Patient & Survivor Care

SAN ANTONIO — Women 65-70 years old are often offered the option of skipping radiation after lumpectomy for hormone receptor–positive early-stage breast cancer and moving straight to endocrine therapy.

The recurrence rate with and without radiation is well known so women can be counseled accurately about their options. For some, the 10% risk of recurrence at 10 years without radiation seems reasonable, for others it does not.

Omitting radiation for older postmenopausal women is “very reasonable to offer so long as they are willing to accept the risk,” said Reshma Jagsi, MD, chief of radiation oncology at Emory University, Atlanta.

The option, however, isn’t generally offered to postmenopausal women younger than 65 years old because their risk from skipping adjuvant radiation isn’t known, but that’s about to change.

Several teams are investigating the issue, including one led by Dr. Jagsi, who presented her and her colleagues’ latest results at the San Antonio Breast Cancer Symposium.

In the single-arm IDEA [Individualized Decisions for Endocrine therapy Alone] study, 200 women 50-69 years old with pT1N0 unifocal hormone receptor–positive, HER2-negative invasive breast cancer agreed to the approach when it was offered to them following lumpectomy with sentinel lymph node biopsy. The mean tumor size was 10 mm with margins of at least 2 mm.

The women were at low risk for recurrence, with recurrence risk scores no higher than 18 points on the Oncotype DX 21-gene assay; the mean score was 11 points.

Radiation would have been the usual next step after lumpectomy, but instead the patients went directly to endocrine therapy for 5 years, with adherence above 80%.

At 5 years, the results are “promising,” Dr. Jagsi said at the meeting. Overall and breast cancer–specific survival were both 100%, and the recurrence rate was just 1%, with two recurrences before the 5-year point. The women were a mean of 62 years old.

A similar single-arm trial, LUMINA, recently reported comparable results.

Dr. Jagsi called the findings of the studies “reassuring,” but cautioned that it will be a while before younger postmenopausal women can be offered radiation-free treatment like their older peers.

Even though the results suggest “that this might well be a really good idea,” longer follow-up and randomized data are needed “before we change the standard of care,” she said.

Of concern, for instance, is that there were six additional recurrences in the IDEA study past the 5-year mark, for a total of three recurrences among the 60 women 50-59 years old (5%) and five among the 140 women 60-69 years old (3.6%). Five of the recurrent cases were adherent to endocrine therapy.

Also, so few women in IDEA have passed the 5-year mark that “we can’t [conclude] anything” about long-term relapse risks, Dr. Jagsi said. Besides that, skipping radiation for such women at this point is “not reasonable,” Dr. Jagsi added.

Carlos Arteaga, MD, director of the UT Southwestern Simmons Cancer Center, Dallas, agreed.

“I think we have to wait. We have randomized studies that will test this in a formal way. Be that as it may, this provides the basis for a conversation physicians can have with patients because this could be an option” at some point, said Dr. Arteaga, who moderated Dr. Jagsi’s presentation.

“This is a big step in trying not to do too much for patients who don’t need it,” Virginia Kaklamani, MD, leader of the breast cancer program at UT Health San Antonio, said in an interview.

IDEA was published in the Journal of Clinical Oncology to coincide with Dr. Jagsi’s presentation.

The study was funded by the Susan G. Komen Breast Cancer Foundation and the University of Michigan Rogel Cancer Center. Dr. Jagsi has stock in Equity Quotient and research support form Genentech. Disclosure information for Arteaga was not available. Dr. Kaklamani has extensive industry ties, including being a speaker for Pfizer, Genentech, Novartis, and AstraZeneca.

SAN ANTONIO — Women 65-70 years old are often offered the option of skipping radiation after lumpectomy for hormone receptor–positive early-stage breast cancer and moving straight to endocrine therapy.

The recurrence rate with and without radiation is well known so women can be counseled accurately about their options. For some, the 10% risk of recurrence at 10 years without radiation seems reasonable, for others it does not.

Omitting radiation for older postmenopausal women is “very reasonable to offer so long as they are willing to accept the risk,” said Reshma Jagsi, MD, chief of radiation oncology at Emory University, Atlanta.

The option, however, isn’t generally offered to postmenopausal women younger than 65 years old because their risk from skipping adjuvant radiation isn’t known, but that’s about to change.

Several teams are investigating the issue, including one led by Dr. Jagsi, who presented her and her colleagues’ latest results at the San Antonio Breast Cancer Symposium.

In the single-arm IDEA [Individualized Decisions for Endocrine therapy Alone] study, 200 women 50-69 years old with pT1N0 unifocal hormone receptor–positive, HER2-negative invasive breast cancer agreed to the approach when it was offered to them following lumpectomy with sentinel lymph node biopsy. The mean tumor size was 10 mm with margins of at least 2 mm.

The women were at low risk for recurrence, with recurrence risk scores no higher than 18 points on the Oncotype DX 21-gene assay; the mean score was 11 points.

Radiation would have been the usual next step after lumpectomy, but instead the patients went directly to endocrine therapy for 5 years, with adherence above 80%.

At 5 years, the results are “promising,” Dr. Jagsi said at the meeting. Overall and breast cancer–specific survival were both 100%, and the recurrence rate was just 1%, with two recurrences before the 5-year point. The women were a mean of 62 years old.

A similar single-arm trial, LUMINA, recently reported comparable results.

Dr. Jagsi called the findings of the studies “reassuring,” but cautioned that it will be a while before younger postmenopausal women can be offered radiation-free treatment like their older peers.

Even though the results suggest “that this might well be a really good idea,” longer follow-up and randomized data are needed “before we change the standard of care,” she said.

Of concern, for instance, is that there were six additional recurrences in the IDEA study past the 5-year mark, for a total of three recurrences among the 60 women 50-59 years old (5%) and five among the 140 women 60-69 years old (3.6%). Five of the recurrent cases were adherent to endocrine therapy.

Also, so few women in IDEA have passed the 5-year mark that “we can’t [conclude] anything” about long-term relapse risks, Dr. Jagsi said. Besides that, skipping radiation for such women at this point is “not reasonable,” Dr. Jagsi added.

Carlos Arteaga, MD, director of the UT Southwestern Simmons Cancer Center, Dallas, agreed.

“I think we have to wait. We have randomized studies that will test this in a formal way. Be that as it may, this provides the basis for a conversation physicians can have with patients because this could be an option” at some point, said Dr. Arteaga, who moderated Dr. Jagsi’s presentation.

“This is a big step in trying not to do too much for patients who don’t need it,” Virginia Kaklamani, MD, leader of the breast cancer program at UT Health San Antonio, said in an interview.

IDEA was published in the Journal of Clinical Oncology to coincide with Dr. Jagsi’s presentation.

The study was funded by the Susan G. Komen Breast Cancer Foundation and the University of Michigan Rogel Cancer Center. Dr. Jagsi has stock in Equity Quotient and research support form Genentech. Disclosure information for Arteaga was not available. Dr. Kaklamani has extensive industry ties, including being a speaker for Pfizer, Genentech, Novartis, and AstraZeneca.

SAN ANTONIO — Women 65-70 years old are often offered the option of skipping radiation after lumpectomy for hormone receptor–positive early-stage breast cancer and moving straight to endocrine therapy.

The recurrence rate with and without radiation is well known so women can be counseled accurately about their options. For some, the 10% risk of recurrence at 10 years without radiation seems reasonable, for others it does not.

Omitting radiation for older postmenopausal women is “very reasonable to offer so long as they are willing to accept the risk,” said Reshma Jagsi, MD, chief of radiation oncology at Emory University, Atlanta.

The option, however, isn’t generally offered to postmenopausal women younger than 65 years old because their risk from skipping adjuvant radiation isn’t known, but that’s about to change.

Several teams are investigating the issue, including one led by Dr. Jagsi, who presented her and her colleagues’ latest results at the San Antonio Breast Cancer Symposium.

In the single-arm IDEA [Individualized Decisions for Endocrine therapy Alone] study, 200 women 50-69 years old with pT1N0 unifocal hormone receptor–positive, HER2-negative invasive breast cancer agreed to the approach when it was offered to them following lumpectomy with sentinel lymph node biopsy. The mean tumor size was 10 mm with margins of at least 2 mm.

The women were at low risk for recurrence, with recurrence risk scores no higher than 18 points on the Oncotype DX 21-gene assay; the mean score was 11 points.

Radiation would have been the usual next step after lumpectomy, but instead the patients went directly to endocrine therapy for 5 years, with adherence above 80%.

At 5 years, the results are “promising,” Dr. Jagsi said at the meeting. Overall and breast cancer–specific survival were both 100%, and the recurrence rate was just 1%, with two recurrences before the 5-year point. The women were a mean of 62 years old.

A similar single-arm trial, LUMINA, recently reported comparable results.

Dr. Jagsi called the findings of the studies “reassuring,” but cautioned that it will be a while before younger postmenopausal women can be offered radiation-free treatment like their older peers.

Even though the results suggest “that this might well be a really good idea,” longer follow-up and randomized data are needed “before we change the standard of care,” she said.

Of concern, for instance, is that there were six additional recurrences in the IDEA study past the 5-year mark, for a total of three recurrences among the 60 women 50-59 years old (5%) and five among the 140 women 60-69 years old (3.6%). Five of the recurrent cases were adherent to endocrine therapy.

Also, so few women in IDEA have passed the 5-year mark that “we can’t [conclude] anything” about long-term relapse risks, Dr. Jagsi said. Besides that, skipping radiation for such women at this point is “not reasonable,” Dr. Jagsi added.

Carlos Arteaga, MD, director of the UT Southwestern Simmons Cancer Center, Dallas, agreed.

“I think we have to wait. We have randomized studies that will test this in a formal way. Be that as it may, this provides the basis for a conversation physicians can have with patients because this could be an option” at some point, said Dr. Arteaga, who moderated Dr. Jagsi’s presentation.

“This is a big step in trying not to do too much for patients who don’t need it,” Virginia Kaklamani, MD, leader of the breast cancer program at UT Health San Antonio, said in an interview.

IDEA was published in the Journal of Clinical Oncology to coincide with Dr. Jagsi’s presentation.

The study was funded by the Susan G. Komen Breast Cancer Foundation and the University of Michigan Rogel Cancer Center. Dr. Jagsi has stock in Equity Quotient and research support form Genentech. Disclosure information for Arteaga was not available. Dr. Kaklamani has extensive industry ties, including being a speaker for Pfizer, Genentech, Novartis, and AstraZeneca.

SAN ANTONIO — Sleep problems are common in women with breast cancer and often associated with poorer physical and mental health, a new study finds. Poor sleep quality and short sleep duration in particular were associated with poorer mental well-being.

“It’s important to ask patients [with breast cancer] about sleep and provide targeted interventions to improve sleep, when needed, to improve quality of life,” Lin Yang, PhD, with Cancer Care Alberta and University of Calgary, Canada, said in an interview.

The growing population of breast cancer survivors, particularly in developed countries, is burdened by a high prevalence of sleep problems, affecting more than half of the survivors, Dr. Yang said at the San Antonio Breast Cancer Symposium. 

The AMBER cohort study delved into how sleep health aspects, including sleep duration, timing, and quality, relate to the physical and mental well-being of women recently diagnosed with breast cancer. 

The study recruited 1409 women with newly diagnosed early-stage breast cancer from Edmonton and Calgary, Canada, between 2012 and 2019. 

