary-adrenal axis) leads to perceived reduced physical and mental capacity with no clear motor or cognitive deficiencies. Changes in the peripheral nervous system also cause reduced energy metabolism, which hampers the response of muscles to stimuli, possibly even limiting endurance. Finally, several studies have shown that systemic inflammation is involved in the onset of fatigue.

Dr. Scotté also highlighted the importance of psychological factors, citing depression, psychosocial stress before treatment, negative attention to symptoms, and fear of relapse as key features in the development of cancer-related fatigue.

Among the risk factors for developing cancer-related fatigue, the speaker mentioned a combination of genetic, psychological, and biobehavioral factors (such as preexisting risk factors, depression, sleep disorders, physical inactivity, BMI, smoking, alcohol consumption, and adaptability).
 

Screen and diagnose

“Cancer-related fatigue is one of the most underestimated and least researched side effects,” said Christina Ruhlmann, MD, PhD, an oncology consultant at Odense (Denmark) University Hospital. “It is important to screen for fatigue in cancer patients.”

There are several tools available to enable this screening, she noted. The EORTC Core Quality of Life Questionnaire (EORTC QLQ-C30) is a three-item subscale evaluating the symptoms of fatigue, weakness, and lack of energy. The MD Anderson Symptom Inventory (13 items) assesses fatigue, sleep disorders, and drowsiness. The numeric rating scale (NRS) for fatigue is an 11-point visual self-assessment scale comprising a single element, with 0 representing no fatigue and 10 representing intense fatigue.

When screening for cancer-related fatigue, whenever a score of 4 or more is obtained on the NRS, a diagnostic assessment is needed based on clinical history-taking, fatigue assessment, and evaluation of comorbidities.

When taking the clinical history, information should be obtained on the type of condition, its stage, any relapse or progression, metastases, the date of diagnosis, length of treatment, any cancer or surgical treatments carried out, other treatments administered, and the risk for drug interactions.

In addition, to assess fatigue, the diagnostic process consists of documenting the start, type, and duration of the fatigue, as well as the presence of attenuating factors and interference with activities of daily living and leisure activities.

Seeking information regarding environmental factors such as availability of a support network of family and friends or financial resources is also paramount, said Dr. Ruhlmann.

Finally, contributory factors that may require treatment must be assessed. They include pain, emotional distress, anemia, sleep disorders, nutritional deficiencies, inactivity, smoking and alcohol consumption, and comorbidities (such as cardiac, endocrine, gastrointestinal, hepatic, infectious, and renal conditions).

The following two simple questions can be used to screen for symptoms of depression quickly:

• Over the past month, have you often felt despondent, sad, depressed, or in despair?
• Over the past month, have you found less pleasure than usual in doing the things you normally enjoy doing?

How to treat?

“All of the elements associated with fatigue that can be taken into account ought to be,” stressed Dr. Ruhlmann before insisting on the key role played by physical activity in combating the feeling of exhaustion.

The ESMO recommendations indicate that, according to the results of randomized clinical trials and systematic literature reviews, physical exercise can be recommended in patients with cancer who do not have cachexia (level of evidence I, B).

The type of physical activity recommended is moderate, aerobic, and functional strength exercises (I, B). Walking, aerobic exercises at home, and strength exercises are recommended to improve cancer-related fatigue and quality of life (II, B). “They help with fatigue and also with side effects such as depression, anxiety, pain, and muscle strength,” said Dr. Ruhlmann.

Alongside exercise, and with a lower level of evidence, pharmacologic treatments can sometimes be used (II, B; II, D). Short-term use of dexamethasone or methylprednisolone is recommended for managing fatigue linked to metastatic cancer except during the course of immunotherapy (II, B).

The ESMO expert group did not reach a consensus on the use of methylphenidate, dexmethylphenidate, slow-release methylphenidate, and dexamphetamine.

Modafinil and armodafinil, antidepressants (especially paroxetine), donepezil and eszopiclone, megestrol acetate, and melatonin are not recommended (II, D).

No consensus could be reached on nutraceuticals, and they are not recommended, said Dr. Ruhlmann (II, C; II, D).

Finally, psychosocial interventions in the form of information, advice, psychoeducation, and cognitive-behavioral therapy are useful tools (II, B).

Another area being explored is the gut microbiota. “Research into the microbiota and its role in systemic inflammation is underway and could pave the way for future strategies for managing cancer-related fatigue,” said Dr. Ruhlmann. “Fatigue is a subjective experience, unlike other symptoms. It’s what those people suffering from it say it is!”

This article was translated from the Medscape French edition.

MADRID – Cancer-related fatigue is common but often undertreated. Similarly, its impact is underestimated. These were the messages delivered by speakers at the annual meeting of the European Society for Medical Oncology during a session titled “The Multiple Faces of Fatigue in the Cancer Ecosystem.”

Cancer-related fatigue is said to affect 40% of patients at the time of cancer diagnosis, 65% of patients during active or maintenance treatment, 21%-52% of patients in the 5 years following cancer diagnosis, and even one quarter of patients who are between 5 and 30 years post diagnosis, said Florian Scotté, MD, PhD, head of the interdisciplinary department for the Organization of Patient Pathways at Gustave Roussy Institute in Villejuif, France.

However, he underlines that “up to 50% of cancer survivors report never having discussed their cancer-related fatigue or received advice or support on how to manage it.”

What exactly is this fatigue? According to the definition set out in the ESMO 2020 recommendations and repeated word for word in the latest recommendations issued by the National Comprehensive Cancer Network published on Oct. 6, cancer-related fatigue is “a distressing, persistent, subjective sense of physical, emotional, and/or cognitive tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and interferes with usual functioning.”
 

Mechanisms at play

The mechanisms at play in cancer-related fatigue are clinical, molecular, and psychological, stated Dr. Scotté.

