Sharon Worcester, MA

Many patients use cannabis to manage their cancer-related symptoms. However, research indicates that patients often do so without speaking to their oncologists first, and oncologists may be hesitant to broach the topic with their patients.

Updated guidelines from the American Society of Clinical Oncology (ASCO) on the use of cannabis and cannabinoids in adults with cancer stress that it’s an important conversation to have.

According to the ASCO expert panel, access to and use of cannabis alongside cancer care have outpaced the science on evidence-based indications, and overall high-quality data on the effects of cannabis during cancer care are lacking. While several observational studies support cannabis use to help ease chemotherapy-related nausea and vomiting, the literature remains more divided on other potential benefits, such as alleviating cancer pain and sleep problems, and some evidence points to potential downsides of cannabis use.

Oncologists should “absolutely talk to patients” about cannabis, Brooke Worster, MD, medical director for the Master of Science in Medical Cannabis Science & Business program at Thomas Jefferson University, Philadelphia, told Medscape Medical News.

“Patients are interested, and they are going to find access to information. As a medical professional, it’s our job to help guide them through these spaces in a safe, nonjudgmental way.”

But, Worster noted, oncologists don’t have to be experts on cannabis to begin the conversation with patients.

So, “let yourself off the hook,” Worster urged.

Plus, avoiding the conversation won’t stop patients from using cannabis. In a recent study, Worster and her colleagues found that nearly one third of patients at 12 National Cancer Institute-designated cancer centers had used cannabis since their diagnosis — most often for sleep disturbance, pain, stress, and anxiety. Most (60%) felt somewhat or extremely comfortable talking to their healthcare provider about it, but only 21.5% said they had done so. Even fewer — about 10% — had talked to their treating oncologist.

Because patients may not discuss cannabis use, it’s especially important for oncologists to open up a line of communication, said Worster, also the enterprise director of supportive oncology at the Thomas Jefferson University.
 

Evidence on Cannabis During Cancer Care

A substantial proportion of people with cancer believe cannabis can help manage cancer-related symptoms.

In Worster’s recent survey study, regardless of whether patients had used cannabis, almost 90% of those surveyed reported a perceived benefit. Although 65% also reported perceived risks for cannabis use, including difficulty concentrating, lung damage, and impaired memory, the perceived benefits outweighed the risks.

Despite generally positive perceptions, the overall literature on the benefits of cannabis in patients with cancer paints a less clear picture.

The ASCO guidelines, which were based on 13 systematic reviews and five additional primary studies, reported that cannabis can improve refractory, chemotherapy-induced nausea or vomiting when added to guideline-concordant antiemetic regimens, but that there is no clear evidence of benefit or harm for other supportive care outcomes.

The “certainty of evidence for most outcomes was low or very low,” the ASCO authors wrote.

The ASCO experts explained that, outside the context of a clinical trial, the evidence is not sufficient to recommend cannabis or cannabinoids for managing cancer pain, sleep issues, appetite loss, or anxiety and depression. For these outcomes, some studies indicate a benefit, while others don’t.

Real-world data from a large registry study, for instance, have indicated that medical cannabis is “a safe and effective complementary treatment for pain relief in patients with cancer.” However, a 2020 meta-analysis found that, in studies with a low risk for bias, adding cannabinoids to opioids did not reduce cancer pain in adults with advanced cancer.

There can be downsides to cannabis use, too. In one recent study, some patients reported feeling worse physically and psychologically compared with those who didn’t use cannabis. Another study found that oral cannabis was associated with “bothersome” side effects, including sedation, dizziness, and transient anxiety.

The ASCO guidelines also made it clear that cannabis or cannabinoids should not be used as cancer-directed treatment, outside of a clinical trial.
 

Talking to Patients About Cannabis

Given the level of evidence and patient interest in cannabis, it is important for oncologists to raise the topic of cannabis use with their patients.

To help inform decision-making and approaches to care, the ASCO guidelines suggest that oncologists can guide care themselves or direct patients to appropriate “unbiased, evidence-based” resources. For those who use cannabis or cannabinoids outside of evidence-based indications or clinician recommendations, it’s important to explore patients’ goals, educate them, and try to minimize harm.

One strategy for broaching the topic, Worster suggested, is to simply ask patients if they have tried or considered trying cannabis to control symptoms like nausea and vomiting, loss of appetite, or cancer pain.

The conversation with patients should then include an overview of the potential benefits and potential risks for cannabis use as well as risk reduction strategies, Worster noted.

But “approach it in an open and nonjudgmental frame of mind,” she said. “Just have a conversation.”

Discussing the formulation and concentration of tetrahydrocannabinol (THC) and cannabidiol (CBD) in products matters as well.

Will the product be inhaled, ingested, or topical? Inhaled cannabis is not ideal but is sometimes what patients have access to, Worster explained. Inhaled formulations tend to have faster onset, which might be preferable for treating chemotherapy-related nausea and vomiting, whereas edible formulations may take a while to start working.

It’s also important to warn patients about taking too much, she said, explaining that inhaling THC at higher doses can increase the risk for cardiovascular effects, anxiety, paranoia, panic, and psychosis.

CBD, on the other hand, is anti-inflammatory, but early data suggest it may blunt immune responses in high doses and should be used cautiously by patients receiving immunotherapy.

Worster noted that as laws change and the science advances, new cannabis products and formulations will emerge, as will artificial intelligence tools for helping to guide patients and clinicians in optimal use of cannabis for cancer care. State websites are a particularly helpful tool for providing state-specific medical education related to cannabis laws and use, as well, she said.

The bottom line, she said, is that talking to patients about the ins and outs of cannabis use “really matters.”

Worster disclosed that she is a medical consultant for EO Care.
 

A version of this article appeared on Medscape.com.

Many patients use cannabis to manage their cancer-related symptoms. However, research indicates that patients often do so without speaking to their oncologists first, and oncologists may be hesitant to broach the topic with their patients.

Updated guidelines from the American Society of Clinical Oncology (ASCO) on the use of cannabis and cannabinoids in adults with cancer stress that it’s an important conversation to have.

According to the ASCO expert panel, access to and use of cannabis alongside cancer care have outpaced the science on evidence-based indications, and overall high-quality data on the effects of cannabis during cancer care are lacking. While several observational studies support cannabis use to help ease chemotherapy-related nausea and vomiting, the literature remains more divided on other potential benefits, such as alleviating cancer pain and sleep problems, and some evidence points to potential downsides of cannabis use.

Oncologists should “absolutely talk to patients” about cannabis, Brooke Worster, MD, medical director for the Master of Science in Medical Cannabis Science & Business program at Thomas Jefferson University, Philadelphia, told Medscape Medical News.

“Patients are interested, and they are going to find access to information. As a medical professional, it’s our job to help guide them through these spaces in a safe, nonjudgmental way.”

But, Worster noted, oncologists don’t have to be experts on cannabis to begin the conversation with patients.

So, “let yourself off the hook,” Worster urged.

Plus, avoiding the conversation won’t stop patients from using cannabis. In a recent study, Worster and her colleagues found that nearly one third of patients at 12 National Cancer Institute-designated cancer centers had used cannabis since their diagnosis — most often for sleep disturbance, pain, stress, and anxiety. Most (60%) felt somewhat or extremely comfortable talking to their healthcare provider about it, but only 21.5% said they had done so. Even fewer — about 10% — had talked to their treating oncologist.

Because patients may not discuss cannabis use, it’s especially important for oncologists to open up a line of communication, said Worster, also the enterprise director of supportive oncology at the Thomas Jefferson University.
 

Evidence on Cannabis During Cancer Care

A substantial proportion of people with cancer believe cannabis can help manage cancer-related symptoms.

In Worster’s recent survey study, regardless of whether patients had used cannabis, almost 90% of those surveyed reported a perceived benefit. Although 65% also reported perceived risks for cannabis use, including difficulty concentrating, lung damage, and impaired memory, the perceived benefits outweighed the risks.

Despite generally positive perceptions, the overall literature on the benefits of cannabis in patients with cancer paints a less clear picture.

The ASCO guidelines, which were based on 13 systematic reviews and five additional primary studies, reported that cannabis can improve refractory, chemotherapy-induced nausea or vomiting when added to guideline-concordant antiemetic regimens, but that there is no clear evidence of benefit or harm for other supportive care outcomes.

The “certainty of evidence for most outcomes was low or very low,” the ASCO authors wrote.

The ASCO experts explained that, outside the context of a clinical trial, the evidence is not sufficient to recommend cannabis or cannabinoids for managing cancer pain, sleep issues, appetite loss, or anxiety and depression. For these outcomes, some studies indicate a benefit, while others don’t.

Real-world data from a large registry study, for instance, have indicated that medical cannabis is “a safe and effective complementary treatment for pain relief in patients with cancer.” However, a 2020 meta-analysis found that, in studies with a low risk for bias, adding cannabinoids to opioids did not reduce cancer pain in adults with advanced cancer.

There can be downsides to cannabis use, too. In one recent study, some patients reported feeling worse physically and psychologically compared with those who didn’t use cannabis. Another study found that oral cannabis was associated with “bothersome” side effects, including sedation, dizziness, and transient anxiety.

The ASCO guidelines also made it clear that cannabis or cannabinoids should not be used as cancer-directed treatment, outside of a clinical trial.
 

Talking to Patients About Cannabis

Given the level of evidence and patient interest in cannabis, it is important for oncologists to raise the topic of cannabis use with their patients.

To help inform decision-making and approaches to care, the ASCO guidelines suggest that oncologists can guide care themselves or direct patients to appropriate “unbiased, evidence-based” resources. For those who use cannabis or cannabinoids outside of evidence-based indications or clinician recommendations, it’s important to explore patients’ goals, educate them, and try to minimize harm.

One strategy for broaching the topic, Worster suggested, is to simply ask patients if they have tried or considered trying cannabis to control symptoms like nausea and vomiting, loss of appetite, or cancer pain.

The conversation with patients should then include an overview of the potential benefits and potential risks for cannabis use as well as risk reduction strategies, Worster noted.

But “approach it in an open and nonjudgmental frame of mind,” she said. “Just have a conversation.”

Discussing the formulation and concentration of tetrahydrocannabinol (THC) and cannabidiol (CBD) in products matters as well.

Will the product be inhaled, ingested, or topical? Inhaled cannabis is not ideal but is sometimes what patients have access to, Worster explained. Inhaled formulations tend to have faster onset, which might be preferable for treating chemotherapy-related nausea and vomiting, whereas edible formulations may take a while to start working.

It’s also important to warn patients about taking too much, she said, explaining that inhaling THC at higher doses can increase the risk for cardiovascular effects, anxiety, paranoia, panic, and psychosis.

CBD, on the other hand, is anti-inflammatory, but early data suggest it may blunt immune responses in high doses and should be used cautiously by patients receiving immunotherapy.

Worster noted that as laws change and the science advances, new cannabis products and formulations will emerge, as will artificial intelligence tools for helping to guide patients and clinicians in optimal use of cannabis for cancer care. State websites are a particularly helpful tool for providing state-specific medical education related to cannabis laws and use, as well, she said.

The bottom line, she said, is that talking to patients about the ins and outs of cannabis use “really matters.”

Worster disclosed that she is a medical consultant for EO Care.
 

A version of this article appeared on Medscape.com.

Many patients use cannabis to manage their cancer-related symptoms. However, research indicates that patients often do so without speaking to their oncologists first, and oncologists may be hesitant to broach the topic with their patients.

Updated guidelines from the American Society of Clinical Oncology (ASCO) on the use of cannabis and cannabinoids in adults with cancer stress that it’s an important conversation to have.

According to the ASCO expert panel, access to and use of cannabis alongside cancer care have outpaced the science on evidence-based indications, and overall high-quality data on the effects of cannabis during cancer care are lacking. While several observational studies support cannabis use to help ease chemotherapy-related nausea and vomiting, the literature remains more divided on other potential benefits, such as alleviating cancer pain and sleep problems, and some evidence points to potential downsides of cannabis use.

Oncologists should “absolutely talk to patients” about cannabis, Brooke Worster, MD, medical director for the Master of Science in Medical Cannabis Science & Business program at Thomas Jefferson University, Philadelphia, told Medscape Medical News.

“Patients are interested, and they are going to find access to information. As a medical professional, it’s our job to help guide them through these spaces in a safe, nonjudgmental way.”

But, Worster noted, oncologists don’t have to be experts on cannabis to begin the conversation with patients.

So, “let yourself off the hook,” Worster urged.

Plus, avoiding the conversation won’t stop patients from using cannabis. In a recent study, Worster and her colleagues found that nearly one third of patients at 12 National Cancer Institute-designated cancer centers had used cannabis since their diagnosis — most often for sleep disturbance, pain, stress, and anxiety. Most (60%) felt somewhat or extremely comfortable talking to their healthcare provider about it, but only 21.5% said they had done so. Even fewer — about 10% — had talked to their treating oncologist.

Because patients may not discuss cannabis use, it’s especially important for oncologists to open up a line of communication, said Worster, also the enterprise director of supportive oncology at the Thomas Jefferson University.
 

Evidence on Cannabis During Cancer Care

A substantial proportion of people with cancer believe cannabis can help manage cancer-related symptoms.

In Worster’s recent survey study, regardless of whether patients had used cannabis, almost 90% of those surveyed reported a perceived benefit. Although 65% also reported perceived risks for cannabis use, including difficulty concentrating, lung damage, and impaired memory, the perceived benefits outweighed the risks.

Despite generally positive perceptions, the overall literature on the benefits of cannabis in patients with cancer paints a less clear picture.

The ASCO guidelines, which were based on 13 systematic reviews and five additional primary studies, reported that cannabis can improve refractory, chemotherapy-induced nausea or vomiting when added to guideline-concordant antiemetic regimens, but that there is no clear evidence of benefit or harm for other supportive care outcomes.

The “certainty of evidence for most outcomes was low or very low,” the ASCO authors wrote.

The ASCO experts explained that, outside the context of a clinical trial, the evidence is not sufficient to recommend cannabis or cannabinoids for managing cancer pain, sleep issues, appetite loss, or anxiety and depression. For these outcomes, some studies indicate a benefit, while others don’t.

Real-world data from a large registry study, for instance, have indicated that medical cannabis is “a safe and effective complementary treatment for pain relief in patients with cancer.” However, a 2020 meta-analysis found that, in studies with a low risk for bias, adding cannabinoids to opioids did not reduce cancer pain in adults with advanced cancer.

There can be downsides to cannabis use, too. In one recent study, some patients reported feeling worse physically and psychologically compared with those who didn’t use cannabis. Another study found that oral cannabis was associated with “bothersome” side effects, including sedation, dizziness, and transient anxiety.

The ASCO guidelines also made it clear that cannabis or cannabinoids should not be used as cancer-directed treatment, outside of a clinical trial.
 

