TBD Meeting (3035-24)

Advances in breast cancer detection and treatment over the past decades have led to an increase in the number of women diagnosed at earlier stages and successfully treated, ushering in a new era of survivorship.

According to the American Cancer Society, there are currently roughly four million breast cancer survivors in the United States, including those still receiving treatment. The mortality rates for women with breast cancer have been decreasing since 1989, with an overall decline of 42% through 2021.

As the population of breast cancer survivors continues to grow, developing and delivering comprehensive survivorship care is crucial, Thelma Brown told attendees at the American Society of Clinical Oncology (ASCO) 2024 annual meeting. Ms. Brown’s talk was part of an educational session focused on addressing issues among early breast cancer survivors, evolving practices in breast cancer surveillance, and mitigating recurrence risk.

The challenges following breast cancer diagnosis and treatment can be both visible and invisible, said Ms. Brown, a patient advocate and member of the Breast Cancer Working Group at the University of Alabama at Birmingham.

Up to 90% of early breast cancer survivors experience long-term effects from treatment, which often include fatigue, loss of mobility, chronic pain, peripheral neuropathy, lymphedema, and infertility.

Survivors face an elevated risk for depression, anxiety, and fear of recurrence. “Fear of recurrence is a big issue, and it’s almost universal,” she noted.

Cancer treatment is also costly, leading to financial toxicity for many patients, which also “affects adherence to treatment and overall family well-being,” Ms. Brown explained. Survivors may struggle to access financial assistance due to complex eligibility requirements and a lack of awareness about available resources. 

There is a need for holistic and coordinated survivorship care that includes management of long-term effects and surveillance for recurrence to help breast cancer survivors to transition from merely surviving to thriving, said Ms. Brown.
 

Surveilling and Mitigating Recurrence

Surveillance in patients with breast cancer post treatment remains a debated area, particularly when it comes to detecting distant recurrences, David Cescon, MD, PhD, with Princess Margaret Cancer Center, University Health Network, Toronto, said in his talk.

While breast imaging standards are well established, systemic surveillance through imaging and laboratory tests for asymptomatic patients lacks consensus and uniform guidelines, he explained.

Several clinical trials conducted from the late 1980s to the early 2000s showed no survival benefit from intensive surveillance strategies, including imaging and laboratory tests, compared to routine clinical follow-up. Some studies even demonstrated a trend toward harm, given the number of false positives.

These studies formed the basis for guidelines that discourage surveillance among asymptomatic survivors. Currently, no major guideline organization — the National Comprehensive Cancer Network, ASCO, and the European Society for Medical Oncology — recommends routine (nonbreast) radiologic surveillance or laboratory tests for detecting asymptomatic distant breast cancer recurrence, Dr. Cescon said.

Yet, that may change in the coming years, he told attendees.

Ongoing prospective studies will hopefully generate high-quality evidence on the effectiveness of modern surveillance techniques, particularly detection of circulating tumor DNA (ctDNA) and its effect on survival and quality of life, said Dr. Cescon.

These liquid biopsy assays have shown promise in identifying minimal residual disease before radiographic recurrence, he explained. Retrospective studies suggest high prognostic value, with nearly all patients with detectable ctDNA post therapy experiencing recurrence. 

He cautioned, however, that while sensitive ctDNA tests exist and have clinical validity in identifying minimal residual disease, “their clinical utility has not yet been demonstrated,” Dr. Cescon said, adding that any surveillance strategy must consider the psychological effect of frequent testing and the potential for false positives or negatives.

The ultimate goal is preventing disease recurrence, said Neil M. Iyengar, MD, with Memorial Sloan Kettering Cancer Center in New York, in his talk on mitigating recurrence risk. 

Lifestyle modifications are an important targeted intervention for patients entering the survivorship phase, with a “robust level of evidence” supporting their use to mitigate adverse effects associated with cancer therapy and improve quality of life, he told attendees. Most notably, smoking cessation, healthy dietary patterns, physical activity, and reduced alcohol have been associated with improvements in breast cancer outcomes.

Going forward, it will be important to “understand the antitumor potential of lifestyle modification and how we can wield this type of intervention as a precision tool to potentially enhance the effects of cancer therapy and potentially cancer biology,” said Dr. Iyengar.

Ms. Brown disclosed relationships with AstraZeneca. Dr. Cescon disclosed relationships with AstraZeneca, Gilead Sciences, Daiichi Sankyo Europe GmbH, Eisai, GlaxoSmithKline, and other companies. Dr. Iyengar disclosed relationships with Curio Science, DAVA Oncology, Novartis, Pfizer, and others.

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

Advances in breast cancer detection and treatment over the past decades have led to an increase in the number of women diagnosed at earlier stages and successfully treated, ushering in a new era of survivorship.

According to the American Cancer Society, there are currently roughly four million breast cancer survivors in the United States, including those still receiving treatment. The mortality rates for women with breast cancer have been decreasing since 1989, with an overall decline of 42% through 2021.

As the population of breast cancer survivors continues to grow, developing and delivering comprehensive survivorship care is crucial, Thelma Brown told attendees at the American Society of Clinical Oncology (ASCO) 2024 annual meeting. Ms. Brown’s talk was part of an educational session focused on addressing issues among early breast cancer survivors, evolving practices in breast cancer surveillance, and mitigating recurrence risk.

The challenges following breast cancer diagnosis and treatment can be both visible and invisible, said Ms. Brown, a patient advocate and member of the Breast Cancer Working Group at the University of Alabama at Birmingham.

Up to 90% of early breast cancer survivors experience long-term effects from treatment, which often include fatigue, loss of mobility, chronic pain, peripheral neuropathy, lymphedema, and infertility.

Survivors face an elevated risk for depression, anxiety, and fear of recurrence. “Fear of recurrence is a big issue, and it’s almost universal,” she noted.

Cancer treatment is also costly, leading to financial toxicity for many patients, which also “affects adherence to treatment and overall family well-being,” Ms. Brown explained. Survivors may struggle to access financial assistance due to complex eligibility requirements and a lack of awareness about available resources. 

There is a need for holistic and coordinated survivorship care that includes management of long-term effects and surveillance for recurrence to help breast cancer survivors to transition from merely surviving to thriving, said Ms. Brown.
 

Surveilling and Mitigating Recurrence

Surveillance in patients with breast cancer post treatment remains a debated area, particularly when it comes to detecting distant recurrences, David Cescon, MD, PhD, with Princess Margaret Cancer Center, University Health Network, Toronto, said in his talk.

While breast imaging standards are well established, systemic surveillance through imaging and laboratory tests for asymptomatic patients lacks consensus and uniform guidelines, he explained.

Several clinical trials conducted from the late 1980s to the early 2000s showed no survival benefit from intensive surveillance strategies, including imaging and laboratory tests, compared to routine clinical follow-up. Some studies even demonstrated a trend toward harm, given the number of false positives.

These studies formed the basis for guidelines that discourage surveillance among asymptomatic survivors. Currently, no major guideline organization — the National Comprehensive Cancer Network, ASCO, and the European Society for Medical Oncology — recommends routine (nonbreast) radiologic surveillance or laboratory tests for detecting asymptomatic distant breast cancer recurrence, Dr. Cescon said.

Yet, that may change in the coming years, he told attendees.

Ongoing prospective studies will hopefully generate high-quality evidence on the effectiveness of modern surveillance techniques, particularly detection of circulating tumor DNA (ctDNA) and its effect on survival and quality of life, said Dr. Cescon.

These liquid biopsy assays have shown promise in identifying minimal residual disease before radiographic recurrence, he explained. Retrospective studies suggest high prognostic value, with nearly all patients with detectable ctDNA post therapy experiencing recurrence. 

He cautioned, however, that while sensitive ctDNA tests exist and have clinical validity in identifying minimal residual disease, “their clinical utility has not yet been demonstrated,” Dr. Cescon said, adding that any surveillance strategy must consider the psychological effect of frequent testing and the potential for false positives or negatives.

The ultimate goal is preventing disease recurrence, said Neil M. Iyengar, MD, with Memorial Sloan Kettering Cancer Center in New York, in his talk on mitigating recurrence risk. 

Lifestyle modifications are an important targeted intervention for patients entering the survivorship phase, with a “robust level of evidence” supporting their use to mitigate adverse effects associated with cancer therapy and improve quality of life, he told attendees. Most notably, smoking cessation, healthy dietary patterns, physical activity, and reduced alcohol have been associated with improvements in breast cancer outcomes.

Going forward, it will be important to “understand the antitumor potential of lifestyle modification and how we can wield this type of intervention as a precision tool to potentially enhance the effects of cancer therapy and potentially cancer biology,” said Dr. Iyengar.

Ms. Brown disclosed relationships with AstraZeneca. Dr. Cescon disclosed relationships with AstraZeneca, Gilead Sciences, Daiichi Sankyo Europe GmbH, Eisai, GlaxoSmithKline, and other companies. Dr. Iyengar disclosed relationships with Curio Science, DAVA Oncology, Novartis, Pfizer, and others.

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

Advances in breast cancer detection and treatment over the past decades have led to an increase in the number of women diagnosed at earlier stages and successfully treated, ushering in a new era of survivorship.

According to the American Cancer Society, there are currently roughly four million breast cancer survivors in the United States, including those still receiving treatment. The mortality rates for women with breast cancer have been decreasing since 1989, with an overall decline of 42% through 2021.

As the population of breast cancer survivors continues to grow, developing and delivering comprehensive survivorship care is crucial, Thelma Brown told attendees at the American Society of Clinical Oncology (ASCO) 2024 annual meeting. Ms. Brown’s talk was part of an educational session focused on addressing issues among early breast cancer survivors, evolving practices in breast cancer surveillance, and mitigating recurrence risk.

The challenges following breast cancer diagnosis and treatment can be both visible and invisible, said Ms. Brown, a patient advocate and member of the Breast Cancer Working Group at the University of Alabama at Birmingham.

Up to 90% of early breast cancer survivors experience long-term effects from treatment, which often include fatigue, loss of mobility, chronic pain, peripheral neuropathy, lymphedema, and infertility.

Survivors face an elevated risk for depression, anxiety, and fear of recurrence. “Fear of recurrence is a big issue, and it’s almost universal,” she noted.

Cancer treatment is also costly, leading to financial toxicity for many patients, which also “affects adherence to treatment and overall family well-being,” Ms. Brown explained. Survivors may struggle to access financial assistance due to complex eligibility requirements and a lack of awareness about available resources. 

There is a need for holistic and coordinated survivorship care that includes management of long-term effects and surveillance for recurrence to help breast cancer survivors to transition from merely surviving to thriving, said Ms. Brown.
 

Surveilling and Mitigating Recurrence

Surveillance in patients with breast cancer post treatment remains a debated area, particularly when it comes to detecting distant recurrences, David Cescon, MD, PhD, with Princess Margaret Cancer Center, University Health Network, Toronto, said in his talk.

While breast imaging standards are well established, systemic surveillance through imaging and laboratory tests for asymptomatic patients lacks consensus and uniform guidelines, he explained.

Several clinical trials conducted from the late 1980s to the early 2000s showed no survival benefit from intensive surveillance strategies, including imaging and laboratory tests, compared to routine clinical follow-up. Some studies even demonstrated a trend toward harm, given the number of false positives.

These studies formed the basis for guidelines that discourage surveillance among asymptomatic survivors. Currently, no major guideline organization — the National Comprehensive Cancer Network, ASCO, and the European Society for Medical Oncology — recommends routine (nonbreast) radiologic surveillance or laboratory tests for detecting asymptomatic distant breast cancer recurrence, Dr. Cescon said.

Yet, that may change in the coming years, he told attendees.

Ongoing prospective studies will hopefully generate high-quality evidence on the effectiveness of modern surveillance techniques, particularly detection of circulating tumor DNA (ctDNA) and its effect on survival and quality of life, said Dr. Cescon.

These liquid biopsy assays have shown promise in identifying minimal residual disease before radiographic recurrence, he explained. Retrospective studies suggest high prognostic value, with nearly all patients with detectable ctDNA post therapy experiencing recurrence. 

He cautioned, however, that while sensitive ctDNA tests exist and have clinical validity in identifying minimal residual disease, “their clinical utility has not yet been demonstrated,” Dr. Cescon said, adding that any surveillance strategy must consider the psychological effect of frequent testing and the potential for false positives or negatives.

The ultimate goal is preventing disease recurrence, said Neil M. Iyengar, MD, with Memorial Sloan Kettering Cancer Center in New York, in his talk on mitigating recurrence risk. 

Lifestyle modifications are an important targeted intervention for patients entering the survivorship phase, with a “robust level of evidence” supporting their use to mitigate adverse effects associated with cancer therapy and improve quality of life, he told attendees. Most notably, smoking cessation, healthy dietary patterns, physical activity, and reduced alcohol have been associated with improvements in breast cancer outcomes.

Going forward, it will be important to “understand the antitumor potential of lifestyle modification and how we can wield this type of intervention as a precision tool to potentially enhance the effects of cancer therapy and potentially cancer biology,” said Dr. Iyengar.

Ms. Brown disclosed relationships with AstraZeneca. Dr. Cescon disclosed relationships with AstraZeneca, Gilead Sciences, Daiichi Sankyo Europe GmbH, Eisai, GlaxoSmithKline, and other companies. Dr. Iyengar disclosed relationships with Curio Science, DAVA Oncology, Novartis, Pfizer, and others.

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

Two decades after the landmark Women’s Health Initiative (WHI) changed the way clinicians thought about hormone therapy and cancer, new findings suggest this national health study is "the gift that keeps on giving."

Follow-up from two of the WHI’s randomized trials have found that estrogen alone in women with prior hysterectomy significantly increased ovarian cancer incidence and mortality in postmenopausal women. Estrogen and progesterone together, meanwhile, did not increase ovarian cancer risk, and significantly reduced the risk of endometrial cancer. Rowan T. Chlebowski, MD, PhD, of The Lundquist Institute in Torrance, California, presented these results from the latest WHI findings, at the annual meeting of the American Society of Clinical Oncology in Chicago.

Dr. Chlebowski and his colleagues conducted an analysis from two randomized, placebo-controlled trials, which between 1993 and 1998 enrolled nearly 28,000 postmenopausal women aged 50-79 years without prior cancer from 40 centers across the United States. (The full WHI effort involved a total cohort of 161,000 patients, and included an observational study and two other non-drug trials.)

In one of the hormone therapy trials, 17,000 women with a uterus at baseline were randomized to combined equine estrogen plus medroxyprogesterone acetate, or placebo. In the other trial, about 11,000 women with prior hysterectomy were randomized to daily estrogen alone or placebo. Both trials were stopped early: the estrogen-only trial due to an increased stroke risk, and the combined therapy trial due to findings of increased breast cancer and cardiovascular risk.

Mean exposure to hormone therapy was 5.6 years for the combined therapy trial and 7.2 years for estrogen alone trial.
 

Ovarian Cancer Incidence Doubles with Estrogen

At 20 years’ follow up, with mortality information available for nearly the full cohort, Dr. Chlebowski and his colleagues could determine that ovarian cancer incidence doubled among women who had taken estrogen alone (hazard ratio = 2.04; 95% CI 1.14-3.65; P = .01), a difference that reached statistical significance at 12 years’ follow up. Ovarian cancer mortality was also significantly increased (HR = 2.79 95% CI 1.30-5.99, P = .006). Absolute numbers were small, however, with 35 cases of ovarian cancer compared with 17 in the placebo group.

Combined therapy recipients saw no increased risk for ovarian cancer and significantly lower endometrial cancer incidence (106 cases vs. 140 HR = 0.72; 95% CI, 0.56-0.92; P = .01).

Conjugated equine estrogen, Dr. Chlebowski said during his presentation at the meeting, “was introduced in US clinical practice in 1943 and used for over half a century, yet the question about hormone therapy’s influence on endometrial and ovarian cancer remains unsettled. Endometrial cancer and ovarian cancer are the fourth and fifth leading causes of cancer deaths in women ... and there’s some discordant findings from observational studies.”

Care of Ovarian Cancer Survivors Should Change

The new findings should prompt practice and guideline changes regarding the use of estrogen alone in ovarian cancer survivors, Dr. Chlebowski said.

In an interview, oncologist Eleonora Teplinsky, MD, of Valley-Mount Sinai Comprehensive Cancer Care in Paramus, New Jersey, said that apart from this subgroup of ovarian cancer survivors, the findings would not likely have much impact on how clinicians and patients approach hormone replacement therapy today.

“Twenty years ago the Women’s Health Initiative showed that hormone replacement therapy increases breast cancer risk, and everyone stopped taking HRT. And now people pushing back on it and saying wait a second – it was the estrogen plus progesterone that increased breast cancer, not estrogen alone. And now we’ve got these newer [estrogen] formulations.

“Yes, there’s a little bit of an increased risk [for ovarian cancer]. Patients should be aware. They should know the symptoms of ovarian cancer. But if they have indications and have been recommended HRT, this is not something that we would advise them against because of this very slightly increased risk,” Dr. Teplinsky said.

Oncologist Allison Kurian, MD of Stanford University in Stanford, California, who specializes in breast cancer, also noted that the duration of hormone treatment, treatment timing relative to age of menopause onset, and commonly used estrogen preparations had indeed changed since the time the WHI trials were conducted, making it harder to generalize the findings to current practice. Nonetheless, she argued, they still have real significance.