In terms of the clinical factors responsible for patients’ fatigue, comorbidities such as anemia, diabetes, heart disease, and even psychological conditions are significant elements. In addition, taking medicinal products such as antidepressants or beta-blockers can also cause fatigue. Furthermore, cancer treatment itself has many possible side effects, such as anemia, hypothyroidism, insomnia, pain, and hypopituitarism.

In terms of molecular and physiologic factors, central nervous system dysfunction (inflammation, hypothalamic-pituitary-adrenal axis) leads to perceived reduced physical and mental capacity with no clear motor or cognitive deficiencies. Changes in the peripheral nervous system also cause reduced energy metabolism, which hampers the response of muscles to stimuli, possibly even limiting endurance. Finally, several studies have shown that systemic inflammation is involved in the onset of fatigue.

Dr. Scotté also highlighted the importance of psychological factors, citing depression, psychosocial stress before treatment, negative attention to symptoms, and fear of relapse as key features in the development of cancer-related fatigue.

Among the risk factors for developing cancer-related fatigue, the speaker mentioned a combination of genetic, psychological, and biobehavioral factors (such as preexisting risk factors, depression, sleep disorders, physical inactivity, BMI, smoking, alcohol consumption, and adaptability).
 

Screen and diagnose

“Cancer-related fatigue is one of the most underestimated and least researched side effects,” said Christina Ruhlmann, MD, PhD, an oncology consultant at Odense (Denmark) University Hospital. “It is important to screen for fatigue in cancer patients.”

There are several tools available to enable this screening, she noted. The EORTC Core Quality of Life Questionnaire (EORTC QLQ-C30) is a three-item subscale evaluating the symptoms of fatigue, weakness, and lack of energy. The MD Anderson Symptom Inventory (13 items) assesses fatigue, sleep disorders, and drowsiness. The numeric rating scale (NRS) for fatigue is an 11-point visual self-assessment scale comprising a single element, with 0 representing no fatigue and 10 representing intense fatigue.

When screening for cancer-related fatigue, whenever a score of 4 or more is obtained on the NRS, a diagnostic assessment is needed based on clinical history-taking, fatigue assessment, and evaluation of comorbidities.

When taking the clinical history, information should be obtained on the type of condition, its stage, any relapse or progression, metastases, the date of diagnosis, length of treatment, any cancer or surgical treatments carried out, other treatments administered, and the risk for drug interactions.

In addition, to assess fatigue, the diagnostic process consists of documenting the start, type, and duration of the fatigue, as well as the presence of attenuating factors and interference with activities of daily living and leisure activities.

Seeking information regarding environmental factors such as availability of a support network of family and friends or financial resources is also paramount, said Dr. Ruhlmann.

Finally, contributory factors that may require treatment must be assessed. They include pain, emotional distress, anemia, sleep disorders, nutritional deficiencies, inactivity, smoking and alcohol consumption, and comorbidities (such as cardiac, endocrine, gastrointestinal, hepatic, infectious, and renal conditions).

The following two simple questions can be used to screen for symptoms of depression quickly:

• Over the past month, have you often felt despondent, sad, depressed, or in despair?
• Over the past month, have you found less pleasure than usual in doing the things you normally enjoy doing?

How to treat?

“All of the elements associated with fatigue that can be taken into account ought to be,” stressed Dr. Ruhlmann before insisting on the key role played by physical activity in combating the feeling of exhaustion.

The ESMO recommendations indicate that, according to the results of randomized clinical trials and systematic literature reviews, physical exercise can be recommended in patients with cancer who do not have cachexia (level of evidence I, B).

The type of physical activity recommended is moderate, aerobic, and functional strength exercises (I, B). Walking, aerobic exercises at home, and strength exercises are recommended to improve cancer-related fatigue and quality of life (II, B). “They help with fatigue and also with side effects such as depression, anxiety, pain, and muscle strength,” said Dr. Ruhlmann.

Alongside exercise, and with a lower level of evidence, pharmacologic treatments can sometimes be used (II, B; II, D). Short-term use of dexamethasone or methylprednisolone is recommended for managing fatigue linked to metastatic cancer except during the course of immunotherapy (II, B).

The ESMO expert group did not reach a consensus on the use of methylphenidate, dexmethylphenidate, slow-release methylphenidate, and dexamphetamine.

Modafinil and armodafinil, antidepressants (especially paroxetine), donepezil and eszopiclone, megestrol acetate, and melatonin are not recommended (II, D).

No consensus could be reached on nutraceuticals, and they are not recommended, said Dr. Ruhlmann (II, C; II, D).

Finally, psychosocial interventions in the form of information, advice, psychoeducation, and cognitive-behavioral therapy are useful tools (II, B).

Another area being explored is the gut microbiota. “Research into the microbiota and its role in systemic inflammation is underway and could pave the way for future strategies for managing cancer-related fatigue,” said Dr. Ruhlmann. “Fatigue is a subjective experience, unlike other symptoms. It’s what those people suffering from it say it is!”

This article was translated from the Medscape French edition.

MADRID – Cancer-related fatigue is common but often undertreated. Similarly, its impact is underestimated. These were the messages delivered by speakers at the annual meeting of the European Society for Medical Oncology during a session titled “The Multiple Faces of Fatigue in the Cancer Ecosystem.”

Cancer-related fatigue is said to affect 40% of patients at the time of cancer diagnosis, 65% of patients during active or maintenance treatment, 21%-52% of patients in the 5 years following cancer diagnosis, and even one quarter of patients who are between 5 and 30 years post diagnosis, said Florian Scotté, MD, PhD, head of the interdisciplinary department for the Organization of Patient Pathways at Gustave Roussy Institute in Villejuif, France.

However, he underlines that “up to 50% of cancer survivors report never having discussed their cancer-related fatigue or received advice or support on how to manage it.”

What exactly is this fatigue? According to the definition set out in the ESMO 2020 recommendations and repeated word for word in the latest recommendations issued by the National Comprehensive Cancer Network published on Oct. 6, cancer-related fatigue is “a distressing, persistent, subjective sense of physical, emotional, and/or cognitive tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and interferes with usual functioning.”
 