The women completed the Pittsburgh Sleep Quality Index (PSQI) to assess habitual sleep duration and timing as well as sleep latency, efficiency, disturbance, medication, and daytime dysfunction and version two of the Short Form-36 (SF-36) to assess physical and mental well-being. 

Multivariable linear regressions were used to estimate the association of sleep characteristics with physical and mental well-being, adjusting for sociodemographic, disease, clinical, and lifestyle behavior factors.

Among the total patient cohort (mean age, 55 years), 41% experienced either short sleep duration (less than 6 h/d) or long sleep duration (more than 9 h/d), and the same percentage also reported regularly going to bed after 11 PM.

Of note, said Dr. Yang, in the multivariable model, short sleep duration was significantly associated with poorer mental well-being (beta-coefficient, -3.6; 95% CI, -4.7 to -2.4) but not poorer physical well-being (beta-coefficient, -1.5; 95% CI, -2.3 to -0.7). 

Sleep timing didn’t appear to have a meaningful impact on quality of life. 

However, poor sleep quality, measured through various metrics like sleep efficiency, disturbances, medication use, and daytime dysfunction, correlated with reduced physical and mental well-being, Dr. Yang said. 

She noted that targeted interventions to improve sleep health may lead to improvements in the quality of life among women with newly diagnosed breast cancer.

“Sleep is something we don’t necessarily think about in patients with breast cancer,” said Don Dizon, MD, with Brown University, Providence, Rhode Island, discussant for the study presentation.

However, this study shows the “clinical significance” of sleep, he said. “Notably 35% of this population is taking a sleeping pill.” 

Dr. Yang is an editorial board member of the Journal of Healthy Eating and Active Living. Dr. Dizon receives consulting fees from Astra Zeneca, Glaxo Smith Kline, Kronos Bio, and Pfizer and industry grant support from Bristol-Myers Squibb.

A version of this article appeared on Medscape.com.

SAN ANTONIO — Sleep problems are common in women with breast cancer and often associated with poorer physical and mental health, a new study finds. Poor sleep quality and short sleep duration in particular were associated with poorer mental well-being.

“It’s important to ask patients [with breast cancer] about sleep and provide targeted interventions to improve sleep, when needed, to improve quality of life,” Lin Yang, PhD, with Cancer Care Alberta and University of Calgary, Canada, said in an interview.

The growing population of breast cancer survivors, particularly in developed countries, is burdened by a high prevalence of sleep problems, affecting more than half of the survivors, Dr. Yang said at the San Antonio Breast Cancer Symposium. 

The AMBER cohort study delved into how sleep health aspects, including sleep duration, timing, and quality, relate to the physical and mental well-being of women recently diagnosed with breast cancer. 

The study recruited 1409 women with newly diagnosed early-stage breast cancer from Edmonton and Calgary, Canada, between 2012 and 2019. 

The women completed the Pittsburgh Sleep Quality Index (PSQI) to assess habitual sleep duration and timing as well as sleep latency, efficiency, disturbance, medication, and daytime dysfunction and version two of the Short Form-36 (SF-36) to assess physical and mental well-being. 

Multivariable linear regressions were used to estimate the association of sleep characteristics with physical and mental well-being, adjusting for sociodemographic, disease, clinical, and lifestyle behavior factors.

Among the total patient cohort (mean age, 55 years), 41% experienced either short sleep duration (less than 6 h/d) or long sleep duration (more than 9 h/d), and the same percentage also reported regularly going to bed after 11 PM.

Of note, said Dr. Yang, in the multivariable model, short sleep duration was significantly associated with poorer mental well-being (beta-coefficient, -3.6; 95% CI, -4.7 to -2.4) but not poorer physical well-being (beta-coefficient, -1.5; 95% CI, -2.3 to -0.7). 

Sleep timing didn’t appear to have a meaningful impact on quality of life. 

However, poor sleep quality, measured through various metrics like sleep efficiency, disturbances, medication use, and daytime dysfunction, correlated with reduced physical and mental well-being, Dr. Yang said. 

She noted that targeted interventions to improve sleep health may lead to improvements in the quality of life among women with newly diagnosed breast cancer.

“Sleep is something we don’t necessarily think about in patients with breast cancer,” said Don Dizon, MD, with Brown University, Providence, Rhode Island, discussant for the study presentation.

However, this study shows the “clinical significance” of sleep, he said. “Notably 35% of this population is taking a sleeping pill.” 

Dr. Yang is an editorial board member of the Journal of Healthy Eating and Active Living. Dr. Dizon receives consulting fees from Astra Zeneca, Glaxo Smith Kline, Kronos Bio, and Pfizer and industry grant support from Bristol-Myers Squibb.

A version of this article appeared on Medscape.com.

SAN ANTONIO — Sleep problems are common in women with breast cancer and often associated with poorer physical and mental health, a new study finds. Poor sleep quality and short sleep duration in particular were associated with poorer mental well-being.

“It’s important to ask patients [with breast cancer] about sleep and provide targeted interventions to improve sleep, when needed, to improve quality of life,” Lin Yang, PhD, with Cancer Care Alberta and University of Calgary, Canada, said in an interview.

The growing population of breast cancer survivors, particularly in developed countries, is burdened by a high prevalence of sleep problems, affecting more than half of the survivors, Dr. Yang said at the San Antonio Breast Cancer Symposium. 

The AMBER cohort study delved into how sleep health aspects, including sleep duration, timing, and quality, relate to the physical and mental well-being of women recently diagnosed with breast cancer. 

The study recruited 1409 women with newly diagnosed early-stage breast cancer from Edmonton and Calgary, Canada, between 2012 and 2019. 

The women completed the Pittsburgh Sleep Quality Index (PSQI) to assess habitual sleep duration and timing as well as sleep latency, efficiency, disturbance, medication, and daytime dysfunction and version two of the Short Form-36 (SF-36) to assess physical and mental well-being. 

Multivariable linear regressions were used to estimate the association of sleep characteristics with physical and mental well-being, adjusting for sociodemographic, disease, clinical, and lifestyle behavior factors.

Among the total patient cohort (mean age, 55 years), 41% experienced either short sleep duration (less than 6 h/d) or long sleep duration (more than 9 h/d), and the same percentage also reported regularly going to bed after 11 PM.

Of note, said Dr. Yang, in the multivariable model, short sleep duration was significantly associated with poorer mental well-being (beta-coefficient, -3.6; 95% CI, -4.7 to -2.4) but not poorer physical well-being (beta-coefficient, -1.5; 95% CI, -2.3 to -0.7). 

Sleep timing didn’t appear to have a meaningful impact on quality of life. 

However, poor sleep quality, measured through various metrics like sleep efficiency, disturbances, medication use, and daytime dysfunction, correlated with reduced physical and mental well-being, Dr. Yang said. 

She noted that targeted interventions to improve sleep health may lead to improvements in the quality of life among women with newly diagnosed breast cancer.

“Sleep is something we don’t necessarily think about in patients with breast cancer,” said Don Dizon, MD, with Brown University, Providence, Rhode Island, discussant for the study presentation.

However, this study shows the “clinical significance” of sleep, he said. “Notably 35% of this population is taking a sleeping pill.” 

Dr. Yang is an editorial board member of the Journal of Healthy Eating and Active Living. Dr. Dizon receives consulting fees from Astra Zeneca, Glaxo Smith Kline, Kronos Bio, and Pfizer and industry grant support from Bristol-Myers Squibb.

A version of this article appeared on Medscape.com.

SAN ANTONIO — There’s a long-standing debate in breast oncology about what to do when positive axillary lymph nodes turn negative after neoadjuvant chemotherapy.

Do patients still need regional nodal irradiation or can they skip it? 

Currently, it’s about a 50/50 split among oncologists, according to breast cancer surgeon Eleftherios P. Mamounas, MD, medical director of the Comprehensive Breast Program at the Orlando Health Cancer Institute in Florida.

Until now, Dr. Mamounas’s own institution has opted for regional irradiation just to be on the safe side, but he said that’s going to change in the wake of a multicenter trial he presented at the San Antonio Breast Cancer Symposium. 

Dr. Mamounas led a team that randomized 1556 women equally to either regional nodal irradiation or no nodal irradiation following surgery, which was lumpectomy in just over half the subjects and mastectomy in the rest. 

Women were a median of 52 years old. Almost 60% had T2 disease and the rest were split about evenly between T1 and T3 disease. Nearly a quarter of the tumors were triple-negative, and over half were HER2 positive.

In the regional nodal irradiation arm, women who had mastectomies had chest wall irradiation in addition to regional nodal irradiation, while women who underwent lumpectomies had whole breast irradiation with regional nodal irradiation. In the no-irradiation group, mastectomies were followed by observation and lumpectomies by whole breast irradiation alone. 

All the women had positive axillary lymph nodes (N1) on needle biopsies at baseline that were found to be free of cancer at surgery (ypN0) following neoadjuvant chemotherapy. Neoadjuvant therapy consisted of at least 8 weeks of chemotherapy plus anti-HER2 therapy for HER2-positive patients. 

Dr. Mamounas and colleagues observed no meaningful differences in outcomes between the two groups: 92.7% of women in the nodal irradiation arm and 91.8% in the no-irradiation arm were free from invasive recurrences 5 years after surgery.

Patients in both groups demonstrated similar 5-year disease-free survival and overall survival. The 5-year disease-free survival was 88.5% without and 88.3% with regional nodal irradiation and 5-year overall survival was 94% without and 93.6% with regional nodal irradiation.

The team did not observe study-related deaths or unexpected toxicities. Overall, 6.5% of patients without regional nodal irradiation developed grade 3 toxicity vs. 10% of patients with irradiation. Grade 4 toxicity was rare, occurring in 0.1% of patients in the no-irradiation group vs. 0.5% in the irradiation group.

The trial answers “a very important question,” according to Kate Lathrop, MD, a breast medical oncologist at UT Health San Antonio, who moderated the presentation. 

The trial results were “highly awaited” because “we didn’t have the data to make these” decisions, Dr. Lathrop said. 

Knowing these patients do just as well without regional nodal irradiation is “going to change a lot of opinions,” said Dr. Lathrop, because we can avoid subjecting patients to unnecessary toxicity, including lymphedema with regional nodal irradiation as well as problems with breast reconstruction after mastectomy.

Because recurrences can still occur after 5 years, Dr. Mamounas’s team will continue to follow the women, but he believes “it’s very unlikely that long-term distant disease-free survival will change.” 

Based on the study, “we will omit” regional nodal irradiation for women who fit the study criteria, Dr. Mamounas said.

When asked if women should ask their doctors about skipping regional nodal irradiation, Dr. Mamounas said “absolutely.” 

“I think it requires a discussion at this point,” he explained. “Based on the data, it’s a reasonable conclusion that radiotherapy can be avoided” in many cases, such as in lower-stage women with one initially positive node. 

Dr. Mamounas said he thinks patients will be interested in the approach “because they are really looking to avoid radiotherapy” if they can. 

The work was funded by the National Cancer Institute. Dr. Mamounas has been a consultant and speaker for Genentech, Merck, and an adviser for TerSera Therapeutics, Biotheranostics Inc., and Sanofi. He owns stock in Moderna. Dr. Lathrop is a consultant for Pfizer, GE Healthcare, and Biotheranostics, and a speaker for Biotheranostics.
 