“WHI is an incredibly complex but also incredibly valuable resource,” said Dr. Kurian, who has conducted studies using WHI data. “The first big results came out in 2002, and we’re still learning from it. These are randomized trials, which offer the strongest form of scientific evidence that exists. So whenever we see results from this study, we have to take note of them,” she said.

Because the WHI trials had shown combined therapy, not estrogen alone, to be associated with breast cancer risk, clinicians have felt reassured over the years about using estrogen alone.

“You can’t give it to a person unless they have their uterus removed, because we know it will cause uterine cancer if the uterus is in place. But if the uterus is removed, the feeling was that you can give estrogen alone. I think the new piece that is going to get everyone’s attention is this signal for ovarian cancer.”

Something else the new findings show, Dr. Kurian said, is that WHI is “the gift that keeps on giving,” even after decades. “Some of the participants had a relatively short-term exposure to HRT. They took a medication for just a little while. But you didn’t see the effects until you followed people 12 years. So we’re now going to be a little more worried about ovarian cancer in this setting than we used to be. And that’s going to be something we’re all going to keep an eye on and think twice about in terms of talking to patients.”

These results help demonstrate what happens when a society invests in science on a national scale, Dr. Kurian said. “Here we have a really long-term, incredibly informative study that keeps generating knowledge to help women.”

When the WHI began, it “really was the first time that people decided it was important to systematically study women at midlife. It was a remarkable thing then that society got mobilized to do this, and we’re still seeing the benefits.”

Dr. Chlebowski disclosed receiving consulting or advisory fees from Pfizer. Dr. Teplinsky and Dr. Kurian disclosed no financial conflicts of interest.

Two decades after the landmark Women’s Health Initiative (WHI) changed the way clinicians thought about hormone therapy and cancer, new findings suggest this national health study is "the gift that keeps on giving."

Follow-up from two of the WHI’s randomized trials have found that estrogen alone in women with prior hysterectomy significantly increased ovarian cancer incidence and mortality in postmenopausal women. Estrogen and progesterone together, meanwhile, did not increase ovarian cancer risk, and significantly reduced the risk of endometrial cancer. Rowan T. Chlebowski, MD, PhD, of The Lundquist Institute in Torrance, California, presented these results from the latest WHI findings, at the annual meeting of the American Society of Clinical Oncology in Chicago.

Dr. Chlebowski and his colleagues conducted an analysis from two randomized, placebo-controlled trials, which between 1993 and 1998 enrolled nearly 28,000 postmenopausal women aged 50-79 years without prior cancer from 40 centers across the United States. (The full WHI effort involved a total cohort of 161,000 patients, and included an observational study and two other non-drug trials.)

In one of the hormone therapy trials, 17,000 women with a uterus at baseline were randomized to combined equine estrogen plus medroxyprogesterone acetate, or placebo. In the other trial, about 11,000 women with prior hysterectomy were randomized to daily estrogen alone or placebo. Both trials were stopped early: the estrogen-only trial due to an increased stroke risk, and the combined therapy trial due to findings of increased breast cancer and cardiovascular risk.

Mean exposure to hormone therapy was 5.6 years for the combined therapy trial and 7.2 years for estrogen alone trial.
 

Ovarian Cancer Incidence Doubles with Estrogen

At 20 years’ follow up, with mortality information available for nearly the full cohort, Dr. Chlebowski and his colleagues could determine that ovarian cancer incidence doubled among women who had taken estrogen alone (hazard ratio = 2.04; 95% CI 1.14-3.65; P = .01), a difference that reached statistical significance at 12 years’ follow up. Ovarian cancer mortality was also significantly increased (HR = 2.79 95% CI 1.30-5.99, P = .006). Absolute numbers were small, however, with 35 cases of ovarian cancer compared with 17 in the placebo group.

Combined therapy recipients saw no increased risk for ovarian cancer and significantly lower endometrial cancer incidence (106 cases vs. 140 HR = 0.72; 95% CI, 0.56-0.92; P = .01).

Conjugated equine estrogen, Dr. Chlebowski said during his presentation at the meeting, “was introduced in US clinical practice in 1943 and used for over half a century, yet the question about hormone therapy’s influence on endometrial and ovarian cancer remains unsettled. Endometrial cancer and ovarian cancer are the fourth and fifth leading causes of cancer deaths in women ... and there’s some discordant findings from observational studies.”

Care of Ovarian Cancer Survivors Should Change

The new findings should prompt practice and guideline changes regarding the use of estrogen alone in ovarian cancer survivors, Dr. Chlebowski said.

In an interview, oncologist Eleonora Teplinsky, MD, of Valley-Mount Sinai Comprehensive Cancer Care in Paramus, New Jersey, said that apart from this subgroup of ovarian cancer survivors, the findings would not likely have much impact on how clinicians and patients approach hormone replacement therapy today.

“Twenty years ago the Women’s Health Initiative showed that hormone replacement therapy increases breast cancer risk, and everyone stopped taking HRT. And now people pushing back on it and saying wait a second – it was the estrogen plus progesterone that increased breast cancer, not estrogen alone. And now we’ve got these newer [estrogen] formulations.

“Yes, there’s a little bit of an increased risk [for ovarian cancer]. Patients should be aware. They should know the symptoms of ovarian cancer. But if they have indications and have been recommended HRT, this is not something that we would advise them against because of this very slightly increased risk,” Dr. Teplinsky said.

Oncologist Allison Kurian, MD of Stanford University in Stanford, California, who specializes in breast cancer, also noted that the duration of hormone treatment, treatment timing relative to age of menopause onset, and commonly used estrogen preparations had indeed changed since the time the WHI trials were conducted, making it harder to generalize the findings to current practice. Nonetheless, she argued, they still have real significance.

“WHI is an incredibly complex but also incredibly valuable resource,” said Dr. Kurian, who has conducted studies using WHI data. “The first big results came out in 2002, and we’re still learning from it. These are randomized trials, which offer the strongest form of scientific evidence that exists. So whenever we see results from this study, we have to take note of them,” she said.

Because the WHI trials had shown combined therapy, not estrogen alone, to be associated with breast cancer risk, clinicians have felt reassured over the years about using estrogen alone.

“You can’t give it to a person unless they have their uterus removed, because we know it will cause uterine cancer if the uterus is in place. But if the uterus is removed, the feeling was that you can give estrogen alone. I think the new piece that is going to get everyone’s attention is this signal for ovarian cancer.”

Something else the new findings show, Dr. Kurian said, is that WHI is “the gift that keeps on giving,” even after decades. “Some of the participants had a relatively short-term exposure to HRT. They took a medication for just a little while. But you didn’t see the effects until you followed people 12 years. So we’re now going to be a little more worried about ovarian cancer in this setting than we used to be. And that’s going to be something we’re all going to keep an eye on and think twice about in terms of talking to patients.”

These results help demonstrate what happens when a society invests in science on a national scale, Dr. Kurian said. “Here we have a really long-term, incredibly informative study that keeps generating knowledge to help women.”

When the WHI began, it “really was the first time that people decided it was important to systematically study women at midlife. It was a remarkable thing then that society got mobilized to do this, and we’re still seeing the benefits.”

Dr. Chlebowski disclosed receiving consulting or advisory fees from Pfizer. Dr. Teplinsky and Dr. Kurian disclosed no financial conflicts of interest.

Two decades after the landmark Women’s Health Initiative (WHI) changed the way clinicians thought about hormone therapy and cancer, new findings suggest this national health study is "the gift that keeps on giving."

Follow-up from two of the WHI’s randomized trials have found that estrogen alone in women with prior hysterectomy significantly increased ovarian cancer incidence and mortality in postmenopausal women. Estrogen and progesterone together, meanwhile, did not increase ovarian cancer risk, and significantly reduced the risk of endometrial cancer. Rowan T. Chlebowski, MD, PhD, of The Lundquist Institute in Torrance, California, presented these results from the latest WHI findings, at the annual meeting of the American Society of Clinical Oncology in Chicago.

Dr. Chlebowski and his colleagues conducted an analysis from two randomized, placebo-controlled trials, which between 1993 and 1998 enrolled nearly 28,000 postmenopausal women aged 50-79 years without prior cancer from 40 centers across the United States. (The full WHI effort involved a total cohort of 161,000 patients, and included an observational study and two other non-drug trials.)

In one of the hormone therapy trials, 17,000 women with a uterus at baseline were randomized to combined equine estrogen plus medroxyprogesterone acetate, or placebo. In the other trial, about 11,000 women with prior hysterectomy were randomized to daily estrogen alone or placebo. Both trials were stopped early: the estrogen-only trial due to an increased stroke risk, and the combined therapy trial due to findings of increased breast cancer and cardiovascular risk.

Mean exposure to hormone therapy was 5.6 years for the combined therapy trial and 7.2 years for estrogen alone trial.
 

Ovarian Cancer Incidence Doubles with Estrogen

At 20 years’ follow up, with mortality information available for nearly the full cohort, Dr. Chlebowski and his colleagues could determine that ovarian cancer incidence doubled among women who had taken estrogen alone (hazard ratio = 2.04; 95% CI 1.14-3.65; P = .01), a difference that reached statistical significance at 12 years’ follow up. Ovarian cancer mortality was also significantly increased (HR = 2.79 95% CI 1.30-5.99, P = .006). Absolute numbers were small, however, with 35 cases of ovarian cancer compared with 17 in the placebo group.

Combined therapy recipients saw no increased risk for ovarian cancer and significantly lower endometrial cancer incidence (106 cases vs. 140 HR = 0.72; 95% CI, 0.56-0.92; P = .01).

Conjugated equine estrogen, Dr. Chlebowski said during his presentation at the meeting, “was introduced in US clinical practice in 1943 and used for over half a century, yet the question about hormone therapy’s influence on endometrial and ovarian cancer remains unsettled. Endometrial cancer and ovarian cancer are the fourth and fifth leading causes of cancer deaths in women ... and there’s some discordant findings from observational studies.”

Care of Ovarian Cancer Survivors Should Change

The new findings should prompt practice and guideline changes regarding the use of estrogen alone in ovarian cancer survivors, Dr. Chlebowski said.

In an interview, oncologist Eleonora Teplinsky, MD, of Valley-Mount Sinai Comprehensive Cancer Care in Paramus, New Jersey, said that apart from this subgroup of ovarian cancer survivors, the findings would not likely have much impact on how clinicians and patients approach hormone replacement therapy today.

“Twenty years ago the Women’s Health Initiative showed that hormone replacement therapy increases breast cancer risk, and everyone stopped taking HRT. And now people pushing back on it and saying wait a second – it was the estrogen plus progesterone that increased breast cancer, not estrogen alone. And now we’ve got these newer [estrogen] formulations.

“Yes, there’s a little bit of an increased risk [for ovarian cancer]. Patients should be aware. They should know the symptoms of ovarian cancer. But if they have indications and have been recommended HRT, this is not something that we would advise them against because of this very slightly increased risk,” Dr. Teplinsky said.

Oncologist Allison Kurian, MD of Stanford University in Stanford, California, who specializes in breast cancer, also noted that the duration of hormone treatment, treatment timing relative to age of menopause onset, and commonly used estrogen preparations had indeed changed since the time the WHI trials were conducted, making it harder to generalize the findings to current practice. Nonetheless, she argued, they still have real significance.

“WHI is an incredibly complex but also incredibly valuable resource,” said Dr. Kurian, who has conducted studies using WHI data. “The first big results came out in 2002, and we’re still learning from it. These are randomized trials, which offer the strongest form of scientific evidence that exists. So whenever we see results from this study, we have to take note of them,” she said.

Because the WHI trials had shown combined therapy, not estrogen alone, to be associated with breast cancer risk, clinicians have felt reassured over the years about using estrogen alone.

“You can’t give it to a person unless they have their uterus removed, because we know it will cause uterine cancer if the uterus is in place. But if the uterus is removed, the feeling was that you can give estrogen alone. I think the new piece that is going to get everyone’s attention is this signal for ovarian cancer.”

Something else the new findings show, Dr. Kurian said, is that WHI is “the gift that keeps on giving,” even after decades. “Some of the participants had a relatively short-term exposure to HRT. They took a medication for just a little while. But you didn’t see the effects until you followed people 12 years. So we’re now going to be a little more worried about ovarian cancer in this setting than we used to be. And that’s going to be something we’re all going to keep an eye on and think twice about in terms of talking to patients.”

These results help demonstrate what happens when a society invests in science on a national scale, Dr. Kurian said. “Here we have a really long-term, incredibly informative study that keeps generating knowledge to help women.”

When the WHI began, it “really was the first time that people decided it was important to systematically study women at midlife. It was a remarkable thing then that society got mobilized to do this, and we’re still seeing the benefits.”

Dr. Chlebowski disclosed receiving consulting or advisory fees from Pfizer. Dr. Teplinsky and Dr. Kurian disclosed no financial conflicts of interest.

TOPLINE:

Some vulnerable older patients with untreated metastatic pancreatic cancer can benefit from chemotherapy, but only if they can tolerate enough cycles of treatment, according to results of the randomized phase 2 GIANT study.

METHODOLOGY:

Pancreatic cancer is most often diagnosed in adults aged 65 years or older. Providing cancer treatment for this older, often vulnerable, population comes with significant challenges and can lead to worse survival.

To examine real-world outcomes of older adults with untreated metastatic pancreatic cancer, researchers recruited patients aged 70 years or older and performed a geriatric assessment to identify comorbidities, cognitive issues, and other geriatric abnormalities.

Those who were deemed “fit” (ie, with no geriatric abnormalities) were assigned to receive off-study standard-of-care treatment, whereas those classified as “frail” (ie, with severe abnormalities) received off-study supportive care.

The remaining 176 “vulnerable” patients with mild to moderate geriatric abnormalities completed a geriatric and quality-of-life assessment and were then randomly assigned to receive either dose-reduced 5-fluorouracil (5-FU), leucovorin plus liposomal irinotecan (n = 88) or modified gemcitabine plus nab-paclitaxel (n = 88) every 2 weeks. Ultimately, 79 patients started the 5-FU combination and 75 received gemcitabine plus nab-paclitaxel. Patients were assessed every 8 weeks until disease progression or intolerance.

Overall, patients had a median age of 77 years; 61.9% were aged 75 years or older. About half were female, and 81.5% were White. The majority (87.5%) had a performance status of 0 or 1.

TAKEAWAY:

• Median overall survival was 4.7 months in the gemcitabine plus nab-paclitaxel arm and 4.4 months in the 5-FU combination group, with no significant survival difference observed between the two arms (P = .72).
• When the overall survival analysis was restricted to patients who received at least 4 weeks, or two cycles, of treatment (about 62% of patients), the median overall survival across the two treatment arms reached 8.0 months, in line with expectations for these regimens.
• Patient stratification revealed that those with a performance status of 2 had significantly worse overall survival than those with a status of 0: 1.4 months vs 6.9 months, respectively (hazard ratio [HR], 2.77; P < .001). A similar divide was seen when patients were stratified by physical/functional status and well-being. Age, however, did not significantly influence the results.
• Overall, more than half of patients experienced grade 3 or higher adverse events. Just over 38% of patients received only one to three cycles of therapy, whereas 26% remained on treatment for 12 or more cycles. The adverse event rates were similar between the two regimens, but the toxicity profile was slightly different — the researchers, for instance, observed more peripheral neuropathy with gemcitabine plus nab-paclitaxel and more diarrhea in the 5-FU combination arm.

IN PRACTICE:

• Overall, the “survival outcomes among vulnerable older patients were lower than expected, with high percentage of patients not able to start treatment, or complete one month of therapy due to clinical deterioration,” said study presenter Efrat Dotan, MD, chief, Division of Gastrointestinal Medical Oncology, Fox Chase Cancer Center, Philadelphia. 
• “For vulnerable older adults who can tolerate treatment, these two regimens provide clinicians with options for tailoring therapy based on toxicity profile,” Dr. Dotan added. But “tools are needed to better identify patients who can benefit from treatment.”
• The results underline the need to perform geriatric assessments, as opposed to merely looking at performance status, commented David F. Chang, PhD, MS, MBBS, professor of Surgical Oncology, University of Glasgow, Scotland, who was not involved in the study. 

SOURCE:

The research, presented at the 2024 annual meeting of the American Society of Clinical Oncology, was funded by the National Cancer Institute and the Eastern Cooperative Oncology Group.

LIMITATIONS:

Dr. Chang noted that the study did not reveal which treatment regimen was more effective.

DISCLOSURES:

Dr. Dotan declared relationships with Agenus, Amgen, G1 Therapeutics, Incyte, Olympus, and Taiho Pharmaceutical and institutional relationships with Dragonfly Therapeutics, Gilead Sciences, Ipsen, Kinnate Biopharma, Leap Therapeutics, Lilly, Lutris, NGM Biopharmaceuticals, Relay Therapeutics, and Zymeworks. Dr. Chang declared relationships with Immodulon Therapeutics and Mylan and institutional relationships with AstraZeneca, BMS GmbH & Co. KG, Immodulon Therapeutics, and Merck.

A version of this article appeared on Medscape.com.

TOPLINE:

Some vulnerable older patients with untreated metastatic pancreatic cancer can benefit from chemotherapy, but only if they can tolerate enough cycles of treatment, according to results of the randomized phase 2 GIANT study.