Talking to Patients About Cannabis

Given the level of evidence and patient interest in cannabis, it is important for oncologists to raise the topic of cannabis use with their patients.

To help inform decision-making and approaches to care, the ASCO guidelines suggest that oncologists can guide care themselves or direct patients to appropriate “unbiased, evidence-based” resources. For those who use cannabis or cannabinoids outside of evidence-based indications or clinician recommendations, it’s important to explore patients’ goals, educate them, and try to minimize harm.

One strategy for broaching the topic, Worster suggested, is to simply ask patients if they have tried or considered trying cannabis to control symptoms like nausea and vomiting, loss of appetite, or cancer pain.

The conversation with patients should then include an overview of the potential benefits and potential risks for cannabis use as well as risk reduction strategies, Worster noted.

But “approach it in an open and nonjudgmental frame of mind,” she said. “Just have a conversation.”

Discussing the formulation and concentration of tetrahydrocannabinol (THC) and cannabidiol (CBD) in products matters as well.

Will the product be inhaled, ingested, or topical? Inhaled cannabis is not ideal but is sometimes what patients have access to, Worster explained. Inhaled formulations tend to have faster onset, which might be preferable for treating chemotherapy-related nausea and vomiting, whereas edible formulations may take a while to start working.

It’s also important to warn patients about taking too much, she said, explaining that inhaling THC at higher doses can increase the risk for cardiovascular effects, anxiety, paranoia, panic, and psychosis.

CBD, on the other hand, is anti-inflammatory, but early data suggest it may blunt immune responses in high doses and should be used cautiously by patients receiving immunotherapy.

Worster noted that as laws change and the science advances, new cannabis products and formulations will emerge, as will artificial intelligence tools for helping to guide patients and clinicians in optimal use of cannabis for cancer care. State websites are a particularly helpful tool for providing state-specific medical education related to cannabis laws and use, as well, she said.

The bottom line, she said, is that talking to patients about the ins and outs of cannabis use “really matters.”

Worster disclosed that she is a medical consultant for EO Care.
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has placed a partial clinical hold on the phase 3 PRESERVE-003 trial of BNT316/ONC-392 (gotistobart, BioNTech and OncoC4) for non–small cell lung cancer (NSCLC) due to varying results in patients with squamous and non-squamous NSCLC.

Gotistobart is a next-generation anti-cytotoxic T-lymphocyte-associated protein 4 antibody candidate in late-stage clinical development for various cancer indications. PRESERVE-003 is an open-label randomized trial assessing the safety and efficacy of the agent vs docetaxel as monotherapy in patients with metastatic NSCLC that progressed despite prior treatment with a programmed cell death protein 1 or programmed death ligand 1 inhibitor.

“A recent assessment of the trial data by the independent data monitoring committee identified a possible variance in population results,” according to a regulatory document from the United States Securities and Exchange Commission relating to the clinical hold. “Consequently, OncoC4 and BioNTech decided to proactively pause enrollment of new patients and informed the FDA of the possible variance for further alignment.”

Patients already enrolled in the trial will continue to receive treatment. Ongoing trials of gotistobart for other indications are not affected by the hold, according to the notice.
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has placed a partial clinical hold on the phase 3 PRESERVE-003 trial of BNT316/ONC-392 (gotistobart, BioNTech and OncoC4) for non–small cell lung cancer (NSCLC) due to varying results in patients with squamous and non-squamous NSCLC.

Gotistobart is a next-generation anti-cytotoxic T-lymphocyte-associated protein 4 antibody candidate in late-stage clinical development for various cancer indications. PRESERVE-003 is an open-label randomized trial assessing the safety and efficacy of the agent vs docetaxel as monotherapy in patients with metastatic NSCLC that progressed despite prior treatment with a programmed cell death protein 1 or programmed death ligand 1 inhibitor.

“A recent assessment of the trial data by the independent data monitoring committee identified a possible variance in population results,” according to a regulatory document from the United States Securities and Exchange Commission relating to the clinical hold. “Consequently, OncoC4 and BioNTech decided to proactively pause enrollment of new patients and informed the FDA of the possible variance for further alignment.”

Patients already enrolled in the trial will continue to receive treatment. Ongoing trials of gotistobart for other indications are not affected by the hold, according to the notice.
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has placed a partial clinical hold on the phase 3 PRESERVE-003 trial of BNT316/ONC-392 (gotistobart, BioNTech and OncoC4) for non–small cell lung cancer (NSCLC) due to varying results in patients with squamous and non-squamous NSCLC.

Gotistobart is a next-generation anti-cytotoxic T-lymphocyte-associated protein 4 antibody candidate in late-stage clinical development for various cancer indications. PRESERVE-003 is an open-label randomized trial assessing the safety and efficacy of the agent vs docetaxel as monotherapy in patients with metastatic NSCLC that progressed despite prior treatment with a programmed cell death protein 1 or programmed death ligand 1 inhibitor.

“A recent assessment of the trial data by the independent data monitoring committee identified a possible variance in population results,” according to a regulatory document from the United States Securities and Exchange Commission relating to the clinical hold. “Consequently, OncoC4 and BioNTech decided to proactively pause enrollment of new patients and informed the FDA of the possible variance for further alignment.”

Patients already enrolled in the trial will continue to receive treatment. Ongoing trials of gotistobart for other indications are not affected by the hold, according to the notice.
 

A version of this article appeared on Medscape.com.

Breast cancer incidence has been on the rise, particularly among White women under age 50, but breast cancer deaths — for some, but not all, populations — have been steadily decreasing, according to a biennial update from the American Cancer Society (ACS).

The ACS update, which underscores the persistence of racial and ethnic disparities in breast cancer incidence and outcomes, noted an overall 1% annual increase in breast cancer incidence from 2012 to 2021. The additional cases were largely composed of localized-stage and hormone receptor (HR)–positive disease, which generally have better prognoses than more advanced and HR–negative disease.

Deaths from breast cancer, however, declined from 1989 to 2022, with an overall drop of 44%. That percentage drop “translates to almost 518,000 fewer women dying from breast cancer in the United States during this time,” Angela N. Giaquinto and ACS colleagues noted in the report, published in CA: A Cancer Journal for Clinicians.

“This progress is the result of advances in treatment and earlier detection through screening,” the authors wrote, while stressing that “these interventions have not been disseminated equally.”

The ACS also published an educational companion — Breast Cancer Facts & Figures 2024-2025 — that provides additional insights about trends in breast cancer and steps needed to bolster prevention, detection, and treatment advances.
 

Incidence and Mortality

Although the overall annual increase in breast cancer incidence from 2012 to 2021 was 1%, the increase was steeper among women under age 50, at 1.4% annually vs 0.7% among those aged 50 or older.

Asian American/Pacific Islander women had the greatest increases in breast cancer incidence among both age groups, with a 2.7% annual increase for those aged under 50 and a 2.5% increase for those aged 50 or older. This group, however, had the second lowest breast cancer rate in 2000 at 57.4 cases per 100,000 persons, but the highest rate in 2021 at 86.3 cases per 100,000, alongside White women (86.4 cases per 100,000). Black women were not far behind at 81.5 cases per 100,000.

Black women were least likely to be diagnosed with localized-stage breast cancer and most likely to be diagnosed with distant-stage or unstaged cancer, with American Indian/Alaska Native women not far behind.

Despite the rising incidence of breast cancer, death rates from the disease have gone down considerably overall from about 33 deaths per 100,000 women in 1989 to 19 deaths per 100,000 in 2022.

However, not all women have experienced these survival gains equally, Ms. Giaquinto and colleagues noted.

Since 1990, the mortality rate has remained unchanged among American Indian/Alaska Native women. Black women, however, have experienced a 38% higher mortality rate than White women, despite having a 5% lower incidence of breast cancer.

In fact, Black women have the lowest survival of any racial and ethnic group for every breast cancer subtype and stage of disease except localized disease.

Additional key findings from the report:

• In 2024, an estimated 310,720 new invasive breast cancers and 56,500 cases of ductal carcinoma in situ will be diagnosed among women in the United States, and an additional 2790 cases will be diagnosed in men.
• On the mortality front, in 2024, approximately 42,250 women are expected to die of breast cancer; 530 breast cancer deaths are anticipated in men.
• As for the lifetime risk for breast cancer, approximately one in eight women in the United States (13.1%) will be diagnosed with invasive breast cancer; 1 in 43 (2.3%) will die from the disease.
• The 5-year relative survival rate for breast cancer is 91%, but that drops to 86% at 10 years and 81% at 15 years.
• The 5-year relative survival rate is over 99% for breast cancer diagnosed at a localized stage but drops to 87% for regional-stage and 32% for distant-stage disease.
• American Indian/Alaska Native women have a 10% lower breast cancer incidence than White women but 6% higher mortality.

Similar to the ACS report, a recent study published in JAMA Network Open reported rising breast cancer incidence among US women aged 20-49 years of different races in different age groups over the past 2 decades.

The increased incidence of breast cancer in younger women “is an area of concern and an area where we really need to spend more effort trying to understand why,” said lead study author and breast surgeon Adetunji T. Toriola, MD, PhD, MPH, of Washington University in St Louis, Missouri.

Although reproductive and lifestyle factors, such as weight gain, diet, and physical activity, may contribute to the growing breast cancer incidence in younger women — and preliminary findings from Dr. Toriola’s own research suggest that reproductive factors may be a particularly strong driver — environmental factors, including exposure to forever chemicals, may also play a role.

Early-life factors, such as exposure to toxins, remain an underexplored area, Dr. Toriola noted, stressing the importance of teasing out the long-term effects of environmental exposures in puberty and during adolescence.

Overall, the trends observed both in this study and the ACS report highlight the need for enhanced prevention efforts that address racial disparities as well as the rising incidence in young women, said Dr. Toriola, also professor of surgery at the Washington University Institute of Public Health, St Louis.

For now, Dr. Toriola urges women to “engage with mammographic screening as soon as qualified” as per guidelines. Women at average risk should go for screening beginning at age 40, and those with a family history or other risk factors should talk to their physician about earlier screening, he said.

Ms. Giaquinto is employed by the ACS, which receives grants from private and corporate foundations, including foundations associated with companies in the health sector, for research outside of the submitted work. Dr. Toriola reported having no disclosures.

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

Breast cancer incidence has been on the rise, particularly among White women under age 50, but breast cancer deaths — for some, but not all, populations — have been steadily decreasing, according to a biennial update from the American Cancer Society (ACS).

The ACS update, which underscores the persistence of racial and ethnic disparities in breast cancer incidence and outcomes, noted an overall 1% annual increase in breast cancer incidence from 2012 to 2021. The additional cases were largely composed of localized-stage and hormone receptor (HR)–positive disease, which generally have better prognoses than more advanced and HR–negative disease.

Deaths from breast cancer, however, declined from 1989 to 2022, with an overall drop of 44%. That percentage drop “translates to almost 518,000 fewer women dying from breast cancer in the United States during this time,” Angela N. Giaquinto and ACS colleagues noted in the report, published in CA: A Cancer Journal for Clinicians.

“This progress is the result of advances in treatment and earlier detection through screening,” the authors wrote, while stressing that “these interventions have not been disseminated equally.”

The ACS also published an educational companion — Breast Cancer Facts & Figures 2024-2025 — that provides additional insights about trends in breast cancer and steps needed to bolster prevention, detection, and treatment advances.
 

Incidence and Mortality

Although the overall annual increase in breast cancer incidence from 2012 to 2021 was 1%, the increase was steeper among women under age 50, at 1.4% annually vs 0.7% among those aged 50 or older.

Asian American/Pacific Islander women had the greatest increases in breast cancer incidence among both age groups, with a 2.7% annual increase for those aged under 50 and a 2.5% increase for those aged 50 or older. This group, however, had the second lowest breast cancer rate in 2000 at 57.4 cases per 100,000 persons, but the highest rate in 2021 at 86.3 cases per 100,000, alongside White women (86.4 cases per 100,000). Black women were not far behind at 81.5 cases per 100,000.

Black women were least likely to be diagnosed with localized-stage breast cancer and most likely to be diagnosed with distant-stage or unstaged cancer, with American Indian/Alaska Native women not far behind.

Despite the rising incidence of breast cancer, death rates from the disease have gone down considerably overall from about 33 deaths per 100,000 women in 1989 to 19 deaths per 100,000 in 2022.

However, not all women have experienced these survival gains equally, Ms. Giaquinto and colleagues noted.

Since 1990, the mortality rate has remained unchanged among American Indian/Alaska Native women. Black women, however, have experienced a 38% higher mortality rate than White women, despite having a 5% lower incidence of breast cancer.

In fact, Black women have the lowest survival of any racial and ethnic group for every breast cancer subtype and stage of disease except localized disease.

Additional key findings from the report:

• In 2024, an estimated 310,720 new invasive breast cancers and 56,500 cases of ductal carcinoma in situ will be diagnosed among women in the United States, and an additional 2790 cases will be diagnosed in men.
• On the mortality front, in 2024, approximately 42,250 women are expected to die of breast cancer; 530 breast cancer deaths are anticipated in men.
• As for the lifetime risk for breast cancer, approximately one in eight women in the United States (13.1%) will be diagnosed with invasive breast cancer; 1 in 43 (2.3%) will die from the disease.
• The 5-year relative survival rate for breast cancer is 91%, but that drops to 86% at 10 years and 81% at 15 years.
• The 5-year relative survival rate is over 99% for breast cancer diagnosed at a localized stage but drops to 87% for regional-stage and 32% for distant-stage disease.
• American Indian/Alaska Native women have a 10% lower breast cancer incidence than White women but 6% higher mortality.

Similar to the ACS report, a recent study published in JAMA Network Open reported rising breast cancer incidence among US women aged 20-49 years of different races in different age groups over the past 2 decades.

The increased incidence of breast cancer in younger women “is an area of concern and an area where we really need to spend more effort trying to understand why,” said lead study author and breast surgeon Adetunji T. Toriola, MD, PhD, MPH, of Washington University in St Louis, Missouri.

Although reproductive and lifestyle factors, such as weight gain, diet, and physical activity, may contribute to the growing breast cancer incidence in younger women — and preliminary findings from Dr. Toriola’s own research suggest that reproductive factors may be a particularly strong driver — environmental factors, including exposure to forever chemicals, may also play a role.

Early-life factors, such as exposure to toxins, remain an underexplored area, Dr. Toriola noted, stressing the importance of teasing out the long-term effects of environmental exposures in puberty and during adolescence.

Overall, the trends observed both in this study and the ACS report highlight the need for enhanced prevention efforts that address racial disparities as well as the rising incidence in young women, said Dr. Toriola, also professor of surgery at the Washington University Institute of Public Health, St Louis.

For now, Dr. Toriola urges women to “engage with mammographic screening as soon as qualified” as per guidelines. Women at average risk should go for screening beginning at age 40, and those with a family history or other risk factors should talk to their physician about earlier screening, he said.