Mechanisms at play

The mechanisms at play in cancer-related fatigue are clinical, molecular, and psychological, stated Dr. Scotté.

In terms of the clinical factors responsible for patients’ fatigue, comorbidities such as anemia, diabetes, heart disease, and even psychological conditions are significant elements. In addition, taking medicinal products such as antidepressants or beta-blockers can also cause fatigue. Furthermore, cancer treatment itself has many possible side effects, such as anemia, hypothyroidism, insomnia, pain, and hypopituitarism.

In terms of molecular and physiologic factors, central nervous system dysfunction (inflammation, hypothalamic-pituitary-adrenal axis) leads to perceived reduced physical and mental capacity with no clear motor or cognitive deficiencies. Changes in the peripheral nervous system also cause reduced energy metabolism, which hampers the response of muscles to stimuli, possibly even limiting endurance. Finally, several studies have shown that systemic inflammation is involved in the onset of fatigue.

Dr. Scotté also highlighted the importance of psychological factors, citing depression, psychosocial stress before treatment, negative attention to symptoms, and fear of relapse as key features in the development of cancer-related fatigue.

Among the risk factors for developing cancer-related fatigue, the speaker mentioned a combination of genetic, psychological, and biobehavioral factors (such as preexisting risk factors, depression, sleep disorders, physical inactivity, BMI, smoking, alcohol consumption, and adaptability).
 

Screen and diagnose

“Cancer-related fatigue is one of the most underestimated and least researched side effects,” said Christina Ruhlmann, MD, PhD, an oncology consultant at Odense (Denmark) University Hospital. “It is important to screen for fatigue in cancer patients.”

There are several tools available to enable this screening, she noted. The EORTC Core Quality of Life Questionnaire (EORTC QLQ-C30) is a three-item subscale evaluating the symptoms of fatigue, weakness, and lack of energy. The MD Anderson Symptom Inventory (13 items) assesses fatigue, sleep disorders, and drowsiness. The numeric rating scale (NRS) for fatigue is an 11-point visual self-assessment scale comprising a single element, with 0 representing no fatigue and 10 representing intense fatigue.

When screening for cancer-related fatigue, whenever a score of 4 or more is obtained on the NRS, a diagnostic assessment is needed based on clinical history-taking, fatigue assessment, and evaluation of comorbidities.

When taking the clinical history, information should be obtained on the type of condition, its stage, any relapse or progression, metastases, the date of diagnosis, length of treatment, any cancer or surgical treatments carried out, other treatments administered, and the risk for drug interactions.

In addition, to assess fatigue, the diagnostic process consists of documenting the start, type, and duration of the fatigue, as well as the presence of attenuating factors and interference with activities of daily living and leisure activities.

Seeking information regarding environmental factors such as availability of a support network of family and friends or financial resources is also paramount, said Dr. Ruhlmann.

Finally, contributory factors that may require treatment must be assessed. They include pain, emotional distress, anemia, sleep disorders, nutritional deficiencies, inactivity, smoking and alcohol consumption, and comorbidities (such as cardiac, endocrine, gastrointestinal, hepatic, infectious, and renal conditions).

The following two simple questions can be used to screen for symptoms of depression quickly:

• Over the past month, have you often felt despondent, sad, depressed, or in despair?
• Over the past month, have you found less pleasure than usual in doing the things you normally enjoy doing?

How to treat?

“All of the elements associated with fatigue that can be taken into account ought to be,” stressed Dr. Ruhlmann before insisting on the key role played by physical activity in combating the feeling of exhaustion.

The ESMO recommendations indicate that, according to the results of randomized clinical trials and systematic literature reviews, physical exercise can be recommended in patients with cancer who do not have cachexia (level of evidence I, B).

The type of physical activity recommended is moderate, aerobic, and functional strength exercises (I, B). Walking, aerobic exercises at home, and strength exercises are recommended to improve cancer-related fatigue and quality of life (II, B). “They help with fatigue and also with side effects such as depression, anxiety, pain, and muscle strength,” said Dr. Ruhlmann.

Alongside exercise, and with a lower level of evidence, pharmacologic treatments can sometimes be used (II, B; II, D). Short-term use of dexamethasone or methylprednisolone is recommended for managing fatigue linked to metastatic cancer except during the course of immunotherapy (II, B).

The ESMO expert group did not reach a consensus on the use of methylphenidate, dexmethylphenidate, slow-release methylphenidate, and dexamphetamine.

Modafinil and armodafinil, antidepressants (especially paroxetine), donepezil and eszopiclone, megestrol acetate, and melatonin are not recommended (II, D).

No consensus could be reached on nutraceuticals, and they are not recommended, said Dr. Ruhlmann (II, C; II, D).

Finally, psychosocial interventions in the form of information, advice, psychoeducation, and cognitive-behavioral therapy are useful tools (II, B).

Another area being explored is the gut microbiota. “Research into the microbiota and its role in systemic inflammation is underway and could pave the way for future strategies for managing cancer-related fatigue,” said Dr. Ruhlmann. “Fatigue is a subjective experience, unlike other symptoms. It’s what those people suffering from it say it is!”

This article was translated from the Medscape French edition.

Recent data suggest that the incidence of early-onset cancer, defined as cancer diagnosed in people younger than 50 years, is on the rise in several countries. Two recent studies confirm this trend, including one published in early September in BMJ Oncology that presents worldwide data on the matter.

Early-onset cancer

The article published in BMJ Oncology shows that over the past 30 years (1990 to 2019), new cancer cases in patients younger than 50 years have increased by 79% worldwide, reaching 3.26 million cases. Among them, early-onset breast cancer had the highest incidence (13.7) and mortality (3.5 per 100k) rates in the global population.

Tracheal (nasopharyngeal) and prostate cancer have increased the most rapidly since 1990, with annual percentage changes estimated at 2.28% and 2.23%, respectively. At the other end of the scale, cases of early-onset liver cancer dropped by around 2.88% year on year.
 