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

SAN ANTONIO — There’s a long-standing debate in breast oncology about what to do when positive axillary lymph nodes turn negative after neoadjuvant chemotherapy.

Do patients still need regional nodal irradiation or can they skip it? 

Currently, it’s about a 50/50 split among oncologists, according to breast cancer surgeon Eleftherios P. Mamounas, MD, medical director of the Comprehensive Breast Program at the Orlando Health Cancer Institute in Florida.

Until now, Dr. Mamounas’s own institution has opted for regional irradiation just to be on the safe side, but he said that’s going to change in the wake of a multicenter trial he presented at the San Antonio Breast Cancer Symposium. 

Dr. Mamounas led a team that randomized 1556 women equally to either regional nodal irradiation or no nodal irradiation following surgery, which was lumpectomy in just over half the subjects and mastectomy in the rest. 

Women were a median of 52 years old. Almost 60% had T2 disease and the rest were split about evenly between T1 and T3 disease. Nearly a quarter of the tumors were triple-negative, and over half were HER2 positive.

In the regional nodal irradiation arm, women who had mastectomies had chest wall irradiation in addition to regional nodal irradiation, while women who underwent lumpectomies had whole breast irradiation with regional nodal irradiation. In the no-irradiation group, mastectomies were followed by observation and lumpectomies by whole breast irradiation alone. 

All the women had positive axillary lymph nodes (N1) on needle biopsies at baseline that were found to be free of cancer at surgery (ypN0) following neoadjuvant chemotherapy. Neoadjuvant therapy consisted of at least 8 weeks of chemotherapy plus anti-HER2 therapy for HER2-positive patients. 

Dr. Mamounas and colleagues observed no meaningful differences in outcomes between the two groups: 92.7% of women in the nodal irradiation arm and 91.8% in the no-irradiation arm were free from invasive recurrences 5 years after surgery.

Patients in both groups demonstrated similar 5-year disease-free survival and overall survival. The 5-year disease-free survival was 88.5% without and 88.3% with regional nodal irradiation and 5-year overall survival was 94% without and 93.6% with regional nodal irradiation.

The team did not observe study-related deaths or unexpected toxicities. Overall, 6.5% of patients without regional nodal irradiation developed grade 3 toxicity vs. 10% of patients with irradiation. Grade 4 toxicity was rare, occurring in 0.1% of patients in the no-irradiation group vs. 0.5% in the irradiation group.

The trial answers “a very important question,” according to Kate Lathrop, MD, a breast medical oncologist at UT Health San Antonio, who moderated the presentation. 

The trial results were “highly awaited” because “we didn’t have the data to make these” decisions, Dr. Lathrop said. 

Knowing these patients do just as well without regional nodal irradiation is “going to change a lot of opinions,” said Dr. Lathrop, because we can avoid subjecting patients to unnecessary toxicity, including lymphedema with regional nodal irradiation as well as problems with breast reconstruction after mastectomy.

Because recurrences can still occur after 5 years, Dr. Mamounas’s team will continue to follow the women, but he believes “it’s very unlikely that long-term distant disease-free survival will change.” 

Based on the study, “we will omit” regional nodal irradiation for women who fit the study criteria, Dr. Mamounas said.

When asked if women should ask their doctors about skipping regional nodal irradiation, Dr. Mamounas said “absolutely.” 

“I think it requires a discussion at this point,” he explained. “Based on the data, it’s a reasonable conclusion that radiotherapy can be avoided” in many cases, such as in lower-stage women with one initially positive node. 

Dr. Mamounas said he thinks patients will be interested in the approach “because they are really looking to avoid radiotherapy” if they can. 

The work was funded by the National Cancer Institute. Dr. Mamounas has been a consultant and speaker for Genentech, Merck, and an adviser for TerSera Therapeutics, Biotheranostics Inc., and Sanofi. He owns stock in Moderna. Dr. Lathrop is a consultant for Pfizer, GE Healthcare, and Biotheranostics, and a speaker for Biotheranostics.
 

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

SAN ANTONIO — There’s a long-standing debate in breast oncology about what to do when positive axillary lymph nodes turn negative after neoadjuvant chemotherapy.

Do patients still need regional nodal irradiation or can they skip it? 

Currently, it’s about a 50/50 split among oncologists, according to breast cancer surgeon Eleftherios P. Mamounas, MD, medical director of the Comprehensive Breast Program at the Orlando Health Cancer Institute in Florida.

Until now, Dr. Mamounas’s own institution has opted for regional irradiation just to be on the safe side, but he said that’s going to change in the wake of a multicenter trial he presented at the San Antonio Breast Cancer Symposium. 

Dr. Mamounas led a team that randomized 1556 women equally to either regional nodal irradiation or no nodal irradiation following surgery, which was lumpectomy in just over half the subjects and mastectomy in the rest. 

Women were a median of 52 years old. Almost 60% had T2 disease and the rest were split about evenly between T1 and T3 disease. Nearly a quarter of the tumors were triple-negative, and over half were HER2 positive.

In the regional nodal irradiation arm, women who had mastectomies had chest wall irradiation in addition to regional nodal irradiation, while women who underwent lumpectomies had whole breast irradiation with regional nodal irradiation. In the no-irradiation group, mastectomies were followed by observation and lumpectomies by whole breast irradiation alone. 

All the women had positive axillary lymph nodes (N1) on needle biopsies at baseline that were found to be free of cancer at surgery (ypN0) following neoadjuvant chemotherapy. Neoadjuvant therapy consisted of at least 8 weeks of chemotherapy plus anti-HER2 therapy for HER2-positive patients. 

Dr. Mamounas and colleagues observed no meaningful differences in outcomes between the two groups: 92.7% of women in the nodal irradiation arm and 91.8% in the no-irradiation arm were free from invasive recurrences 5 years after surgery.

Patients in both groups demonstrated similar 5-year disease-free survival and overall survival. The 5-year disease-free survival was 88.5% without and 88.3% with regional nodal irradiation and 5-year overall survival was 94% without and 93.6% with regional nodal irradiation.

The team did not observe study-related deaths or unexpected toxicities. Overall, 6.5% of patients without regional nodal irradiation developed grade 3 toxicity vs. 10% of patients with irradiation. Grade 4 toxicity was rare, occurring in 0.1% of patients in the no-irradiation group vs. 0.5% in the irradiation group.

The trial answers “a very important question,” according to Kate Lathrop, MD, a breast medical oncologist at UT Health San Antonio, who moderated the presentation. 

The trial results were “highly awaited” because “we didn’t have the data to make these” decisions, Dr. Lathrop said. 

Knowing these patients do just as well without regional nodal irradiation is “going to change a lot of opinions,” said Dr. Lathrop, because we can avoid subjecting patients to unnecessary toxicity, including lymphedema with regional nodal irradiation as well as problems with breast reconstruction after mastectomy.

Because recurrences can still occur after 5 years, Dr. Mamounas’s team will continue to follow the women, but he believes “it’s very unlikely that long-term distant disease-free survival will change.” 

Based on the study, “we will omit” regional nodal irradiation for women who fit the study criteria, Dr. Mamounas said.

When asked if women should ask their doctors about skipping regional nodal irradiation, Dr. Mamounas said “absolutely.” 

“I think it requires a discussion at this point,” he explained. “Based on the data, it’s a reasonable conclusion that radiotherapy can be avoided” in many cases, such as in lower-stage women with one initially positive node. 

Dr. Mamounas said he thinks patients will be interested in the approach “because they are really looking to avoid radiotherapy” if they can. 

The work was funded by the National Cancer Institute. Dr. Mamounas has been a consultant and speaker for Genentech, Merck, and an adviser for TerSera Therapeutics, Biotheranostics Inc., and Sanofi. He owns stock in Moderna. Dr. Lathrop is a consultant for Pfizer, GE Healthcare, and Biotheranostics, and a speaker for Biotheranostics.
 

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

SAN ANTONIO — Breast cancer care can cause significant financial stress for patients, but certain interventions may help patients cope with these financial burdens, new survey findings show. 

Almost half of patients surveyed reported a “significant” or “catastrophic” financial burden related to their breast cancer care. But patients also found a range of resources helpful for minimizing this burden, including direct assistance programs that reduce the cost of medications, grants from nonprofits that can cover cancer-related expenses, as well as programs that offer free or low-cost transportation to medical appointments. 

Financial toxicity remains a “pervasive problem in the breast cancer community and we really need to go to the next step, which is designing patient-centered, patient-facing interventions to make improvements,” Fumiko Chino, MD, with Memorial Sloan Kettering Cancer Center in New York City, said when presenting the survey results at the San Antonio Breast Cancer Symposium. 

A growing body of evidence shows that cancer care, especially for breast cancer, can take a heavy financial toll on patients. However, routine screening for financial toxicity is not necessarily a routine part of clinical care, and providers may not know the types of financial assistance patients value most, Dr. Chino explained.

Dr. Chino and colleagues surveyed 1437 women with breast cancer about their level of financial distress as well as the specific interventions or education initiatives they found most helpful.

Most patients (60%) were White, 27% were Hispanic, and 8% Black. Three quarters of patients were on active treatments, 89% had nonmetastatic disease, and 11% had metastatic disease.

Overall, 47% of patients reported a significant or catastrophic financial burden related to their breast cancer diagnosis and care. This burden was higher for those with metastatic disease (61% vs 45%).

Patients assessed 10 strategies for coping with the financial burdens of care. The top-rated interventions included patient assistance programs offered by pharmaceutical or medical test companies, rated highly by 32% of respondents, and grants from nonprofits, rated highly by 31% of respondents. Patients also found financial assistance departments at cancer centers or hospitals helpful (29%); coupons and savings cards to reduce the cost of prescription drugs (28%); and programs that provide free or low-cost transportation to medical appointments (28%).

In terms of education, respondents said having a checklist of questions to ask their oncology team as well as a list of breast cancer-specific financial grants to apply for would be especially helpful when navigating the financial burdens of breast cancer care.

These preferences, however, did vary by race/ethnicity and disease status. Hispanic patients, for instance, found patient assistance programs offered by companies and cancer centers as well as transportation assistance more helpful than other groups. 

Patients with metastatic disease found patient assistance programs offered by medical companies particularly helpful compared with patients with nonmetastatic disease. And compared with patients with metastatic disease, those with nonmetastatic breast cancer found assistance through clinical trials and professional medical billing advocates helpful.

This study confirms the high rates of financial burden in women with breast cancer and clearly demonstrates that intervention preferences vary by sociodemographic and clinical characteristics, study discussant Claire C. Conley, PhD, from Georgetown University, Washington, DC, commented.

“This highlights that one size really doesn’t fit all when it comes to those financial burden interventions,” Dr. Conley said. “We need to think about factors at the patient level, the organizational level, and the environment level.”

The study had no commercial funding. Dr. Chino and Dr. Conley have disclosed no relevant financial relationships.

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

SAN ANTONIO — Breast cancer care can cause significant financial stress for patients, but certain interventions may help patients cope with these financial burdens, new survey findings show. 

Almost half of patients surveyed reported a “significant” or “catastrophic” financial burden related to their breast cancer care. But patients also found a range of resources helpful for minimizing this burden, including direct assistance programs that reduce the cost of medications, grants from nonprofits that can cover cancer-related expenses, as well as programs that offer free or low-cost transportation to medical appointments. 