METHODOLOGY:

Pancreatic cancer is most often diagnosed in adults aged 65 years or older. Providing cancer treatment for this older, often vulnerable, population comes with significant challenges and can lead to worse survival.

To examine real-world outcomes of older adults with untreated metastatic pancreatic cancer, researchers recruited patients aged 70 years or older and performed a geriatric assessment to identify comorbidities, cognitive issues, and other geriatric abnormalities.

Those who were deemed “fit” (ie, with no geriatric abnormalities) were assigned to receive off-study standard-of-care treatment, whereas those classified as “frail” (ie, with severe abnormalities) received off-study supportive care.

The remaining 176 “vulnerable” patients with mild to moderate geriatric abnormalities completed a geriatric and quality-of-life assessment and were then randomly assigned to receive either dose-reduced 5-fluorouracil (5-FU), leucovorin plus liposomal irinotecan (n = 88) or modified gemcitabine plus nab-paclitaxel (n = 88) every 2 weeks. Ultimately, 79 patients started the 5-FU combination and 75 received gemcitabine plus nab-paclitaxel. Patients were assessed every 8 weeks until disease progression or intolerance.

Overall, patients had a median age of 77 years; 61.9% were aged 75 years or older. About half were female, and 81.5% were White. The majority (87.5%) had a performance status of 0 or 1.

TAKEAWAY:

• Median overall survival was 4.7 months in the gemcitabine plus nab-paclitaxel arm and 4.4 months in the 5-FU combination group, with no significant survival difference observed between the two arms (P = .72).
• When the overall survival analysis was restricted to patients who received at least 4 weeks, or two cycles, of treatment (about 62% of patients), the median overall survival across the two treatment arms reached 8.0 months, in line with expectations for these regimens.
• Patient stratification revealed that those with a performance status of 2 had significantly worse overall survival than those with a status of 0: 1.4 months vs 6.9 months, respectively (hazard ratio [HR], 2.77; P < .001). A similar divide was seen when patients were stratified by physical/functional status and well-being. Age, however, did not significantly influence the results.
• Overall, more than half of patients experienced grade 3 or higher adverse events. Just over 38% of patients received only one to three cycles of therapy, whereas 26% remained on treatment for 12 or more cycles. The adverse event rates were similar between the two regimens, but the toxicity profile was slightly different — the researchers, for instance, observed more peripheral neuropathy with gemcitabine plus nab-paclitaxel and more diarrhea in the 5-FU combination arm.

IN PRACTICE:

• Overall, the “survival outcomes among vulnerable older patients were lower than expected, with high percentage of patients not able to start treatment, or complete one month of therapy due to clinical deterioration,” said study presenter Efrat Dotan, MD, chief, Division of Gastrointestinal Medical Oncology, Fox Chase Cancer Center, Philadelphia. 
• “For vulnerable older adults who can tolerate treatment, these two regimens provide clinicians with options for tailoring therapy based on toxicity profile,” Dr. Dotan added. But “tools are needed to better identify patients who can benefit from treatment.”
• The results underline the need to perform geriatric assessments, as opposed to merely looking at performance status, commented David F. Chang, PhD, MS, MBBS, professor of Surgical Oncology, University of Glasgow, Scotland, who was not involved in the study. 

SOURCE:

The research, presented at the 2024 annual meeting of the American Society of Clinical Oncology, was funded by the National Cancer Institute and the Eastern Cooperative Oncology Group.

LIMITATIONS:

Dr. Chang noted that the study did not reveal which treatment regimen was more effective.

DISCLOSURES:

Dr. Dotan declared relationships with Agenus, Amgen, G1 Therapeutics, Incyte, Olympus, and Taiho Pharmaceutical and institutional relationships with Dragonfly Therapeutics, Gilead Sciences, Ipsen, Kinnate Biopharma, Leap Therapeutics, Lilly, Lutris, NGM Biopharmaceuticals, Relay Therapeutics, and Zymeworks. Dr. Chang declared relationships with Immodulon Therapeutics and Mylan and institutional relationships with AstraZeneca, BMS GmbH & Co. KG, Immodulon Therapeutics, and Merck.

A version of this article appeared on Medscape.com.

TOPLINE:

Some vulnerable older patients with untreated metastatic pancreatic cancer can benefit from chemotherapy, but only if they can tolerate enough cycles of treatment, according to results of the randomized phase 2 GIANT study.

METHODOLOGY:

Pancreatic cancer is most often diagnosed in adults aged 65 years or older. Providing cancer treatment for this older, often vulnerable, population comes with significant challenges and can lead to worse survival.

To examine real-world outcomes of older adults with untreated metastatic pancreatic cancer, researchers recruited patients aged 70 years or older and performed a geriatric assessment to identify comorbidities, cognitive issues, and other geriatric abnormalities.

Those who were deemed “fit” (ie, with no geriatric abnormalities) were assigned to receive off-study standard-of-care treatment, whereas those classified as “frail” (ie, with severe abnormalities) received off-study supportive care.

The remaining 176 “vulnerable” patients with mild to moderate geriatric abnormalities completed a geriatric and quality-of-life assessment and were then randomly assigned to receive either dose-reduced 5-fluorouracil (5-FU), leucovorin plus liposomal irinotecan (n = 88) or modified gemcitabine plus nab-paclitaxel (n = 88) every 2 weeks. Ultimately, 79 patients started the 5-FU combination and 75 received gemcitabine plus nab-paclitaxel. Patients were assessed every 8 weeks until disease progression or intolerance.

Overall, patients had a median age of 77 years; 61.9% were aged 75 years or older. About half were female, and 81.5% were White. The majority (87.5%) had a performance status of 0 or 1.

TAKEAWAY:

• Median overall survival was 4.7 months in the gemcitabine plus nab-paclitaxel arm and 4.4 months in the 5-FU combination group, with no significant survival difference observed between the two arms (P = .72).
• When the overall survival analysis was restricted to patients who received at least 4 weeks, or two cycles, of treatment (about 62% of patients), the median overall survival across the two treatment arms reached 8.0 months, in line with expectations for these regimens.
• Patient stratification revealed that those with a performance status of 2 had significantly worse overall survival than those with a status of 0: 1.4 months vs 6.9 months, respectively (hazard ratio [HR], 2.77; P < .001). A similar divide was seen when patients were stratified by physical/functional status and well-being. Age, however, did not significantly influence the results.
• Overall, more than half of patients experienced grade 3 or higher adverse events. Just over 38% of patients received only one to three cycles of therapy, whereas 26% remained on treatment for 12 or more cycles. The adverse event rates were similar between the two regimens, but the toxicity profile was slightly different — the researchers, for instance, observed more peripheral neuropathy with gemcitabine plus nab-paclitaxel and more diarrhea in the 5-FU combination arm.

IN PRACTICE:

• Overall, the “survival outcomes among vulnerable older patients were lower than expected, with high percentage of patients not able to start treatment, or complete one month of therapy due to clinical deterioration,” said study presenter Efrat Dotan, MD, chief, Division of Gastrointestinal Medical Oncology, Fox Chase Cancer Center, Philadelphia. 
• “For vulnerable older adults who can tolerate treatment, these two regimens provide clinicians with options for tailoring therapy based on toxicity profile,” Dr. Dotan added. But “tools are needed to better identify patients who can benefit from treatment.”
• The results underline the need to perform geriatric assessments, as opposed to merely looking at performance status, commented David F. Chang, PhD, MS, MBBS, professor of Surgical Oncology, University of Glasgow, Scotland, who was not involved in the study. 

SOURCE:

The research, presented at the 2024 annual meeting of the American Society of Clinical Oncology, was funded by the National Cancer Institute and the Eastern Cooperative Oncology Group.

LIMITATIONS:

Dr. Chang noted that the study did not reveal which treatment regimen was more effective.

DISCLOSURES:

Dr. Dotan declared relationships with Agenus, Amgen, G1 Therapeutics, Incyte, Olympus, and Taiho Pharmaceutical and institutional relationships with Dragonfly Therapeutics, Gilead Sciences, Ipsen, Kinnate Biopharma, Leap Therapeutics, Lilly, Lutris, NGM Biopharmaceuticals, Relay Therapeutics, and Zymeworks. Dr. Chang declared relationships with Immodulon Therapeutics and Mylan and institutional relationships with AstraZeneca, BMS GmbH & Co. KG, Immodulon Therapeutics, and Merck.

A version of this article appeared on Medscape.com.

Vaccination against human papillomavirus (HPV) is an effective way to prevent HPV infection and cancers typically caused by HPV, including cervical cancer and head and neck cancers, new research showed.

The analysis, featured at a press briefing ahead of the presentation at the American Society of Clinical Oncology (ASCO) 2024 annual meeting, notably found that men who received the HPV vaccine had a 56% lower risk for head and neck cancers.

“We’ve known for a long time that having the HPV vaccine can prevent the development of HPV infection, yes, but importantly, cancer,” primarily cervical cancer, said briefing moderator and ASCO president Lynn Schuchter, MD, Abramson Cancer Center, University of Pennsylvania, Philadelphia. “This is a really important study that extends the information about the impact.”

Using the US TriNetX database, lead investigator Jefferson DeKloe, BS, a research fellow with Thomas Jefferson University, Philadelphia, and colleagues created a matched cohort of 760,540 HPV-vaccinated and unvaccinated men and 945,999 HPV-vaccinated and unvaccinated women.

HPV-vaccinated men had a 54% lower risk for all HPV-related cancers (odds ratio [OR], 0.46; P < .001) and a 56% lower risk for head and neck cancers (OR, 0.44; P < .001) than unvaccinated men. There were not enough cases of anal and penile cancers for analysis.

HPV-vaccinated women had a 27% lower risk for all HPV-related cancers (OR, 0.73; P < .05), a 54% lower risk for cervical cancer (OR, 0.46; P < .05), and a 33% lower risk for head and neck cancers (OR, 0.67; 95% CI, 0.42-1.08) than HPV-unvaccinated women, but this finding was not significant. There were not enough cases of anal cancers for analysis, and the odds of developing vulvar or vaginal cancer was not significantly different in HPV-vaccinated vs unvaccinated women.

Vaccinated women, however, were less likely than unvaccinated women to develop high-grade squamous intraepithelial lesions (OR, 0.44), cervical carcinoma in situ (OR, 0.42), or abnormal Pap findings (OR, 0.87), and were less likely to undergo cone biopsy and loop electrosurgical excision (OR, 0.45).

“This study really highlights the importance of getting the HPV vaccine,” Dr. Schuchter said at the briefing.

“HPV vaccination is cancer prevention,” Glenn Hanna, MD, with Dana-Farber Cancer Institute, Boston, said in an ASCO statement.

Still, HPV vaccination rates in the United States remain relatively low. According to the National Cancer Institute, in 2022, only about 58% of adolescents aged 13-15 years had received two or three doses of HPV vaccine as recommended.

“The goal,” Dr. Schuchter said at the briefing, “is that younger girls and young boys get vaccinated to prevent development of HPV infection, and that should decrease the risk of cancer, which is what we’ve seen.”

Mr. DeKloe agreed and highlighted the importance of improving vaccination rates. “Identifying effective interventions that increase HPV vaccination rates is critical in reducing undue cancer burden in the United States,” Mr. DeKloe said in a statement.

The study had no funding source. Mr. DeKloe had no relevant disclosures. Dr. Hanna has disclosed relationships with Bicara Therapeutics, Bristol Myers Squibb, Coherus BioSciences, and others. Dr. Schuchter had no relevant disclosures.

A version of this article appeared on Medscape.com .

Vaccination against human papillomavirus (HPV) is an effective way to prevent HPV infection and cancers typically caused by HPV, including cervical cancer and head and neck cancers, new research showed.

The analysis, featured at a press briefing ahead of the presentation at the American Society of Clinical Oncology (ASCO) 2024 annual meeting, notably found that men who received the HPV vaccine had a 56% lower risk for head and neck cancers.

“We’ve known for a long time that having the HPV vaccine can prevent the development of HPV infection, yes, but importantly, cancer,” primarily cervical cancer, said briefing moderator and ASCO president Lynn Schuchter, MD, Abramson Cancer Center, University of Pennsylvania, Philadelphia. “This is a really important study that extends the information about the impact.”

Using the US TriNetX database, lead investigator Jefferson DeKloe, BS, a research fellow with Thomas Jefferson University, Philadelphia, and colleagues created a matched cohort of 760,540 HPV-vaccinated and unvaccinated men and 945,999 HPV-vaccinated and unvaccinated women.

HPV-vaccinated men had a 54% lower risk for all HPV-related cancers (odds ratio [OR], 0.46; P < .001) and a 56% lower risk for head and neck cancers (OR, 0.44; P < .001) than unvaccinated men. There were not enough cases of anal and penile cancers for analysis.

HPV-vaccinated women had a 27% lower risk for all HPV-related cancers (OR, 0.73; P < .05), a 54% lower risk for cervical cancer (OR, 0.46; P < .05), and a 33% lower risk for head and neck cancers (OR, 0.67; 95% CI, 0.42-1.08) than HPV-unvaccinated women, but this finding was not significant. There were not enough cases of anal cancers for analysis, and the odds of developing vulvar or vaginal cancer was not significantly different in HPV-vaccinated vs unvaccinated women.

Vaccinated women, however, were less likely than unvaccinated women to develop high-grade squamous intraepithelial lesions (OR, 0.44), cervical carcinoma in situ (OR, 0.42), or abnormal Pap findings (OR, 0.87), and were less likely to undergo cone biopsy and loop electrosurgical excision (OR, 0.45).

“This study really highlights the importance of getting the HPV vaccine,” Dr. Schuchter said at the briefing.

“HPV vaccination is cancer prevention,” Glenn Hanna, MD, with Dana-Farber Cancer Institute, Boston, said in an ASCO statement.

Still, HPV vaccination rates in the United States remain relatively low. According to the National Cancer Institute, in 2022, only about 58% of adolescents aged 13-15 years had received two or three doses of HPV vaccine as recommended.

“The goal,” Dr. Schuchter said at the briefing, “is that younger girls and young boys get vaccinated to prevent development of HPV infection, and that should decrease the risk of cancer, which is what we’ve seen.”

Mr. DeKloe agreed and highlighted the importance of improving vaccination rates. “Identifying effective interventions that increase HPV vaccination rates is critical in reducing undue cancer burden in the United States,” Mr. DeKloe said in a statement.

The study had no funding source. Mr. DeKloe had no relevant disclosures. Dr. Hanna has disclosed relationships with Bicara Therapeutics, Bristol Myers Squibb, Coherus BioSciences, and others. Dr. Schuchter had no relevant disclosures.

A version of this article appeared on Medscape.com .

Vaccination against human papillomavirus (HPV) is an effective way to prevent HPV infection and cancers typically caused by HPV, including cervical cancer and head and neck cancers, new research showed.

The analysis, featured at a press briefing ahead of the presentation at the American Society of Clinical Oncology (ASCO) 2024 annual meeting, notably found that men who received the HPV vaccine had a 56% lower risk for head and neck cancers.

“We’ve known for a long time that having the HPV vaccine can prevent the development of HPV infection, yes, but importantly, cancer,” primarily cervical cancer, said briefing moderator and ASCO president Lynn Schuchter, MD, Abramson Cancer Center, University of Pennsylvania, Philadelphia. “This is a really important study that extends the information about the impact.”

Using the US TriNetX database, lead investigator Jefferson DeKloe, BS, a research fellow with Thomas Jefferson University, Philadelphia, and colleagues created a matched cohort of 760,540 HPV-vaccinated and unvaccinated men and 945,999 HPV-vaccinated and unvaccinated women.

HPV-vaccinated men had a 54% lower risk for all HPV-related cancers (odds ratio [OR], 0.46; P < .001) and a 56% lower risk for head and neck cancers (OR, 0.44; P < .001) than unvaccinated men. There were not enough cases of anal and penile cancers for analysis.

HPV-vaccinated women had a 27% lower risk for all HPV-related cancers (OR, 0.73; P < .05), a 54% lower risk for cervical cancer (OR, 0.46; P < .05), and a 33% lower risk for head and neck cancers (OR, 0.67; 95% CI, 0.42-1.08) than HPV-unvaccinated women, but this finding was not significant. There were not enough cases of anal cancers for analysis, and the odds of developing vulvar or vaginal cancer was not significantly different in HPV-vaccinated vs unvaccinated women.

Vaccinated women, however, were less likely than unvaccinated women to develop high-grade squamous intraepithelial lesions (OR, 0.44), cervical carcinoma in situ (OR, 0.42), or abnormal Pap findings (OR, 0.87), and were less likely to undergo cone biopsy and loop electrosurgical excision (OR, 0.45).

“This study really highlights the importance of getting the HPV vaccine,” Dr. Schuchter said at the briefing.

“HPV vaccination is cancer prevention,” Glenn Hanna, MD, with Dana-Farber Cancer Institute, Boston, said in an ASCO statement.

Still, HPV vaccination rates in the United States remain relatively low. According to the National Cancer Institute, in 2022, only about 58% of adolescents aged 13-15 years had received two or three doses of HPV vaccine as recommended.

“The goal,” Dr. Schuchter said at the briefing, “is that younger girls and young boys get vaccinated to prevent development of HPV infection, and that should decrease the risk of cancer, which is what we’ve seen.”