Ms. Giaquinto is employed by the ACS, which receives grants from private and corporate foundations, including foundations associated with companies in the health sector, for research outside of the submitted work. Dr. Toriola reported having no disclosures.

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

Breast cancer incidence has been on the rise, particularly among White women under age 50, but breast cancer deaths — for some, but not all, populations — have been steadily decreasing, according to a biennial update from the American Cancer Society (ACS).

The ACS update, which underscores the persistence of racial and ethnic disparities in breast cancer incidence and outcomes, noted an overall 1% annual increase in breast cancer incidence from 2012 to 2021. The additional cases were largely composed of localized-stage and hormone receptor (HR)–positive disease, which generally have better prognoses than more advanced and HR–negative disease.

Deaths from breast cancer, however, declined from 1989 to 2022, with an overall drop of 44%. That percentage drop “translates to almost 518,000 fewer women dying from breast cancer in the United States during this time,” Angela N. Giaquinto and ACS colleagues noted in the report, published in CA: A Cancer Journal for Clinicians.

“This progress is the result of advances in treatment and earlier detection through screening,” the authors wrote, while stressing that “these interventions have not been disseminated equally.”

The ACS also published an educational companion — Breast Cancer Facts & Figures 2024-2025 — that provides additional insights about trends in breast cancer and steps needed to bolster prevention, detection, and treatment advances.
 

Incidence and Mortality

Although the overall annual increase in breast cancer incidence from 2012 to 2021 was 1%, the increase was steeper among women under age 50, at 1.4% annually vs 0.7% among those aged 50 or older.

Asian American/Pacific Islander women had the greatest increases in breast cancer incidence among both age groups, with a 2.7% annual increase for those aged under 50 and a 2.5% increase for those aged 50 or older. This group, however, had the second lowest breast cancer rate in 2000 at 57.4 cases per 100,000 persons, but the highest rate in 2021 at 86.3 cases per 100,000, alongside White women (86.4 cases per 100,000). Black women were not far behind at 81.5 cases per 100,000.

Black women were least likely to be diagnosed with localized-stage breast cancer and most likely to be diagnosed with distant-stage or unstaged cancer, with American Indian/Alaska Native women not far behind.

Despite the rising incidence of breast cancer, death rates from the disease have gone down considerably overall from about 33 deaths per 100,000 women in 1989 to 19 deaths per 100,000 in 2022.

However, not all women have experienced these survival gains equally, Ms. Giaquinto and colleagues noted.

Since 1990, the mortality rate has remained unchanged among American Indian/Alaska Native women. Black women, however, have experienced a 38% higher mortality rate than White women, despite having a 5% lower incidence of breast cancer.

In fact, Black women have the lowest survival of any racial and ethnic group for every breast cancer subtype and stage of disease except localized disease.

Additional key findings from the report:

• In 2024, an estimated 310,720 new invasive breast cancers and 56,500 cases of ductal carcinoma in situ will be diagnosed among women in the United States, and an additional 2790 cases will be diagnosed in men.
• On the mortality front, in 2024, approximately 42,250 women are expected to die of breast cancer; 530 breast cancer deaths are anticipated in men.
• As for the lifetime risk for breast cancer, approximately one in eight women in the United States (13.1%) will be diagnosed with invasive breast cancer; 1 in 43 (2.3%) will die from the disease.
• The 5-year relative survival rate for breast cancer is 91%, but that drops to 86% at 10 years and 81% at 15 years.
• The 5-year relative survival rate is over 99% for breast cancer diagnosed at a localized stage but drops to 87% for regional-stage and 32% for distant-stage disease.
• American Indian/Alaska Native women have a 10% lower breast cancer incidence than White women but 6% higher mortality.

Similar to the ACS report, a recent study published in JAMA Network Open reported rising breast cancer incidence among US women aged 20-49 years of different races in different age groups over the past 2 decades.

The increased incidence of breast cancer in younger women “is an area of concern and an area where we really need to spend more effort trying to understand why,” said lead study author and breast surgeon Adetunji T. Toriola, MD, PhD, MPH, of Washington University in St Louis, Missouri.

Although reproductive and lifestyle factors, such as weight gain, diet, and physical activity, may contribute to the growing breast cancer incidence in younger women — and preliminary findings from Dr. Toriola’s own research suggest that reproductive factors may be a particularly strong driver — environmental factors, including exposure to forever chemicals, may also play a role.

Early-life factors, such as exposure to toxins, remain an underexplored area, Dr. Toriola noted, stressing the importance of teasing out the long-term effects of environmental exposures in puberty and during adolescence.

Overall, the trends observed both in this study and the ACS report highlight the need for enhanced prevention efforts that address racial disparities as well as the rising incidence in young women, said Dr. Toriola, also professor of surgery at the Washington University Institute of Public Health, St Louis.

For now, Dr. Toriola urges women to “engage with mammographic screening as soon as qualified” as per guidelines. Women at average risk should go for screening beginning at age 40, and those with a family history or other risk factors should talk to their physician about earlier screening, he said.

Ms. Giaquinto is employed by the ACS, which receives grants from private and corporate foundations, including foundations associated with companies in the health sector, for research outside of the submitted work. Dr. Toriola reported having no disclosures.

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

Adding isatuximab, or Isa (Sarclisa, Sanofi-Aventis), to bortezomib, lenalidomide, and dexamethasone (VRd) for the treatment of patients with newly diagnosed, transplant-ineligible multiple myeloma reduced the risk for disease progression or death by more than 40% vs VRd alone in the randomized, global, open-label, phase 3 IMROZ trial.

The findings, presented on September 26 at the annual meeting of the International Myeloma Society, support the four-drug combination known as Isa-VRd as a potential new standard of care (SOC) supplanting VRd alone as the SOC in this setting, according to Meletios Dimopoulos, MD, of the University of Athens, Greece.

The IMROZ findings — the first from a phase 3 study of an anti-CD38 monoclonal antibody given in combination with VRd — were also reported in May at the annual meeting of the American Society of Clinical Oncology (ASCO) and published simultaneously in The New England Journal of Medicine. 

“The significant progression-free benefit observed with Sarclisa with combination therapy compared to VRd is important and encouraging for patients with newly diagnosed multiple myeloma,” first author Thierry Facon, MD, told this news organization at ASCO.

Dr. Thierry, of the University of Lille, and the French Academy of Medicine in Paris, France, added that Isa-VRd has the potential as “a first-in-class combination to address gaps in care for newly diagnosed multiple myeloma transplant-ineligible patients.”

Isatuximab in combination with VRd was subsequently approved by the US Food and Drug Administration (FDA) for this indication, as reported on September 23 by this news organization.

So, what will this quadruplet mean for the treatment of multiple myeloma? IMROZ study coauthors Meral Beksac, MD, of Istinye University, Istanbul, and Liv Hospital Ankara, Turkey, and Mohamad Mohty, MD, of Sorbonne University, Saint-Antoine Hospital, Paris, France, provided some insights in a recent interview, telling the European Medical Journal (EMJ) Hematology that Isa-VRd is a “welcome addition” to the multiple myeloma armamentarium.
 

Should Isa-VRd Be Considered the New First-Choice Frontline Treatment for Transplant-Ineligible Patients?

“The short answer is yes,” Dr. Mohty told EMJ. “Based on this trial, quadruplet should become the preferred regimen in the population of patients represented by these inclusion criteria.”

Dr. Beksac agreed that Isa-VRd will play a role in frontline management for transplant-ineligible patients.

However, both noted that despite having a favorable safety profile similar to VRd, Isa-VRd may not be well tolerated in elderly and frail patients. Demonstrably frail patients were excluded from IMROZ, and this is a factor that should be considered in the practice setting, they agreed.
 

Will Isa-VRd Change How Patients Are Evaluated for Transplant Eligibility?

“The cutoff for transplant eligibility differs from one country to another, and today, we do not have consensus around an agreed-upon age limit,” Dr. Beksac said. “We further rely on frailty and the patient’s performance status, not only at diagnosis but at later stages as well.”

She also noted that “[t]he introduction of very effective systemic regimens with similar efficacy to [hematopoietic stem cell transplant (HSCT)] has seen a shift towards non-transplant regimens, particularly in the USA.”

“In many centers in Europe, these patients [in IMROZ] would be considered transplant eligible. Hence, for this group of patients who are not too old, but not too young, and fit, IMROZ is offering a non-transplant-based treatment with similar efficacy to what can be achieved with HSCT,” Dr. Mohty added.

Patient preference and access are also important considerations, as is cost, he noted.

Younger transplant-eligible patients may prefer transplant over continuous treatment for life, whereas some might prefer long-term treatment over a stem cell protocol that will require months off of work, he and Dr. Beksac explained.

“Based on this trial, we will likely see a decline in the number of transplants,” Dr. Mohty predicted. “With the IMROZ data, we have something valid that we can offer patients without any prejudice to their outcome.”
 

How Will This Combination Be Integrated Into Daily Clinical Practice?

“My interpretation would be that this protocol will be conceived as an applicable protocol that can be adapted to our daily practice,” Dr. Beksac said.

Dr. Mohty added that the multiple myeloma story is changing and evolving.

“It’s not transplant versus no transplant, it’s who is going to receive quadruplet and who’s going to receive less than a quadruplet, who is fit and who is unfit,” he explained, adding that physicians will likely adapt the Isa-VRd regimen for real-world use based on clinical judgment.

For example, the quadruplet may be combined “in a kind of VRd-light version to start with, and maybe we can adapt later depending on the tolerability of the patient,” Dr. Beksac added.

“Until recently, we thought that transplant is the gold standard for everybody whenever possible. Now, we have a more nuanced answer, offering a regimen that actually is as effective, and may even be better, than transplant,” Dr. Mohty said. “So, it’s a most welcome addition to what we do.”

Both the IMROZ study and the EMJ article were funded by Sanofi.

Dr. Dimopoulos reported ties with Amgen, BeiGene, BMS, Janssen, Sanofi, and Takeda. Dr. Beksac disclosed relationships with Amgen, BMS, GSK, Janssen, Sanofi, and Takeda. Dr. Mohty reported ties with Adaptive Biotechnologies, Amgen, Astellas Pharma, BMS, GSK, Janssen-Cilag, Jazz Pharmaceuticals, and others.
 

A version of this article appeared on Medscape.com.

Adding isatuximab, or Isa (Sarclisa, Sanofi-Aventis), to bortezomib, lenalidomide, and dexamethasone (VRd) for the treatment of patients with newly diagnosed, transplant-ineligible multiple myeloma reduced the risk for disease progression or death by more than 40% vs VRd alone in the randomized, global, open-label, phase 3 IMROZ trial.

The findings, presented on September 26 at the annual meeting of the International Myeloma Society, support the four-drug combination known as Isa-VRd as a potential new standard of care (SOC) supplanting VRd alone as the SOC in this setting, according to Meletios Dimopoulos, MD, of the University of Athens, Greece.

The IMROZ findings — the first from a phase 3 study of an anti-CD38 monoclonal antibody given in combination with VRd — were also reported in May at the annual meeting of the American Society of Clinical Oncology (ASCO) and published simultaneously in The New England Journal of Medicine. 

“The significant progression-free benefit observed with Sarclisa with combination therapy compared to VRd is important and encouraging for patients with newly diagnosed multiple myeloma,” first author Thierry Facon, MD, told this news organization at ASCO.

Dr. Thierry, of the University of Lille, and the French Academy of Medicine in Paris, France, added that Isa-VRd has the potential as “a first-in-class combination to address gaps in care for newly diagnosed multiple myeloma transplant-ineligible patients.”

Isatuximab in combination with VRd was subsequently approved by the US Food and Drug Administration (FDA) for this indication, as reported on September 23 by this news organization.

So, what will this quadruplet mean for the treatment of multiple myeloma? IMROZ study coauthors Meral Beksac, MD, of Istinye University, Istanbul, and Liv Hospital Ankara, Turkey, and Mohamad Mohty, MD, of Sorbonne University, Saint-Antoine Hospital, Paris, France, provided some insights in a recent interview, telling the European Medical Journal (EMJ) Hematology that Isa-VRd is a “welcome addition” to the multiple myeloma armamentarium.
 

Should Isa-VRd Be Considered the New First-Choice Frontline Treatment for Transplant-Ineligible Patients?

“The short answer is yes,” Dr. Mohty told EMJ. “Based on this trial, quadruplet should become the preferred regimen in the population of patients represented by these inclusion criteria.”

Dr. Beksac agreed that Isa-VRd will play a role in frontline management for transplant-ineligible patients.

However, both noted that despite having a favorable safety profile similar to VRd, Isa-VRd may not be well tolerated in elderly and frail patients. Demonstrably frail patients were excluded from IMROZ, and this is a factor that should be considered in the practice setting, they agreed.
 

Will Isa-VRd Change How Patients Are Evaluated for Transplant Eligibility?

“The cutoff for transplant eligibility differs from one country to another, and today, we do not have consensus around an agreed-upon age limit,” Dr. Beksac said. “We further rely on frailty and the patient’s performance status, not only at diagnosis but at later stages as well.”

She also noted that “[t]he introduction of very effective systemic regimens with similar efficacy to [hematopoietic stem cell transplant (HSCT)] has seen a shift towards non-transplant regimens, particularly in the USA.”

“In many centers in Europe, these patients [in IMROZ] would be considered transplant eligible. Hence, for this group of patients who are not too old, but not too young, and fit, IMROZ is offering a non-transplant-based treatment with similar efficacy to what can be achieved with HSCT,” Dr. Mohty added.

Patient preference and access are also important considerations, as is cost, he noted.

Younger transplant-eligible patients may prefer transplant over continuous treatment for life, whereas some might prefer long-term treatment over a stem cell protocol that will require months off of work, he and Dr. Beksac explained.

“Based on this trial, we will likely see a decline in the number of transplants,” Dr. Mohty predicted. “With the IMROZ data, we have something valid that we can offer patients without any prejudice to their outcome.”
 

How Will This Combination Be Integrated Into Daily Clinical Practice?

“My interpretation would be that this protocol will be conceived as an applicable protocol that can be adapted to our daily practice,” Dr. Beksac said.

Dr. Mohty added that the multiple myeloma story is changing and evolving.

“It’s not transplant versus no transplant, it’s who is going to receive quadruplet and who’s going to receive less than a quadruplet, who is fit and who is unfit,” he explained, adding that physicians will likely adapt the Isa-VRd regimen for real-world use based on clinical judgment.

For example, the quadruplet may be combined “in a kind of VRd-light version to start with, and maybe we can adapt later depending on the tolerability of the patient,” Dr. Beksac added.

“Until recently, we thought that transplant is the gold standard for everybody whenever possible. Now, we have a more nuanced answer, offering a regimen that actually is as effective, and may even be better, than transplant,” Dr. Mohty said. “So, it’s a most welcome addition to what we do.”