Financial toxicity remains a “pervasive problem in the breast cancer community and we really need to go to the next step, which is designing patient-centered, patient-facing interventions to make improvements,” Fumiko Chino, MD, with Memorial Sloan Kettering Cancer Center in New York City, said when presenting the survey results at the San Antonio Breast Cancer Symposium. 

A growing body of evidence shows that cancer care, especially for breast cancer, can take a heavy financial toll on patients. However, routine screening for financial toxicity is not necessarily a routine part of clinical care, and providers may not know the types of financial assistance patients value most, Dr. Chino explained.

Dr. Chino and colleagues surveyed 1437 women with breast cancer about their level of financial distress as well as the specific interventions or education initiatives they found most helpful.

Most patients (60%) were White, 27% were Hispanic, and 8% Black. Three quarters of patients were on active treatments, 89% had nonmetastatic disease, and 11% had metastatic disease.

Overall, 47% of patients reported a significant or catastrophic financial burden related to their breast cancer diagnosis and care. This burden was higher for those with metastatic disease (61% vs 45%).

Patients assessed 10 strategies for coping with the financial burdens of care. The top-rated interventions included patient assistance programs offered by pharmaceutical or medical test companies, rated highly by 32% of respondents, and grants from nonprofits, rated highly by 31% of respondents. Patients also found financial assistance departments at cancer centers or hospitals helpful (29%); coupons and savings cards to reduce the cost of prescription drugs (28%); and programs that provide free or low-cost transportation to medical appointments (28%).

In terms of education, respondents said having a checklist of questions to ask their oncology team as well as a list of breast cancer-specific financial grants to apply for would be especially helpful when navigating the financial burdens of breast cancer care.

These preferences, however, did vary by race/ethnicity and disease status. Hispanic patients, for instance, found patient assistance programs offered by companies and cancer centers as well as transportation assistance more helpful than other groups. 

Patients with metastatic disease found patient assistance programs offered by medical companies particularly helpful compared with patients with nonmetastatic disease. And compared with patients with metastatic disease, those with nonmetastatic breast cancer found assistance through clinical trials and professional medical billing advocates helpful.

This study confirms the high rates of financial burden in women with breast cancer and clearly demonstrates that intervention preferences vary by sociodemographic and clinical characteristics, study discussant Claire C. Conley, PhD, from Georgetown University, Washington, DC, commented.

“This highlights that one size really doesn’t fit all when it comes to those financial burden interventions,” Dr. Conley said. “We need to think about factors at the patient level, the organizational level, and the environment level.”

The study had no commercial funding. Dr. Chino and Dr. Conley have disclosed no relevant financial relationships.

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

SAN ANTONIO — Breast cancer care can cause significant financial stress for patients, but certain interventions may help patients cope with these financial burdens, new survey findings show. 

Almost half of patients surveyed reported a “significant” or “catastrophic” financial burden related to their breast cancer care. But patients also found a range of resources helpful for minimizing this burden, including direct assistance programs that reduce the cost of medications, grants from nonprofits that can cover cancer-related expenses, as well as programs that offer free or low-cost transportation to medical appointments. 

Financial toxicity remains a “pervasive problem in the breast cancer community and we really need to go to the next step, which is designing patient-centered, patient-facing interventions to make improvements,” Fumiko Chino, MD, with Memorial Sloan Kettering Cancer Center in New York City, said when presenting the survey results at the San Antonio Breast Cancer Symposium. 

A growing body of evidence shows that cancer care, especially for breast cancer, can take a heavy financial toll on patients. However, routine screening for financial toxicity is not necessarily a routine part of clinical care, and providers may not know the types of financial assistance patients value most, Dr. Chino explained.

Dr. Chino and colleagues surveyed 1437 women with breast cancer about their level of financial distress as well as the specific interventions or education initiatives they found most helpful.

Most patients (60%) were White, 27% were Hispanic, and 8% Black. Three quarters of patients were on active treatments, 89% had nonmetastatic disease, and 11% had metastatic disease.

Overall, 47% of patients reported a significant or catastrophic financial burden related to their breast cancer diagnosis and care. This burden was higher for those with metastatic disease (61% vs 45%).

Patients assessed 10 strategies for coping with the financial burdens of care. The top-rated interventions included patient assistance programs offered by pharmaceutical or medical test companies, rated highly by 32% of respondents, and grants from nonprofits, rated highly by 31% of respondents. Patients also found financial assistance departments at cancer centers or hospitals helpful (29%); coupons and savings cards to reduce the cost of prescription drugs (28%); and programs that provide free or low-cost transportation to medical appointments (28%).

In terms of education, respondents said having a checklist of questions to ask their oncology team as well as a list of breast cancer-specific financial grants to apply for would be especially helpful when navigating the financial burdens of breast cancer care.

These preferences, however, did vary by race/ethnicity and disease status. Hispanic patients, for instance, found patient assistance programs offered by companies and cancer centers as well as transportation assistance more helpful than other groups. 

Patients with metastatic disease found patient assistance programs offered by medical companies particularly helpful compared with patients with nonmetastatic disease. And compared with patients with metastatic disease, those with nonmetastatic breast cancer found assistance through clinical trials and professional medical billing advocates helpful.

This study confirms the high rates of financial burden in women with breast cancer and clearly demonstrates that intervention preferences vary by sociodemographic and clinical characteristics, study discussant Claire C. Conley, PhD, from Georgetown University, Washington, DC, commented.

“This highlights that one size really doesn’t fit all when it comes to those financial burden interventions,” Dr. Conley said. “We need to think about factors at the patient level, the organizational level, and the environment level.”

The study had no commercial funding. Dr. Chino and Dr. Conley have disclosed no relevant financial relationships.

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

SAN ANTONIO – In previously treated patients with locally advanced unresectable or metastatic HER2-positive breast cancer, tucatinib (Tukysa, Seagen) and trastuzumab emtansine (Kadcyla, T-DM1, Genentech) improved progression-free survival (PFS) versus T-DM1 alone, according to results from the phase III HER2CLIMB-02 study. A subanalysis of patients with brain metastases at baseline also showed an improvement in this population.

Brain metastases are common HER2+ breast cancer, and this is associated with poor outcomes, according to Sara A. Hurvitz, MD, who presented the study at the San Antonio Breast Cancer Symposium. There are few treatment options available for this population.

“Adding tucatinib to TDM-1 significantly improved progression free survival in patients with previously treated HER2+ advanced disease. The types of adverse events were consistent with previous reporting, and this is the second randomized study which included patients with brain metastases to demonstrate that a tucatinib-based regimen delays disease progression in this disease setting,” said Dr. Hurvitz, professor and head of the division of hematology and oncology at the University of Washington Department of Medicine and senior vice president and director of the Clinical Research Division at Fred Hutchinson Cancer Center.

Both tucatinib and TDM-1 target the HER2 receptor. T-DM1 is an antibody-drug conjugate (ADC) of trastuzumab (Herceptin) and the drug emtansine that has received FDA approval as monotherapy for both early- and late-stage HER2-positive breast cancer. Tucatinib is a small-molecule HER2 inhibitor and has efficacy against disease progression in the central nervous system, which is unusual among HER2-targeted therapies.

The earlier HER2CLIMB trial showed improved outcomes among heavily pretreated patients — including those with brain metastases — when tucatinib was added to trastuzumab and capecitabine (Xeloda, Genentech). In 2020, the FDA approved the combination for advanced unresectable or metastatic HER2-positive breast cancer, including brain metastases.

To determine if tucatinib could also improve responses when combined with a trastuzumab-based ADC, the researchers randomized 463 patients to tucatinib plus T-DM1 or placebo plus T-DM1. Nearly half (44.1%) of patients had brain metastases at baseline. Over a median follow-up of 24.4 months, the combination group had a 24% lower risk of progression or death (hazard ratio [HR], 0.76; P = .0163) and a longer median progression-free survival (9.5 months versus 7.4 months).

The PFS benefit was also seen in patients with baseline brain metastases (HR, 0.64; 95% CI, 0.46-0.89]). An insufficient number of survival events had occurred at the interim analysis to determine OS at the time of the presentation.

There was no statistically significant difference in overall response rate in the intervention arm. Treatment-emergent adverse events (TEAEs) that were more common in the tucatinib arm included nausea (65.4% vs. 49.4%), diarrhea (56.7% vs. 26.6%), and fatigue (48.9% vs. 37.3%). Grade 3 or higher TEAEs in the tucatinib arm included alanine and aspartate aminotransferase elevations (16.5% for both), versus 2.6% in the control arm for both. TEAEs associated treatment discontinuation occurred among 22.1% in the tucatinib arm and 11.6% in the control arm. TEAEs that led to mortality occurred in 1.3% of the tucatinib group and 0.9% of the control arm.

“I think tucatinib really does contain level one evidence for use in the setting of CNS metastases. There’s not yet data that has replaced that, so I will continue to consider using it in the second line setting, as it’s currently indicated in the presence of brain metastases. Without brain metastases, based on [the DESTINY-Breast03 trial], I’d probably opt for [trastuzumab deroxtecan], which is still the standard,” said Dr. Hurvitz.

Following the talk, Valentina Guarneri, MD, PhD, served as a discussant. She underscored the clinical need for treatment of patients with brain metastases.

“Brain metastases represent a devastating event for our patients and remain an unmet need considering that all of these patients will eventually require local therapies, with potentially debilitating sequelae. Since optimal therapy for these patients should not be an afterthought, clinical trials taking the risk of including these patients must be valued,” said Dr. Guarneri, professor of oncology at the University of Padua in Italy.

She acknowledged the success of the dual HER2 inhibitor strategy, and said it opens up avenues for combinations with novel antibody-drug conjugates. “HER2CLIMB-02 is unlikely to change the current algorithm, but it reinforces the role of tucatinib in the treatment of HER2+ metastatic breast cancer. The data further support studies in the early disease setting aiming to prevent the development of brain metastases,” said Dr. Guarneri.

The study was funded by Seagen. Dr. Hurvitz has received research funding from Ambrx, Arvinas, AstraZeneca, Bayer, Celcuity, CytomX Therapeutics, Daiichi Sankyo, Dantari Inc., Dignitana, Genentech, (Roche), G1 Therapeutics, Gilead Sciences Inc., Greenwich LifeSciences Inc., GSK, Immunomedics, Eli Lilly and Company, Loxo Oncology, MacroGenics, Novartis, OBI Pharma Inc., Orinove Inc., Orum Therapeutics, Pfizer, Phoenix Molecular Designs, Pieris Pharmaceuticals Inc., Puma Biotechnology, Radius Health, Sanofi, Seagen, and Zymeworks; has received royalties from McGraw Hill, Sage Publications, Wiley, and Wolters Kluwer; has served on the data and safety monitoring board for Alliance Foundation Trials LLC, Atossa Therapeutics, and the Quantum Leap Healthcare Collaborative; and has received honoraria from the Vaniam Group and OncLive. Her husband holds stock in ROMTech. Dr. Guarneri has been a member of the advisory boards for AstraZeneca, Daiichi Sankyo, Eisai, Eli Lilly, Exact Sciences, Gilead, Merck Serono, MSD, Novartis, Pfizer, Olema Oncology, and Pierre Fabre. She has been an invited speaker for AstraZeneca, Daiichi Sankyo, Eli Lilly, Exact Sciences, Gilead, GSK Novartis, and Zentiva.