Mr. DeKloe agreed and highlighted the importance of improving vaccination rates. “Identifying effective interventions that increase HPV vaccination rates is critical in reducing undue cancer burden in the United States,” Mr. DeKloe said in a statement.

The study had no funding source. Mr. DeKloe had no relevant disclosures. Dr. Hanna has disclosed relationships with Bicara Therapeutics, Bristol Myers Squibb, Coherus BioSciences, and others. Dr. Schuchter had no relevant disclosures.

A version of this article appeared on Medscape.com .

The addition of an anti-CD38 monoclonal antibody to the standard first-line combination treatment significantly improved outcomes in newly diagnosed, transplant-ineligible patients with multiple myeloma (MM), according to an interim analysis of an open-label, randomized, phase 3 trial.

Patients who took isatuximab (Sarclisa) plus bortezomib, lenalidomide, and dexamethasone (VRd) reached higher estimated progression-free survival at a median 59.7 months vs. those who took VRd alone (63.2% vs. 45.2%, respectively, 98.5% CI, hazard ratio [HR] = 0.60, P < .001), reported Thierry Facon, MD, professor of hematology at Lille University Hospital, France, and colleagues at the annual meeting of the American Society of Clinical Oncology in Chicago. The study was simultaneously published 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,” Dr. Facon said in an interview. The findings demonstrated the VRd-isatuximab’s potential as “a first-in-class combination to address gaps in care for newly diagnosed multiple myeloma transplant-ineligible patients,” he said.

According to Dr. Facon, more than 180,000 people worldwide are diagnosed with MM each year, he said, making it the second-most common hematologic malignancy. 

“There is a need for new frontline therapeutic options for all MM patients,” he said. “Effective frontline therapy has the potential to modify the course of the disease, which is a key outcome for transplant-ineligible patients who often face high rates of attrition in later lines of therapy.”

For the industry-funded IMROZ study, researchers recruited patients aged 18-80 at 93 sites in 21 nations from 2017-2019. All were ineligible for transplant due to comorbidities or being aged 65 or older. Exclusions included Eastern Cooperative Oncology Group (ECOG) performance status scores of more than 2.

The subjects were randomly assigned in a 3-to-2 ratio to isatuximab-VRd (n = 265) or VRd alone (n = 181) and received four induction cycles (6 weeks per cycle) followed by 4-week cycles of continuous treatment until disease progression, unacceptable adverse event, or other criteria for discontinuation. If progression occurred, patients could be switched from the VRd-only group to the isatuximab-VRd group.

The median age in both the isatuximab-VRd and VRd groups was 72. The percentages of women were 46.0% and 48.1%, respectively, and 72.5% and 72.4%, respectively, were White. The next largest race/ethnic group was Asian (11.7% and 9.4%, respectively). Almost all had ECOG status of 0 or 1 (88.7% and 89.5%, respectively).

At study cut-off in September 2023, the percentages of subjects in the isatuximab-VRd and VRd groups who were still receiving treatment were 47.2% and 24.3%, respectively.

An intention-to-treat analysis found that the two groups had similar rates of overall response (91.3% for isatuximab-VRd vs. 92.3% for VRd), but the isatuximab-VRd group had higher complete or better response (74.7% vs. 64.1%, P = .01).

The percentage of patients who were minimal residual disease (MRD)-negative and had a complete response was also higher in the VRd-isatuximab group vs. the VRd group (55.5% vs. 40.9%, respectively, P = .003). A total of 26.0% of patients in the VRd-isatuximab group died vs. 32.6% in the VRd group; the estimated overall survival rates at 60 months were 72.3% and 66.3%, respectively, HR = 0.78, 99.97% CI).

As for adverse events, grade 5 events were more common in the VRd-isatuximab group (11.0% vs. 5.5%), as were deaths within the first 60 days of treatment (1.5% vs. 0.6%). “The difference was driven in part by different treatment exposures,” the researchers reported. Treatment-emergent events led to treatment discontinuation in 22.8% and 26.0% of patients, respectively.

“The safety and tolerability of Sarclisa observed was consistent with the established safety profile of Sarclisa and VRd with no new safety signals observed,” Dr. Facon said.

In an interview, Zandra Klippel, MD, global product head for multiple myeloma at Sanofi — the maker of isatuximab and funder of the study — said the Food and Drug Administration has accepted a priority review application for the investigational use of isatuximab in combination with VRd for the treatment of patients with transplant-ineligible, newly diagnosed MM.

“Our FDA approval date is expected on September 27, 2024,” Dr. Klippel said. “If all goes well, we anticipate launching as early as 2024 in the US and rolling out in other key countries starting in 2025 and continuing through 2026.”

Dr. Klippel added that isatuximab “continues to be evaluated in multiple ongoing phase 3 clinical trials in combination with current standard treatments across the MM treatment continuum.”

In an interview, Sagar Lonial, MD, chair and professor of hematology and medical oncology and chief medical officer at Winship Cancer Institute at Emory University in Atlanta, said the study is “important.”

However, Dr. Lonial, who is familiar with the findings but didn’t take part in the study, said it’s difficult to understand the impact of the treatment on frail patients. It appears that the combination treatment may be good for frail patients, he said, “but I need to better understand the magnitude of the benefit in that subset a little more.”

As for adverse events, he said “they are what would be expected for a trial like this.”

Pneumonia and COVID-19 infections were higher in the VRd-isatuximab group, he said, and “we know in general that vaccine responses are blocked by CD38 antibodies.” This can be managed, he said, via intravenous immunoglobulin support.

Manni Mohyuddin, MD, assistant professor at Huntsman Cancer Institute in Utah, said in an interview that the findings suggest that in older, fit patients, “you can get fairly good outcomes without use of transplant.”

In the United States, many more patients in the cohort would have been considered transplant-eligible, he said, and not eliminated from consideration for transplant due to age over 65. However, as patients age, “you get more diminishing returns for transplants,” said Dr. Mohyuddin, who is familiar with the study findings but didn’t take part in the research.

All the drugs in the new combination are FDA approved, he said, although the combination isn’t. “I suspect this will make it to our guidelines very soon and then be reimbursed by insurance companies and Medicare.”

The study was funded by Sanofi and an M.D. Anderson Cancer Center support grant. Dr. Facon has no disclosures. Other study authors report multiple ties relationships with various drug makers. Dr. Lonial disclosed ties with Takeda, Amgen, Novartis, BMS, GSK, AbbVie, Genentech, Pfizer, Regeneron, Janssen, AstraZeneca, and TG Therapeutics). Dr. Mohyuddin disclosed a relationship with Janssen.

The addition of an anti-CD38 monoclonal antibody to the standard first-line combination treatment significantly improved outcomes in newly diagnosed, transplant-ineligible patients with multiple myeloma (MM), according to an interim analysis of an open-label, randomized, phase 3 trial.

Patients who took isatuximab (Sarclisa) plus bortezomib, lenalidomide, and dexamethasone (VRd) reached higher estimated progression-free survival at a median 59.7 months vs. those who took VRd alone (63.2% vs. 45.2%, respectively, 98.5% CI, hazard ratio [HR] = 0.60, P < .001), reported Thierry Facon, MD, professor of hematology at Lille University Hospital, France, and colleagues at the annual meeting of the American Society of Clinical Oncology in Chicago. The study was simultaneously published 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,” Dr. Facon said in an interview. The findings demonstrated the VRd-isatuximab’s potential as “a first-in-class combination to address gaps in care for newly diagnosed multiple myeloma transplant-ineligible patients,” he said.

According to Dr. Facon, more than 180,000 people worldwide are diagnosed with MM each year, he said, making it the second-most common hematologic malignancy. 

“There is a need for new frontline therapeutic options for all MM patients,” he said. “Effective frontline therapy has the potential to modify the course of the disease, which is a key outcome for transplant-ineligible patients who often face high rates of attrition in later lines of therapy.”

For the industry-funded IMROZ study, researchers recruited patients aged 18-80 at 93 sites in 21 nations from 2017-2019. All were ineligible for transplant due to comorbidities or being aged 65 or older. Exclusions included Eastern Cooperative Oncology Group (ECOG) performance status scores of more than 2.

The subjects were randomly assigned in a 3-to-2 ratio to isatuximab-VRd (n = 265) or VRd alone (n = 181) and received four induction cycles (6 weeks per cycle) followed by 4-week cycles of continuous treatment until disease progression, unacceptable adverse event, or other criteria for discontinuation. If progression occurred, patients could be switched from the VRd-only group to the isatuximab-VRd group.

The median age in both the isatuximab-VRd and VRd groups was 72. The percentages of women were 46.0% and 48.1%, respectively, and 72.5% and 72.4%, respectively, were White. The next largest race/ethnic group was Asian (11.7% and 9.4%, respectively). Almost all had ECOG status of 0 or 1 (88.7% and 89.5%, respectively).

At study cut-off in September 2023, the percentages of subjects in the isatuximab-VRd and VRd groups who were still receiving treatment were 47.2% and 24.3%, respectively.

An intention-to-treat analysis found that the two groups had similar rates of overall response (91.3% for isatuximab-VRd vs. 92.3% for VRd), but the isatuximab-VRd group had higher complete or better response (74.7% vs. 64.1%, P = .01).

The percentage of patients who were minimal residual disease (MRD)-negative and had a complete response was also higher in the VRd-isatuximab group vs. the VRd group (55.5% vs. 40.9%, respectively, P = .003). A total of 26.0% of patients in the VRd-isatuximab group died vs. 32.6% in the VRd group; the estimated overall survival rates at 60 months were 72.3% and 66.3%, respectively, HR = 0.78, 99.97% CI).

As for adverse events, grade 5 events were more common in the VRd-isatuximab group (11.0% vs. 5.5%), as were deaths within the first 60 days of treatment (1.5% vs. 0.6%). “The difference was driven in part by different treatment exposures,” the researchers reported. Treatment-emergent events led to treatment discontinuation in 22.8% and 26.0% of patients, respectively.

“The safety and tolerability of Sarclisa observed was consistent with the established safety profile of Sarclisa and VRd with no new safety signals observed,” Dr. Facon said.

In an interview, Zandra Klippel, MD, global product head for multiple myeloma at Sanofi — the maker of isatuximab and funder of the study — said the Food and Drug Administration has accepted a priority review application for the investigational use of isatuximab in combination with VRd for the treatment of patients with transplant-ineligible, newly diagnosed MM.

“Our FDA approval date is expected on September 27, 2024,” Dr. Klippel said. “If all goes well, we anticipate launching as early as 2024 in the US and rolling out in other key countries starting in 2025 and continuing through 2026.”

Dr. Klippel added that isatuximab “continues to be evaluated in multiple ongoing phase 3 clinical trials in combination with current standard treatments across the MM treatment continuum.”

In an interview, Sagar Lonial, MD, chair and professor of hematology and medical oncology and chief medical officer at Winship Cancer Institute at Emory University in Atlanta, said the study is “important.”

However, Dr. Lonial, who is familiar with the findings but didn’t take part in the study, said it’s difficult to understand the impact of the treatment on frail patients. It appears that the combination treatment may be good for frail patients, he said, “but I need to better understand the magnitude of the benefit in that subset a little more.”

As for adverse events, he said “they are what would be expected for a trial like this.”

Pneumonia and COVID-19 infections were higher in the VRd-isatuximab group, he said, and “we know in general that vaccine responses are blocked by CD38 antibodies.” This can be managed, he said, via intravenous immunoglobulin support.

Manni Mohyuddin, MD, assistant professor at Huntsman Cancer Institute in Utah, said in an interview that the findings suggest that in older, fit patients, “you can get fairly good outcomes without use of transplant.”

In the United States, many more patients in the cohort would have been considered transplant-eligible, he said, and not eliminated from consideration for transplant due to age over 65. However, as patients age, “you get more diminishing returns for transplants,” said Dr. Mohyuddin, who is familiar with the study findings but didn’t take part in the research.

All the drugs in the new combination are FDA approved, he said, although the combination isn’t. “I suspect this will make it to our guidelines very soon and then be reimbursed by insurance companies and Medicare.”

The study was funded by Sanofi and an M.D. Anderson Cancer Center support grant. Dr. Facon has no disclosures. Other study authors report multiple ties relationships with various drug makers. Dr. Lonial disclosed ties with Takeda, Amgen, Novartis, BMS, GSK, AbbVie, Genentech, Pfizer, Regeneron, Janssen, AstraZeneca, and TG Therapeutics). Dr. Mohyuddin disclosed a relationship with Janssen.

The addition of an anti-CD38 monoclonal antibody to the standard first-line combination treatment significantly improved outcomes in newly diagnosed, transplant-ineligible patients with multiple myeloma (MM), according to an interim analysis of an open-label, randomized, phase 3 trial.

Patients who took isatuximab (Sarclisa) plus bortezomib, lenalidomide, and dexamethasone (VRd) reached higher estimated progression-free survival at a median 59.7 months vs. those who took VRd alone (63.2% vs. 45.2%, respectively, 98.5% CI, hazard ratio [HR] = 0.60, P < .001), reported Thierry Facon, MD, professor of hematology at Lille University Hospital, France, and colleagues at the annual meeting of the American Society of Clinical Oncology in Chicago. The study was simultaneously published 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,” Dr. Facon said in an interview. The findings demonstrated the VRd-isatuximab’s potential as “a first-in-class combination to address gaps in care for newly diagnosed multiple myeloma transplant-ineligible patients,” he said.

According to Dr. Facon, more than 180,000 people worldwide are diagnosed with MM each year, he said, making it the second-most common hematologic malignancy. 

“There is a need for new frontline therapeutic options for all MM patients,” he said. “Effective frontline therapy has the potential to modify the course of the disease, which is a key outcome for transplant-ineligible patients who often face high rates of attrition in later lines of therapy.”

For the industry-funded IMROZ study, researchers recruited patients aged 18-80 at 93 sites in 21 nations from 2017-2019. All were ineligible for transplant due to comorbidities or being aged 65 or older. Exclusions included Eastern Cooperative Oncology Group (ECOG) performance status scores of more than 2.

The subjects were randomly assigned in a 3-to-2 ratio to isatuximab-VRd (n = 265) or VRd alone (n = 181) and received four induction cycles (6 weeks per cycle) followed by 4-week cycles of continuous treatment until disease progression, unacceptable adverse event, or other criteria for discontinuation. If progression occurred, patients could be switched from the VRd-only group to the isatuximab-VRd group.

The median age in both the isatuximab-VRd and VRd groups was 72. The percentages of women were 46.0% and 48.1%, respectively, and 72.5% and 72.4%, respectively, were White. The next largest race/ethnic group was Asian (11.7% and 9.4%, respectively). Almost all had ECOG status of 0 or 1 (88.7% and 89.5%, respectively).

At study cut-off in September 2023, the percentages of subjects in the isatuximab-VRd and VRd groups who were still receiving treatment were 47.2% and 24.3%, respectively.

An intention-to-treat analysis found that the two groups had similar rates of overall response (91.3% for isatuximab-VRd vs. 92.3% for VRd), but the isatuximab-VRd group had higher complete or better response (74.7% vs. 64.1%, P = .01).

The percentage of patients who were minimal residual disease (MRD)-negative and had a complete response was also higher in the VRd-isatuximab group vs. the VRd group (55.5% vs. 40.9%, respectively, P = .003). A total of 26.0% of patients in the VRd-isatuximab group died vs. 32.6% in the VRd group; the estimated overall survival rates at 60 months were 72.3% and 66.3%, respectively, HR = 0.78, 99.97% CI).

As for adverse events, grade 5 events were more common in the VRd-isatuximab group (11.0% vs. 5.5%), as were deaths within the first 60 days of treatment (1.5% vs. 0.6%). “The difference was driven in part by different treatment exposures,” the researchers reported. Treatment-emergent events led to treatment discontinuation in 22.8% and 26.0% of patients, respectively.

“The safety and tolerability of Sarclisa observed was consistent with the established safety profile of Sarclisa and VRd with no new safety signals observed,” Dr. Facon said.

In an interview, Zandra Klippel, MD, global product head for multiple myeloma at Sanofi — the maker of isatuximab and funder of the study — said the Food and Drug Administration has accepted a priority review application for the investigational use of isatuximab in combination with VRd for the treatment of patients with transplant-ineligible, newly diagnosed MM.

“Our FDA approval date is expected on September 27, 2024,” Dr. Klippel said. “If all goes well, we anticipate launching as early as 2024 in the US and rolling out in other key countries starting in 2025 and continuing through 2026.”

Dr. Klippel added that isatuximab “continues to be evaluated in multiple ongoing phase 3 clinical trials in combination with current standard treatments across the MM treatment continuum.”

In an interview, Sagar Lonial, MD, chair and professor of hematology and medical oncology and chief medical officer at Winship Cancer Institute at Emory University in Atlanta, said the study is “important.”

However, Dr. Lonial, who is familiar with the findings but didn’t take part in the study, said it’s difficult to understand the impact of the treatment on frail patients. It appears that the combination treatment may be good for frail patients, he said, “but I need to better understand the magnitude of the benefit in that subset a little more.”

As for adverse events, he said “they are what would be expected for a trial like this.”