Both the IMROZ study and the EMJ article were funded by Sanofi.

Dr. Dimopoulos reported ties with Amgen, BeiGene, BMS, Janssen, Sanofi, and Takeda. Dr. Beksac disclosed relationships with Amgen, BMS, GSK, Janssen, Sanofi, and Takeda. Dr. Mohty reported ties with Adaptive Biotechnologies, Amgen, Astellas Pharma, BMS, GSK, Janssen-Cilag, Jazz Pharmaceuticals, and others.
 

A version of this article appeared on Medscape.com.

Adding isatuximab, or Isa (Sarclisa, Sanofi-Aventis), to bortezomib, lenalidomide, and dexamethasone (VRd) for the treatment of patients with newly diagnosed, transplant-ineligible multiple myeloma reduced the risk for disease progression or death by more than 40% vs VRd alone in the randomized, global, open-label, phase 3 IMROZ trial.

The findings, presented on September 26 at the annual meeting of the International Myeloma Society, support the four-drug combination known as Isa-VRd as a potential new standard of care (SOC) supplanting VRd alone as the SOC in this setting, according to Meletios Dimopoulos, MD, of the University of Athens, Greece.

The IMROZ findings — the first from a phase 3 study of an anti-CD38 monoclonal antibody given in combination with VRd — were also reported in May at the annual meeting of the American Society of Clinical Oncology (ASCO) and published simultaneously in The New England Journal of Medicine. 

“The significant progression-free benefit observed with Sarclisa with combination therapy compared to VRd is important and encouraging for patients with newly diagnosed multiple myeloma,” first author Thierry Facon, MD, told this news organization at ASCO.

Dr. Thierry, of the University of Lille, and the French Academy of Medicine in Paris, France, added that Isa-VRd has the potential as “a first-in-class combination to address gaps in care for newly diagnosed multiple myeloma transplant-ineligible patients.”

Isatuximab in combination with VRd was subsequently approved by the US Food and Drug Administration (FDA) for this indication, as reported on September 23 by this news organization.

So, what will this quadruplet mean for the treatment of multiple myeloma? IMROZ study coauthors Meral Beksac, MD, of Istinye University, Istanbul, and Liv Hospital Ankara, Turkey, and Mohamad Mohty, MD, of Sorbonne University, Saint-Antoine Hospital, Paris, France, provided some insights in a recent interview, telling the European Medical Journal (EMJ) Hematology that Isa-VRd is a “welcome addition” to the multiple myeloma armamentarium.
 

Should Isa-VRd Be Considered the New First-Choice Frontline Treatment for Transplant-Ineligible Patients?

“The short answer is yes,” Dr. Mohty told EMJ. “Based on this trial, quadruplet should become the preferred regimen in the population of patients represented by these inclusion criteria.”

Dr. Beksac agreed that Isa-VRd will play a role in frontline management for transplant-ineligible patients.

However, both noted that despite having a favorable safety profile similar to VRd, Isa-VRd may not be well tolerated in elderly and frail patients. Demonstrably frail patients were excluded from IMROZ, and this is a factor that should be considered in the practice setting, they agreed.
 

Will Isa-VRd Change How Patients Are Evaluated for Transplant Eligibility?

“The cutoff for transplant eligibility differs from one country to another, and today, we do not have consensus around an agreed-upon age limit,” Dr. Beksac said. “We further rely on frailty and the patient’s performance status, not only at diagnosis but at later stages as well.”

She also noted that “[t]he introduction of very effective systemic regimens with similar efficacy to [hematopoietic stem cell transplant (HSCT)] has seen a shift towards non-transplant regimens, particularly in the USA.”

“In many centers in Europe, these patients [in IMROZ] would be considered transplant eligible. Hence, for this group of patients who are not too old, but not too young, and fit, IMROZ is offering a non-transplant-based treatment with similar efficacy to what can be achieved with HSCT,” Dr. Mohty added.

Patient preference and access are also important considerations, as is cost, he noted.

Younger transplant-eligible patients may prefer transplant over continuous treatment for life, whereas some might prefer long-term treatment over a stem cell protocol that will require months off of work, he and Dr. Beksac explained.

“Based on this trial, we will likely see a decline in the number of transplants,” Dr. Mohty predicted. “With the IMROZ data, we have something valid that we can offer patients without any prejudice to their outcome.”
 

How Will This Combination Be Integrated Into Daily Clinical Practice?

“My interpretation would be that this protocol will be conceived as an applicable protocol that can be adapted to our daily practice,” Dr. Beksac said.

Dr. Mohty added that the multiple myeloma story is changing and evolving.

“It’s not transplant versus no transplant, it’s who is going to receive quadruplet and who’s going to receive less than a quadruplet, who is fit and who is unfit,” he explained, adding that physicians will likely adapt the Isa-VRd regimen for real-world use based on clinical judgment.

For example, the quadruplet may be combined “in a kind of VRd-light version to start with, and maybe we can adapt later depending on the tolerability of the patient,” Dr. Beksac added.

“Until recently, we thought that transplant is the gold standard for everybody whenever possible. Now, we have a more nuanced answer, offering a regimen that actually is as effective, and may even be better, than transplant,” Dr. Mohty said. “So, it’s a most welcome addition to what we do.”

Both the IMROZ study and the EMJ article were funded by Sanofi.

Dr. Dimopoulos reported ties with Amgen, BeiGene, BMS, Janssen, Sanofi, and Takeda. Dr. Beksac disclosed relationships with Amgen, BMS, GSK, Janssen, Sanofi, and Takeda. Dr. Mohty reported ties with Adaptive Biotechnologies, Amgen, Astellas Pharma, BMS, GSK, Janssen-Cilag, Jazz Pharmaceuticals, and others.
 

A version of this article appeared on Medscape.com.

A single infusion of the chimeric antigen receptor (CAR) T-cell therapy ciltacabtagene autoleucel, or cilta-cel (CARVYKTI, Janssen Biotech, Inc.), reduces the risk for death by 45% vs standard-of-care (SoC) therapies in patients with lenalidomide-refractory multiple myeloma, according to the latest data from the phase 3 CARTITUDE-4 study.

“Cilta-cel is the first CAR T-cell therapy to demonstrate an overall survival benefit in multiple myeloma,” María-Victoria Mateos, MD, PhD, said during a presentation of the updated CARTITUDE-4 data at the annual meeting of the International Myeloma Society in late September.

A prespecified overall survival (OS) analysis at a median follow-up of 34 months showed that median OS was not reached in either the cilta-cel or SoC therapy arm (hazard ratio [HR], 0.55). The 30-month OS rates were 76% and 64% in the arms, respectively, said Dr. Mateos, a professor at the University Hospital of Salamanca, Spain.

The significant OS benefit was sustained across all prespecified subgroups, she noted.

The US Food and Drug Administration first approved cilta-cel in 2022 for use after at least four prior lines of therapy in patients with lenalidomide-resistant multiple myeloma based on findings from the CARTITUDE-1 trial. In April 2024, based on progression-free survival (PFS) findings at median follow-up of 16 months in CARTITUDE-4 (HR for progression/death vs SoC, 0.26), that approval was expanded to include patients with lenalidomide-refractory multiple myeloma after one or more prior lines of therapy.

“CARVYKTI demonstrated remarkable efficacy as a personalized, one-time infusion in the earlier treatment of relapsed/refractory multiple myeloma as shown through the CARTITUDE-4 study results,” study coauthor Binod Dhakal, MD, of the Medical College of Wisconsin, in Milwaukee, stated in a press release announcing that expansion. “With this approval, I’m excited for patients who may have the opportunity for a treatment-free period for their multiple myeloma as early as first relapse, with the hope of eliminating the burden of having to be on continuous treatment while living with this challenging disease.”

At the latest analysis, PFS was not reached in the cilta-cel arm and was 11.79 months with SoC, Dr. Mateos said.

The 30-month PFS rates were 59% and 26%, respectively (HR, 0.29), and the PFS benefit was observed across prespecified subgroups.

Patients in the cilta-cel arm also had better complete response rates (77% vs 24%), overall response rates (85% vs 67%), and minimal residual disease-negativity rates (62% vs 18%).

Median duration of response was not reached with cilta-cel and was 18.69 months with SoC, and median time to symptom worsening was not reached vs 34.33 months, respectively.

Safety at the latest update was consistent with prior analyses.

The CARTITUDE findings continue to support the overall benefit-risk profile of cilta-cel vs SoC in patients with lenalidomide-refractory multiple myeloma as early as after the first relapse, Dr. Mateos concluded.

Despite the “compelling efficacy” of cilta-cel, there remains a need for “a safer and equally (if not more) effective CAR-T product” in this setting, Manni Mohyuddin, MD, told this news organization.

“The trial does not change my practice,” said Dr. Mohyuddin, an assistant professor in the multiple myeloma program at Huntsman Cancer Institute, University of Utah, Salt Lake City.

“We must recognize that the control arm [in CARTITUDE-4] isn’t the best available standard of care,” he explained, noting that carfilzomib-containing triplets were not allowed. “Furthermore, overall survival is dependent on access to good therapies upon relapse, and patients in the control arm did not cross over to get cilta-cel at the time of relapse.

“We do not know if overall survival benefit would have been present if the control arm was better and if there was access to better post-protocol therapy.”

Toxicity is also a concern, he said.

“I think of it as high risk-high reward. There was a sevenfold increased incidence of secondary hematological malignancies in the cilta-cel arm compared to standard of care — this is a very concerning signal that dampens my enthusiasm to use this drug early for everyone,” he added.

For example, although Parkinsonism was rare, it generally did not resolve and lasted years, resolving in only 13% of affected patients, with a median time to resolution of 523 days.

“These are horrible odds, and for many patients there may be safer options,” he noted, adding that “cilta-cel is an option I would consider for some relapses (very early relapse while still on multi-agent therapy, high-risk disease), but otherwise I think personally it’s too toxic for most first relapses.”

Dr. Mateos reported relationships with AbbVie, Amgen, BMS, GSK, Janssen, Kite, Oncopeptides, Pfizer, Regeneron, Roche, Sanofi, Stemline Therapeutics, and Takeda. Dr. Mohyuddin had no disclosures.
 

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

A single infusion of the chimeric antigen receptor (CAR) T-cell therapy ciltacabtagene autoleucel, or cilta-cel (CARVYKTI, Janssen Biotech, Inc.), reduces the risk for death by 45% vs standard-of-care (SoC) therapies in patients with lenalidomide-refractory multiple myeloma, according to the latest data from the phase 3 CARTITUDE-4 study.

“Cilta-cel is the first CAR T-cell therapy to demonstrate an overall survival benefit in multiple myeloma,” María-Victoria Mateos, MD, PhD, said during a presentation of the updated CARTITUDE-4 data at the annual meeting of the International Myeloma Society in late September.

A prespecified overall survival (OS) analysis at a median follow-up of 34 months showed that median OS was not reached in either the cilta-cel or SoC therapy arm (hazard ratio [HR], 0.55). The 30-month OS rates were 76% and 64% in the arms, respectively, said Dr. Mateos, a professor at the University Hospital of Salamanca, Spain.

The significant OS benefit was sustained across all prespecified subgroups, she noted.

The US Food and Drug Administration first approved cilta-cel in 2022 for use after at least four prior lines of therapy in patients with lenalidomide-resistant multiple myeloma based on findings from the CARTITUDE-1 trial. In April 2024, based on progression-free survival (PFS) findings at median follow-up of 16 months in CARTITUDE-4 (HR for progression/death vs SoC, 0.26), that approval was expanded to include patients with lenalidomide-refractory multiple myeloma after one or more prior lines of therapy.

“CARVYKTI demonstrated remarkable efficacy as a personalized, one-time infusion in the earlier treatment of relapsed/refractory multiple myeloma as shown through the CARTITUDE-4 study results,” study coauthor Binod Dhakal, MD, of the Medical College of Wisconsin, in Milwaukee, stated in a press release announcing that expansion. “With this approval, I’m excited for patients who may have the opportunity for a treatment-free period for their multiple myeloma as early as first relapse, with the hope of eliminating the burden of having to be on continuous treatment while living with this challenging disease.”

At the latest analysis, PFS was not reached in the cilta-cel arm and was 11.79 months with SoC, Dr. Mateos said.

The 30-month PFS rates were 59% and 26%, respectively (HR, 0.29), and the PFS benefit was observed across prespecified subgroups.

Patients in the cilta-cel arm also had better complete response rates (77% vs 24%), overall response rates (85% vs 67%), and minimal residual disease-negativity rates (62% vs 18%).

Median duration of response was not reached with cilta-cel and was 18.69 months with SoC, and median time to symptom worsening was not reached vs 34.33 months, respectively.

Safety at the latest update was consistent with prior analyses.

The CARTITUDE findings continue to support the overall benefit-risk profile of cilta-cel vs SoC in patients with lenalidomide-refractory multiple myeloma as early as after the first relapse, Dr. Mateos concluded.

Despite the “compelling efficacy” of cilta-cel, there remains a need for “a safer and equally (if not more) effective CAR-T product” in this setting, Manni Mohyuddin, MD, told this news organization.

“The trial does not change my practice,” said Dr. Mohyuddin, an assistant professor in the multiple myeloma program at Huntsman Cancer Institute, University of Utah, Salt Lake City.

“We must recognize that the control arm [in CARTITUDE-4] isn’t the best available standard of care,” he explained, noting that carfilzomib-containing triplets were not allowed. “Furthermore, overall survival is dependent on access to good therapies upon relapse, and patients in the control arm did not cross over to get cilta-cel at the time of relapse.

“We do not know if overall survival benefit would have been present if the control arm was better and if there was access to better post-protocol therapy.”

Toxicity is also a concern, he said.

“I think of it as high risk-high reward. There was a sevenfold increased incidence of secondary hematological malignancies in the cilta-cel arm compared to standard of care — this is a very concerning signal that dampens my enthusiasm to use this drug early for everyone,” he added.

For example, although Parkinsonism was rare, it generally did not resolve and lasted years, resolving in only 13% of affected patients, with a median time to resolution of 523 days.

“These are horrible odds, and for many patients there may be safer options,” he noted, adding that “cilta-cel is an option I would consider for some relapses (very early relapse while still on multi-agent therapy, high-risk disease), but otherwise I think personally it’s too toxic for most first relapses.”

Dr. Mateos reported relationships with AbbVie, Amgen, BMS, GSK, Janssen, Kite, Oncopeptides, Pfizer, Regeneron, Roche, Sanofi, Stemline Therapeutics, and Takeda. Dr. Mohyuddin had no disclosures.
 

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

A single infusion of the chimeric antigen receptor (CAR) T-cell therapy ciltacabtagene autoleucel, or cilta-cel (CARVYKTI, Janssen Biotech, Inc.), reduces the risk for death by 45% vs standard-of-care (SoC) therapies in patients with lenalidomide-refractory multiple myeloma, according to the latest data from the phase 3 CARTITUDE-4 study.