Increase in deaths

There were more than a million (1.06) cancer deaths among patients younger than 50 years in 2019, which is an increase of slightly less than 28% compared with the figures from 1990.

The top four early-onset cancers with the highest mortality and disability-adjusted life year rates among young adults in 2019 were early-onset breast; tracheal, bronchus and lung; stomach; and colorectal cancers. The mortality rates of early-onset kidney cancer and ovarian cancer showed the fastest increasing trends.

“These results contrast with a more traditionally held view of ‘typical’ cancers in adults aged under 50 years,” Ashleigh C. Hamilton, MD, an academic clinical lecturer, and Helen G. Coleman, PhD, a professor, both at Queen’s University Belfast’s Centre for Public Health in the United Kingdom, explained in an accompanying editorial. An important aspect of this study is that it tackled the issue of increasing cancer rates among young people on a global scale, they added. Here, the researchers made use of 2019 data from the Global Burden of Disease database for 29 types of cancer in 204 countries and regions.
 

Industrialized countries

The highest rates of early-onset cancer in 2019 were reported in North America, Australasia, and Western Europe. However, the burden of early-onset cancers in low- to middle-income countries is also of major public health concern. The highest death rates among patients younger than 50 years were in Oceania, Eastern Europe, and Central Asia.

In low- or middle-income regions, early-onset cancer had a significantly higher impact on women than on men in terms of mortality and disease burden, the researchers reported.

On the basis of trends observed over the past 30 years, they estimate that the global incidence and deaths of early-onset cancer would increase by 31% and 21% in 2030, respectively, with 40-year-olds being the most affected.
 

Hypotheses and limitations

How can this increase in the incidence of cancer among patients younger than 50 years be explained? For the authors, genetic factors likely play a role. But dietary risk factors (diet high in red meat, low in fruits, high in sodium, and low in milk, etc.), alcohol consumption, and tobacco use are the main risk factors underlying early-onset cancers in patients under age 50 years. Physical inactivity, excess weight, and hyperglycemia were shown to be contributing factors.

The researchers recognized several limitations to their conclusions. First, the accuracy of Global Burden of Disease data was compromised by the quality of cancer registry data in different countries, which may have led to underreporting and underdiagnosis. Also, questions remain about how screening and early exposure to environmental factors can affect the observed trends.

For the authors of the editorial, “Full understanding of the reasons driving the observed trends remains elusive, although lifestyle factors are likely contributing, and novel areas of research such as antibiotic usage, the gut microbiome, outdoor air pollution, and early life exposures are being explored.”

They concluded, “Prevention and early detection measures are urgently required, along with identifying optimal treatment strategies for early-onset cancers, which should include a holistic approach addressing the unique supportive care needs of younger patients.”

The authors added, “It is worth exploring whether early screening and prevention programs for early-onset cancer should be expanded to include individuals aged 40-44 and 45-49, but further systematic studies and randomized trials are necessary to make a definitive determination.”
 

Trend in the United States

Between 2010 and 2019, although the incidence of cancer dropped in people over age 50 years in the United States, a study published in JAMA Network Open in August showed that the standardized incidence rate of early-onset cancer increased overall. More specifically, the rate increased in women but decreased in men.

In 2019, most early-onset cancer cases involved breast cancer. Between 2010 and 2019, gastrointestinal cancers saw the fastest rise. And among gastrointestinal cancers, those whose incidence rate increased the most rapidly were those affecting the appendix, the intrahepatic bile ducts, and the pancreas.
 

This article was translated from the Medscape French Edition. A version of this article appeared on Medscape.com.

Recent data suggest that the incidence of early-onset cancer, defined as cancer diagnosed in people younger than 50 years, is on the rise in several countries. Two recent studies confirm this trend, including one published in early September in BMJ Oncology that presents worldwide data on the matter.

Early-onset cancer

The article published in BMJ Oncology shows that over the past 30 years (1990 to 2019), new cancer cases in patients younger than 50 years have increased by 79% worldwide, reaching 3.26 million cases. Among them, early-onset breast cancer had the highest incidence (13.7) and mortality (3.5 per 100k) rates in the global population.

Tracheal (nasopharyngeal) and prostate cancer have increased the most rapidly since 1990, with annual percentage changes estimated at 2.28% and 2.23%, respectively. At the other end of the scale, cases of early-onset liver cancer dropped by around 2.88% year on year.
 

Increase in deaths

There were more than a million (1.06) cancer deaths among patients younger than 50 years in 2019, which is an increase of slightly less than 28% compared with the figures from 1990.

The top four early-onset cancers with the highest mortality and disability-adjusted life year rates among young adults in 2019 were early-onset breast; tracheal, bronchus and lung; stomach; and colorectal cancers. The mortality rates of early-onset kidney cancer and ovarian cancer showed the fastest increasing trends.

“These results contrast with a more traditionally held view of ‘typical’ cancers in adults aged under 50 years,” Ashleigh C. Hamilton, MD, an academic clinical lecturer, and Helen G. Coleman, PhD, a professor, both at Queen’s University Belfast’s Centre for Public Health in the United Kingdom, explained in an accompanying editorial. An important aspect of this study is that it tackled the issue of increasing cancer rates among young people on a global scale, they added. Here, the researchers made use of 2019 data from the Global Burden of Disease database for 29 types of cancer in 204 countries and regions.
 

Industrialized countries

The highest rates of early-onset cancer in 2019 were reported in North America, Australasia, and Western Europe. However, the burden of early-onset cancers in low- to middle-income countries is also of major public health concern. The highest death rates among patients younger than 50 years were in Oceania, Eastern Europe, and Central Asia.

In low- or middle-income regions, early-onset cancer had a significantly higher impact on women than on men in terms of mortality and disease burden, the researchers reported.

On the basis of trends observed over the past 30 years, they estimate that the global incidence and deaths of early-onset cancer would increase by 31% and 21% in 2030, respectively, with 40-year-olds being the most affected.
 