Pneumonia and COVID-19 infections were higher in the VRd-isatuximab group, he said, and “we know in general that vaccine responses are blocked by CD38 antibodies.” This can be managed, he said, via intravenous immunoglobulin support.

Manni Mohyuddin, MD, assistant professor at Huntsman Cancer Institute in Utah, said in an interview that the findings suggest that in older, fit patients, “you can get fairly good outcomes without use of transplant.”

In the United States, many more patients in the cohort would have been considered transplant-eligible, he said, and not eliminated from consideration for transplant due to age over 65. However, as patients age, “you get more diminishing returns for transplants,” said Dr. Mohyuddin, who is familiar with the study findings but didn’t take part in the research.

All the drugs in the new combination are FDA approved, he said, although the combination isn’t. “I suspect this will make it to our guidelines very soon and then be reimbursed by insurance companies and Medicare.”

The study was funded by Sanofi and an M.D. Anderson Cancer Center support grant. Dr. Facon has no disclosures. Other study authors report multiple ties relationships with various drug makers. Dr. Lonial disclosed ties with Takeda, Amgen, Novartis, BMS, GSK, AbbVie, Genentech, Pfizer, Regeneron, Janssen, AstraZeneca, and TG Therapeutics). Dr. Mohyuddin disclosed a relationship with Janssen.

The antibody-drug conjugate trastuzumab deruxtecan, or T-DXd, is an effective first-line treatment in patients with HER2-low metastatic breast cancer, conferring an additional 5 months’ progression-free survival over chemotherapy.

HER2-low cancers express levels of human epidermal growth factor receptor 2 that are below standard thresholds for HER2-positive immunohistochemistry. In 2022, results from the DESTINY-Breast04 trial showed T-DXd (Enhertu, AstraZeneca) to be an effective second-line chemotherapy in patients with HER2-low metastatic breast cancer.

The highly awaited new findings, from the manufacturer-sponsored, open-label Phase 3 DESTINY-Breast06 trial, were presented at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, Illinois.

The findings not only definitively establish a role for T-DXd earlier in the treatment sequence for HER2-low cancers, they also suggest benefit in a group of patients designated for the purposes of this trial to be HER2-ultralow. These patients have cancers with only faintly detectable HER2 expression on currently used assays (J Clin Oncol 42, 2024 [suppl 17; abstr LBA 1000]).

In a separate set of findings also presented at ASCO, from the randomized phase 1B open-label study, DESTINY-Breast07, T-Dxd showed efficacy in previously untreated HER2-positive metastatic breast cancer patients both alone and in combination with the monoclonal antibody pertuzumab (Perjeta, Genentech).
 

DESTINY-Breast06 Methods and Results

The DESTINY-Breast06 findings were presented by lead investigator Guiseppe Curigliano, MD, PhD, of the University of Milan and European Institute of Oncology. Dr. Curigliano and his colleagues randomized 866 patients with metastatic breast cancer: 436 to intravenous T-Dxd and 430 to the investigator’s choice of capecitabine, nab-paclitaxel, or paclitaxel chemotherapy. The investigators chose capecitabine 60% of the time.

Most patients had cancers classed as HER2 low (immunohistochemistry 1+ or 2+), while 153 had cancers classed by investigators as HER2-ultralow (IHC 0 with membrane staining or IHC under 1+). Patients enrolled in the study were those whose disease had progressed after endocrine therapy with or without targeted therapy. Patients’ median age was between 57 and 58, and all were chemotherapy-naive in the metastatic breast cancer setting.

The main outcome of the study was median progression-free survival in the HER2-low group. T-Dxd was seen improving progression-free survival, with median 13.2 months vs. 8.1 months (hazard ratio, 0.62; 95% confidence interval, 0.51-0.74; P < .0001). In the intention-to-treat population, which included the HER2 ultralow patients, the benefit was the same (HR, 0.63; 95% CI, 0.53-0.75; P < .0001). This suggested that T-DXd is also effective in these patients, and it will be extremely important going forward to identify the lowest level of HER2 expression in metastatic breast cancers that can still benefit from therapy with T-DxD, Dr. Curigliano said.

Overall survival could not be assessed in the study cohort because complete data were not yet available, Dr. Curigliano said. However, trends pointed to an advantage for T-DXd, and tumor response rates were markedly higher with T-DXd: 57% compared with 31% for standard chemotherapy in the full cohort.

Serious treatment-emergent adverse events were more common in the T-Dxd–treated patients, with 11% of that arm developing drug-related interstitial lung disease, and three patients dying of it. Five patients in the T-DXd arm died of adverse events deemed treatment-related, and none died from treatment-related adverse events in the standard chemotherapy arm. Altogether 11 patients died in the T-DXd arm and 6 in the chemotherapy arm.
 

Clinical Implications of DESTINY-Breast06

The DESTINY-Breast06 data show that “we have to again change how we think about HER2 expression. Even very low levels of HER2 expression matter, and they can be leveraged to improve the treatment for our patients,” said Ian Krop, MD, PhD, of the Yale Cancer Center in New Haven, Connecticut, during the session where the results were presented.

But T-DXd may not be an appropriate first choice for all patients, especially given the safety concerns associated with T-DXd, he continued. With overall survival and quality-of-life data still lacking, clinicians will have to determine on a case-by-case basis who should get T-DXd in the first line.

“For patients who have symptomatic metastatic disease, who need a response to address those symptoms, those in whom you think chemotherapy may not work as well because they had, for example, a short recurrence interval after their adjuvant chemotherapy — using T-DXd in that first-line setting makes perfect sense to take advantage of the substantially higher response rate compared to chemo,” Dr. Krop said. “But for patients who have asymptomatic low burdens of disease, it seems very reasonable to consider using a well-tolerated chemotherapy like capecitabine in the first line, and then using T-DXd in the second line.”

In an interview, Erica Mayer, MD, of the Dana Farber Cancer Institute in Boston, Massachusetts, said patient choice will also matter in determining whether T-DXd is a first-line option. The known toxicity of T-DXd was underscored by the latest findings, she noted, while capecitabine, one of the chemotherapy choices in the control arm of the study, “really reflects what the majority of breast cancer doctors tend to offer, both because of the efficacy of the drug, but also because it’s oral, it’s well tolerated, and you don’t lose your hair.”
 

DESTINY-Breast07 Results

The DESTINY-Breast07 findings, from a Phase 1B open-label trial measuring safety and tolerability, were presented by Fabrice Andre, MD, PhD, of Université Paris Saclay in Paris, France. Dr. Andre and his colleagues presented the first data comparing T-DXd monotherapy and T-DXd with pertuzumab — a monoclonal antibody targeting HER2 — as a first-line treatment in patients with HER2-overexpressing (immunohistochemistry 3 and above) metastatic breast cancer. (J Clin Oncol 42, 2024 [suppl 16; abstr 1009]).

Current first-line standard of care for these patients is pertuzumab, trastuzumab, and docetaxel, based on results from the 2015 CLEOPATRA trial. T-DXd is currently approved as a second-line treatment.

Dr. Andre and his colleagues randomized 75 patients to monotherapy with T-DXd and 50 to combined therapy, with a median follow-up of 2 years.

After 1 year of treatment, combination of T-DXd and pertuzumab was seen to be associated with a progression-free survival of 89% at 1 year (80% CI, 81.9-93.9), compared with 80% in patients treated with T-DXd alone (80% CI, 73.7-86.1). Objective tumor response rate was 84% for the combined therapy at 12 weeks, with 20% of patients seeing a complete response, compared with 76% and 8%, respectively, for monotherapy.

As in the DESTINY-Breast06 trial, adverse events were high, with interstitial lung disease seen in 9% of patients in the monotherapy group and in 14% of the combined-therapy patients, although no treatment-related deaths occurred.

A randomized phase 3 trial, DESTINY Breast09, will now compare the monotherapy and the combined therapy with standard care.

T-DXd has seen a rapidly expanding role in treating breast and other solid tumors. The DESTINY Breast06 findings will move up its place in the treatment algorithm for metastatic breast cancer, “allowing us to now offer T-DXd as the first chemotherapy choice for patients who are making that transition to chemotherapy over many of the traditional provider choices that we previously have offered,” Dr. Mayer said.

The results “support the use of not only this specific agent, but also the concept of antibody drug conjugates as a very effective way to treat malignancy,” she added.

Dr. Curigliano reported receiving speaker’s fees, research funding, and other support from AstraZeneca and Daiichi Sankyo, among other companies, as did most of his co-authors, of whom three were AstraZeneca employees. Dr. Fabrice disclosed receiving research funding, travel compensation, and/or advisory fees from AstraZeneca and other entities, as did several of his co-authors. Two of his co-authors were employed by AstraZeneca and Roche, manufacturers of the study drugs. Dr. Krop and Dr. Mayer disclosed relationships with AstraZeneca and others.

The antibody-drug conjugate trastuzumab deruxtecan, or T-DXd, is an effective first-line treatment in patients with HER2-low metastatic breast cancer, conferring an additional 5 months’ progression-free survival over chemotherapy.

HER2-low cancers express levels of human epidermal growth factor receptor 2 that are below standard thresholds for HER2-positive immunohistochemistry. In 2022, results from the DESTINY-Breast04 trial showed T-DXd (Enhertu, AstraZeneca) to be an effective second-line chemotherapy in patients with HER2-low metastatic breast cancer.

The highly awaited new findings, from the manufacturer-sponsored, open-label Phase 3 DESTINY-Breast06 trial, were presented at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, Illinois.

The findings not only definitively establish a role for T-DXd earlier in the treatment sequence for HER2-low cancers, they also suggest benefit in a group of patients designated for the purposes of this trial to be HER2-ultralow. These patients have cancers with only faintly detectable HER2 expression on currently used assays (J Clin Oncol 42, 2024 [suppl 17; abstr LBA 1000]).

In a separate set of findings also presented at ASCO, from the randomized phase 1B open-label study, DESTINY-Breast07, T-Dxd showed efficacy in previously untreated HER2-positive metastatic breast cancer patients both alone and in combination with the monoclonal antibody pertuzumab (Perjeta, Genentech).
 

DESTINY-Breast06 Methods and Results

The DESTINY-Breast06 findings were presented by lead investigator Guiseppe Curigliano, MD, PhD, of the University of Milan and European Institute of Oncology. Dr. Curigliano and his colleagues randomized 866 patients with metastatic breast cancer: 436 to intravenous T-Dxd and 430 to the investigator’s choice of capecitabine, nab-paclitaxel, or paclitaxel chemotherapy. The investigators chose capecitabine 60% of the time.

Most patients had cancers classed as HER2 low (immunohistochemistry 1+ or 2+), while 153 had cancers classed by investigators as HER2-ultralow (IHC 0 with membrane staining or IHC under 1+). Patients enrolled in the study were those whose disease had progressed after endocrine therapy with or without targeted therapy. Patients’ median age was between 57 and 58, and all were chemotherapy-naive in the metastatic breast cancer setting.

The main outcome of the study was median progression-free survival in the HER2-low group. T-Dxd was seen improving progression-free survival, with median 13.2 months vs. 8.1 months (hazard ratio, 0.62; 95% confidence interval, 0.51-0.74; P < .0001). In the intention-to-treat population, which included the HER2 ultralow patients, the benefit was the same (HR, 0.63; 95% CI, 0.53-0.75; P < .0001). This suggested that T-DXd is also effective in these patients, and it will be extremely important going forward to identify the lowest level of HER2 expression in metastatic breast cancers that can still benefit from therapy with T-DxD, Dr. Curigliano said.

Overall survival could not be assessed in the study cohort because complete data were not yet available, Dr. Curigliano said. However, trends pointed to an advantage for T-DXd, and tumor response rates were markedly higher with T-DXd: 57% compared with 31% for standard chemotherapy in the full cohort.

Serious treatment-emergent adverse events were more common in the T-Dxd–treated patients, with 11% of that arm developing drug-related interstitial lung disease, and three patients dying of it. Five patients in the T-DXd arm died of adverse events deemed treatment-related, and none died from treatment-related adverse events in the standard chemotherapy arm. Altogether 11 patients died in the T-DXd arm and 6 in the chemotherapy arm.
 

Clinical Implications of DESTINY-Breast06

The DESTINY-Breast06 data show that “we have to again change how we think about HER2 expression. Even very low levels of HER2 expression matter, and they can be leveraged to improve the treatment for our patients,” said Ian Krop, MD, PhD, of the Yale Cancer Center in New Haven, Connecticut, during the session where the results were presented.

But T-DXd may not be an appropriate first choice for all patients, especially given the safety concerns associated with T-DXd, he continued. With overall survival and quality-of-life data still lacking, clinicians will have to determine on a case-by-case basis who should get T-DXd in the first line.

“For patients who have symptomatic metastatic disease, who need a response to address those symptoms, those in whom you think chemotherapy may not work as well because they had, for example, a short recurrence interval after their adjuvant chemotherapy — using T-DXd in that first-line setting makes perfect sense to take advantage of the substantially higher response rate compared to chemo,” Dr. Krop said. “But for patients who have asymptomatic low burdens of disease, it seems very reasonable to consider using a well-tolerated chemotherapy like capecitabine in the first line, and then using T-DXd in the second line.”

In an interview, Erica Mayer, MD, of the Dana Farber Cancer Institute in Boston, Massachusetts, said patient choice will also matter in determining whether T-DXd is a first-line option. The known toxicity of T-DXd was underscored by the latest findings, she noted, while capecitabine, one of the chemotherapy choices in the control arm of the study, “really reflects what the majority of breast cancer doctors tend to offer, both because of the efficacy of the drug, but also because it’s oral, it’s well tolerated, and you don’t lose your hair.”
 

DESTINY-Breast07 Results

The DESTINY-Breast07 findings, from a Phase 1B open-label trial measuring safety and tolerability, were presented by Fabrice Andre, MD, PhD, of Université Paris Saclay in Paris, France. Dr. Andre and his colleagues presented the first data comparing T-DXd monotherapy and T-DXd with pertuzumab — a monoclonal antibody targeting HER2 — as a first-line treatment in patients with HER2-overexpressing (immunohistochemistry 3 and above) metastatic breast cancer. (J Clin Oncol 42, 2024 [suppl 16; abstr 1009]).

Current first-line standard of care for these patients is pertuzumab, trastuzumab, and docetaxel, based on results from the 2015 CLEOPATRA trial. T-DXd is currently approved as a second-line treatment.

Dr. Andre and his colleagues randomized 75 patients to monotherapy with T-DXd and 50 to combined therapy, with a median follow-up of 2 years.

After 1 year of treatment, combination of T-DXd and pertuzumab was seen to be associated with a progression-free survival of 89% at 1 year (80% CI, 81.9-93.9), compared with 80% in patients treated with T-DXd alone (80% CI, 73.7-86.1). Objective tumor response rate was 84% for the combined therapy at 12 weeks, with 20% of patients seeing a complete response, compared with 76% and 8%, respectively, for monotherapy.

As in the DESTINY-Breast06 trial, adverse events were high, with interstitial lung disease seen in 9% of patients in the monotherapy group and in 14% of the combined-therapy patients, although no treatment-related deaths occurred.

A randomized phase 3 trial, DESTINY Breast09, will now compare the monotherapy and the combined therapy with standard care.

T-DXd has seen a rapidly expanding role in treating breast and other solid tumors. The DESTINY Breast06 findings will move up its place in the treatment algorithm for metastatic breast cancer, “allowing us to now offer T-DXd as the first chemotherapy choice for patients who are making that transition to chemotherapy over many of the traditional provider choices that we previously have offered,” Dr. Mayer said.

The results “support the use of not only this specific agent, but also the concept of antibody drug conjugates as a very effective way to treat malignancy,” she added.

Dr. Curigliano reported receiving speaker’s fees, research funding, and other support from AstraZeneca and Daiichi Sankyo, among other companies, as did most of his co-authors, of whom three were AstraZeneca employees. Dr. Fabrice disclosed receiving research funding, travel compensation, and/or advisory fees from AstraZeneca and other entities, as did several of his co-authors. Two of his co-authors were employed by AstraZeneca and Roche, manufacturers of the study drugs. Dr. Krop and Dr. Mayer disclosed relationships with AstraZeneca and others.

The antibody-drug conjugate trastuzumab deruxtecan, or T-DXd, is an effective first-line treatment in patients with HER2-low metastatic breast cancer, conferring an additional 5 months’ progression-free survival over chemotherapy.

HER2-low cancers express levels of human epidermal growth factor receptor 2 that are below standard thresholds for HER2-positive immunohistochemistry. In 2022, results from the DESTINY-Breast04 trial showed T-DXd (Enhertu, AstraZeneca) to be an effective second-line chemotherapy in patients with HER2-low metastatic breast cancer.

The highly awaited new findings, from the manufacturer-sponsored, open-label Phase 3 DESTINY-Breast06 trial, were presented at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, Illinois.

The findings not only definitively establish a role for T-DXd earlier in the treatment sequence for HER2-low cancers, they also suggest benefit in a group of patients designated for the purposes of this trial to be HER2-ultralow. These patients have cancers with only faintly detectable HER2 expression on currently used assays (J Clin Oncol 42, 2024 [suppl 17; abstr LBA 1000]).

In a separate set of findings also presented at ASCO, from the randomized phase 1B open-label study, DESTINY-Breast07, T-Dxd showed efficacy in previously untreated HER2-positive metastatic breast cancer patients both alone and in combination with the monoclonal antibody pertuzumab (Perjeta, Genentech).
 