“Cilta-cel is the first CAR T-cell therapy to demonstrate an overall survival benefit in multiple myeloma,” María-Victoria Mateos, MD, PhD, said during a presentation of the updated CARTITUDE-4 data at the annual meeting of the International Myeloma Society in late September.

A prespecified overall survival (OS) analysis at a median follow-up of 34 months showed that median OS was not reached in either the cilta-cel or SoC therapy arm (hazard ratio [HR], 0.55). The 30-month OS rates were 76% and 64% in the arms, respectively, said Dr. Mateos, a professor at the University Hospital of Salamanca, Spain.

The significant OS benefit was sustained across all prespecified subgroups, she noted.

The US Food and Drug Administration first approved cilta-cel in 2022 for use after at least four prior lines of therapy in patients with lenalidomide-resistant multiple myeloma based on findings from the CARTITUDE-1 trial. In April 2024, based on progression-free survival (PFS) findings at median follow-up of 16 months in CARTITUDE-4 (HR for progression/death vs SoC, 0.26), that approval was expanded to include patients with lenalidomide-refractory multiple myeloma after one or more prior lines of therapy.

“CARVYKTI demonstrated remarkable efficacy as a personalized, one-time infusion in the earlier treatment of relapsed/refractory multiple myeloma as shown through the CARTITUDE-4 study results,” study coauthor Binod Dhakal, MD, of the Medical College of Wisconsin, in Milwaukee, stated in a press release announcing that expansion. “With this approval, I’m excited for patients who may have the opportunity for a treatment-free period for their multiple myeloma as early as first relapse, with the hope of eliminating the burden of having to be on continuous treatment while living with this challenging disease.”

At the latest analysis, PFS was not reached in the cilta-cel arm and was 11.79 months with SoC, Dr. Mateos said.

The 30-month PFS rates were 59% and 26%, respectively (HR, 0.29), and the PFS benefit was observed across prespecified subgroups.

Patients in the cilta-cel arm also had better complete response rates (77% vs 24%), overall response rates (85% vs 67%), and minimal residual disease-negativity rates (62% vs 18%).

Median duration of response was not reached with cilta-cel and was 18.69 months with SoC, and median time to symptom worsening was not reached vs 34.33 months, respectively.

Safety at the latest update was consistent with prior analyses.

The CARTITUDE findings continue to support the overall benefit-risk profile of cilta-cel vs SoC in patients with lenalidomide-refractory multiple myeloma as early as after the first relapse, Dr. Mateos concluded.

Despite the “compelling efficacy” of cilta-cel, there remains a need for “a safer and equally (if not more) effective CAR-T product” in this setting, Manni Mohyuddin, MD, told this news organization.

“The trial does not change my practice,” said Dr. Mohyuddin, an assistant professor in the multiple myeloma program at Huntsman Cancer Institute, University of Utah, Salt Lake City.

“We must recognize that the control arm [in CARTITUDE-4] isn’t the best available standard of care,” he explained, noting that carfilzomib-containing triplets were not allowed. “Furthermore, overall survival is dependent on access to good therapies upon relapse, and patients in the control arm did not cross over to get cilta-cel at the time of relapse.

“We do not know if overall survival benefit would have been present if the control arm was better and if there was access to better post-protocol therapy.”

Toxicity is also a concern, he said.

“I think of it as high risk-high reward. There was a sevenfold increased incidence of secondary hematological malignancies in the cilta-cel arm compared to standard of care — this is a very concerning signal that dampens my enthusiasm to use this drug early for everyone,” he added.

For example, although Parkinsonism was rare, it generally did not resolve and lasted years, resolving in only 13% of affected patients, with a median time to resolution of 523 days.

“These are horrible odds, and for many patients there may be safer options,” he noted, adding that “cilta-cel is an option I would consider for some relapses (very early relapse while still on multi-agent therapy, high-risk disease), but otherwise I think personally it’s too toxic for most first relapses.”

Dr. Mateos reported relationships with AbbVie, Amgen, BMS, GSK, Janssen, Kite, Oncopeptides, Pfizer, Regeneron, Roche, Sanofi, Stemline Therapeutics, and Takeda. Dr. Mohyuddin had no disclosures.
 

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

The US Food and Drug Administration (FDA) has approved osimertinib (Tagrisso, AstraZeneca) for the treatment of locally advanced, unresectable non–small cell lung cancer (NSCLC) in certain adult patients.

Specifically, the third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) was approved for patients whose disease has not progressed during or after concurrent or sequential platinum-based chemoradiation therapy and whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations. Such EGFR mutations can be detected by an FDA-approved test.

The FDA approved osimertinib in combination with platinum-based chemotherapy as first-line treatment for patients with locally advanced or metastatic NSCLC with the same mutations in February. The EGFR-TKI also carries other indications, including as first-line monotherapy for locally advanced or metastatic EGFR-mutated NSCLC.
 

Trial Findings Supporting Latest Approval

AstraZeneca announced in June that osimertinib had been granted Priority Review and Breakthrough Therapy Designation for its newest indication.

The September 25 approval was based on findings from the randomized, placebo-controlled LAURA trial of 216 patients, which demonstrated improved median progression-free survival with osimertinib vs placebo (39.1 vs 5.6 months; hazard ratio, 0.16). Overall survival results were immature at the most recent analysis, but “no trend towards a detriment was observed,” with 36% of prespecified deaths for the final analysis reported, according to an FDA press release.
 

Adverse Events

Study participants were randomized 2:1 to receive the osimertinib recommended dose of 80 mg given orally once daily or placebo until disease progression or unacceptable toxicity. The most common adverse reactions, occurring in at least 20% of patients, were lymphopenia, leukopenia, interstitial lung disease/pneumonitis, thrombocytopenia, neutropenia, rash, diarrhea, nail toxicity, musculoskeletal pain, cough, and COVID-19 infection.

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

The US Food and Drug Administration (FDA) has approved osimertinib (Tagrisso, AstraZeneca) for the treatment of locally advanced, unresectable non–small cell lung cancer (NSCLC) in certain adult patients.

Specifically, the third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) was approved for patients whose disease has not progressed during or after concurrent or sequential platinum-based chemoradiation therapy and whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations. Such EGFR mutations can be detected by an FDA-approved test.

The FDA approved osimertinib in combination with platinum-based chemotherapy as first-line treatment for patients with locally advanced or metastatic NSCLC with the same mutations in February. The EGFR-TKI also carries other indications, including as first-line monotherapy for locally advanced or metastatic EGFR-mutated NSCLC.
 

Trial Findings Supporting Latest Approval

AstraZeneca announced in June that osimertinib had been granted Priority Review and Breakthrough Therapy Designation for its newest indication.

The September 25 approval was based on findings from the randomized, placebo-controlled LAURA trial of 216 patients, which demonstrated improved median progression-free survival with osimertinib vs placebo (39.1 vs 5.6 months; hazard ratio, 0.16). Overall survival results were immature at the most recent analysis, but “no trend towards a detriment was observed,” with 36% of prespecified deaths for the final analysis reported, according to an FDA press release.
 

Adverse Events

Study participants were randomized 2:1 to receive the osimertinib recommended dose of 80 mg given orally once daily or placebo until disease progression or unacceptable toxicity. The most common adverse reactions, occurring in at least 20% of patients, were lymphopenia, leukopenia, interstitial lung disease/pneumonitis, thrombocytopenia, neutropenia, rash, diarrhea, nail toxicity, musculoskeletal pain, cough, and COVID-19 infection.

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

The US Food and Drug Administration (FDA) has approved osimertinib (Tagrisso, AstraZeneca) for the treatment of locally advanced, unresectable non–small cell lung cancer (NSCLC) in certain adult patients.

Specifically, the third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) was approved for patients whose disease has not progressed during or after concurrent or sequential platinum-based chemoradiation therapy and whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations. Such EGFR mutations can be detected by an FDA-approved test.

The FDA approved osimertinib in combination with platinum-based chemotherapy as first-line treatment for patients with locally advanced or metastatic NSCLC with the same mutations in February. The EGFR-TKI also carries other indications, including as first-line monotherapy for locally advanced or metastatic EGFR-mutated NSCLC.
 

Trial Findings Supporting Latest Approval

AstraZeneca announced in June that osimertinib had been granted Priority Review and Breakthrough Therapy Designation for its newest indication.

The September 25 approval was based on findings from the randomized, placebo-controlled LAURA trial of 216 patients, which demonstrated improved median progression-free survival with osimertinib vs placebo (39.1 vs 5.6 months; hazard ratio, 0.16). Overall survival results were immature at the most recent analysis, but “no trend towards a detriment was observed,” with 36% of prespecified deaths for the final analysis reported, according to an FDA press release.
 

Adverse Events

Study participants were randomized 2:1 to receive the osimertinib recommended dose of 80 mg given orally once daily or placebo until disease progression or unacceptable toxicity. The most common adverse reactions, occurring in at least 20% of patients, were lymphopenia, leukopenia, interstitial lung disease/pneumonitis, thrombocytopenia, neutropenia, rash, diarrhea, nail toxicity, musculoskeletal pain, cough, and COVID-19 infection.

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

Despite the “remarkable progress” in cancer research and care, cancer remains “an ongoing public health challenge,” which requires significant attention and funding, according to the Cancer Progress Report 2024 from the American Association for Cancer Research (AACR).

The AACR’s 216-page report — an annual endeavor now in its 14th year — focused on the “tremendous” strides made in cancer care, prevention, and early detection and highlighted areas where more research and attention are warranted. 

One key area is funding. For the first time since 2016, federal funding for the National Institutes of Health (NIH) and National Cancer Institute (NCI) decreased in the past year. The cuts followed nearly a decade of funding increases that saw the NIH budget expand by nearly $15 billion, and that allowed for a “rapid pace and broad scope” of advances in cancer, AACR’s chief executive officer Margaret Foti, MD, PhD, said during a press briefing.

These recent cuts “threaten to curtail the medical progress seen in recent years and stymie future advancements,” said Dr. Foti, who called on Congress to commit to funding cancer research at significant and consistent levels to “maintain the momentum of progress against cancer.”
 

Inside the Report: Big Progress

Overall, advances in prevention, early detection, and treatment have helped catch more cancers earlier and save lives. 

According to the AACR report, the age-adjusted overall cancer death rate in the United States fell by 33% between 1991 and 2021, meaning about 4.1 million cancer deaths were averted. The overall cancer death rate for children and adolescents has declined by 24% in the past 2 decades. The 5-year relative survival rate for children diagnosed with cancer in the US has improved from 58% for those diagnosed in the mid-1970s to 85% for those diagnosed between 2013 and 2019.

The past fiscal year has seen many new approvals for cancer drugs, diagnostics, and screening tests. From July 1, 2023, to June 30, 2024, the Food and Drug Administration (FDA) approved 15 new anticancer therapeutics, as well as 15 new indications for previously approved agents, one new imaging agent, several artificial intelligence (AI) tools to improve early cancer detection and diagnosis, and two minimally invasive tests for assessing inherited cancer risk or early cancer detection, according to the report.

“Cancer diagnostics are becoming more sophisticated,” AACR president Patricia M. LoRusso, DO, PhD, said during the briefing. “New technologies, such as spatial transcriptomics, are helping us study tumors at a cellular level, and helping to unveil things that we did not initially even begin to understand or think of. AI-based approaches are beginning to transform cancer detection, diagnosis, clinical decision-making, and treatment response monitoring.” 

The report also highlights the significant progress in many childhood and adolescent/young adult cancers, Dr. LoRusso noted. These include FDA approvals for two new molecularly targeted therapeutics: tovorafenib for children with certain types of brain tumor and repotrectinib for children with a wide array of cancer types that have a specific genetic alteration known as NTRK gene fusion. It also includes an expanded approval for eflornithine to reduce the risk for relapse in children with high-risk neuroblastoma.

“Decades — decades — of basic research discoveries, have led to these clinical breakthroughs,” she stressed. “These gains against cancer are because of the rapid progress in our ability to decode the cancer genome, which has opened new and innovative avenues for drug development.”
 

The Gaps

Even with progress in cancer prevention, early detection, and treatment, cancer remains a significant issue.

“In 2024, it is estimated that more than 2 million new cases of cancer will be diagnosed in the United States. More than 611,000 people will die from the disease,” according to the report.

The 2024 report shows that incidence rates for some cancers are increasing in the United States, including vaccine-preventable cancers such as human papillomavirus (HPV)–associated oral cancers and, in young adults, cervical cancers. A recent analysis also found that overall cervical cancer incidence among women aged 30-34 years increased by 2.5% a year between 2012 and 2019.

Furthermore, despite clear evidence demonstrating that the HPV vaccine reduces cervical cancer incidence, uptake has remained poor, with only 38.6% of US children and adolescents aged 9-17 years receiving at least one dose of the vaccine in 2022.

Early-onset cancers are also increasing. Rates of breast, colorectal, and other cancers are on the rise in adults younger than 50 years, the report noted.

The report also pointed to data that 40% of all cancer cases in the United States can be attributed to preventable factors, such as smoking, excess body weight, and alcohol. However, our understanding of these risk factors has improved. Excessive levels of alcohol consumption have, for instance, been shown to increase the risk for six different types of cancer: certain types of head and neck cancer, esophageal squamous cell carcinoma, and breast, colorectal, liver, and stomach cancers.

Financial toxicity remains prevalent as well.

The report explains that financial hardship following a cancer diagnosis is widespread, and the effects can last for years. In fact, more than 40% of patients can spend their entire life savings within the first 2 years of cancer treatment. Among adult survivors of childhood cancers, 20.7% had trouble paying their medical bills, 29.9% said they had been sent to debt collection for unpaid bills, 14.1% had forgone medical care, and 26.8% could not afford nutritious meals.

For young cancer survivors, the lifetime costs associated with a diagnosis of cancer are substantial, reaching an average of $259,324 per person.

On a global level, it is estimated that from 2020 to 2050, the cumulative economic burden of cancer will be $25.2 trillion.
 

The Path Forward

Despite these challenges, Dr. LoRusso said, “it is unquestionable that we are in a time of unparalleled opportunities in cancer research.

“I am excited about what the future holds for cancer research, and especially for patient care,” she said. 

However, funding commitments are needed to avoid impeding this momentum and losing a “talented and creative young workforce” that has brought new ideas and new technologies to the table.

Continued robust funding will help “to markedly improve cancer care, increase cancer survivorship, spur economic growth, and maintain the United States’ position as the global leader in science and medical research,” she added.