Hypotheses and limitations

How can this increase in the incidence of cancer among patients younger than 50 years be explained? For the authors, genetic factors likely play a role. But dietary risk factors (diet high in red meat, low in fruits, high in sodium, and low in milk, etc.), alcohol consumption, and tobacco use are the main risk factors underlying early-onset cancers in patients under age 50 years. Physical inactivity, excess weight, and hyperglycemia were shown to be contributing factors.

The researchers recognized several limitations to their conclusions. First, the accuracy of Global Burden of Disease data was compromised by the quality of cancer registry data in different countries, which may have led to underreporting and underdiagnosis. Also, questions remain about how screening and early exposure to environmental factors can affect the observed trends.

For the authors of the editorial, “Full understanding of the reasons driving the observed trends remains elusive, although lifestyle factors are likely contributing, and novel areas of research such as antibiotic usage, the gut microbiome, outdoor air pollution, and early life exposures are being explored.”

They concluded, “Prevention and early detection measures are urgently required, along with identifying optimal treatment strategies for early-onset cancers, which should include a holistic approach addressing the unique supportive care needs of younger patients.”

The authors added, “It is worth exploring whether early screening and prevention programs for early-onset cancer should be expanded to include individuals aged 40-44 and 45-49, but further systematic studies and randomized trials are necessary to make a definitive determination.”
 

Trend in the United States

Between 2010 and 2019, although the incidence of cancer dropped in people over age 50 years in the United States, a study published in JAMA Network Open in August showed that the standardized incidence rate of early-onset cancer increased overall. More specifically, the rate increased in women but decreased in men.

In 2019, most early-onset cancer cases involved breast cancer. Between 2010 and 2019, gastrointestinal cancers saw the fastest rise. And among gastrointestinal cancers, those whose incidence rate increased the most rapidly were those affecting the appendix, the intrahepatic bile ducts, and the pancreas.
 

This article was translated from the Medscape French Edition. A version of this article appeared on Medscape.com.

Recent data suggest that the incidence of early-onset cancer, defined as cancer diagnosed in people younger than 50 years, is on the rise in several countries. Two recent studies confirm this trend, including one published in early September in BMJ Oncology that presents worldwide data on the matter.

Early-onset cancer

The article published in BMJ Oncology shows that over the past 30 years (1990 to 2019), new cancer cases in patients younger than 50 years have increased by 79% worldwide, reaching 3.26 million cases. Among them, early-onset breast cancer had the highest incidence (13.7) and mortality (3.5 per 100k) rates in the global population.

Tracheal (nasopharyngeal) and prostate cancer have increased the most rapidly since 1990, with annual percentage changes estimated at 2.28% and 2.23%, respectively. At the other end of the scale, cases of early-onset liver cancer dropped by around 2.88% year on year.
 

Increase in deaths

There were more than a million (1.06) cancer deaths among patients younger than 50 years in 2019, which is an increase of slightly less than 28% compared with the figures from 1990.

The top four early-onset cancers with the highest mortality and disability-adjusted life year rates among young adults in 2019 were early-onset breast; tracheal, bronchus and lung; stomach; and colorectal cancers. The mortality rates of early-onset kidney cancer and ovarian cancer showed the fastest increasing trends.

“These results contrast with a more traditionally held view of ‘typical’ cancers in adults aged under 50 years,” Ashleigh C. Hamilton, MD, an academic clinical lecturer, and Helen G. Coleman, PhD, a professor, both at Queen’s University Belfast’s Centre for Public Health in the United Kingdom, explained in an accompanying editorial. An important aspect of this study is that it tackled the issue of increasing cancer rates among young people on a global scale, they added. Here, the researchers made use of 2019 data from the Global Burden of Disease database for 29 types of cancer in 204 countries and regions.
 

Industrialized countries

The highest rates of early-onset cancer in 2019 were reported in North America, Australasia, and Western Europe. However, the burden of early-onset cancers in low- to middle-income countries is also of major public health concern. The highest death rates among patients younger than 50 years were in Oceania, Eastern Europe, and Central Asia.

In low- or middle-income regions, early-onset cancer had a significantly higher impact on women than on men in terms of mortality and disease burden, the researchers reported.

On the basis of trends observed over the past 30 years, they estimate that the global incidence and deaths of early-onset cancer would increase by 31% and 21% in 2030, respectively, with 40-year-olds being the most affected.
 

Hypotheses and limitations

How can this increase in the incidence of cancer among patients younger than 50 years be explained? For the authors, genetic factors likely play a role. But dietary risk factors (diet high in red meat, low in fruits, high in sodium, and low in milk, etc.), alcohol consumption, and tobacco use are the main risk factors underlying early-onset cancers in patients under age 50 years. Physical inactivity, excess weight, and hyperglycemia were shown to be contributing factors.

The researchers recognized several limitations to their conclusions. First, the accuracy of Global Burden of Disease data was compromised by the quality of cancer registry data in different countries, which may have led to underreporting and underdiagnosis. Also, questions remain about how screening and early exposure to environmental factors can affect the observed trends.

For the authors of the editorial, “Full understanding of the reasons driving the observed trends remains elusive, although lifestyle factors are likely contributing, and novel areas of research such as antibiotic usage, the gut microbiome, outdoor air pollution, and early life exposures are being explored.”

They concluded, “Prevention and early detection measures are urgently required, along with identifying optimal treatment strategies for early-onset cancers, which should include a holistic approach addressing the unique supportive care needs of younger patients.”

The authors added, “It is worth exploring whether early screening and prevention programs for early-onset cancer should be expanded to include individuals aged 40-44 and 45-49, but further systematic studies and randomized trials are necessary to make a definitive determination.”
 

Trend in the United States

Between 2010 and 2019, although the incidence of cancer dropped in people over age 50 years in the United States, a study published in JAMA Network Open in August showed that the standardized incidence rate of early-onset cancer increased overall. More specifically, the rate increased in women but decreased in men.