DESTINY-Breast06 Methods and Results

The DESTINY-Breast06 findings were presented by lead investigator Guiseppe Curigliano, MD, PhD, of the University of Milan and European Institute of Oncology. Dr. Curigliano and his colleagues randomized 866 patients with metastatic breast cancer: 436 to intravenous T-Dxd and 430 to the investigator’s choice of capecitabine, nab-paclitaxel, or paclitaxel chemotherapy. The investigators chose capecitabine 60% of the time.

Most patients had cancers classed as HER2 low (immunohistochemistry 1+ or 2+), while 153 had cancers classed by investigators as HER2-ultralow (IHC 0 with membrane staining or IHC under 1+). Patients enrolled in the study were those whose disease had progressed after endocrine therapy with or without targeted therapy. Patients’ median age was between 57 and 58, and all were chemotherapy-naive in the metastatic breast cancer setting.

The main outcome of the study was median progression-free survival in the HER2-low group. T-Dxd was seen improving progression-free survival, with median 13.2 months vs. 8.1 months (hazard ratio, 0.62; 95% confidence interval, 0.51-0.74; P < .0001). In the intention-to-treat population, which included the HER2 ultralow patients, the benefit was the same (HR, 0.63; 95% CI, 0.53-0.75; P < .0001). This suggested that T-DXd is also effective in these patients, and it will be extremely important going forward to identify the lowest level of HER2 expression in metastatic breast cancers that can still benefit from therapy with T-DxD, Dr. Curigliano said.

Overall survival could not be assessed in the study cohort because complete data were not yet available, Dr. Curigliano said. However, trends pointed to an advantage for T-DXd, and tumor response rates were markedly higher with T-DXd: 57% compared with 31% for standard chemotherapy in the full cohort.

Serious treatment-emergent adverse events were more common in the T-Dxd–treated patients, with 11% of that arm developing drug-related interstitial lung disease, and three patients dying of it. Five patients in the T-DXd arm died of adverse events deemed treatment-related, and none died from treatment-related adverse events in the standard chemotherapy arm. Altogether 11 patients died in the T-DXd arm and 6 in the chemotherapy arm.
 

Clinical Implications of DESTINY-Breast06

The DESTINY-Breast06 data show that “we have to again change how we think about HER2 expression. Even very low levels of HER2 expression matter, and they can be leveraged to improve the treatment for our patients,” said Ian Krop, MD, PhD, of the Yale Cancer Center in New Haven, Connecticut, during the session where the results were presented.

But T-DXd may not be an appropriate first choice for all patients, especially given the safety concerns associated with T-DXd, he continued. With overall survival and quality-of-life data still lacking, clinicians will have to determine on a case-by-case basis who should get T-DXd in the first line.

“For patients who have symptomatic metastatic disease, who need a response to address those symptoms, those in whom you think chemotherapy may not work as well because they had, for example, a short recurrence interval after their adjuvant chemotherapy — using T-DXd in that first-line setting makes perfect sense to take advantage of the substantially higher response rate compared to chemo,” Dr. Krop said. “But for patients who have asymptomatic low burdens of disease, it seems very reasonable to consider using a well-tolerated chemotherapy like capecitabine in the first line, and then using T-DXd in the second line.”

In an interview, Erica Mayer, MD, of the Dana Farber Cancer Institute in Boston, Massachusetts, said patient choice will also matter in determining whether T-DXd is a first-line option. The known toxicity of T-DXd was underscored by the latest findings, she noted, while capecitabine, one of the chemotherapy choices in the control arm of the study, “really reflects what the majority of breast cancer doctors tend to offer, both because of the efficacy of the drug, but also because it’s oral, it’s well tolerated, and you don’t lose your hair.”
 

DESTINY-Breast07 Results

The DESTINY-Breast07 findings, from a Phase 1B open-label trial measuring safety and tolerability, were presented by Fabrice Andre, MD, PhD, of Université Paris Saclay in Paris, France. Dr. Andre and his colleagues presented the first data comparing T-DXd monotherapy and T-DXd with pertuzumab — a monoclonal antibody targeting HER2 — as a first-line treatment in patients with HER2-overexpressing (immunohistochemistry 3 and above) metastatic breast cancer. (J Clin Oncol 42, 2024 [suppl 16; abstr 1009]).

Current first-line standard of care for these patients is pertuzumab, trastuzumab, and docetaxel, based on results from the 2015 CLEOPATRA trial. T-DXd is currently approved as a second-line treatment.

Dr. Andre and his colleagues randomized 75 patients to monotherapy with T-DXd and 50 to combined therapy, with a median follow-up of 2 years.

After 1 year of treatment, combination of T-DXd and pertuzumab was seen to be associated with a progression-free survival of 89% at 1 year (80% CI, 81.9-93.9), compared with 80% in patients treated with T-DXd alone (80% CI, 73.7-86.1). Objective tumor response rate was 84% for the combined therapy at 12 weeks, with 20% of patients seeing a complete response, compared with 76% and 8%, respectively, for monotherapy.

As in the DESTINY-Breast06 trial, adverse events were high, with interstitial lung disease seen in 9% of patients in the monotherapy group and in 14% of the combined-therapy patients, although no treatment-related deaths occurred.

A randomized phase 3 trial, DESTINY Breast09, will now compare the monotherapy and the combined therapy with standard care.

T-DXd has seen a rapidly expanding role in treating breast and other solid tumors. The DESTINY Breast06 findings will move up its place in the treatment algorithm for metastatic breast cancer, “allowing us to now offer T-DXd as the first chemotherapy choice for patients who are making that transition to chemotherapy over many of the traditional provider choices that we previously have offered,” Dr. Mayer said.

The results “support the use of not only this specific agent, but also the concept of antibody drug conjugates as a very effective way to treat malignancy,” she added.

Dr. Curigliano reported receiving speaker’s fees, research funding, and other support from AstraZeneca and Daiichi Sankyo, among other companies, as did most of his co-authors, of whom three were AstraZeneca employees. Dr. Fabrice disclosed receiving research funding, travel compensation, and/or advisory fees from AstraZeneca and other entities, as did several of his co-authors. Two of his co-authors were employed by AstraZeneca and Roche, manufacturers of the study drugs. Dr. Krop and Dr. Mayer disclosed relationships with AstraZeneca and others.

Dual therapy of ibrutinib (Imbruvica) and venetoclax (Venclexta) produced “promising” and comparable efficacy across cohorts of patients with mantle cell lymphoma (MCL) and TP53 mutations, a new analysis of the randomized, double-blind, phase 3 Sympatico study finds.

In first-line patients (n = 29) and relapsed/refractory patients (n = 45) with TP53 mutations, complete response rates were 55% and 58%, respectively, reported hematologist-oncologist Michael Wang, MD, of the University of Texas MD Anderson Cancer Center, and colleagues, at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago.

“These results are encouraging in light of the poor responses and shorter survival outcomes with standard chemotherapy,” Dr. Wang said in an ASCO presentation.

The current standard of care for relapsed/refractory MCL includes Bruton tyrosine kinase inhibitors for first relapse and CAR T-cell therapy (CAR-T) for second relapse in eligible patients or pirtobrutinib (Jaypirca) in patients ineligible for CAR T-cell therapy, Ohio State University Comprehensive Cancer Center hematology specialist Narendranath Epperla, MD, MS, said in an interview. Dr. Epperla is familiar with the new study findings but didn’t take part in the research.

Options for third relapse and beyond include clinical trial, rituximab [Rituxan] and lenalidomide [Revlimid], and bortezomib [Velcade],” Dr. Epperla said. “Venetoclax is not currently FDA-approved but can also be considered at third relapse.”

Better therapies are needed for a number of reasons, including poor outcomes in high-risk patients, such as those with TP53 mutations and those who progress following CAR T, Dr. Epperla said. Also, “as the novel agents are being moved into earlier lines of therapy, there remains an unmet need in those who progress on these agents with fewer options in the relapsed setting.”

At last December’s American Society of Hematology annual meeting, Dr. Wang and colleagues reported on the primary analysis results from the Sympatico study. Patients with relapsed/refractory MCL after 1-5 prior therapies were randomly assigned to receive 560 mg of ibrutinib once daily with either placebo (n = 133) or 400 mg daily of venetoclax after ramp-up (n = 134) for 2 years. Then subjects continued taking ibrutinib alone until their disease progressed or they reached unacceptable toxicity.

At a median follow-up of 51.2 months, median progression-free survival was longer in the ibrutinib-venetoclax group vs. ibrutinib alone (hazard ratio [HR] = 0.65, 95% CI, P = .0052).

The new analysis pools several cohorts of patients with TP53 mutations who all took the combination therapy: 5 from a safety run-in phase, 40 from the randomized phase, and 29 from a first-line cohort (median age at baseline = 67).

Median overall survival was not reached in the first-line group and 35.0 months in the relapsed/refractory group (total = 47.1 months). Median progress-free survival in the groups was 22.0 months and 20.9 months, respectively, and median duration of response was 20.5 months and 26.5 months, respectively.

With regard to the new findings, “it is good to see the responses with ibrutinib and venetoclax were deep and durable,” Dr. Epperla said. The combination treatment “provides a good alternative option for TP53-mutated MCL patients who are ineligible for CAR-T.”

Dr. Epperla added that the findings about the addition of ibrutinib could apply to newer-generation Bruton tyrosine kinase inhibitors that have relatively better safety profiles.

However, Dr. Epperla cautioned that the treatment needs to be weighed against the toxicity and cost of the regimen of ibrutinib and venetoclax for 2 years then single-agent ibrutinib until progression or unacceptable toxicity.

This news organization reported in 2023 that estimated net spending on ibrutinib per Medicare data increased by nearly half from 2014-2020, reaching $11,980 in 2020 vs. $7,787 for venetoclax.

Dr. Epperla also noted that “there are newer therapies that are emerging, such as T-cell-engaging bispecific antibodies, and they have shown promising results.”

In an interview, Brad S. Kahl, MD, a hematologist-oncologist at Washington University, St. Louis, said the improvement in outcomes are “modestly significant.”

Dr. Kahl, who is familiar with the study findings but didn’t take part in the research, said it is “worth adding the venetoclax, particularly in these biologically high risk patients with p53 mutations. Venetoclax is not FDA-approved, so insurance approval will need to be determined on a case-by-case basis. The combination is very expensive.”

Dr. Kahl agreed with Dr. Epperla that the findings could be extrapolated to other Bruton tyrosine kinase inhibitors.

The study was funded by Pharmacyclics, an AbbVie Company. Dr. Epperla disclosed relationships with BeiGene and Eli Lilly. Dr. Kahl reported ties with AstraZeneca, BeiGene, Abbvie, and Genentech.

Dual therapy of ibrutinib (Imbruvica) and venetoclax (Venclexta) produced “promising” and comparable efficacy across cohorts of patients with mantle cell lymphoma (MCL) and TP53 mutations, a new analysis of the randomized, double-blind, phase 3 Sympatico study finds.

In first-line patients (n = 29) and relapsed/refractory patients (n = 45) with TP53 mutations, complete response rates were 55% and 58%, respectively, reported hematologist-oncologist Michael Wang, MD, of the University of Texas MD Anderson Cancer Center, and colleagues, at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago.

“These results are encouraging in light of the poor responses and shorter survival outcomes with standard chemotherapy,” Dr. Wang said in an ASCO presentation.

The current standard of care for relapsed/refractory MCL includes Bruton tyrosine kinase inhibitors for first relapse and CAR T-cell therapy (CAR-T) for second relapse in eligible patients or pirtobrutinib (Jaypirca) in patients ineligible for CAR T-cell therapy, Ohio State University Comprehensive Cancer Center hematology specialist Narendranath Epperla, MD, MS, said in an interview. Dr. Epperla is familiar with the new study findings but didn’t take part in the research.

Options for third relapse and beyond include clinical trial, rituximab [Rituxan] and lenalidomide [Revlimid], and bortezomib [Velcade],” Dr. Epperla said. “Venetoclax is not currently FDA-approved but can also be considered at third relapse.”

Better therapies are needed for a number of reasons, including poor outcomes in high-risk patients, such as those with TP53 mutations and those who progress following CAR T, Dr. Epperla said. Also, “as the novel agents are being moved into earlier lines of therapy, there remains an unmet need in those who progress on these agents with fewer options in the relapsed setting.”

At last December’s American Society of Hematology annual meeting, Dr. Wang and colleagues reported on the primary analysis results from the Sympatico study. Patients with relapsed/refractory MCL after 1-5 prior therapies were randomly assigned to receive 560 mg of ibrutinib once daily with either placebo (n = 133) or 400 mg daily of venetoclax after ramp-up (n = 134) for 2 years. Then subjects continued taking ibrutinib alone until their disease progressed or they reached unacceptable toxicity.

At a median follow-up of 51.2 months, median progression-free survival was longer in the ibrutinib-venetoclax group vs. ibrutinib alone (hazard ratio [HR] = 0.65, 95% CI, P = .0052).

The new analysis pools several cohorts of patients with TP53 mutations who all took the combination therapy: 5 from a safety run-in phase, 40 from the randomized phase, and 29 from a first-line cohort (median age at baseline = 67).

Median overall survival was not reached in the first-line group and 35.0 months in the relapsed/refractory group (total = 47.1 months). Median progress-free survival in the groups was 22.0 months and 20.9 months, respectively, and median duration of response was 20.5 months and 26.5 months, respectively.

With regard to the new findings, “it is good to see the responses with ibrutinib and venetoclax were deep and durable,” Dr. Epperla said. The combination treatment “provides a good alternative option for TP53-mutated MCL patients who are ineligible for CAR-T.”

Dr. Epperla added that the findings about the addition of ibrutinib could apply to newer-generation Bruton tyrosine kinase inhibitors that have relatively better safety profiles.

However, Dr. Epperla cautioned that the treatment needs to be weighed against the toxicity and cost of the regimen of ibrutinib and venetoclax for 2 years then single-agent ibrutinib until progression or unacceptable toxicity.

This news organization reported in 2023 that estimated net spending on ibrutinib per Medicare data increased by nearly half from 2014-2020, reaching $11,980 in 2020 vs. $7,787 for venetoclax.

Dr. Epperla also noted that “there are newer therapies that are emerging, such as T-cell-engaging bispecific antibodies, and they have shown promising results.”

In an interview, Brad S. Kahl, MD, a hematologist-oncologist at Washington University, St. Louis, said the improvement in outcomes are “modestly significant.”

Dr. Kahl, who is familiar with the study findings but didn’t take part in the research, said it is “worth adding the venetoclax, particularly in these biologically high risk patients with p53 mutations. Venetoclax is not FDA-approved, so insurance approval will need to be determined on a case-by-case basis. The combination is very expensive.”

Dr. Kahl agreed with Dr. Epperla that the findings could be extrapolated to other Bruton tyrosine kinase inhibitors.

The study was funded by Pharmacyclics, an AbbVie Company. Dr. Epperla disclosed relationships with BeiGene and Eli Lilly. Dr. Kahl reported ties with AstraZeneca, BeiGene, Abbvie, and Genentech.

Dual therapy of ibrutinib (Imbruvica) and venetoclax (Venclexta) produced “promising” and comparable efficacy across cohorts of patients with mantle cell lymphoma (MCL) and TP53 mutations, a new analysis of the randomized, double-blind, phase 3 Sympatico study finds.

In first-line patients (n = 29) and relapsed/refractory patients (n = 45) with TP53 mutations, complete response rates were 55% and 58%, respectively, reported hematologist-oncologist Michael Wang, MD, of the University of Texas MD Anderson Cancer Center, and colleagues, at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago.

“These results are encouraging in light of the poor responses and shorter survival outcomes with standard chemotherapy,” Dr. Wang said in an ASCO presentation.

The current standard of care for relapsed/refractory MCL includes Bruton tyrosine kinase inhibitors for first relapse and CAR T-cell therapy (CAR-T) for second relapse in eligible patients or pirtobrutinib (Jaypirca) in patients ineligible for CAR T-cell therapy, Ohio State University Comprehensive Cancer Center hematology specialist Narendranath Epperla, MD, MS, said in an interview. Dr. Epperla is familiar with the new study findings but didn’t take part in the research.

Options for third relapse and beyond include clinical trial, rituximab [Rituxan] and lenalidomide [Revlimid], and bortezomib [Velcade],” Dr. Epperla said. “Venetoclax is not currently FDA-approved but can also be considered at third relapse.”

Better therapies are needed for a number of reasons, including poor outcomes in high-risk patients, such as those with TP53 mutations and those who progress following CAR T, Dr. Epperla said. Also, “as the novel agents are being moved into earlier lines of therapy, there remains an unmet need in those who progress on these agents with fewer options in the relapsed setting.”

At last December’s American Society of Hematology annual meeting, Dr. Wang and colleagues reported on the primary analysis results from the Sympatico study. Patients with relapsed/refractory MCL after 1-5 prior therapies were randomly assigned to receive 560 mg of ibrutinib once daily with either placebo (n = 133) or 400 mg daily of venetoclax after ramp-up (n = 134) for 2 years. Then subjects continued taking ibrutinib alone until their disease progressed or they reached unacceptable toxicity.