The AACR report specifically calls on Congress to:

• Appropriate at least $51.3 billion in fiscal year 2025 for the base budget of the NIH and at least $7.934 billion for the NCI.
• Provide $3.6 billion in dedicated funding for Cancer Moonshot activities through fiscal year 2026 in addition to other funding, consistent with the President’s fiscal year 2025 budget.
• Appropriate at least $472.4 million in fiscal year 2025 for the CDC’s Division of Cancer Prevention to support comprehensive cancer control, central cancer registries, and screening and awareness programs for specific cancers.
• Allocate $55 million in funding for the Oncology Center of Excellence at FDA in fiscal year 2025 to provide regulators with the staff and tools necessary to conduct expedited review of cancer-related medical products.

By working together with Congress and other stakeholders, “we will be able to accelerate the pace of progress and make major strides toward the lifesaving goal of preventing and curing all cancers at the earliest possible time,” Dr. Foti said. “I believe if we do that ... one day we will win this war on cancer.”

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

Despite the “remarkable progress” in cancer research and care, cancer remains “an ongoing public health challenge,” which requires significant attention and funding, according to the Cancer Progress Report 2024 from the American Association for Cancer Research (AACR).

The AACR’s 216-page report — an annual endeavor now in its 14th year — focused on the “tremendous” strides made in cancer care, prevention, and early detection and highlighted areas where more research and attention are warranted. 

One key area is funding. For the first time since 2016, federal funding for the National Institutes of Health (NIH) and National Cancer Institute (NCI) decreased in the past year. The cuts followed nearly a decade of funding increases that saw the NIH budget expand by nearly $15 billion, and that allowed for a “rapid pace and broad scope” of advances in cancer, AACR’s chief executive officer Margaret Foti, MD, PhD, said during a press briefing.

These recent cuts “threaten to curtail the medical progress seen in recent years and stymie future advancements,” said Dr. Foti, who called on Congress to commit to funding cancer research at significant and consistent levels to “maintain the momentum of progress against cancer.”
 

Inside the Report: Big Progress

Overall, advances in prevention, early detection, and treatment have helped catch more cancers earlier and save lives. 

According to the AACR report, the age-adjusted overall cancer death rate in the United States fell by 33% between 1991 and 2021, meaning about 4.1 million cancer deaths were averted. The overall cancer death rate for children and adolescents has declined by 24% in the past 2 decades. The 5-year relative survival rate for children diagnosed with cancer in the US has improved from 58% for those diagnosed in the mid-1970s to 85% for those diagnosed between 2013 and 2019.

The past fiscal year has seen many new approvals for cancer drugs, diagnostics, and screening tests. From July 1, 2023, to June 30, 2024, the Food and Drug Administration (FDA) approved 15 new anticancer therapeutics, as well as 15 new indications for previously approved agents, one new imaging agent, several artificial intelligence (AI) tools to improve early cancer detection and diagnosis, and two minimally invasive tests for assessing inherited cancer risk or early cancer detection, according to the report.

“Cancer diagnostics are becoming more sophisticated,” AACR president Patricia M. LoRusso, DO, PhD, said during the briefing. “New technologies, such as spatial transcriptomics, are helping us study tumors at a cellular level, and helping to unveil things that we did not initially even begin to understand or think of. AI-based approaches are beginning to transform cancer detection, diagnosis, clinical decision-making, and treatment response monitoring.” 

The report also highlights the significant progress in many childhood and adolescent/young adult cancers, Dr. LoRusso noted. These include FDA approvals for two new molecularly targeted therapeutics: tovorafenib for children with certain types of brain tumor and repotrectinib for children with a wide array of cancer types that have a specific genetic alteration known as NTRK gene fusion. It also includes an expanded approval for eflornithine to reduce the risk for relapse in children with high-risk neuroblastoma.

“Decades — decades — of basic research discoveries, have led to these clinical breakthroughs,” she stressed. “These gains against cancer are because of the rapid progress in our ability to decode the cancer genome, which has opened new and innovative avenues for drug development.”
 

The Gaps

Even with progress in cancer prevention, early detection, and treatment, cancer remains a significant issue.

“In 2024, it is estimated that more than 2 million new cases of cancer will be diagnosed in the United States. More than 611,000 people will die from the disease,” according to the report.

The 2024 report shows that incidence rates for some cancers are increasing in the United States, including vaccine-preventable cancers such as human papillomavirus (HPV)–associated oral cancers and, in young adults, cervical cancers. A recent analysis also found that overall cervical cancer incidence among women aged 30-34 years increased by 2.5% a year between 2012 and 2019.

Furthermore, despite clear evidence demonstrating that the HPV vaccine reduces cervical cancer incidence, uptake has remained poor, with only 38.6% of US children and adolescents aged 9-17 years receiving at least one dose of the vaccine in 2022.

Early-onset cancers are also increasing. Rates of breast, colorectal, and other cancers are on the rise in adults younger than 50 years, the report noted.

The report also pointed to data that 40% of all cancer cases in the United States can be attributed to preventable factors, such as smoking, excess body weight, and alcohol. However, our understanding of these risk factors has improved. Excessive levels of alcohol consumption have, for instance, been shown to increase the risk for six different types of cancer: certain types of head and neck cancer, esophageal squamous cell carcinoma, and breast, colorectal, liver, and stomach cancers.

Financial toxicity remains prevalent as well.

The report explains that financial hardship following a cancer diagnosis is widespread, and the effects can last for years. In fact, more than 40% of patients can spend their entire life savings within the first 2 years of cancer treatment. Among adult survivors of childhood cancers, 20.7% had trouble paying their medical bills, 29.9% said they had been sent to debt collection for unpaid bills, 14.1% had forgone medical care, and 26.8% could not afford nutritious meals.

For young cancer survivors, the lifetime costs associated with a diagnosis of cancer are substantial, reaching an average of $259,324 per person.

On a global level, it is estimated that from 2020 to 2050, the cumulative economic burden of cancer will be $25.2 trillion.
 

The Path Forward

Despite these challenges, Dr. LoRusso said, “it is unquestionable that we are in a time of unparalleled opportunities in cancer research.

“I am excited about what the future holds for cancer research, and especially for patient care,” she said. 

However, funding commitments are needed to avoid impeding this momentum and losing a “talented and creative young workforce” that has brought new ideas and new technologies to the table.

Continued robust funding will help “to markedly improve cancer care, increase cancer survivorship, spur economic growth, and maintain the United States’ position as the global leader in science and medical research,” she added.

The AACR report specifically calls on Congress to:

• Appropriate at least $51.3 billion in fiscal year 2025 for the base budget of the NIH and at least $7.934 billion for the NCI.
• Provide $3.6 billion in dedicated funding for Cancer Moonshot activities through fiscal year 2026 in addition to other funding, consistent with the President’s fiscal year 2025 budget.
• Appropriate at least $472.4 million in fiscal year 2025 for the CDC’s Division of Cancer Prevention to support comprehensive cancer control, central cancer registries, and screening and awareness programs for specific cancers.
• Allocate $55 million in funding for the Oncology Center of Excellence at FDA in fiscal year 2025 to provide regulators with the staff and tools necessary to conduct expedited review of cancer-related medical products.

By working together with Congress and other stakeholders, “we will be able to accelerate the pace of progress and make major strides toward the lifesaving goal of preventing and curing all cancers at the earliest possible time,” Dr. Foti said. “I believe if we do that ... one day we will win this war on cancer.”

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

Despite the “remarkable progress” in cancer research and care, cancer remains “an ongoing public health challenge,” which requires significant attention and funding, according to the Cancer Progress Report 2024 from the American Association for Cancer Research (AACR).

The AACR’s 216-page report — an annual endeavor now in its 14th year — focused on the “tremendous” strides made in cancer care, prevention, and early detection and highlighted areas where more research and attention are warranted. 

One key area is funding. For the first time since 2016, federal funding for the National Institutes of Health (NIH) and National Cancer Institute (NCI) decreased in the past year. The cuts followed nearly a decade of funding increases that saw the NIH budget expand by nearly $15 billion, and that allowed for a “rapid pace and broad scope” of advances in cancer, AACR’s chief executive officer Margaret Foti, MD, PhD, said during a press briefing.

These recent cuts “threaten to curtail the medical progress seen in recent years and stymie future advancements,” said Dr. Foti, who called on Congress to commit to funding cancer research at significant and consistent levels to “maintain the momentum of progress against cancer.”
 

Inside the Report: Big Progress

Overall, advances in prevention, early detection, and treatment have helped catch more cancers earlier and save lives. 

According to the AACR report, the age-adjusted overall cancer death rate in the United States fell by 33% between 1991 and 2021, meaning about 4.1 million cancer deaths were averted. The overall cancer death rate for children and adolescents has declined by 24% in the past 2 decades. The 5-year relative survival rate for children diagnosed with cancer in the US has improved from 58% for those diagnosed in the mid-1970s to 85% for those diagnosed between 2013 and 2019.

The past fiscal year has seen many new approvals for cancer drugs, diagnostics, and screening tests. From July 1, 2023, to June 30, 2024, the Food and Drug Administration (FDA) approved 15 new anticancer therapeutics, as well as 15 new indications for previously approved agents, one new imaging agent, several artificial intelligence (AI) tools to improve early cancer detection and diagnosis, and two minimally invasive tests for assessing inherited cancer risk or early cancer detection, according to the report.

“Cancer diagnostics are becoming more sophisticated,” AACR president Patricia M. LoRusso, DO, PhD, said during the briefing. “New technologies, such as spatial transcriptomics, are helping us study tumors at a cellular level, and helping to unveil things that we did not initially even begin to understand or think of. AI-based approaches are beginning to transform cancer detection, diagnosis, clinical decision-making, and treatment response monitoring.” 

The report also highlights the significant progress in many childhood and adolescent/young adult cancers, Dr. LoRusso noted. These include FDA approvals for two new molecularly targeted therapeutics: tovorafenib for children with certain types of brain tumor and repotrectinib for children with a wide array of cancer types that have a specific genetic alteration known as NTRK gene fusion. It also includes an expanded approval for eflornithine to reduce the risk for relapse in children with high-risk neuroblastoma.

“Decades — decades — of basic research discoveries, have led to these clinical breakthroughs,” she stressed. “These gains against cancer are because of the rapid progress in our ability to decode the cancer genome, which has opened new and innovative avenues for drug development.”
 

The Gaps

Even with progress in cancer prevention, early detection, and treatment, cancer remains a significant issue.

“In 2024, it is estimated that more than 2 million new cases of cancer will be diagnosed in the United States. More than 611,000 people will die from the disease,” according to the report.

The 2024 report shows that incidence rates for some cancers are increasing in the United States, including vaccine-preventable cancers such as human papillomavirus (HPV)–associated oral cancers and, in young adults, cervical cancers. A recent analysis also found that overall cervical cancer incidence among women aged 30-34 years increased by 2.5% a year between 2012 and 2019.

Furthermore, despite clear evidence demonstrating that the HPV vaccine reduces cervical cancer incidence, uptake has remained poor, with only 38.6% of US children and adolescents aged 9-17 years receiving at least one dose of the vaccine in 2022.

Early-onset cancers are also increasing. Rates of breast, colorectal, and other cancers are on the rise in adults younger than 50 years, the report noted.

The report also pointed to data that 40% of all cancer cases in the United States can be attributed to preventable factors, such as smoking, excess body weight, and alcohol. However, our understanding of these risk factors has improved. Excessive levels of alcohol consumption have, for instance, been shown to increase the risk for six different types of cancer: certain types of head and neck cancer, esophageal squamous cell carcinoma, and breast, colorectal, liver, and stomach cancers.

Financial toxicity remains prevalent as well.

The report explains that financial hardship following a cancer diagnosis is widespread, and the effects can last for years. In fact, more than 40% of patients can spend their entire life savings within the first 2 years of cancer treatment. Among adult survivors of childhood cancers, 20.7% had trouble paying their medical bills, 29.9% said they had been sent to debt collection for unpaid bills, 14.1% had forgone medical care, and 26.8% could not afford nutritious meals.

For young cancer survivors, the lifetime costs associated with a diagnosis of cancer are substantial, reaching an average of $259,324 per person.

On a global level, it is estimated that from 2020 to 2050, the cumulative economic burden of cancer will be $25.2 trillion.
 

The Path Forward

Despite these challenges, Dr. LoRusso said, “it is unquestionable that we are in a time of unparalleled opportunities in cancer research.

“I am excited about what the future holds for cancer research, and especially for patient care,” she said. 

However, funding commitments are needed to avoid impeding this momentum and losing a “talented and creative young workforce” that has brought new ideas and new technologies to the table.

Continued robust funding will help “to markedly improve cancer care, increase cancer survivorship, spur economic growth, and maintain the United States’ position as the global leader in science and medical research,” she added.

The AACR report specifically calls on Congress to:

• Appropriate at least $51.3 billion in fiscal year 2025 for the base budget of the NIH and at least $7.934 billion for the NCI.
• Provide $3.6 billion in dedicated funding for Cancer Moonshot activities through fiscal year 2026 in addition to other funding, consistent with the President’s fiscal year 2025 budget.
• Appropriate at least $472.4 million in fiscal year 2025 for the CDC’s Division of Cancer Prevention to support comprehensive cancer control, central cancer registries, and screening and awareness programs for specific cancers.
• Allocate $55 million in funding for the Oncology Center of Excellence at FDA in fiscal year 2025 to provide regulators with the staff and tools necessary to conduct expedited review of cancer-related medical products.

By working together with Congress and other stakeholders, “we will be able to accelerate the pace of progress and make major strides toward the lifesaving goal of preventing and curing all cancers at the earliest possible time,” Dr. Foti said. “I believe if we do that ... one day we will win this war on cancer.”

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

The Food and Drug Administration (FDA) has approved atezolizumab and hyaluronidase-tqjs (Tecentriq Hybreza, Genentech) as a subcutaneous injection in adults, covering all approved indications of the intravenous (IV) formulation.

Approved indications include non–small cell lung cancer (NSCLC), SCLC, hepatocellular carcinoma, melanoma, and alveolar soft part sarcoma. Specific indications are available with the full prescribing information at Drugs@FDA.

This is the first programmed death–ligand 1 inhibitor to gain approval for subcutaneous administration.

“This approval represents a significant option to improve the patient experience,” Ann Fish-Steagall, RN, Senior Vice President of Patient Services at the LUNGevity Foundation stated in a Genentech press release.

Subcutaneous atezolizumab and hyaluronidase-tqjs was evaluated in the open-label, randomized IMscin001 trial of 371 adult patients with locally advanced or metastatic NSCLC who were not previously exposed to cancer immunotherapy and who had disease progression following treatment with platinum-based chemotherapy. Patients were randomized 2:1 to receive subcutaneous or IV administration until disease progression or unacceptable toxicity.

Atezolizumab exposure, the primary outcome measure of the study, met the lower limit of geometric mean ratio above the prespecified threshold of 0.8 (cycle 1C trough, 1.05; area under the curve for days 0-21, 0.87).

No notable differences were observed in overall response rate, progression-free survival, or overall survival between the two formulations, according to the FDA approval notice.