SAN ANTONIO – In previously treated patients with locally advanced unresectable or metastatic HER2-positive breast cancer, tucatinib (Tukysa, Seagen) and trastuzumab emtansine (Kadcyla, T-DM1, Genentech) improved progression-free survival (PFS) versus T-DM1 alone, according to results from the phase III HER2CLIMB-02 study. A subanalysis of patients with brain metastases at baseline also showed an improvement in this population.

Brain metastases are common HER2+ breast cancer, and this is associated with poor outcomes, according to Sara A. Hurvitz, MD, who presented the study at the San Antonio Breast Cancer Symposium. There are few treatment options available for this population.

“Adding tucatinib to TDM-1 significantly improved progression free survival in patients with previously treated HER2+ advanced disease. The types of adverse events were consistent with previous reporting, and this is the second randomized study which included patients with brain metastases to demonstrate that a tucatinib-based regimen delays disease progression in this disease setting,” said Dr. Hurvitz, professor and head of the division of hematology and oncology at the University of Washington Department of Medicine and senior vice president and director of the Clinical Research Division at Fred Hutchinson Cancer Center.

Both tucatinib and TDM-1 target the HER2 receptor. T-DM1 is an antibody-drug conjugate (ADC) of trastuzumab (Herceptin) and the drug emtansine that has received FDA approval as monotherapy for both early- and late-stage HER2-positive breast cancer. Tucatinib is a small-molecule HER2 inhibitor and has efficacy against disease progression in the central nervous system, which is unusual among HER2-targeted therapies.

The earlier HER2CLIMB trial showed improved outcomes among heavily pretreated patients — including those with brain metastases — when tucatinib was added to trastuzumab and capecitabine (Xeloda, Genentech). In 2020, the FDA approved the combination for advanced unresectable or metastatic HER2-positive breast cancer, including brain metastases.

To determine if tucatinib could also improve responses when combined with a trastuzumab-based ADC, the researchers randomized 463 patients to tucatinib plus T-DM1 or placebo plus T-DM1. Nearly half (44.1%) of patients had brain metastases at baseline. Over a median follow-up of 24.4 months, the combination group had a 24% lower risk of progression or death (hazard ratio [HR], 0.76; P = .0163) and a longer median progression-free survival (9.5 months versus 7.4 months).

The PFS benefit was also seen in patients with baseline brain metastases (HR, 0.64; 95% CI, 0.46-0.89]). An insufficient number of survival events had occurred at the interim analysis to determine OS at the time of the presentation.

There was no statistically significant difference in overall response rate in the intervention arm. Treatment-emergent adverse events (TEAEs) that were more common in the tucatinib arm included nausea (65.4% vs. 49.4%), diarrhea (56.7% vs. 26.6%), and fatigue (48.9% vs. 37.3%). Grade 3 or higher TEAEs in the tucatinib arm included alanine and aspartate aminotransferase elevations (16.5% for both), versus 2.6% in the control arm for both. TEAEs associated treatment discontinuation occurred among 22.1% in the tucatinib arm and 11.6% in the control arm. TEAEs that led to mortality occurred in 1.3% of the tucatinib group and 0.9% of the control arm.

“I think tucatinib really does contain level one evidence for use in the setting of CNS metastases. There’s not yet data that has replaced that, so I will continue to consider using it in the second line setting, as it’s currently indicated in the presence of brain metastases. Without brain metastases, based on [the DESTINY-Breast03 trial], I’d probably opt for [trastuzumab deroxtecan], which is still the standard,” said Dr. Hurvitz.

Following the talk, Valentina Guarneri, MD, PhD, served as a discussant. She underscored the clinical need for treatment of patients with brain metastases.

“Brain metastases represent a devastating event for our patients and remain an unmet need considering that all of these patients will eventually require local therapies, with potentially debilitating sequelae. Since optimal therapy for these patients should not be an afterthought, clinical trials taking the risk of including these patients must be valued,” said Dr. Guarneri, professor of oncology at the University of Padua in Italy.

She acknowledged the success of the dual HER2 inhibitor strategy, and said it opens up avenues for combinations with novel antibody-drug conjugates. “HER2CLIMB-02 is unlikely to change the current algorithm, but it reinforces the role of tucatinib in the treatment of HER2+ metastatic breast cancer. The data further support studies in the early disease setting aiming to prevent the development of brain metastases,” said Dr. Guarneri.

The study was funded by Seagen. Dr. Hurvitz has received research funding from Ambrx, Arvinas, AstraZeneca, Bayer, Celcuity, CytomX Therapeutics, Daiichi Sankyo, Dantari Inc., Dignitana, Genentech, (Roche), G1 Therapeutics, Gilead Sciences Inc., Greenwich LifeSciences Inc., GSK, Immunomedics, Eli Lilly and Company, Loxo Oncology, MacroGenics, Novartis, OBI Pharma Inc., Orinove Inc., Orum Therapeutics, Pfizer, Phoenix Molecular Designs, Pieris Pharmaceuticals Inc., Puma Biotechnology, Radius Health, Sanofi, Seagen, and Zymeworks; has received royalties from McGraw Hill, Sage Publications, Wiley, and Wolters Kluwer; has served on the data and safety monitoring board for Alliance Foundation Trials LLC, Atossa Therapeutics, and the Quantum Leap Healthcare Collaborative; and has received honoraria from the Vaniam Group and OncLive. Her husband holds stock in ROMTech. Dr. Guarneri has been a member of the advisory boards for AstraZeneca, Daiichi Sankyo, Eisai, Eli Lilly, Exact Sciences, Gilead, Merck Serono, MSD, Novartis, Pfizer, Olema Oncology, and Pierre Fabre. She has been an invited speaker for AstraZeneca, Daiichi Sankyo, Eli Lilly, Exact Sciences, Gilead, GSK Novartis, and Zentiva.

SAN ANTONIO – In previously treated patients with locally advanced unresectable or metastatic HER2-positive breast cancer, tucatinib (Tukysa, Seagen) and trastuzumab emtansine (Kadcyla, T-DM1, Genentech) improved progression-free survival (PFS) versus T-DM1 alone, according to results from the phase III HER2CLIMB-02 study. A subanalysis of patients with brain metastases at baseline also showed an improvement in this population.

Brain metastases are common HER2+ breast cancer, and this is associated with poor outcomes, according to Sara A. Hurvitz, MD, who presented the study at the San Antonio Breast Cancer Symposium. There are few treatment options available for this population.

“Adding tucatinib to TDM-1 significantly improved progression free survival in patients with previously treated HER2+ advanced disease. The types of adverse events were consistent with previous reporting, and this is the second randomized study which included patients with brain metastases to demonstrate that a tucatinib-based regimen delays disease progression in this disease setting,” said Dr. Hurvitz, professor and head of the division of hematology and oncology at the University of Washington Department of Medicine and senior vice president and director of the Clinical Research Division at Fred Hutchinson Cancer Center.

Both tucatinib and TDM-1 target the HER2 receptor. T-DM1 is an antibody-drug conjugate (ADC) of trastuzumab (Herceptin) and the drug emtansine that has received FDA approval as monotherapy for both early- and late-stage HER2-positive breast cancer. Tucatinib is a small-molecule HER2 inhibitor and has efficacy against disease progression in the central nervous system, which is unusual among HER2-targeted therapies.

The earlier HER2CLIMB trial showed improved outcomes among heavily pretreated patients — including those with brain metastases — when tucatinib was added to trastuzumab and capecitabine (Xeloda, Genentech). In 2020, the FDA approved the combination for advanced unresectable or metastatic HER2-positive breast cancer, including brain metastases.

To determine if tucatinib could also improve responses when combined with a trastuzumab-based ADC, the researchers randomized 463 patients to tucatinib plus T-DM1 or placebo plus T-DM1. Nearly half (44.1%) of patients had brain metastases at baseline. Over a median follow-up of 24.4 months, the combination group had a 24% lower risk of progression or death (hazard ratio [HR], 0.76; P = .0163) and a longer median progression-free survival (9.5 months versus 7.4 months).

The PFS benefit was also seen in patients with baseline brain metastases (HR, 0.64; 95% CI, 0.46-0.89]). An insufficient number of survival events had occurred at the interim analysis to determine OS at the time of the presentation.

There was no statistically significant difference in overall response rate in the intervention arm. Treatment-emergent adverse events (TEAEs) that were more common in the tucatinib arm included nausea (65.4% vs. 49.4%), diarrhea (56.7% vs. 26.6%), and fatigue (48.9% vs. 37.3%). Grade 3 or higher TEAEs in the tucatinib arm included alanine and aspartate aminotransferase elevations (16.5% for both), versus 2.6% in the control arm for both. TEAEs associated treatment discontinuation occurred among 22.1% in the tucatinib arm and 11.6% in the control arm. TEAEs that led to mortality occurred in 1.3% of the tucatinib group and 0.9% of the control arm.

“I think tucatinib really does contain level one evidence for use in the setting of CNS metastases. There’s not yet data that has replaced that, so I will continue to consider using it in the second line setting, as it’s currently indicated in the presence of brain metastases. Without brain metastases, based on [the DESTINY-Breast03 trial], I’d probably opt for [trastuzumab deroxtecan], which is still the standard,” said Dr. Hurvitz.

Following the talk, Valentina Guarneri, MD, PhD, served as a discussant. She underscored the clinical need for treatment of patients with brain metastases.

“Brain metastases represent a devastating event for our patients and remain an unmet need considering that all of these patients will eventually require local therapies, with potentially debilitating sequelae. Since optimal therapy for these patients should not be an afterthought, clinical trials taking the risk of including these patients must be valued,” said Dr. Guarneri, professor of oncology at the University of Padua in Italy.

She acknowledged the success of the dual HER2 inhibitor strategy, and said it opens up avenues for combinations with novel antibody-drug conjugates. “HER2CLIMB-02 is unlikely to change the current algorithm, but it reinforces the role of tucatinib in the treatment of HER2+ metastatic breast cancer. The data further support studies in the early disease setting aiming to prevent the development of brain metastases,” said Dr. Guarneri.

The study was funded by Seagen. Dr. Hurvitz has received research funding from Ambrx, Arvinas, AstraZeneca, Bayer, Celcuity, CytomX Therapeutics, Daiichi Sankyo, Dantari Inc., Dignitana, Genentech, (Roche), G1 Therapeutics, Gilead Sciences Inc., Greenwich LifeSciences Inc., GSK, Immunomedics, Eli Lilly and Company, Loxo Oncology, MacroGenics, Novartis, OBI Pharma Inc., Orinove Inc., Orum Therapeutics, Pfizer, Phoenix Molecular Designs, Pieris Pharmaceuticals Inc., Puma Biotechnology, Radius Health, Sanofi, Seagen, and Zymeworks; has received royalties from McGraw Hill, Sage Publications, Wiley, and Wolters Kluwer; has served on the data and safety monitoring board for Alliance Foundation Trials LLC, Atossa Therapeutics, and the Quantum Leap Healthcare Collaborative; and has received honoraria from the Vaniam Group and OncLive. Her husband holds stock in ROMTech. Dr. Guarneri has been a member of the advisory boards for AstraZeneca, Daiichi Sankyo, Eisai, Eli Lilly, Exact Sciences, Gilead, Merck Serono, MSD, Novartis, Pfizer, Olema Oncology, and Pierre Fabre. She has been an invited speaker for AstraZeneca, Daiichi Sankyo, Eli Lilly, Exact Sciences, Gilead, GSK Novartis, and Zentiva.