In 2019, most early-onset cancer cases involved breast cancer. Between 2010 and 2019, gastrointestinal cancers saw the fastest rise. And among gastrointestinal cancers, those whose incidence rate increased the most rapidly were those affecting the appendix, the intrahepatic bile ducts, and the pancreas.
 

This article was translated from the Medscape French Edition. A version of this article appeared on Medscape.com.

SINGAPORE – A few months after releasing its phase 1 and 2 data, OSE Immunotherapeutics, which is based in Nantes, France, has announced positive results for its therapeutic vaccine to treat cancer. Following its promising findings concerning early-stage melanoma, pancreatic cancer, ENT cancers, and HPV-associated anogenital cancer, the company-funded phase 3 Atalante-1 trial has shown the benefits of the Tedopi (OSE2101) vaccine in treating patients with advanced non–small cell lung cancer who are on their second or third line of treatment.

The results suggest that Tedopi is the most developmentally advanced therapeutic vaccine for cancer.

The data from Atalante-1 were presented at the World Conference on Lung Cancer and were simultaneously published in Annals of Oncology.

Tedopi is composed of synthetic tumoral neo-epitopes (peptide fragments) that target five tumoral antigens, permitting the activation of tumor-specific T-lymphocytes for patients who are HLA-A2 positive. In 95% of cases, tumors express at least one of these five antigens. The aim of integrating these five antigens is to prevent immune escape. The technology uses the human leukocyte antigen (HLA) system, one of the keys for presenting antigens to T-lymphocytes. The vaccine is effective for patients who express the HLA-A2 gene, which is present in around half of the population. The HLA-A2 biomarker, detected via a blood test, can identify appropriate patients.
 

Study protocol

In the Atalante-1 trial, participants had locally advanced (unresectable and not eligible for radiotherapy) or metastatic (without alteration of the EGFR and ALK genes) non–small cell lung cancer that was resistant to previous immunotherapy. They had an HLA-A2 phenotype, as determined by a blood draw to determine whether their immune system could respond to the vaccine.

In this trial, 219 patients were randomly assigned in a 2:1 ratio to receive the vaccine or standard-of-care chemotherapy (80% received docetaxel). The vaccine was administered subcutaneously on day 1 every 3 weeks for six cycles. After that point, the vaccine was administered every 8 weeks until 1 year of treatment and every 12 weeks thereafter. The primary endpoint was overall survival.
 

Secondary resistance

The plan was to enroll 363 patients in the protocol, but the study did not complete its recruitment phase because of the COVID-19 pandemic. As a result, the study was stopped after the enrollment of 219 patients.

“It didn’t have the power we would have liked, but it helped us understand that the people who benefited the most from the vaccine were patients who had responded to immunotherapy in the past. These patients have what is called ‘secondary resistance,’ ” explained Benjamin Besse, MD, PhD, during a press conference organized by OSE Immunotherapeutics. Dr. Besse, the study’s principal investigator, is the director of clinical research at Gustave Roussy, Villejuif, France.

Overall, the results weren’t significant. But the results were positive for patients who had previously responded well to immunotherapy for at least 3 months. Of the 219 patients, 118 (54%) had a positive response.

Among these patients with secondary resistance to immunotherapy, median OS was 11.1 months with Tedopi versus 7.5 months with docetaxel.

For these patients, the risk of death was reduced by 41% with the vaccine, compared with chemotherapy. Overall, 44% of patients lived for another year after receiving Tedopi, versus 27.5% with docetaxel.

“This study is a positive signal for overall survival in the selected population. In this study of 219 patients, we realized that just half of patients really benefited from the vaccine: those who had previously responded to immunotherapy,” said Dr. Besse. “The study needs confirmation from a further, larger phase 3 study in more than 300 patients with secondary resistance to immunotherapy to give us the statistical power we need to convince the regulatory authorities.”
 

Tolerability profile

Fewer serious adverse effects were reported with the vaccine than with chemotherapy (11.4% with Tedopi and 35.1% with docetaxel).

The vaccine also allowed patients to maintain a better quality of life. Scores from the Quality of Life Questionnaire Core 30, which explores several areas of daily life, were better with the vaccine. Change in patients’ overall well-being was delayed in the vaccine group: 3.3 months in the chemotherapy arm versus 9 months in the vaccine arm.

“The vaccine was well tolerated. It has benefits in terms of controlling disease symptoms and causes few side effects. Chemotherapy with docetaxel, meanwhile, is more toxic and may affect a patient’s overall well-being. It causes hair loss in practically 100% of patients, induces neuropathy, makes hands and feet swell, damages the nails, is associated with nausea and vomiting ...” noted Dr. Besse. He went on to say that after the trial, of the patients who stopped receiving the vaccine or chemotherapy (either for toxicity reasons or for disease progression), those who had been given the vaccine responded better to the subsequent chemotherapy “because their overall health was better.”
 

Clinical development

The clinical development of Tedopi is ongoing. Three trials are currently taking place. One study is comparing the Tedopi vaccine plus docetaxel with Tedopi plus nivolumab (immunotherapy not used as a first-line treatment) to determine whether the effects of these treatment combinations might might be enhanced for patients with previously treated lung cancer.

Another study relating to ovarian cancer is in the recruitment phase. The researchers seek to evaluate the vaccine alone or in combination with pembrolizumab for patients with platinum-sensitive ovarian cancer. Results from both trials are expected in 2025.

The third trial seeks to assess FOLFIRI as maintenance therapy or FOLFIRI as maintenance plus Tedopi for patients with pancreatic cancer to improve disease management. Efficacy data are expected next year.

OSE Immunotherapeutics is simultaneously working on a companion biomarker, the HLA-A2 test.

The study was funded by OSE Immunotherapeutics. Dr. Besse disclosed the following conflicts of interest (research funding, institution): AbbVie, Amgen, AstraZeneca, Chugai Pharmaceutical, Daiichi-Sankyo, Ellipse Pharma, EISAI, Genmab, Genzyme Corporation, Hedera Dx, Inivata, IPSEN, Janssen, MSD, Pharmamar, Roche-Genentech, Sanofi, Socar Research, Taiho Oncology, and Turning Point Therapeutics.