At a median follow-up of 51.2 months, median progression-free survival was longer in the ibrutinib-venetoclax group vs. ibrutinib alone (hazard ratio [HR] = 0.65, 95% CI, P = .0052).

The new analysis pools several cohorts of patients with TP53 mutations who all took the combination therapy: 5 from a safety run-in phase, 40 from the randomized phase, and 29 from a first-line cohort (median age at baseline = 67).

Median overall survival was not reached in the first-line group and 35.0 months in the relapsed/refractory group (total = 47.1 months). Median progress-free survival in the groups was 22.0 months and 20.9 months, respectively, and median duration of response was 20.5 months and 26.5 months, respectively.

With regard to the new findings, “it is good to see the responses with ibrutinib and venetoclax were deep and durable,” Dr. Epperla said. The combination treatment “provides a good alternative option for TP53-mutated MCL patients who are ineligible for CAR-T.”

Dr. Epperla added that the findings about the addition of ibrutinib could apply to newer-generation Bruton tyrosine kinase inhibitors that have relatively better safety profiles.

However, Dr. Epperla cautioned that the treatment needs to be weighed against the toxicity and cost of the regimen of ibrutinib and venetoclax for 2 years then single-agent ibrutinib until progression or unacceptable toxicity.

This news organization reported in 2023 that estimated net spending on ibrutinib per Medicare data increased by nearly half from 2014-2020, reaching $11,980 in 2020 vs. $7,787 for venetoclax.

Dr. Epperla also noted that “there are newer therapies that are emerging, such as T-cell-engaging bispecific antibodies, and they have shown promising results.”

In an interview, Brad S. Kahl, MD, a hematologist-oncologist at Washington University, St. Louis, said the improvement in outcomes are “modestly significant.”

Dr. Kahl, who is familiar with the study findings but didn’t take part in the research, said it is “worth adding the venetoclax, particularly in these biologically high risk patients with p53 mutations. Venetoclax is not FDA-approved, so insurance approval will need to be determined on a case-by-case basis. The combination is very expensive.”

Dr. Kahl agreed with Dr. Epperla that the findings could be extrapolated to other Bruton tyrosine kinase inhibitors.

The study was funded by Pharmacyclics, an AbbVie Company. Dr. Epperla disclosed relationships with BeiGene and Eli Lilly. Dr. Kahl reported ties with AstraZeneca, BeiGene, Abbvie, and Genentech.

In just 4 years, there’s been a significant evolution in the profile of pediatric and young adult patients who’ve taken the chimeric antigen receptor (CAR) T-cell immunotherapy known as tisagenlecleucel (Kymriah) for relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL), a new industry-funded study finds.

It’s becoming more common for patients with less severe disease to undergo the treatment, often bypassing hematopoietic stem cell transplantation (HSCT), and survival is on the rise.

From 2018 to 2022, the percentage of patients in an international cohort who had disease burden of ≥50% fell from 18% to 4%, researchers reported at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago. Median relapse-free survival in patients who didn’t undergo post-infusion HSCT grew from 18 months in 2018 to 27 months in 2020. It was not estimable in 2021.

“This introduction of the therapy is changing the treatment landscape of how we look at refractory B-ALL, where the standard of care previously would be to proceed to transplant. This therapy is actually reducing the use of transplant, which has lots of morbidity and mortality associated with it,” Texas Children’s Cancer Center hematologist-oncologist Rayne H. Rouce, MD, who led the study, said in an interview.

Tisagenlecleucel received Food and Drug Administration approval in 2017, said Nirali N. Shah, MD, MHSc, head of the Pediatric Oncology Branch’s Hematologic Malignancies Section at the National Cancer Institute, in an interview. Dr. Shah is familiar with the study findings but didn’t take part in the research.

Remission rates have been around 60%-70%, Dr. Shah said, although that rate is “likely higher” now because of gains in experience and improvement in disease burden prior to therapy. 

The new findings fill a knowledge gap about real-world outcomes since a lot of the prior data was based on investigational CAR T-cell products, she said.

The noninterventional, prospective, longitudinal study, funded by tisagenlecleucel manufacturer Novartis, tracked 974 patients up to age 25 who received tisagenlecleucel in the United States, Canada, Korea, and Taiwan.

The study found that between 2018 and 2022:

• The percentage of patients who received treatment while in morphological complete remission grew from 34% to 51%.
• The percentages who were in third or greater relapse fell from 14% to 2%.
• The percentages undergoing ≥1 HSCT before tisagenlecleucel infusion fell from 37% to 15%.
• Overall, 34.5% of 911 patients received post-infusion HSCT.

In the big picture, the findings suggest that the therapy can be considered more than “a last resort for patients in a second or greater relapse or who are refractory,” Dr. Rouce said. By offering CAR T-cell therapy to earlier-stage patients, she said, “when they’re less sick, when they have less comorbidities, and when their organs are functioning better, we could potentially save them from having to go on to a transplant.”

Dr. Shah said the findings indicate that “a substantial number of patients are surviving. It’s remarkable actually. Prior to tisagenlecleucel, patients had dismal outcomes from standard chemotherapy.”

She added that the study suggests “providers are getting much more comfortable with getting their patients in the best shape prior to getting CAR T-cell therapy. Outcomes are improving as providers expand the use of CAR T-cell therapy to patients who are less heavily pretreated and have lower disease burden.”

Moving forward, “at some point there will likely be a plateau in terms of how good the outcomes can be.” And there will be discussion of the role of HSCT.

“We’ll figure out some of the nuances about which patients need transplants and which can avoid them. But curative potential is growing. With or without transplant, this is ultimately going to lead to a much higher fraction of patients being cured who previously would not have been cured,” she said. “That’s the bottom line.”

As for adverse effects, Dr. Shah said “disease burden has a pretty direct relationship with side effects and toxicities. If you have more disease, you have more severe side effects.”

Reducing disease burden will reduce side effects, she said. Also, “we’re getting a lot better at managing these toxicities. Eliminating some of the more toxic chemotherapy through earlier use of CAR T-cells in chemotherapy-refractory patients may well help reduce therapy burden and improve long-term survival outcomes, she added.

As for cost, drugs.com reports that the therapy runs to more than $612,000 per infusion. But Dr. Shah said insurers are covering the treatment. She added that there are efforts to expand the indication so CAR T-cell therapy can be used earlier in patients who are chemotherapy-refractory.

Novartis funded the study. Dr. Shah discloses ties with Lentigen, VOR, and CARGO, ImmunoACT, and Sobi. Dr. Rouce reports relationships with Pfizer and Novartis.

In just 4 years, there’s been a significant evolution in the profile of pediatric and young adult patients who’ve taken the chimeric antigen receptor (CAR) T-cell immunotherapy known as tisagenlecleucel (Kymriah) for relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL), a new industry-funded study finds.

It’s becoming more common for patients with less severe disease to undergo the treatment, often bypassing hematopoietic stem cell transplantation (HSCT), and survival is on the rise.

From 2018 to 2022, the percentage of patients in an international cohort who had disease burden of ≥50% fell from 18% to 4%, researchers reported at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago. Median relapse-free survival in patients who didn’t undergo post-infusion HSCT grew from 18 months in 2018 to 27 months in 2020. It was not estimable in 2021.

“This introduction of the therapy is changing the treatment landscape of how we look at refractory B-ALL, where the standard of care previously would be to proceed to transplant. This therapy is actually reducing the use of transplant, which has lots of morbidity and mortality associated with it,” Texas Children’s Cancer Center hematologist-oncologist Rayne H. Rouce, MD, who led the study, said in an interview.

Tisagenlecleucel received Food and Drug Administration approval in 2017, said Nirali N. Shah, MD, MHSc, head of the Pediatric Oncology Branch’s Hematologic Malignancies Section at the National Cancer Institute, in an interview. Dr. Shah is familiar with the study findings but didn’t take part in the research.

Remission rates have been around 60%-70%, Dr. Shah said, although that rate is “likely higher” now because of gains in experience and improvement in disease burden prior to therapy. 

The new findings fill a knowledge gap about real-world outcomes since a lot of the prior data was based on investigational CAR T-cell products, she said.

The noninterventional, prospective, longitudinal study, funded by tisagenlecleucel manufacturer Novartis, tracked 974 patients up to age 25 who received tisagenlecleucel in the United States, Canada, Korea, and Taiwan.

The study found that between 2018 and 2022:

• The percentage of patients who received treatment while in morphological complete remission grew from 34% to 51%.
• The percentages who were in third or greater relapse fell from 14% to 2%.
• The percentages undergoing ≥1 HSCT before tisagenlecleucel infusion fell from 37% to 15%.
• Overall, 34.5% of 911 patients received post-infusion HSCT.

In the big picture, the findings suggest that the therapy can be considered more than “a last resort for patients in a second or greater relapse or who are refractory,” Dr. Rouce said. By offering CAR T-cell therapy to earlier-stage patients, she said, “when they’re less sick, when they have less comorbidities, and when their organs are functioning better, we could potentially save them from having to go on to a transplant.”

Dr. Shah said the findings indicate that “a substantial number of patients are surviving. It’s remarkable actually. Prior to tisagenlecleucel, patients had dismal outcomes from standard chemotherapy.”

She added that the study suggests “providers are getting much more comfortable with getting their patients in the best shape prior to getting CAR T-cell therapy. Outcomes are improving as providers expand the use of CAR T-cell therapy to patients who are less heavily pretreated and have lower disease burden.”

Moving forward, “at some point there will likely be a plateau in terms of how good the outcomes can be.” And there will be discussion of the role of HSCT.

“We’ll figure out some of the nuances about which patients need transplants and which can avoid them. But curative potential is growing. With or without transplant, this is ultimately going to lead to a much higher fraction of patients being cured who previously would not have been cured,” she said. “That’s the bottom line.”

As for adverse effects, Dr. Shah said “disease burden has a pretty direct relationship with side effects and toxicities. If you have more disease, you have more severe side effects.”

Reducing disease burden will reduce side effects, she said. Also, “we’re getting a lot better at managing these toxicities. Eliminating some of the more toxic chemotherapy through earlier use of CAR T-cells in chemotherapy-refractory patients may well help reduce therapy burden and improve long-term survival outcomes, she added.

As for cost, drugs.com reports that the therapy runs to more than $612,000 per infusion. But Dr. Shah said insurers are covering the treatment. She added that there are efforts to expand the indication so CAR T-cell therapy can be used earlier in patients who are chemotherapy-refractory.

Novartis funded the study. Dr. Shah discloses ties with Lentigen, VOR, and CARGO, ImmunoACT, and Sobi. Dr. Rouce reports relationships with Pfizer and Novartis.

In just 4 years, there’s been a significant evolution in the profile of pediatric and young adult patients who’ve taken the chimeric antigen receptor (CAR) T-cell immunotherapy known as tisagenlecleucel (Kymriah) for relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL), a new industry-funded study finds.

It’s becoming more common for patients with less severe disease to undergo the treatment, often bypassing hematopoietic stem cell transplantation (HSCT), and survival is on the rise.

From 2018 to 2022, the percentage of patients in an international cohort who had disease burden of ≥50% fell from 18% to 4%, researchers reported at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago. Median relapse-free survival in patients who didn’t undergo post-infusion HSCT grew from 18 months in 2018 to 27 months in 2020. It was not estimable in 2021.

“This introduction of the therapy is changing the treatment landscape of how we look at refractory B-ALL, where the standard of care previously would be to proceed to transplant. This therapy is actually reducing the use of transplant, which has lots of morbidity and mortality associated with it,” Texas Children’s Cancer Center hematologist-oncologist Rayne H. Rouce, MD, who led the study, said in an interview.

Tisagenlecleucel received Food and Drug Administration approval in 2017, said Nirali N. Shah, MD, MHSc, head of the Pediatric Oncology Branch’s Hematologic Malignancies Section at the National Cancer Institute, in an interview. Dr. Shah is familiar with the study findings but didn’t take part in the research.

Remission rates have been around 60%-70%, Dr. Shah said, although that rate is “likely higher” now because of gains in experience and improvement in disease burden prior to therapy. 

The new findings fill a knowledge gap about real-world outcomes since a lot of the prior data was based on investigational CAR T-cell products, she said.

The noninterventional, prospective, longitudinal study, funded by tisagenlecleucel manufacturer Novartis, tracked 974 patients up to age 25 who received tisagenlecleucel in the United States, Canada, Korea, and Taiwan.

The study found that between 2018 and 2022:

• The percentage of patients who received treatment while in morphological complete remission grew from 34% to 51%.
• The percentages who were in third or greater relapse fell from 14% to 2%.
• The percentages undergoing ≥1 HSCT before tisagenlecleucel infusion fell from 37% to 15%.
• Overall, 34.5% of 911 patients received post-infusion HSCT.

In the big picture, the findings suggest that the therapy can be considered more than “a last resort for patients in a second or greater relapse or who are refractory,” Dr. Rouce said. By offering CAR T-cell therapy to earlier-stage patients, she said, “when they’re less sick, when they have less comorbidities, and when their organs are functioning better, we could potentially save them from having to go on to a transplant.”

Dr. Shah said the findings indicate that “a substantial number of patients are surviving. It’s remarkable actually. Prior to tisagenlecleucel, patients had dismal outcomes from standard chemotherapy.”

She added that the study suggests “providers are getting much more comfortable with getting their patients in the best shape prior to getting CAR T-cell therapy. Outcomes are improving as providers expand the use of CAR T-cell therapy to patients who are less heavily pretreated and have lower disease burden.”

Moving forward, “at some point there will likely be a plateau in terms of how good the outcomes can be.” And there will be discussion of the role of HSCT.

“We’ll figure out some of the nuances about which patients need transplants and which can avoid them. But curative potential is growing. With or without transplant, this is ultimately going to lead to a much higher fraction of patients being cured who previously would not have been cured,” she said. “That’s the bottom line.”

As for adverse effects, Dr. Shah said “disease burden has a pretty direct relationship with side effects and toxicities. If you have more disease, you have more severe side effects.”

Reducing disease burden will reduce side effects, she said. Also, “we’re getting a lot better at managing these toxicities. Eliminating some of the more toxic chemotherapy through earlier use of CAR T-cells in chemotherapy-refractory patients may well help reduce therapy burden and improve long-term survival outcomes, she added.

As for cost, drugs.com reports that the therapy runs to more than $612,000 per infusion. But Dr. Shah said insurers are covering the treatment. She added that there are efforts to expand the indication so CAR T-cell therapy can be used earlier in patients who are chemotherapy-refractory.

Novartis funded the study. Dr. Shah discloses ties with Lentigen, VOR, and CARGO, ImmunoACT, and Sobi. Dr. Rouce reports relationships with Pfizer and Novartis.

CHICAGO — Genetics and diet have been among the top theories for what may be fueling the troubling rise of colorectal cancer in young adults. Now, an early look at genetic data from people with colorectal cancer further suggests that the cause is linked to what is happening in the gut.

The findings were presented at the annual meeting of the American Society for Clinical Oncology (ASCO) by researchers from Ohio State University. For the analysis, they analyzed genetic data on tumors.

The researchers found signs that a high-fat, low-fiber diet may increase inflammation in the gut that prevents it from naturally suppressing tumors. The cells of young people with colorectal cancer also appeared to have aged more quickly — by 15 years on average — than a person’s actual age. That’s unusual, because older people with colorectal cancer don’t have the same boost in cellular aging.

The rate of colorectal cancer among young people has been rising at an alarming rate, according to a 2023 report from the American Cancer Society. In 2019, one in five colorectal cancer cases were among people younger than 55. That’s up from 1 in 10 in 1995, which means the rate has doubled in less than 30 years.
 

Need Colon Cancer Screening?

Who needs a colorectal cancer screening? Ask colorectal cancer specialist Nancy Kemeny, MD.

A 2017 analysis estimated that a person’s risk of colorectal cancer increased 12% by eating 3.5 ounces of red or processed meat daily, which is the equivalent of the size of a deck of playing cards. The same study also linked colorectal cancer risk to alcohol intake, citing its ethanol content. Eating a diet high in fiber can reduce a person’s risk.

This latest study aligned with previous findings that link bacteria called Fusobacterium to colorectal cancer. It’s not unusual for Fusobacterium to be present in a person’s mouth, but it is more likely to be found in the intestines of colorectal cancer patients, compared with those of healthy people. One study even found that people with colorectal cancer were five times more likely to have Fusobacterium in their stool, compared with healthy people.

Colorectal cancer is more common among men than women, “likely reflecting differences in risk factor prevalence, such as excess body weight and processed meat consumption,” the authors of the 2023 American Cancer Society report explained.

People younger than 45 should alert their medical provider if they have constipation, rectal bleeding, or sudden changes in bowel movements, which can be symptoms of colorectal cancer. Screening for colorectal cancer should begin for most people at age 45.

A version of this article appeared on WebMD.com.

CHICAGO — Genetics and diet have been among the top theories for what may be fueling the troubling rise of colorectal cancer in young adults. Now, an early look at genetic data from people with colorectal cancer further suggests that the cause is linked to what is happening in the gut.

The findings were presented at the annual meeting of the American Society for Clinical Oncology (ASCO) by researchers from Ohio State University. For the analysis, they analyzed genetic data on tumors.