Results of the PROSPECT trial provide compelling evidence that high-quality preoperative MRI in combination with postoperative analysis of pathologic features can identify a substantial subset of women with localized early breast cancer who could safely skip radiation therapy. 

Omitting radiation therapy after breast-conserving surgery in patients with no occult malignancy and favorable pathology led to a very low local recurrence rate (1%) at 5 years, reported lead investigator Gregory Bruce Mann, MBBS, PhD, of The Royal Women’s Hospital, Melbourne, Australia, at the San Antonio Breast Cancer Symposium (abstract PS02-03). 

Additionally, women who skipped radiation had superior health-related quality of life relative to peers who underwent the treatment and, quite unexpectedly, their fear of cancer recurrence was “dramatically reduced,” Dr, Mann said in an interview.

“The hypothesis was that less treatment [would] lead to more fear of cancer recurrence” because patients would worry that they hadn’t received standard treatment, “but patients who omitted RT actually had less fear of cancer recurrence,” he said. 

This may come down to positive perceptions about tailored care and trust, he explained. “If the patient got the impression that the doctor wasn’t worried about recurrence, then the patient wasn’t worried. If they trusted you and you had that relationship with the patient, they were less likely to experience a fear of recurrence.” 

Results of the PROSPECT trial were published online on December 5 in The Lancet. 

PROSPECT was a prospective, nonrandomized study that evaluated whether preoperative bilateral contrast-enhanced 3-Tesla breast MRI and postoperative tumor pathology could identify patients with “truly localized” disease who might feasibly skip radiation therapy after breast-conserving surgery.

The researchers hypothesised that radiation therapy reduces local recurrence risk by treating occult synchronous disease that has not been identified by conventional imaging techniques. Exclusion of such occult disease using preoperative MRI, in association with low-risk pathology, could define a group of patients with early breast cancer in whom radiation can be omitted without substantially compromising local recurrence rates. 

Women aged 50 years or older with cT1N0 non–triple-negative breast cancer were eligible for the trial. Among 443 patients, preoperative MRI detected 61 malignant occult lesions separate from the index cancer in 48 patients (11%) of the total cohort. 

Patients with apparently unifocal cancer had breast-conserving surgery and, if pT1N0 or N1mi, did not undergo radiation therapy (group 1: 201 women). Standard treatment including radiation therapy was offered to the others (group 2: 242 women). All women were recommended for systemic therapy. The primary endpoint was the ipsilateral invasive recurrence rate at 5 years, with follow-up to continue to 10 years. 

At a median follow-up of 5.4 years, the ipsilateral invasive recurrence rate in group 1 was exceedingly low — just 1.0% (upper 95% CI, 5.4%) — with one local recurrence at 4.5 years and a second at 7.5 years. In group 2, local recurrence at 5 years was also low, at 1.7% (upper 95% CI, 6.1%). 

The only case of distant metastasis in the entire cohort was genetically distinct from the index cancer.

Omitting radiation therapy led to better health-related quality of life and functional and cosmetic outcomes, and the women viewed not having radiation as highly acceptable and appropriate treatment, not undertreatment.

PROSPECT has defined a role for “very high quality” preoperative MRI in identifying patients who can be considered for deintensified treatment, Dr. Mann said. 

The findings need to be replicated in multicenter, international trials, “and that’s what we are working on,” he added.

 

Risk Tolerance and Personal Preferences

Writing in a comment for The Lancet, Lior Z. Braunstein, MD, with Memorial Sloan Kettering Cancer Center in New York, says that overall, PROSPECT and comparable trials of radiation therapy omission, “rather than setting uniform clinical practice, will empower patients to delineate their individual risk tolerance and personal preferences.”

He notes, however, that “the use of preoperative MRI among patients at low risk remains somewhat controversial. Indeed, the MRI intervention in PROSPECT was not entirely benign, prompting nearly 200 biopsies and five of the nine observed mastectomies.”

Dr. Braunstein concludes that with numerous approaches to risk profiling, “informed patients might very reasonably choose differing paths. Indeed, it is precisely this individualized approach to breast cancer management that has long been the promise of personalized medicine — PROSPECT adds laudably to that tradition.”

Funding for the trial was provided by Breast Cancer Trials, National Breast Cancer Foundation, Cancer Council Victoria, the Royal Melbourne Hospital Foundation, and the Breast Cancer Research Foundation. Dr. Mann and Dr. Braunstein have no relevant disclosures.Megan Brooks has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Results of the PROSPECT trial provide compelling evidence that high-quality preoperative MRI in combination with postoperative analysis of pathologic features can identify a substantial subset of women with localized early breast cancer who could safely skip radiation therapy. 

Omitting radiation therapy after breast-conserving surgery in patients with no occult malignancy and favorable pathology led to a very low local recurrence rate (1%) at 5 years, reported lead investigator Gregory Bruce Mann, MBBS, PhD, of The Royal Women’s Hospital, Melbourne, Australia, at the San Antonio Breast Cancer Symposium (abstract PS02-03). 

Additionally, women who skipped radiation had superior health-related quality of life relative to peers who underwent the treatment and, quite unexpectedly, their fear of cancer recurrence was “dramatically reduced,” Dr, Mann said in an interview.

“The hypothesis was that less treatment [would] lead to more fear of cancer recurrence” because patients would worry that they hadn’t received standard treatment, “but patients who omitted RT actually had less fear of cancer recurrence,” he said. 

This may come down to positive perceptions about tailored care and trust, he explained. “If the patient got the impression that the doctor wasn’t worried about recurrence, then the patient wasn’t worried. If they trusted you and you had that relationship with the patient, they were less likely to experience a fear of recurrence.” 

Results of the PROSPECT trial were published online on December 5 in The Lancet. 

PROSPECT was a prospective, nonrandomized study that evaluated whether preoperative bilateral contrast-enhanced 3-Tesla breast MRI and postoperative tumor pathology could identify patients with “truly localized” disease who might feasibly skip radiation therapy after breast-conserving surgery.

The researchers hypothesised that radiation therapy reduces local recurrence risk by treating occult synchronous disease that has not been identified by conventional imaging techniques. Exclusion of such occult disease using preoperative MRI, in association with low-risk pathology, could define a group of patients with early breast cancer in whom radiation can be omitted without substantially compromising local recurrence rates. 

Women aged 50 years or older with cT1N0 non–triple-negative breast cancer were eligible for the trial. Among 443 patients, preoperative MRI detected 61 malignant occult lesions separate from the index cancer in 48 patients (11%) of the total cohort. 

Patients with apparently unifocal cancer had breast-conserving surgery and, if pT1N0 or N1mi, did not undergo radiation therapy (group 1: 201 women). Standard treatment including radiation therapy was offered to the others (group 2: 242 women). All women were recommended for systemic therapy. The primary endpoint was the ipsilateral invasive recurrence rate at 5 years, with follow-up to continue to 10 years. 

At a median follow-up of 5.4 years, the ipsilateral invasive recurrence rate in group 1 was exceedingly low — just 1.0% (upper 95% CI, 5.4%) — with one local recurrence at 4.5 years and a second at 7.5 years. In group 2, local recurrence at 5 years was also low, at 1.7% (upper 95% CI, 6.1%). 

The only case of distant metastasis in the entire cohort was genetically distinct from the index cancer.

Omitting radiation therapy led to better health-related quality of life and functional and cosmetic outcomes, and the women viewed not having radiation as highly acceptable and appropriate treatment, not undertreatment.

PROSPECT has defined a role for “very high quality” preoperative MRI in identifying patients who can be considered for deintensified treatment, Dr. Mann said. 

The findings need to be replicated in multicenter, international trials, “and that’s what we are working on,” he added.

 

Risk Tolerance and Personal Preferences

Writing in a comment for The Lancet, Lior Z. Braunstein, MD, with Memorial Sloan Kettering Cancer Center in New York, says that overall, PROSPECT and comparable trials of radiation therapy omission, “rather than setting uniform clinical practice, will empower patients to delineate their individual risk tolerance and personal preferences.”

He notes, however, that “the use of preoperative MRI among patients at low risk remains somewhat controversial. Indeed, the MRI intervention in PROSPECT was not entirely benign, prompting nearly 200 biopsies and five of the nine observed mastectomies.”

Dr. Braunstein concludes that with numerous approaches to risk profiling, “informed patients might very reasonably choose differing paths. Indeed, it is precisely this individualized approach to breast cancer management that has long been the promise of personalized medicine — PROSPECT adds laudably to that tradition.”

Funding for the trial was provided by Breast Cancer Trials, National Breast Cancer Foundation, Cancer Council Victoria, the Royal Melbourne Hospital Foundation, and the Breast Cancer Research Foundation. Dr. Mann and Dr. Braunstein have no relevant disclosures.Megan Brooks has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Results of the PROSPECT trial provide compelling evidence that high-quality preoperative MRI in combination with postoperative analysis of pathologic features can identify a substantial subset of women with localized early breast cancer who could safely skip radiation therapy. 

Omitting radiation therapy after breast-conserving surgery in patients with no occult malignancy and favorable pathology led to a very low local recurrence rate (1%) at 5 years, reported lead investigator Gregory Bruce Mann, MBBS, PhD, of The Royal Women’s Hospital, Melbourne, Australia, at the San Antonio Breast Cancer Symposium (abstract PS02-03). 

Additionally, women who skipped radiation had superior health-related quality of life relative to peers who underwent the treatment and, quite unexpectedly, their fear of cancer recurrence was “dramatically reduced,” Dr, Mann said in an interview.

“The hypothesis was that less treatment [would] lead to more fear of cancer recurrence” because patients would worry that they hadn’t received standard treatment, “but patients who omitted RT actually had less fear of cancer recurrence,” he said. 

This may come down to positive perceptions about tailored care and trust, he explained. “If the patient got the impression that the doctor wasn’t worried about recurrence, then the patient wasn’t worried. If they trusted you and you had that relationship with the patient, they were less likely to experience a fear of recurrence.” 

Results of the PROSPECT trial were published online on December 5 in The Lancet. 

PROSPECT was a prospective, nonrandomized study that evaluated whether preoperative bilateral contrast-enhanced 3-Tesla breast MRI and postoperative tumor pathology could identify patients with “truly localized” disease who might feasibly skip radiation therapy after breast-conserving surgery.

The researchers hypothesised that radiation therapy reduces local recurrence risk by treating occult synchronous disease that has not been identified by conventional imaging techniques. Exclusion of such occult disease using preoperative MRI, in association with low-risk pathology, could define a group of patients with early breast cancer in whom radiation can be omitted without substantially compromising local recurrence rates. 

Women aged 50 years or older with cT1N0 non–triple-negative breast cancer were eligible for the trial. Among 443 patients, preoperative MRI detected 61 malignant occult lesions separate from the index cancer in 48 patients (11%) of the total cohort. 

Patients with apparently unifocal cancer had breast-conserving surgery and, if pT1N0 or N1mi, did not undergo radiation therapy (group 1: 201 women). Standard treatment including radiation therapy was offered to the others (group 2: 242 women). All women were recommended for systemic therapy. The primary endpoint was the ipsilateral invasive recurrence rate at 5 years, with follow-up to continue to 10 years. 

At a median follow-up of 5.4 years, the ipsilateral invasive recurrence rate in group 1 was exceedingly low — just 1.0% (upper 95% CI, 5.4%) — with one local recurrence at 4.5 years and a second at 7.5 years. In group 2, local recurrence at 5 years was also low, at 1.7% (upper 95% CI, 6.1%). 