This article was translated from the Medscape French Edition and a version appeared on Medscape.com.

SINGAPORE – A few months after releasing its phase 1 and 2 data, OSE Immunotherapeutics, which is based in Nantes, France, has announced positive results for its therapeutic vaccine to treat cancer. Following its promising findings concerning early-stage melanoma, pancreatic cancer, ENT cancers, and HPV-associated anogenital cancer, the company-funded phase 3 Atalante-1 trial has shown the benefits of the Tedopi (OSE2101) vaccine in treating patients with advanced non–small cell lung cancer who are on their second or third line of treatment.

The results suggest that Tedopi is the most developmentally advanced therapeutic vaccine for cancer.

The data from Atalante-1 were presented at the World Conference on Lung Cancer and were simultaneously published in Annals of Oncology.

Tedopi is composed of synthetic tumoral neo-epitopes (peptide fragments) that target five tumoral antigens, permitting the activation of tumor-specific T-lymphocytes for patients who are HLA-A2 positive. In 95% of cases, tumors express at least one of these five antigens. The aim of integrating these five antigens is to prevent immune escape. The technology uses the human leukocyte antigen (HLA) system, one of the keys for presenting antigens to T-lymphocytes. The vaccine is effective for patients who express the HLA-A2 gene, which is present in around half of the population. The HLA-A2 biomarker, detected via a blood test, can identify appropriate patients.
 

Study protocol

In the Atalante-1 trial, participants had locally advanced (unresectable and not eligible for radiotherapy) or metastatic (without alteration of the EGFR and ALK genes) non–small cell lung cancer that was resistant to previous immunotherapy. They had an HLA-A2 phenotype, as determined by a blood draw to determine whether their immune system could respond to the vaccine.

In this trial, 219 patients were randomly assigned in a 2:1 ratio to receive the vaccine or standard-of-care chemotherapy (80% received docetaxel). The vaccine was administered subcutaneously on day 1 every 3 weeks for six cycles. After that point, the vaccine was administered every 8 weeks until 1 year of treatment and every 12 weeks thereafter. The primary endpoint was overall survival.
 

Secondary resistance

The plan was to enroll 363 patients in the protocol, but the study did not complete its recruitment phase because of the COVID-19 pandemic. As a result, the study was stopped after the enrollment of 219 patients.

“It didn’t have the power we would have liked, but it helped us understand that the people who benefited the most from the vaccine were patients who had responded to immunotherapy in the past. These patients have what is called ‘secondary resistance,’ ” explained Benjamin Besse, MD, PhD, during a press conference organized by OSE Immunotherapeutics. Dr. Besse, the study’s principal investigator, is the director of clinical research at Gustave Roussy, Villejuif, France.

Overall, the results weren’t significant. But the results were positive for patients who had previously responded well to immunotherapy for at least 3 months. Of the 219 patients, 118 (54%) had a positive response.

Among these patients with secondary resistance to immunotherapy, median OS was 11.1 months with Tedopi versus 7.5 months with docetaxel.

For these patients, the risk of death was reduced by 41% with the vaccine, compared with chemotherapy. Overall, 44% of patients lived for another year after receiving Tedopi, versus 27.5% with docetaxel.

“This study is a positive signal for overall survival in the selected population. In this study of 219 patients, we realized that just half of patients really benefited from the vaccine: those who had previously responded to immunotherapy,” said Dr. Besse. “The study needs confirmation from a further, larger phase 3 study in more than 300 patients with secondary resistance to immunotherapy to give us the statistical power we need to convince the regulatory authorities.”
 

Tolerability profile

Fewer serious adverse effects were reported with the vaccine than with chemotherapy (11.4% with Tedopi and 35.1% with docetaxel).

The vaccine also allowed patients to maintain a better quality of life. Scores from the Quality of Life Questionnaire Core 30, which explores several areas of daily life, were better with the vaccine. Change in patients’ overall well-being was delayed in the vaccine group: 3.3 months in the chemotherapy arm versus 9 months in the vaccine arm.

“The vaccine was well tolerated. It has benefits in terms of controlling disease symptoms and causes few side effects. Chemotherapy with docetaxel, meanwhile, is more toxic and may affect a patient’s overall well-being. It causes hair loss in practically 100% of patients, induces neuropathy, makes hands and feet swell, damages the nails, is associated with nausea and vomiting ...” noted Dr. Besse. He went on to say that after the trial, of the patients who stopped receiving the vaccine or chemotherapy (either for toxicity reasons or for disease progression), those who had been given the vaccine responded better to the subsequent chemotherapy “because their overall health was better.”
 

Clinical development

The clinical development of Tedopi is ongoing. Three trials are currently taking place. One study is comparing the Tedopi vaccine plus docetaxel with Tedopi plus nivolumab (immunotherapy not used as a first-line treatment) to determine whether the effects of these treatment combinations might might be enhanced for patients with previously treated lung cancer.

Another study relating to ovarian cancer is in the recruitment phase. The researchers seek to evaluate the vaccine alone or in combination with pembrolizumab for patients with platinum-sensitive ovarian cancer. Results from both trials are expected in 2025.

The third trial seeks to assess FOLFIRI as maintenance therapy or FOLFIRI as maintenance plus Tedopi for patients with pancreatic cancer to improve disease management. Efficacy data are expected next year.

OSE Immunotherapeutics is simultaneously working on a companion biomarker, the HLA-A2 test.

The study was funded by OSE Immunotherapeutics. Dr. Besse disclosed the following conflicts of interest (research funding, institution): AbbVie, Amgen, AstraZeneca, Chugai Pharmaceutical, Daiichi-Sankyo, Ellipse Pharma, EISAI, Genmab, Genzyme Corporation, Hedera Dx, Inivata, IPSEN, Janssen, MSD, Pharmamar, Roche-Genentech, Sanofi, Socar Research, Taiho Oncology, and Turning Point Therapeutics.