The researchers found signs that a high-fat, low-fiber diet may increase inflammation in the gut that prevents it from naturally suppressing tumors. The cells of young people with colorectal cancer also appeared to have aged more quickly — by 15 years on average — than a person’s actual age. That’s unusual, because older people with colorectal cancer don’t have the same boost in cellular aging.

The rate of colorectal cancer among young people has been rising at an alarming rate, according to a 2023 report from the American Cancer Society. In 2019, one in five colorectal cancer cases were among people younger than 55. That’s up from 1 in 10 in 1995, which means the rate has doubled in less than 30 years.
 

Need Colon Cancer Screening?

Who needs a colorectal cancer screening? Ask colorectal cancer specialist Nancy Kemeny, MD.

A 2017 analysis estimated that a person’s risk of colorectal cancer increased 12% by eating 3.5 ounces of red or processed meat daily, which is the equivalent of the size of a deck of playing cards. The same study also linked colorectal cancer risk to alcohol intake, citing its ethanol content. Eating a diet high in fiber can reduce a person’s risk.

This latest study aligned with previous findings that link bacteria called Fusobacterium to colorectal cancer. It’s not unusual for Fusobacterium to be present in a person’s mouth, but it is more likely to be found in the intestines of colorectal cancer patients, compared with those of healthy people. One study even found that people with colorectal cancer were five times more likely to have Fusobacterium in their stool, compared with healthy people.

Colorectal cancer is more common among men than women, “likely reflecting differences in risk factor prevalence, such as excess body weight and processed meat consumption,” the authors of the 2023 American Cancer Society report explained.

People younger than 45 should alert their medical provider if they have constipation, rectal bleeding, or sudden changes in bowel movements, which can be symptoms of colorectal cancer. Screening for colorectal cancer should begin for most people at age 45.

A version of this article appeared on WebMD.com.

CHICAGO — Genetics and diet have been among the top theories for what may be fueling the troubling rise of colorectal cancer in young adults. Now, an early look at genetic data from people with colorectal cancer further suggests that the cause is linked to what is happening in the gut.

The findings were presented at the annual meeting of the American Society for Clinical Oncology (ASCO) by researchers from Ohio State University. For the analysis, they analyzed genetic data on tumors.

The researchers found signs that a high-fat, low-fiber diet may increase inflammation in the gut that prevents it from naturally suppressing tumors. The cells of young people with colorectal cancer also appeared to have aged more quickly — by 15 years on average — than a person’s actual age. That’s unusual, because older people with colorectal cancer don’t have the same boost in cellular aging.

The rate of colorectal cancer among young people has been rising at an alarming rate, according to a 2023 report from the American Cancer Society. In 2019, one in five colorectal cancer cases were among people younger than 55. That’s up from 1 in 10 in 1995, which means the rate has doubled in less than 30 years.
 

Need Colon Cancer Screening?

Who needs a colorectal cancer screening? Ask colorectal cancer specialist Nancy Kemeny, MD.

A 2017 analysis estimated that a person’s risk of colorectal cancer increased 12% by eating 3.5 ounces of red or processed meat daily, which is the equivalent of the size of a deck of playing cards. The same study also linked colorectal cancer risk to alcohol intake, citing its ethanol content. Eating a diet high in fiber can reduce a person’s risk.

This latest study aligned with previous findings that link bacteria called Fusobacterium to colorectal cancer. It’s not unusual for Fusobacterium to be present in a person’s mouth, but it is more likely to be found in the intestines of colorectal cancer patients, compared with those of healthy people. One study even found that people with colorectal cancer were five times more likely to have Fusobacterium in their stool, compared with healthy people.

Colorectal cancer is more common among men than women, “likely reflecting differences in risk factor prevalence, such as excess body weight and processed meat consumption,” the authors of the 2023 American Cancer Society report explained.

People younger than 45 should alert their medical provider if they have constipation, rectal bleeding, or sudden changes in bowel movements, which can be symptoms of colorectal cancer. Screening for colorectal cancer should begin for most people at age 45.

A version of this article appeared on WebMD.com.

CHICAGO — Osimertinib (Tagrisso) may soon have approvals across all stages of epidermal growth factor receptor (EGFR)–mutated non–small cell lung cancer (NSCLC).

The third-generation EGFR tyrosine kinase inhibitor (TKI) already carries indications for metastatic disease and for adjuvant use in earlier-stage EGFR-mutated NSCLC.

Results from the phase 3 LAURA trial, presented at the American Society of Clinical Oncology (ASCO) annual meeting and funded by AstraZeneca, will likely lead to an approval for the remaining indication: Unresectable stage III disease.

Among patients randomized to either osimertinib or placebo following definitive chemoradiation, osimertinib extended median progression-free survival by 33.5 months compared with placebo — 39.1 vs 5.6 months, respectively (hazard ratio, 0.16; P = .001).

The news was greeted with a standing ovation at the meeting where it was presented by lead investigator and medical oncologist Suresh S. Ramalingam, MD, a lung cancer specialist at Emory University, Atlanta.

David R. Spigel, MD, a discussant on the trial, called the results “outstanding.”

“To have an 84% reduction in the risk of cancer progression or death is meaningful,” said Dr. Spigel, a medical oncologist at the Sarah Cannon Research Institute, Nashville, Tennessee, who reported ties to AstraZeneca. “This will be practice changing as soon as the label gets expanded.”

In the trial, investigators randomized 216 patients with unresectable stage III EGFR-mutated NSCLC who had not progressed after definitive platinum-based chemoradiation to receive either 80 mg osimertinib (n = 143) or placebo (n = 73). Baseline characteristics were generally balanced between the study arms, with a mostly even split between stage III subtypes.

Patients were staged by biopsy or CT at baseline plus MRI to confirm the absence of brain lesions. Subsequent imaging was repeated at regular intervals.

Twelve-month progression-free survival, assessed by blinded independent central review, was 74% with osimertinib vs 22% with placebo. At 24 months, the rates were 65% and 13%, respectively.

The progression-free survival benefit held across numerous subgroups but was statistically significant only among Asian individuals, who made up over 80% of both study arms.

Although the data are immature, osimertinib is also showing a trend toward improved overall survival, despite 81% of placebo patients crossing over to osimertinib after progression, Dr. Ramalingam reported. Mature overall survival results are expected within 2 years.

Based on these results, “osimertinib will become the new standard of care” after definitive chemoradiation in this patient population, Dr. Ramalingam said.

EGFR mutation testing “is now critical for stage III patients to ensure optimal” treatment, he added. Nearly a third of patients with NSCLC present with stage III disease, and the majority are unresectable. Of those, about a third are EGFR mutated.

Placebo was a fair comparator in the trial, Dr. Ramalingam stressed. While the current standard of care for unresectable stage III disease is 1 year of durvalumab after chemoradiation, durvalumab has proven ineffective in EGFR-mutated disease and often isn›t used in the setting.

If the control arm had been on durvalumab, patients would have needed to wait until it was safe to give them an EGFR TKI after progression, which didn’t seem to be in their best interest, he told this news organization.

A total of 68% of patients receiving placebo developed new lesions during the study, including brain metastases in 29%. New lesions developed in 22% of those on osimertinib, with new brain lesions in 8%.

The incidence of radiation pneumonitis, the most common adverse event, was 48% with osimertinib and 38% with placebo. Skin rash, diarrhea, and other known TKI side effects were also more common with osimertinib.

Treatment-related grade 3 or worse adverse events occurred in 13% of osimertinib patients vs 3% of placebo patients. Overall, 8% of osimertinib patients developed interstitial lung disease; most cases were low grade, but one person died.

About half of patients interrupted osimertinib dosing due to side effects, with a minority discontinuing.

Another study discussant, medical oncologist Lecia Sequist, MD, called the results “practice-changing” and said the findings support immediate consolidation with osimertinib instead of waiting for patients to progress.

Dr. Sequist, who reported ties to AstraZeneca, noted that patients were treated with osimertinib until progression, not for a limited duration as in past EGFR TKI trials, raising the possibility of indefinite, life-long treatment.

Treating until progression acknowledges the fact that for most patients, unresectable stage III NSCLC can’t be cured. However, she said a minority of patients might not need indefinite treatment — an important cohort to identify, given the drug costs more than $18,000 a month.

The study was funded by osimertinib maker AstraZeneca. Investigators included employees. Dr. Ramalingam, Dr. Spigel, and Dr. Sequist are advisers for and disclosed research funding from AstraZeneca. Dr. Spigel also disclosed travel funding.

A version of this article appeared on Medscape.com.

CHICAGO — Osimertinib (Tagrisso) may soon have approvals across all stages of epidermal growth factor receptor (EGFR)–mutated non–small cell lung cancer (NSCLC).

The third-generation EGFR tyrosine kinase inhibitor (TKI) already carries indications for metastatic disease and for adjuvant use in earlier-stage EGFR-mutated NSCLC.

Results from the phase 3 LAURA trial, presented at the American Society of Clinical Oncology (ASCO) annual meeting and funded by AstraZeneca, will likely lead to an approval for the remaining indication: Unresectable stage III disease.

Among patients randomized to either osimertinib or placebo following definitive chemoradiation, osimertinib extended median progression-free survival by 33.5 months compared with placebo — 39.1 vs 5.6 months, respectively (hazard ratio, 0.16; P = .001).

The news was greeted with a standing ovation at the meeting where it was presented by lead investigator and medical oncologist Suresh S. Ramalingam, MD, a lung cancer specialist at Emory University, Atlanta.

David R. Spigel, MD, a discussant on the trial, called the results “outstanding.”

“To have an 84% reduction in the risk of cancer progression or death is meaningful,” said Dr. Spigel, a medical oncologist at the Sarah Cannon Research Institute, Nashville, Tennessee, who reported ties to AstraZeneca. “This will be practice changing as soon as the label gets expanded.”

In the trial, investigators randomized 216 patients with unresectable stage III EGFR-mutated NSCLC who had not progressed after definitive platinum-based chemoradiation to receive either 80 mg osimertinib (n = 143) or placebo (n = 73). Baseline characteristics were generally balanced between the study arms, with a mostly even split between stage III subtypes.

Patients were staged by biopsy or CT at baseline plus MRI to confirm the absence of brain lesions. Subsequent imaging was repeated at regular intervals.

Twelve-month progression-free survival, assessed by blinded independent central review, was 74% with osimertinib vs 22% with placebo. At 24 months, the rates were 65% and 13%, respectively.

The progression-free survival benefit held across numerous subgroups but was statistically significant only among Asian individuals, who made up over 80% of both study arms.

Although the data are immature, osimertinib is also showing a trend toward improved overall survival, despite 81% of placebo patients crossing over to osimertinib after progression, Dr. Ramalingam reported. Mature overall survival results are expected within 2 years.

Based on these results, “osimertinib will become the new standard of care” after definitive chemoradiation in this patient population, Dr. Ramalingam said.

EGFR mutation testing “is now critical for stage III patients to ensure optimal” treatment, he added. Nearly a third of patients with NSCLC present with stage III disease, and the majority are unresectable. Of those, about a third are EGFR mutated.

Placebo was a fair comparator in the trial, Dr. Ramalingam stressed. While the current standard of care for unresectable stage III disease is 1 year of durvalumab after chemoradiation, durvalumab has proven ineffective in EGFR-mutated disease and often isn›t used in the setting.

If the control arm had been on durvalumab, patients would have needed to wait until it was safe to give them an EGFR TKI after progression, which didn’t seem to be in their best interest, he told this news organization.

A total of 68% of patients receiving placebo developed new lesions during the study, including brain metastases in 29%. New lesions developed in 22% of those on osimertinib, with new brain lesions in 8%.

The incidence of radiation pneumonitis, the most common adverse event, was 48% with osimertinib and 38% with placebo. Skin rash, diarrhea, and other known TKI side effects were also more common with osimertinib.

Treatment-related grade 3 or worse adverse events occurred in 13% of osimertinib patients vs 3% of placebo patients. Overall, 8% of osimertinib patients developed interstitial lung disease; most cases were low grade, but one person died.

About half of patients interrupted osimertinib dosing due to side effects, with a minority discontinuing.

Another study discussant, medical oncologist Lecia Sequist, MD, called the results “practice-changing” and said the findings support immediate consolidation with osimertinib instead of waiting for patients to progress.

Dr. Sequist, who reported ties to AstraZeneca, noted that patients were treated with osimertinib until progression, not for a limited duration as in past EGFR TKI trials, raising the possibility of indefinite, life-long treatment.

Treating until progression acknowledges the fact that for most patients, unresectable stage III NSCLC can’t be cured. However, she said a minority of patients might not need indefinite treatment — an important cohort to identify, given the drug costs more than $18,000 a month.

The study was funded by osimertinib maker AstraZeneca. Investigators included employees. Dr. Ramalingam, Dr. Spigel, and Dr. Sequist are advisers for and disclosed research funding from AstraZeneca. Dr. Spigel also disclosed travel funding.

A version of this article appeared on Medscape.com.

CHICAGO — Osimertinib (Tagrisso) may soon have approvals across all stages of epidermal growth factor receptor (EGFR)–mutated non–small cell lung cancer (NSCLC).

The third-generation EGFR tyrosine kinase inhibitor (TKI) already carries indications for metastatic disease and for adjuvant use in earlier-stage EGFR-mutated NSCLC.

Results from the phase 3 LAURA trial, presented at the American Society of Clinical Oncology (ASCO) annual meeting and funded by AstraZeneca, will likely lead to an approval for the remaining indication: Unresectable stage III disease.

Among patients randomized to either osimertinib or placebo following definitive chemoradiation, osimertinib extended median progression-free survival by 33.5 months compared with placebo — 39.1 vs 5.6 months, respectively (hazard ratio, 0.16; P = .001).

The news was greeted with a standing ovation at the meeting where it was presented by lead investigator and medical oncologist Suresh S. Ramalingam, MD, a lung cancer specialist at Emory University, Atlanta.

David R. Spigel, MD, a discussant on the trial, called the results “outstanding.”

“To have an 84% reduction in the risk of cancer progression or death is meaningful,” said Dr. Spigel, a medical oncologist at the Sarah Cannon Research Institute, Nashville, Tennessee, who reported ties to AstraZeneca. “This will be practice changing as soon as the label gets expanded.”

In the trial, investigators randomized 216 patients with unresectable stage III EGFR-mutated NSCLC who had not progressed after definitive platinum-based chemoradiation to receive either 80 mg osimertinib (n = 143) or placebo (n = 73). Baseline characteristics were generally balanced between the study arms, with a mostly even split between stage III subtypes.

Patients were staged by biopsy or CT at baseline plus MRI to confirm the absence of brain lesions. Subsequent imaging was repeated at regular intervals.

Twelve-month progression-free survival, assessed by blinded independent central review, was 74% with osimertinib vs 22% with placebo. At 24 months, the rates were 65% and 13%, respectively.

The progression-free survival benefit held across numerous subgroups but was statistically significant only among Asian individuals, who made up over 80% of both study arms.

Although the data are immature, osimertinib is also showing a trend toward improved overall survival, despite 81% of placebo patients crossing over to osimertinib after progression, Dr. Ramalingam reported. Mature overall survival results are expected within 2 years.

Based on these results, “osimertinib will become the new standard of care” after definitive chemoradiation in this patient population, Dr. Ramalingam said.

EGFR mutation testing “is now critical for stage III patients to ensure optimal” treatment, he added. Nearly a third of patients with NSCLC present with stage III disease, and the majority are unresectable. Of those, about a third are EGFR mutated.

Placebo was a fair comparator in the trial, Dr. Ramalingam stressed. While the current standard of care for unresectable stage III disease is 1 year of durvalumab after chemoradiation, durvalumab has proven ineffective in EGFR-mutated disease and often isn›t used in the setting.

If the control arm had been on durvalumab, patients would have needed to wait until it was safe to give them an EGFR TKI after progression, which didn’t seem to be in their best interest, he told this news organization.

A total of 68% of patients receiving placebo developed new lesions during the study, including brain metastases in 29%. New lesions developed in 22% of those on osimertinib, with new brain lesions in 8%.

The incidence of radiation pneumonitis, the most common adverse event, was 48% with osimertinib and 38% with placebo. Skin rash, diarrhea, and other known TKI side effects were also more common with osimertinib.

Treatment-related grade 3 or worse adverse events occurred in 13% of osimertinib patients vs 3% of placebo patients. Overall, 8% of osimertinib patients developed interstitial lung disease; most cases were low grade, but one person died.

About half of patients interrupted osimertinib dosing due to side effects, with a minority discontinuing.

Another study discussant, medical oncologist Lecia Sequist, MD, called the results “practice-changing” and said the findings support immediate consolidation with osimertinib instead of waiting for patients to progress.

Dr. Sequist, who reported ties to AstraZeneca, noted that patients were treated with osimertinib until progression, not for a limited duration as in past EGFR TKI trials, raising the possibility of indefinite, life-long treatment.

Treating until progression acknowledges the fact that for most patients, unresectable stage III NSCLC can’t be cured. However, she said a minority of patients might not need indefinite treatment — an important cohort to identify, given the drug costs more than $18,000 a month.

The study was funded by osimertinib maker AstraZeneca. Investigators included employees. Dr. Ramalingam, Dr. Spigel, and Dr. Sequist are advisers for and disclosed research funding from AstraZeneca. Dr. Spigel also disclosed travel funding.

A version of this article appeared on Medscape.com.