The only case of distant metastasis in the entire cohort was genetically distinct from the index cancer.

Omitting radiation therapy led to better health-related quality of life and functional and cosmetic outcomes, and the women viewed not having radiation as highly acceptable and appropriate treatment, not undertreatment.

PROSPECT has defined a role for “very high quality” preoperative MRI in identifying patients who can be considered for deintensified treatment, Dr. Mann said. 

The findings need to be replicated in multicenter, international trials, “and that’s what we are working on,” he added.

 

Risk Tolerance and Personal Preferences

Writing in a comment for The Lancet, Lior Z. Braunstein, MD, with Memorial Sloan Kettering Cancer Center in New York, says that overall, PROSPECT and comparable trials of radiation therapy omission, “rather than setting uniform clinical practice, will empower patients to delineate their individual risk tolerance and personal preferences.”

He notes, however, that “the use of preoperative MRI among patients at low risk remains somewhat controversial. Indeed, the MRI intervention in PROSPECT was not entirely benign, prompting nearly 200 biopsies and five of the nine observed mastectomies.”

Dr. Braunstein concludes that with numerous approaches to risk profiling, “informed patients might very reasonably choose differing paths. Indeed, it is precisely this individualized approach to breast cancer management that has long been the promise of personalized medicine — PROSPECT adds laudably to that tradition.”

Funding for the trial was provided by Breast Cancer Trials, National Breast Cancer Foundation, Cancer Council Victoria, the Royal Melbourne Hospital Foundation, and the Breast Cancer Research Foundation. Dr. Mann and Dr. Braunstein have no relevant disclosures.Megan Brooks has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

HAMBURG, Germany — The human microbiome comprises 39 to 44 billion microbes. That is ten times more than the number of cells in our body. Hendrik Poeck, MD, managing senior physician of internal medicine at the University Hospital Regensburg, illustrated this point at the annual meeting of the German Society for Hematology and Medical Oncology. If the gut microbiome falls out of balance, then “intestinal dysbiosis potentially poses a risk for the pathogenesis of local and systemic diseases,” explained Dr. Poeck.

Cancers and their therapies can also be influenced in this way. “Microbial diversity affects whether a tumor grows, whether it leads to inflammation, immune escape mechanisms or genomic instability, or whether therapeutic resistances develop,” said Dr. Poeck.

Microbial diversity could be beneficial for cancer therapy, too. The composition of the microbiome varies significantly from host to host and can mutate. These properties make it a target for precision microbiotics, which involves using the gut microbiome as a biomarker to predict various physical reactions and to develop individualized diets.

Microbiome and Pathogenesis

The body’s microbiome fulfills a barrier function, especially where the body is exposed to an external environment: at the epidermis and the internal mucous membranes, in the gastrointestinal tract, and in the lungs, chest, and urogenital system.

Association studies on humans and experimental manipulations on mouse models of cancer showed that certain microorganisms can have either protective or harmful effects on cancer development, on the progression of a malignant disease, and on the response to therapy.

A Master Regulator?

Disruptions of the microbial system in the gut, as occur during antibiotic therapy, can have significant effects on a patient’s response to immunotherapy. Taking antibiotics shortly before or after starting therapy with immune checkpoint inhibitors (ICIs) significantly affected both overall survival (OS) and progression-free survival (PFS), as reported in a recent review and meta-analysis, for example.

Proton pump inhibitors also affect the gut microbiome and reduce the response to immunotherapy; this effect was demonstrated by an analysis of data from more than 2700 cancer patients that was recently presented at the annual meeting of the European Society for Medical Oncology (ESMO).

The extent to which the gut microbiome influences the efficacy of an ICI or predicts said efficacy was examined in a retrospective analysis published in Science in 2018, which Dr. Poeck presented. Resistance to ICI correlated with the relative frequency of the bacteria Akkermansia muciniphila in the gut of patients with cancer. In mouse models, the researchers restored the efficacy of the PD-1 blockade through a stool transplant.

Predicting Immunotherapy Response

If A muciniphila is present, can the composition of the microbiome act as a predictor for an effective ICI therapy?

Laurence Zitvogel, MD, PhD, and her working group at the National Institute of Health and Medical Research in Villejuif, France, performed a prospective study in 338 patients with non–small cell lung cancer and examined the prognostic significance of the fecal bacteria A muciniphila (Akk). The “Akkerman status” (low Akk vs high Akk) in a patient’s stool correlated with an increased objective response rate and a longer OS, independently of PD-L1 expression, antibiotics, and performance status. The OS for low Akk was 13.4 months, vs 18.8 months for high Akk in first-line treatment.

These results are promising, said Dr. Poeck. But there is no one-size-fits-all solution. No conclusions can be drawn from one bacterium on the efficacy of therapies in humans, since “the entirety of the bacteria is decisive,” said Dr. Poeck. In addition to the gut microbiome, the composition of gut metabolites influences the response to immunotherapies, as shown in a study with ICI.

Therapeutic Interventions

One possible therapeutic intervention to restore the gut microbiome is fecal microbiota transplantation (FMT). In a phase 1 study presented by Dr. Poeck, FMT was effective in the treatment of 20 patients with melanoma with ICI in an advanced and treatment-naive stage. Seven days after the patients received FMT, the first cycle with anti-PD-1 immunotherapy was initiated, with a total administration of three to four cycles. After 12 weeks, most patients were in complete or partial remission, as evidenced on imaging.

However, FMT also carries some risks. Two cases of sepsis with multiresistant Escherichia coli occurred, as well as other serious infections. Since then, there has been an FDA condition for extended screening of the donor stool, said Dr. Poeck. Nevertheless, this intervention is promising. A search of the keywords “FMT in cancer/transplant setting” reveals 46 currently clinical studies on clinicaltrials.gov.

Nutritional Interventions

Dr. Poeck advises caution about over-the-counter products. These products usually contain only a few species, such as Lactobacillus and Bifidobacterium. “Over-the-counter probiotics can even delay the reconstitution of the microbiome after antibiotics,” said Dr. Poeck, according to a study. In some studies, the response rates were significantly lower after probiotic intake or led to controversial results, according to Dr. Poeck.

In contrast, Dr. Poeck said prebiotics (that is, a fiber-rich diet with indigestible carbohydrates) were promising. During digestion, prebiotics are split into short-chain fatty acids by bacterial enzymes and promote the growth of certain microbiota.

In this way, just 20 g of extremely fiber-rich food had a significant effect on PFS in 128 patients with melanoma undergoing anti-PD-1 immunotherapy. With 20 g of fiber-rich food per day, the PFS was stable over 60 months. The most significant benefit was observed in patients with a sufficient fiber intake who were not taking probiotics.

What to Recommend?

In summary, Dr. Poeck said that it is important to “budget” well, particularly with antibiotic administration, and to strive for calculated therapy with as narrow a spectrum as possible. For patients who experience complications such as cytokine release syndrome as a reaction to cell therapy, delaying the use of antibiotics is important. However, it is often difficult to differentiate this syndrome from neutropenic fever. The aim should be to avoid high-risk antibiotics, if clinically justifiable. Patients should avoid taking antibiotics for 30 days before starting immunotherapy.

Regarding nutritional interventions, Dr. Poeck referred to the recent Onkopedia recommendation for nutrition after cancer and the 10 nutritional rules of the German Nutrition Society. According to Dr. Poeck, the important aspects of these recommendations are a fiber-rich diet (> 20 g/d) from various plant products and avoiding artificial sweeteners and flavorings, as well as ultraprocessed (convenience) foods. In addition, meat should be consumed only in moderation, and as little processed meat as possible should be consumed. In addition, regular (aerobic and anaerobic) physical activity is important.

“Looking ahead into the future,” said Dr. Poeck, “we need a uniform and functional understanding and we need a randomized prediction for diagnosis.”


This article was translated from the Medscape German edition.

A version of this article appeared on Medscape.com.

HAMBURG, Germany — The human microbiome comprises 39 to 44 billion microbes. That is ten times more than the number of cells in our body. Hendrik Poeck, MD, managing senior physician of internal medicine at the University Hospital Regensburg, illustrated this point at the annual meeting of the German Society for Hematology and Medical Oncology. If the gut microbiome falls out of balance, then “intestinal dysbiosis potentially poses a risk for the pathogenesis of local and systemic diseases,” explained Dr. Poeck.

Cancers and their therapies can also be influenced in this way. “Microbial diversity affects whether a tumor grows, whether it leads to inflammation, immune escape mechanisms or genomic instability, or whether therapeutic resistances develop,” said Dr. Poeck.

Microbial diversity could be beneficial for cancer therapy, too. The composition of the microbiome varies significantly from host to host and can mutate. These properties make it a target for precision microbiotics, which involves using the gut microbiome as a biomarker to predict various physical reactions and to develop individualized diets.

Microbiome and Pathogenesis

The body’s microbiome fulfills a barrier function, especially where the body is exposed to an external environment: at the epidermis and the internal mucous membranes, in the gastrointestinal tract, and in the lungs, chest, and urogenital system.

Association studies on humans and experimental manipulations on mouse models of cancer showed that certain microorganisms can have either protective or harmful effects on cancer development, on the progression of a malignant disease, and on the response to therapy.

A Master Regulator?

Disruptions of the microbial system in the gut, as occur during antibiotic therapy, can have significant effects on a patient’s response to immunotherapy. Taking antibiotics shortly before or after starting therapy with immune checkpoint inhibitors (ICIs) significantly affected both overall survival (OS) and progression-free survival (PFS), as reported in a recent review and meta-analysis, for example.

Proton pump inhibitors also affect the gut microbiome and reduce the response to immunotherapy; this effect was demonstrated by an analysis of data from more than 2700 cancer patients that was recently presented at the annual meeting of the European Society for Medical Oncology (ESMO).

The extent to which the gut microbiome influences the efficacy of an ICI or predicts said efficacy was examined in a retrospective analysis published in Science in 2018, which Dr. Poeck presented. Resistance to ICI correlated with the relative frequency of the bacteria Akkermansia muciniphila in the gut of patients with cancer. In mouse models, the researchers restored the efficacy of the PD-1 blockade through a stool transplant.

Predicting Immunotherapy Response

If A muciniphila is present, can the composition of the microbiome act as a predictor for an effective ICI therapy?

Laurence Zitvogel, MD, PhD, and her working group at the National Institute of Health and Medical Research in Villejuif, France, performed a prospective study in 338 patients with non–small cell lung cancer and examined the prognostic significance of the fecal bacteria A muciniphila (Akk). The “Akkerman status” (low Akk vs high Akk) in a patient’s stool correlated with an increased objective response rate and a longer OS, independently of PD-L1 expression, antibiotics, and performance status. The OS for low Akk was 13.4 months, vs 18.8 months for high Akk in first-line treatment.

These results are promising, said Dr. Poeck. But there is no one-size-fits-all solution. No conclusions can be drawn from one bacterium on the efficacy of therapies in humans, since “the entirety of the bacteria is decisive,” said Dr. Poeck. In addition to the gut microbiome, the composition of gut metabolites influences the response to immunotherapies, as shown in a study with ICI.