The confirmed overall response rate was 9% in the subcutaneous arm and 8% intravenous arm.

Adverse events of any grade occurring in at least 10% of patients were fatigue, musculoskeletal pain, cough, dyspnea, and decreased appetite.

The recommended dose for subcutaneous injection is one 15 mL injection, which contains 1875 mg of atezolizumab and 30,000 units of hyaluronidase.

Injections should be administered in the thigh over approximately 7 minutes every 3 weeks. By contrast, IV administration generally takes 30-60 minutes.

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

The Food and Drug Administration (FDA) has approved atezolizumab and hyaluronidase-tqjs (Tecentriq Hybreza, Genentech) as a subcutaneous injection in adults, covering all approved indications of the intravenous (IV) formulation.

Approved indications include non–small cell lung cancer (NSCLC), SCLC, hepatocellular carcinoma, melanoma, and alveolar soft part sarcoma. Specific indications are available with the full prescribing information at Drugs@FDA.

This is the first programmed death–ligand 1 inhibitor to gain approval for subcutaneous administration.

“This approval represents a significant option to improve the patient experience,” Ann Fish-Steagall, RN, Senior Vice President of Patient Services at the LUNGevity Foundation stated in a Genentech press release.

Subcutaneous atezolizumab and hyaluronidase-tqjs was evaluated in the open-label, randomized IMscin001 trial of 371 adult patients with locally advanced or metastatic NSCLC who were not previously exposed to cancer immunotherapy and who had disease progression following treatment with platinum-based chemotherapy. Patients were randomized 2:1 to receive subcutaneous or IV administration until disease progression or unacceptable toxicity.

Atezolizumab exposure, the primary outcome measure of the study, met the lower limit of geometric mean ratio above the prespecified threshold of 0.8 (cycle 1C trough, 1.05; area under the curve for days 0-21, 0.87).

No notable differences were observed in overall response rate, progression-free survival, or overall survival between the two formulations, according to the FDA approval notice.

The confirmed overall response rate was 9% in the subcutaneous arm and 8% intravenous arm.

Adverse events of any grade occurring in at least 10% of patients were fatigue, musculoskeletal pain, cough, dyspnea, and decreased appetite.

The recommended dose for subcutaneous injection is one 15 mL injection, which contains 1875 mg of atezolizumab and 30,000 units of hyaluronidase.

Injections should be administered in the thigh over approximately 7 minutes every 3 weeks. By contrast, IV administration generally takes 30-60 minutes.

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

The Food and Drug Administration (FDA) has approved atezolizumab and hyaluronidase-tqjs (Tecentriq Hybreza, Genentech) as a subcutaneous injection in adults, covering all approved indications of the intravenous (IV) formulation.

Approved indications include non–small cell lung cancer (NSCLC), SCLC, hepatocellular carcinoma, melanoma, and alveolar soft part sarcoma. Specific indications are available with the full prescribing information at Drugs@FDA.

This is the first programmed death–ligand 1 inhibitor to gain approval for subcutaneous administration.

“This approval represents a significant option to improve the patient experience,” Ann Fish-Steagall, RN, Senior Vice President of Patient Services at the LUNGevity Foundation stated in a Genentech press release.

Subcutaneous atezolizumab and hyaluronidase-tqjs was evaluated in the open-label, randomized IMscin001 trial of 371 adult patients with locally advanced or metastatic NSCLC who were not previously exposed to cancer immunotherapy and who had disease progression following treatment with platinum-based chemotherapy. Patients were randomized 2:1 to receive subcutaneous or IV administration until disease progression or unacceptable toxicity.

Atezolizumab exposure, the primary outcome measure of the study, met the lower limit of geometric mean ratio above the prespecified threshold of 0.8 (cycle 1C trough, 1.05; area under the curve for days 0-21, 0.87).

No notable differences were observed in overall response rate, progression-free survival, or overall survival between the two formulations, according to the FDA approval notice.

The confirmed overall response rate was 9% in the subcutaneous arm and 8% intravenous arm.

Adverse events of any grade occurring in at least 10% of patients were fatigue, musculoskeletal pain, cough, dyspnea, and decreased appetite.

The recommended dose for subcutaneous injection is one 15 mL injection, which contains 1875 mg of atezolizumab and 30,000 units of hyaluronidase.

Injections should be administered in the thigh over approximately 7 minutes every 3 weeks. By contrast, IV administration generally takes 30-60 minutes.

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

Chimeric antigen receptor (CAR) T-cell therapy has emerged as a game changer for the treatment of multiple myeloma (MM), but questions remain as to how — and when — the immunotherapy will best be used for patients who experience disease relapse.

Will CAR T be best used in early relapse? Experts debated this question at the annual meeting of the Society of Hematologic Oncology. Based on attendees’ votes, at least one side of the debate emerged victorious.

Krina Patel, MD, an associate professor at the University of Texas MD Anderson Cancer Center, Houston, came out swinging with earnest support for using CAR T in early relapse. Saad Z. Usmani, of Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York City, and Cornell University, Ithaca, New York, argued in favor of being “a little more circumspect.”
 

Dr. Patel: Yes, Earlier Is Better

A pre-debate audience poll leaned Dr. Patel’s way, with about 59% of 73 votes favoring CAR T in early relapse, 33% favoring reserving CAR T for patients who relapse after three or more lines of therapy, and 8% undecided.

“CAR T is not just a drug — it’s an actual therapy that takes a lot of logistics, as well as bridging therapy and all these other things to take into account,” said Dr. Patel. “And again, when I can go earlier, I have control over some of this.”

Furthermore, randomized phase 3 data from the KarMMA-3 study and the CARTITUDE-4 study showed that multiple standard therapies were not as good as CAR T in the early relapse setting, she said, pointing to the respective hazard ratios for disease progression or death with CAR T vs standard therapies of 0.49 and 0.26.

CARTITUDE-4 also suggested that manufacturing failures are more likely in later relapse — when time is already of greater essence, she said, noting that it can take an additional 3 months when restarting the process.

When it comes to toxicity, yes, it is a concern, she said.

“But we know how to decrease toxicity,” she stressed. “And again, with our second- and third-line approaches, we actually have better therapies to give for bridging.”

Quality of life is another important consideration, Dr. Patel said, noting only CAR T offers a “one-and-done” therapy that helps patients “truly feel better.”

“They’re not having to come into hospitals as often, and this is not just for months; it’s for years,” she said. “To be able to give that to somebody is huge, and again, we have objective data that show that compared to our standard of care therapies, patients do better in almost every realm of quality of life metrics.”

Dr. Patel also pointed to recent data from a retrospective study showing that for bridging therapy, less is more when disease is controlled, and in the early-line setting, more and safer options are available for reducing tumor burden.

Early CAR T is better for older or frail patients as well, she argued, noting that these patients don’t have time to wait, and a new study demonstrates that they tend to do well with CAR T in the early relapse setting.

The choice for early CAR T is clear in patients with high-risk disease, but Dr. Patel stressed that it shouldn’t be reserved for those patients, asking, “When has anything worked well for patients with high-risk disease and not [also] better for standard-risk patients?”

“And why give only 20%-25% of your patients [who actually reach fifth-line treatment] access to something that we know has really revolutionized myeloma therapy?” she said.

Many patients don’t have access, and that’s an issue, she acknowledged, adding: “But for those who do, we really should be giving it to them as soon as possible.”
 

Dr. Usmani: Reserve CAR T for Later Relapse

Not so fast, said Dr. Usmani. “All of these therapies are doing wonders for our patients, and we believe in them, but we have to be a little circumspect in looking at this data more closely and not just with emotions,” he added, noting that many options exist for patients in a first or second relapse, and new options are emerging.

There is also a “harsh reality” in terms of CAR T availability, he noted, explaining that, in 2021, about 180,000 people were living with MM, and about two thirds of those had relapsed disease. Meanwhile, fewer than 1000 CAR T products have been delivered each year for patients with relapsed MM since they were approved in this setting in the United States.

“So, it’s a pipe dream, seriously, that we will be able to utilize CAR T for all patients in early relapsed disease,” he said, adding that capacity will remain an issue because of limited resources.

The existing data, including from KarMMa-3 and CARTITUDE-4, show little potential for long-term benefit with early vs later CAR T.

“There is no plateau,” he said of the survival curves in KarMMa-3, underscoring the lack of a difference in overall survival benefit based on CAR T timing.

The CARTITUDE-4 curves “look great,” and it may be that a “small plateau emerges,” but they don’t demonstrate a benefit of earlier vs later CAR T, he said.

As Dr. Patel noted, there are few treatment options for patients with anti-CD38 monoclonal antibody and immunomodulatory drug resistance at first relapse. However, that situation will soon change, Dr. Usmani stated.

“Guess what? Belamaf is coming to the rescue!” he said of the off-the-shelf and more accessible B-cell maturation antigen-targeted antibody-drug conjugate belantamab mafodotin, which has recently been evaluated in the DREAMM 7 and DREAMM 8 trials.

DREAMM 7 demonstrated improved survival vs daratumumab, bortezomib, and dexamethasone in the relapsed/refractory MM setting when used in combination with bortezomib and dexamethasone. DREAMM 8 shows similar benefit with belantamab mafodotin, pomalidomide, and dexamethasone vs pomalidomide, bortezomib, and dexamethasone in lenalidomide-exposed patients with relapsed or refractory MM.

“Belamaf combinations in the one to three lines [of prior therapy] setting look really good,” he said, noting a particular benefit for progression-free survival and a trend toward improved overall survival.

Considering these factors, as well as the risk for cytopenias and the subsequent risk for infection in most patients who undergo CAR T-cell therapy and the known potential risk for secondary malignancies, Dr. Usmani said that he will remain “in the camp of being really careful in selecting CAR T patients for early relapse” until more is known about the risks.

“CAR T for all is not the answer. I think we have to be careful in picking CAR T patients; it’s not a zero-sum game here,” he said, stressing that “there are too many unknowns with the use of early CAR T therapy.”

“It makes sense in some, but not for everyone,” he said, emphasizing the importance of including patients in the discussion.

“The great thing is we have all these options for our patients,” he said.

Dr. Usmani persuaded at least a few colleagues: The final vote showed 42% of 124 voters supported early CAR T, compared with 52% who supported CAR T after three or more lines of therapy and 6% who remained undecided.

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

Chimeric antigen receptor (CAR) T-cell therapy has emerged as a game changer for the treatment of multiple myeloma (MM), but questions remain as to how — and when — the immunotherapy will best be used for patients who experience disease relapse.

Will CAR T be best used in early relapse? Experts debated this question at the annual meeting of the Society of Hematologic Oncology. Based on attendees’ votes, at least one side of the debate emerged victorious.

Krina Patel, MD, an associate professor at the University of Texas MD Anderson Cancer Center, Houston, came out swinging with earnest support for using CAR T in early relapse. Saad Z. Usmani, of Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York City, and Cornell University, Ithaca, New York, argued in favor of being “a little more circumspect.”
 

Dr. Patel: Yes, Earlier Is Better

A pre-debate audience poll leaned Dr. Patel’s way, with about 59% of 73 votes favoring CAR T in early relapse, 33% favoring reserving CAR T for patients who relapse after three or more lines of therapy, and 8% undecided.

“CAR T is not just a drug — it’s an actual therapy that takes a lot of logistics, as well as bridging therapy and all these other things to take into account,” said Dr. Patel. “And again, when I can go earlier, I have control over some of this.”

Furthermore, randomized phase 3 data from the KarMMA-3 study and the CARTITUDE-4 study showed that multiple standard therapies were not as good as CAR T in the early relapse setting, she said, pointing to the respective hazard ratios for disease progression or death with CAR T vs standard therapies of 0.49 and 0.26.

CARTITUDE-4 also suggested that manufacturing failures are more likely in later relapse — when time is already of greater essence, she said, noting that it can take an additional 3 months when restarting the process.

When it comes to toxicity, yes, it is a concern, she said.

“But we know how to decrease toxicity,” she stressed. “And again, with our second- and third-line approaches, we actually have better therapies to give for bridging.”

Quality of life is another important consideration, Dr. Patel said, noting only CAR T offers a “one-and-done” therapy that helps patients “truly feel better.”

“They’re not having to come into hospitals as often, and this is not just for months; it’s for years,” she said. “To be able to give that to somebody is huge, and again, we have objective data that show that compared to our standard of care therapies, patients do better in almost every realm of quality of life metrics.”

Dr. Patel also pointed to recent data from a retrospective study showing that for bridging therapy, less is more when disease is controlled, and in the early-line setting, more and safer options are available for reducing tumor burden.

Early CAR T is better for older or frail patients as well, she argued, noting that these patients don’t have time to wait, and a new study demonstrates that they tend to do well with CAR T in the early relapse setting.

The choice for early CAR T is clear in patients with high-risk disease, but Dr. Patel stressed that it shouldn’t be reserved for those patients, asking, “When has anything worked well for patients with high-risk disease and not [also] better for standard-risk patients?”

“And why give only 20%-25% of your patients [who actually reach fifth-line treatment] access to something that we know has really revolutionized myeloma therapy?” she said.

Many patients don’t have access, and that’s an issue, she acknowledged, adding: “But for those who do, we really should be giving it to them as soon as possible.”
 

Dr. Usmani: Reserve CAR T for Later Relapse

Not so fast, said Dr. Usmani. “All of these therapies are doing wonders for our patients, and we believe in them, but we have to be a little circumspect in looking at this data more closely and not just with emotions,” he added, noting that many options exist for patients in a first or second relapse, and new options are emerging.

There is also a “harsh reality” in terms of CAR T availability, he noted, explaining that, in 2021, about 180,000 people were living with MM, and about two thirds of those had relapsed disease. Meanwhile, fewer than 1000 CAR T products have been delivered each year for patients with relapsed MM since they were approved in this setting in the United States.

“So, it’s a pipe dream, seriously, that we will be able to utilize CAR T for all patients in early relapsed disease,” he said, adding that capacity will remain an issue because of limited resources.

The existing data, including from KarMMa-3 and CARTITUDE-4, show little potential for long-term benefit with early vs later CAR T.

“There is no plateau,” he said of the survival curves in KarMMa-3, underscoring the lack of a difference in overall survival benefit based on CAR T timing.

The CARTITUDE-4 curves “look great,” and it may be that a “small plateau emerges,” but they don’t demonstrate a benefit of earlier vs later CAR T, he said.

As Dr. Patel noted, there are few treatment options for patients with anti-CD38 monoclonal antibody and immunomodulatory drug resistance at first relapse. However, that situation will soon change, Dr. Usmani stated.

“Guess what? Belamaf is coming to the rescue!” he said of the off-the-shelf and more accessible B-cell maturation antigen-targeted antibody-drug conjugate belantamab mafodotin, which has recently been evaluated in the DREAMM 7 and DREAMM 8 trials.