This article was translated from the Medscape French Edition and a version appeared on Medscape.com.

SINGAPORE – A few months after releasing its phase 1 and 2 data, OSE Immunotherapeutics, which is based in Nantes, France, has announced positive results for its therapeutic vaccine to treat cancer. Following its promising findings concerning early-stage melanoma, pancreatic cancer, ENT cancers, and HPV-associated anogenital cancer, the company-funded phase 3 Atalante-1 trial has shown the benefits of the Tedopi (OSE2101) vaccine in treating patients with advanced non–small cell lung cancer who are on their second or third line of treatment.

The results suggest that Tedopi is the most developmentally advanced therapeutic vaccine for cancer.

The data from Atalante-1 were presented at the World Conference on Lung Cancer and were simultaneously published in Annals of Oncology.

Tedopi is composed of synthetic tumoral neo-epitopes (peptide fragments) that target five tumoral antigens, permitting the activation of tumor-specific T-lymphocytes for patients who are HLA-A2 positive. In 95% of cases, tumors express at least one of these five antigens. The aim of integrating these five antigens is to prevent immune escape. The technology uses the human leukocyte antigen (HLA) system, one of the keys for presenting antigens to T-lymphocytes. The vaccine is effective for patients who express the HLA-A2 gene, which is present in around half of the population. The HLA-A2 biomarker, detected via a blood test, can identify appropriate patients.
 

Study protocol

In the Atalante-1 trial, participants had locally advanced (unresectable and not eligible for radiotherapy) or metastatic (without alteration of the EGFR and ALK genes) non–small cell lung cancer that was resistant to previous immunotherapy. They had an HLA-A2 phenotype, as determined by a blood draw to determine whether their immune system could respond to the vaccine.

In this trial, 219 patients were randomly assigned in a 2:1 ratio to receive the vaccine or standard-of-care chemotherapy (80% received docetaxel). The vaccine was administered subcutaneously on day 1 every 3 weeks for six cycles. After that point, the vaccine was administered every 8 weeks until 1 year of treatment and every 12 weeks thereafter. The primary endpoint was overall survival.
 

Secondary resistance

The plan was to enroll 363 patients in the protocol, but the study did not complete its recruitment phase because of the COVID-19 pandemic. As a result, the study was stopped after the enrollment of 219 patients.

“It didn’t have the power we would have liked, but it helped us understand that the people who benefited the most from the vaccine were patients who had responded to immunotherapy in the past. These patients have what is called ‘secondary resistance,’ ” explained Benjamin Besse, MD, PhD, during a press conference organized by OSE Immunotherapeutics. Dr. Besse, the study’s principal investigator, is the director of clinical research at Gustave Roussy, Villejuif, France.

Overall, the results weren’t significant. But the results were positive for patients who had previously responded well to immunotherapy for at least 3 months. Of the 219 patients, 118 (54%) had a positive response.

Among these patients with secondary resistance to immunotherapy, median OS was 11.1 months with Tedopi versus 7.5 months with docetaxel.

For these patients, the risk of death was reduced by 41% with the vaccine, compared with chemotherapy. Overall, 44% of patients lived for another year after receiving Tedopi, versus 27.5% with docetaxel.

“This study is a positive signal for overall survival in the selected population. In this study of 219 patients, we realized that just half of patients really benefited from the vaccine: those who had previously responded to immunotherapy,” said Dr. Besse. “The study needs confirmation from a further, larger phase 3 study in more than 300 patients with secondary resistance to immunotherapy to give us the statistical power we need to convince the regulatory authorities.”
 

Tolerability profile

Fewer serious adverse effects were reported with the vaccine than with chemotherapy (11.4% with Tedopi and 35.1% with docetaxel).

The vaccine also allowed patients to maintain a better quality of life. Scores from the Quality of Life Questionnaire Core 30, which explores several areas of daily life, were better with the vaccine. Change in patients’ overall well-being was delayed in the vaccine group: 3.3 months in the chemotherapy arm versus 9 months in the vaccine arm.

“The vaccine was well tolerated. It has benefits in terms of controlling disease symptoms and causes few side effects. Chemotherapy with docetaxel, meanwhile, is more toxic and may affect a patient’s overall well-being. It causes hair loss in practically 100% of patients, induces neuropathy, makes hands and feet swell, damages the nails, is associated with nausea and vomiting ...” noted Dr. Besse. He went on to say that after the trial, of the patients who stopped receiving the vaccine or chemotherapy (either for toxicity reasons or for disease progression), those who had been given the vaccine responded better to the subsequent chemotherapy “because their overall health was better.”
 

Clinical development

The clinical development of Tedopi is ongoing. Three trials are currently taking place. One study is comparing the Tedopi vaccine plus docetaxel with Tedopi plus nivolumab (immunotherapy not used as a first-line treatment) to determine whether the effects of these treatment combinations might might be enhanced for patients with previously treated lung cancer.

Another study relating to ovarian cancer is in the recruitment phase. The researchers seek to evaluate the vaccine alone or in combination with pembrolizumab for patients with platinum-sensitive ovarian cancer. Results from both trials are expected in 2025.

The third trial seeks to assess FOLFIRI as maintenance therapy or FOLFIRI as maintenance plus Tedopi for patients with pancreatic cancer to improve disease management. Efficacy data are expected next year.

OSE Immunotherapeutics is simultaneously working on a companion biomarker, the HLA-A2 test.

The study was funded by OSE Immunotherapeutics. Dr. Besse disclosed the following conflicts of interest (research funding, institution): AbbVie, Amgen, AstraZeneca, Chugai Pharmaceutical, Daiichi-Sankyo, Ellipse Pharma, EISAI, Genmab, Genzyme Corporation, Hedera Dx, Inivata, IPSEN, Janssen, MSD, Pharmamar, Roche-Genentech, Sanofi, Socar Research, Taiho Oncology, and Turning Point Therapeutics.

This article was translated from the Medscape French Edition and a version appeared on Medscape.com.