DREAMM 7 demonstrated improved survival vs daratumumab, bortezomib, and dexamethasone in the relapsed/refractory MM setting when used in combination with bortezomib and dexamethasone. DREAMM 8 shows similar benefit with belantamab mafodotin, pomalidomide, and dexamethasone vs pomalidomide, bortezomib, and dexamethasone in lenalidomide-exposed patients with relapsed or refractory MM.

“Belamaf combinations in the one to three lines [of prior therapy] setting look really good,” he said, noting a particular benefit for progression-free survival and a trend toward improved overall survival.

Considering these factors, as well as the risk for cytopenias and the subsequent risk for infection in most patients who undergo CAR T-cell therapy and the known potential risk for secondary malignancies, Dr. Usmani said that he will remain “in the camp of being really careful in selecting CAR T patients for early relapse” until more is known about the risks.

“CAR T for all is not the answer. I think we have to be careful in picking CAR T patients; it’s not a zero-sum game here,” he said, stressing that “there are too many unknowns with the use of early CAR T therapy.”

“It makes sense in some, but not for everyone,” he said, emphasizing the importance of including patients in the discussion.

“The great thing is we have all these options for our patients,” he said.

Dr. Usmani persuaded at least a few colleagues: The final vote showed 42% of 124 voters supported early CAR T, compared with 52% who supported CAR T after three or more lines of therapy and 6% who remained undecided.

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

Chimeric antigen receptor (CAR) T-cell therapy has emerged as a game changer for the treatment of multiple myeloma (MM), but questions remain as to how — and when — the immunotherapy will best be used for patients who experience disease relapse.

Will CAR T be best used in early relapse? Experts debated this question at the annual meeting of the Society of Hematologic Oncology. Based on attendees’ votes, at least one side of the debate emerged victorious.

Krina Patel, MD, an associate professor at the University of Texas MD Anderson Cancer Center, Houston, came out swinging with earnest support for using CAR T in early relapse. Saad Z. Usmani, of Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York City, and Cornell University, Ithaca, New York, argued in favor of being “a little more circumspect.”
 

Dr. Patel: Yes, Earlier Is Better

A pre-debate audience poll leaned Dr. Patel’s way, with about 59% of 73 votes favoring CAR T in early relapse, 33% favoring reserving CAR T for patients who relapse after three or more lines of therapy, and 8% undecided.

“CAR T is not just a drug — it’s an actual therapy that takes a lot of logistics, as well as bridging therapy and all these other things to take into account,” said Dr. Patel. “And again, when I can go earlier, I have control over some of this.”

Furthermore, randomized phase 3 data from the KarMMA-3 study and the CARTITUDE-4 study showed that multiple standard therapies were not as good as CAR T in the early relapse setting, she said, pointing to the respective hazard ratios for disease progression or death with CAR T vs standard therapies of 0.49 and 0.26.

CARTITUDE-4 also suggested that manufacturing failures are more likely in later relapse — when time is already of greater essence, she said, noting that it can take an additional 3 months when restarting the process.

When it comes to toxicity, yes, it is a concern, she said.

“But we know how to decrease toxicity,” she stressed. “And again, with our second- and third-line approaches, we actually have better therapies to give for bridging.”

Quality of life is another important consideration, Dr. Patel said, noting only CAR T offers a “one-and-done” therapy that helps patients “truly feel better.”

“They’re not having to come into hospitals as often, and this is not just for months; it’s for years,” she said. “To be able to give that to somebody is huge, and again, we have objective data that show that compared to our standard of care therapies, patients do better in almost every realm of quality of life metrics.”

Dr. Patel also pointed to recent data from a retrospective study showing that for bridging therapy, less is more when disease is controlled, and in the early-line setting, more and safer options are available for reducing tumor burden.

Early CAR T is better for older or frail patients as well, she argued, noting that these patients don’t have time to wait, and a new study demonstrates that they tend to do well with CAR T in the early relapse setting.

The choice for early CAR T is clear in patients with high-risk disease, but Dr. Patel stressed that it shouldn’t be reserved for those patients, asking, “When has anything worked well for patients with high-risk disease and not [also] better for standard-risk patients?”

“And why give only 20%-25% of your patients [who actually reach fifth-line treatment] access to something that we know has really revolutionized myeloma therapy?” she said.

Many patients don’t have access, and that’s an issue, she acknowledged, adding: “But for those who do, we really should be giving it to them as soon as possible.”
 

Dr. Usmani: Reserve CAR T for Later Relapse

Not so fast, said Dr. Usmani. “All of these therapies are doing wonders for our patients, and we believe in them, but we have to be a little circumspect in looking at this data more closely and not just with emotions,” he added, noting that many options exist for patients in a first or second relapse, and new options are emerging.

There is also a “harsh reality” in terms of CAR T availability, he noted, explaining that, in 2021, about 180,000 people were living with MM, and about two thirds of those had relapsed disease. Meanwhile, fewer than 1000 CAR T products have been delivered each year for patients with relapsed MM since they were approved in this setting in the United States.

“So, it’s a pipe dream, seriously, that we will be able to utilize CAR T for all patients in early relapsed disease,” he said, adding that capacity will remain an issue because of limited resources.

The existing data, including from KarMMa-3 and CARTITUDE-4, show little potential for long-term benefit with early vs later CAR T.

“There is no plateau,” he said of the survival curves in KarMMa-3, underscoring the lack of a difference in overall survival benefit based on CAR T timing.

The CARTITUDE-4 curves “look great,” and it may be that a “small plateau emerges,” but they don’t demonstrate a benefit of earlier vs later CAR T, he said.

As Dr. Patel noted, there are few treatment options for patients with anti-CD38 monoclonal antibody and immunomodulatory drug resistance at first relapse. However, that situation will soon change, Dr. Usmani stated.

“Guess what? Belamaf is coming to the rescue!” he said of the off-the-shelf and more accessible B-cell maturation antigen-targeted antibody-drug conjugate belantamab mafodotin, which has recently been evaluated in the DREAMM 7 and DREAMM 8 trials.

DREAMM 7 demonstrated improved survival vs daratumumab, bortezomib, and dexamethasone in the relapsed/refractory MM setting when used in combination with bortezomib and dexamethasone. DREAMM 8 shows similar benefit with belantamab mafodotin, pomalidomide, and dexamethasone vs pomalidomide, bortezomib, and dexamethasone in lenalidomide-exposed patients with relapsed or refractory MM.

“Belamaf combinations in the one to three lines [of prior therapy] setting look really good,” he said, noting a particular benefit for progression-free survival and a trend toward improved overall survival.

Considering these factors, as well as the risk for cytopenias and the subsequent risk for infection in most patients who undergo CAR T-cell therapy and the known potential risk for secondary malignancies, Dr. Usmani said that he will remain “in the camp of being really careful in selecting CAR T patients for early relapse” until more is known about the risks.

“CAR T for all is not the answer. I think we have to be careful in picking CAR T patients; it’s not a zero-sum game here,” he said, stressing that “there are too many unknowns with the use of early CAR T therapy.”

“It makes sense in some, but not for everyone,” he said, emphasizing the importance of including patients in the discussion.

“The great thing is we have all these options for our patients,” he said.

Dr. Usmani persuaded at least a few colleagues: The final vote showed 42% of 124 voters supported early CAR T, compared with 52% who supported CAR T after three or more lines of therapy and 6% who remained undecided.

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

When it comes to selecting a cost-effective, first-line tyrosine kinase inhibitor (TKI) for the treatment of chronic myeloid leukemia (CML), consider the treatment goal.

For survival, generic imatinib remains the gold standard, Elias Jabbour, MD, said during a session at the annual meeting of the Society of Hematologic Oncology in Houston.

For treatment-free remission, generic dasatinib or another generic second-generation TKI is needed, but not yet available in the United States, so generic imatinib is the best current choice, said Dr. Jabbour, a professor of medicine in the Department of Leukemia at the University of Texas MD Anderson Cancer Center, Houston.

Prior to the availability of generic imatinib, that wasn’t the case, he noted, explaining that second-generation TKIs met the cost-efficacy criteria, but now — at about $35 per month or about $400 per year — imatinib is far less expensive than the approximately $250,000 per year that brand-name second- and third-generation TKIs can currently cost.

To have treatment value, any new TKI should cost $40,000-$50,000 per quality-adjusted life-year, which is defined as the quality and duration of life after a novel TKI vs with the existing standard of care, Dr. Jabbour said.

And to qualify as a frontline therapy for CML, any new TKI should show efficacy superior to second-generation TKIs, in addition to meeting the cost-effectiveness criteria.

“It is hard to show survival benefit anymore, but we need to improve on the rate of durable deep molecular remission,” he said.

An equivalent or better long-term safety profile over at least 7-8 years is also needed.

Based on the current literature, none of the TKIs currently being evaluated has met that standard, although some trials are ongoing.

In a recent editorial, Dr. Jabbour and colleagues outlined treatment recommendations based on the currently available data. They suggested using lower-than-approved doses of TKIs in both frontline and later therapies to reduce toxicity, improve treatment compliance, and reduce costs.

They also suggested that the absence of an early molecular response might not warrant changing the TKI, especially when a second-generation TKI was used first line. 

When treatment-free remission is not a therapeutic goal or is unlikely, changing the TKI to improve the depth of molecular response, which has been shown to improve the likelihood of treatment-free remission, could do more harm than good, they argued. 

Instead, consider reducing the dose to manage reversible side effects, they suggested, noting that generic imatinib, and eventually generic dasatinib and possibly other generic second-generation TKIs, will likely offer 90% of patients with CML an effective, safe, and affordable treatment that normalizes life expectancy and leads to treatment-free remission in 30%-50% of patients over time.

Dr. Jabbour disclosed ties with AbbVie, Almoosa Specialist Hospital, Amgen, Ascentage Pharma, Biologix FZ, Hikma Pharmaceuticals, Kite, Takeda, and Terns.

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

When it comes to selecting a cost-effective, first-line tyrosine kinase inhibitor (TKI) for the treatment of chronic myeloid leukemia (CML), consider the treatment goal.

For survival, generic imatinib remains the gold standard, Elias Jabbour, MD, said during a session at the annual meeting of the Society of Hematologic Oncology in Houston.

For treatment-free remission, generic dasatinib or another generic second-generation TKI is needed, but not yet available in the United States, so generic imatinib is the best current choice, said Dr. Jabbour, a professor of medicine in the Department of Leukemia at the University of Texas MD Anderson Cancer Center, Houston.

Prior to the availability of generic imatinib, that wasn’t the case, he noted, explaining that second-generation TKIs met the cost-efficacy criteria, but now — at about $35 per month or about $400 per year — imatinib is far less expensive than the approximately $250,000 per year that brand-name second- and third-generation TKIs can currently cost.

To have treatment value, any new TKI should cost $40,000-$50,000 per quality-adjusted life-year, which is defined as the quality and duration of life after a novel TKI vs with the existing standard of care, Dr. Jabbour said.

And to qualify as a frontline therapy for CML, any new TKI should show efficacy superior to second-generation TKIs, in addition to meeting the cost-effectiveness criteria.

“It is hard to show survival benefit anymore, but we need to improve on the rate of durable deep molecular remission,” he said.

An equivalent or better long-term safety profile over at least 7-8 years is also needed.

Based on the current literature, none of the TKIs currently being evaluated has met that standard, although some trials are ongoing.

In a recent editorial, Dr. Jabbour and colleagues outlined treatment recommendations based on the currently available data. They suggested using lower-than-approved doses of TKIs in both frontline and later therapies to reduce toxicity, improve treatment compliance, and reduce costs.

They also suggested that the absence of an early molecular response might not warrant changing the TKI, especially when a second-generation TKI was used first line. 

When treatment-free remission is not a therapeutic goal or is unlikely, changing the TKI to improve the depth of molecular response, which has been shown to improve the likelihood of treatment-free remission, could do more harm than good, they argued. 

Instead, consider reducing the dose to manage reversible side effects, they suggested, noting that generic imatinib, and eventually generic dasatinib and possibly other generic second-generation TKIs, will likely offer 90% of patients with CML an effective, safe, and affordable treatment that normalizes life expectancy and leads to treatment-free remission in 30%-50% of patients over time.

Dr. Jabbour disclosed ties with AbbVie, Almoosa Specialist Hospital, Amgen, Ascentage Pharma, Biologix FZ, Hikma Pharmaceuticals, Kite, Takeda, and Terns.

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

When it comes to selecting a cost-effective, first-line tyrosine kinase inhibitor (TKI) for the treatment of chronic myeloid leukemia (CML), consider the treatment goal.

For survival, generic imatinib remains the gold standard, Elias Jabbour, MD, said during a session at the annual meeting of the Society of Hematologic Oncology in Houston.

For treatment-free remission, generic dasatinib or another generic second-generation TKI is needed, but not yet available in the United States, so generic imatinib is the best current choice, said Dr. Jabbour, a professor of medicine in the Department of Leukemia at the University of Texas MD Anderson Cancer Center, Houston.

Prior to the availability of generic imatinib, that wasn’t the case, he noted, explaining that second-generation TKIs met the cost-efficacy criteria, but now — at about $35 per month or about $400 per year — imatinib is far less expensive than the approximately $250,000 per year that brand-name second- and third-generation TKIs can currently cost.

To have treatment value, any new TKI should cost $40,000-$50,000 per quality-adjusted life-year, which is defined as the quality and duration of life after a novel TKI vs with the existing standard of care, Dr. Jabbour said.

And to qualify as a frontline therapy for CML, any new TKI should show efficacy superior to second-generation TKIs, in addition to meeting the cost-effectiveness criteria.

“It is hard to show survival benefit anymore, but we need to improve on the rate of durable deep molecular remission,” he said.

An equivalent or better long-term safety profile over at least 7-8 years is also needed.

Based on the current literature, none of the TKIs currently being evaluated has met that standard, although some trials are ongoing.

In a recent editorial, Dr. Jabbour and colleagues outlined treatment recommendations based on the currently available data. They suggested using lower-than-approved doses of TKIs in both frontline and later therapies to reduce toxicity, improve treatment compliance, and reduce costs.

They also suggested that the absence of an early molecular response might not warrant changing the TKI, especially when a second-generation TKI was used first line. 

When treatment-free remission is not a therapeutic goal or is unlikely, changing the TKI to improve the depth of molecular response, which has been shown to improve the likelihood of treatment-free remission, could do more harm than good, they argued. 

Instead, consider reducing the dose to manage reversible side effects, they suggested, noting that generic imatinib, and eventually generic dasatinib and possibly other generic second-generation TKIs, will likely offer 90% of patients with CML an effective, safe, and affordable treatment that normalizes life expectancy and leads to treatment-free remission in 30%-50% of patients over time.

Dr. Jabbour disclosed ties with AbbVie, Almoosa Specialist Hospital, Amgen, Ascentage Pharma, Biologix FZ, Hikma Pharmaceuticals, Kite, Takeda, and Terns.

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