Therapeutic Interventions

One possible therapeutic intervention to restore the gut microbiome is fecal microbiota transplantation (FMT). In a phase 1 study presented by Dr. Poeck, FMT was effective in the treatment of 20 patients with melanoma with ICI in an advanced and treatment-naive stage. Seven days after the patients received FMT, the first cycle with anti-PD-1 immunotherapy was initiated, with a total administration of three to four cycles. After 12 weeks, most patients were in complete or partial remission, as evidenced on imaging.

However, FMT also carries some risks. Two cases of sepsis with multiresistant Escherichia coli occurred, as well as other serious infections. Since then, there has been an FDA condition for extended screening of the donor stool, said Dr. Poeck. Nevertheless, this intervention is promising. A search of the keywords “FMT in cancer/transplant setting” reveals 46 currently clinical studies on clinicaltrials.gov.

Nutritional Interventions

Dr. Poeck advises caution about over-the-counter products. These products usually contain only a few species, such as Lactobacillus and Bifidobacterium. “Over-the-counter probiotics can even delay the reconstitution of the microbiome after antibiotics,” said Dr. Poeck, according to a study. In some studies, the response rates were significantly lower after probiotic intake or led to controversial results, according to Dr. Poeck.

In contrast, Dr. Poeck said prebiotics (that is, a fiber-rich diet with indigestible carbohydrates) were promising. During digestion, prebiotics are split into short-chain fatty acids by bacterial enzymes and promote the growth of certain microbiota.

In this way, just 20 g of extremely fiber-rich food had a significant effect on PFS in 128 patients with melanoma undergoing anti-PD-1 immunotherapy. With 20 g of fiber-rich food per day, the PFS was stable over 60 months. The most significant benefit was observed in patients with a sufficient fiber intake who were not taking probiotics.

What to Recommend?

In summary, Dr. Poeck said that it is important to “budget” well, particularly with antibiotic administration, and to strive for calculated therapy with as narrow a spectrum as possible. For patients who experience complications such as cytokine release syndrome as a reaction to cell therapy, delaying the use of antibiotics is important. However, it is often difficult to differentiate this syndrome from neutropenic fever. The aim should be to avoid high-risk antibiotics, if clinically justifiable. Patients should avoid taking antibiotics for 30 days before starting immunotherapy.

Regarding nutritional interventions, Dr. Poeck referred to the recent Onkopedia recommendation for nutrition after cancer and the 10 nutritional rules of the German Nutrition Society. According to Dr. Poeck, the important aspects of these recommendations are a fiber-rich diet (> 20 g/d) from various plant products and avoiding artificial sweeteners and flavorings, as well as ultraprocessed (convenience) foods. In addition, meat should be consumed only in moderation, and as little processed meat as possible should be consumed. In addition, regular (aerobic and anaerobic) physical activity is important.

“Looking ahead into the future,” said Dr. Poeck, “we need a uniform and functional understanding and we need a randomized prediction for diagnosis.”


This article was translated from the Medscape German edition.

A version of this article appeared on Medscape.com.

HAMBURG, Germany — The human microbiome comprises 39 to 44 billion microbes. That is ten times more than the number of cells in our body. Hendrik Poeck, MD, managing senior physician of internal medicine at the University Hospital Regensburg, illustrated this point at the annual meeting of the German Society for Hematology and Medical Oncology. If the gut microbiome falls out of balance, then “intestinal dysbiosis potentially poses a risk for the pathogenesis of local and systemic diseases,” explained Dr. Poeck.

Cancers and their therapies can also be influenced in this way. “Microbial diversity affects whether a tumor grows, whether it leads to inflammation, immune escape mechanisms or genomic instability, or whether therapeutic resistances develop,” said Dr. Poeck.

Microbial diversity could be beneficial for cancer therapy, too. The composition of the microbiome varies significantly from host to host and can mutate. These properties make it a target for precision microbiotics, which involves using the gut microbiome as a biomarker to predict various physical reactions and to develop individualized diets.

Microbiome and Pathogenesis

The body’s microbiome fulfills a barrier function, especially where the body is exposed to an external environment: at the epidermis and the internal mucous membranes, in the gastrointestinal tract, and in the lungs, chest, and urogenital system.

Association studies on humans and experimental manipulations on mouse models of cancer showed that certain microorganisms can have either protective or harmful effects on cancer development, on the progression of a malignant disease, and on the response to therapy.

A Master Regulator?

Disruptions of the microbial system in the gut, as occur during antibiotic therapy, can have significant effects on a patient’s response to immunotherapy. Taking antibiotics shortly before or after starting therapy with immune checkpoint inhibitors (ICIs) significantly affected both overall survival (OS) and progression-free survival (PFS), as reported in a recent review and meta-analysis, for example.

Proton pump inhibitors also affect the gut microbiome and reduce the response to immunotherapy; this effect was demonstrated by an analysis of data from more than 2700 cancer patients that was recently presented at the annual meeting of the European Society for Medical Oncology (ESMO).

The extent to which the gut microbiome influences the efficacy of an ICI or predicts said efficacy was examined in a retrospective analysis published in Science in 2018, which Dr. Poeck presented. Resistance to ICI correlated with the relative frequency of the bacteria Akkermansia muciniphila in the gut of patients with cancer. In mouse models, the researchers restored the efficacy of the PD-1 blockade through a stool transplant.

Predicting Immunotherapy Response

If A muciniphila is present, can the composition of the microbiome act as a predictor for an effective ICI therapy?

Laurence Zitvogel, MD, PhD, and her working group at the National Institute of Health and Medical Research in Villejuif, France, performed a prospective study in 338 patients with non–small cell lung cancer and examined the prognostic significance of the fecal bacteria A muciniphila (Akk). The “Akkerman status” (low Akk vs high Akk) in a patient’s stool correlated with an increased objective response rate and a longer OS, independently of PD-L1 expression, antibiotics, and performance status. The OS for low Akk was 13.4 months, vs 18.8 months for high Akk in first-line treatment.

These results are promising, said Dr. Poeck. But there is no one-size-fits-all solution. No conclusions can be drawn from one bacterium on the efficacy of therapies in humans, since “the entirety of the bacteria is decisive,” said Dr. Poeck. In addition to the gut microbiome, the composition of gut metabolites influences the response to immunotherapies, as shown in a study with ICI.

Therapeutic Interventions

One possible therapeutic intervention to restore the gut microbiome is fecal microbiota transplantation (FMT). In a phase 1 study presented by Dr. Poeck, FMT was effective in the treatment of 20 patients with melanoma with ICI in an advanced and treatment-naive stage. Seven days after the patients received FMT, the first cycle with anti-PD-1 immunotherapy was initiated, with a total administration of three to four cycles. After 12 weeks, most patients were in complete or partial remission, as evidenced on imaging.

However, FMT also carries some risks. Two cases of sepsis with multiresistant Escherichia coli occurred, as well as other serious infections. Since then, there has been an FDA condition for extended screening of the donor stool, said Dr. Poeck. Nevertheless, this intervention is promising. A search of the keywords “FMT in cancer/transplant setting” reveals 46 currently clinical studies on clinicaltrials.gov.

Nutritional Interventions

Dr. Poeck advises caution about over-the-counter products. These products usually contain only a few species, such as Lactobacillus and Bifidobacterium. “Over-the-counter probiotics can even delay the reconstitution of the microbiome after antibiotics,” said Dr. Poeck, according to a study. In some studies, the response rates were significantly lower after probiotic intake or led to controversial results, according to Dr. Poeck.

In contrast, Dr. Poeck said prebiotics (that is, a fiber-rich diet with indigestible carbohydrates) were promising. During digestion, prebiotics are split into short-chain fatty acids by bacterial enzymes and promote the growth of certain microbiota.

In this way, just 20 g of extremely fiber-rich food had a significant effect on PFS in 128 patients with melanoma undergoing anti-PD-1 immunotherapy. With 20 g of fiber-rich food per day, the PFS was stable over 60 months. The most significant benefit was observed in patients with a sufficient fiber intake who were not taking probiotics.

What to Recommend?

In summary, Dr. Poeck said that it is important to “budget” well, particularly with antibiotic administration, and to strive for calculated therapy with as narrow a spectrum as possible. For patients who experience complications such as cytokine release syndrome as a reaction to cell therapy, delaying the use of antibiotics is important. However, it is often difficult to differentiate this syndrome from neutropenic fever. The aim should be to avoid high-risk antibiotics, if clinically justifiable. Patients should avoid taking antibiotics for 30 days before starting immunotherapy.

Regarding nutritional interventions, Dr. Poeck referred to the recent Onkopedia recommendation for nutrition after cancer and the 10 nutritional rules of the German Nutrition Society. According to Dr. Poeck, the important aspects of these recommendations are a fiber-rich diet (> 20 g/d) from various plant products and avoiding artificial sweeteners and flavorings, as well as ultraprocessed (convenience) foods. In addition, meat should be consumed only in moderation, and as little processed meat as possible should be consumed. In addition, regular (aerobic and anaerobic) physical activity is important.

“Looking ahead into the future,” said Dr. Poeck, “we need a uniform and functional understanding and we need a randomized prediction for diagnosis.”


This article was translated from the Medscape German edition.

A version of this article appeared on Medscape.com.

Persistent chemotherapy-related amenorrhea (CRA) after treatment for breast cancer was common and associated with worse long-term quality of life among premenopausal women in a large multicenter French cohort study.

The findings, which showed a particularly increased risk of persistent CRA in older women and those who received adjuvant tamoxifen, can help inform communication, personalized counseling, and supportive care, according to the investigators.

At 1 year after treatment, CRA occurred in 1242 of 1497 women (83.0%) from the prospective, longitudinal Cancers Toxicity Study (CANTO). The rates at years 2 and 4 after treatment were 72.5% and 66.1%, respectively, Rayan Kabirian, MD, of Gustave Roussy, Villejuif, France, and Sorbonne University, Paris, and colleagues reported.

In a quality-of-life analysis conducted among 729 women from the cohort, 416 (57.1%) had persistent CRA, although 11 of 21 women aged 18-34 years who had no menses at year 2 had late menses recovery between years 2 and 4. Those with persistent CRA at year 4, compared with those who had menses recovery at any time, had significantly worse insomnia (mean difference, 9.9 points), worse systemic therapy-related adverse effects (mean difference, 3.0 points), and worse sexual functioning (mean difference, -9.2 points).

Factors associated with greater risk of persistent CRA included receipt versus non-receipt of adjuvant tamoxifen (adjusted odds ratio, 1.97), and hot flashes at diagnosis (aOR, 1.83, and older age versus age 18-34 (aORs, 1.84 for those aged 35-39 years; 5.90 for those aged 40-44 years, and 21.29 for those 45 or older).

The findings were published online November 16 in JAMA Network Open.

The study cohort included 1636 women under age 50 years (mean age of 42.2 years) at the time of diagnosis of stage I to III breast cancer. Outcomes at up to 4 years after diagnosis and enrollment between 2012 and 2017 were reported. QOL was assessed using the European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaires c30 and br23.

“Breast cancer is the most commonly diagnosed tumor in women, and approximately 20% of women with breast cancer are younger than 50 years at diagnosis,” the investigators note, explaining that younger survivors have higher risk of cancer-related symptoms and quality-of-life deterioration. “In particular, treatment-related symptoms linked to the menopausal transition (ie, vasomotor symptoms and sexual problems) represent an important source of distress during and after treatment, highlighting a need to monitor and address survivorship-related problems that are specific to this population.”

The current analysis “helps answer several clinical questions about long-term trajectories of CRA and menses recovery rates by age and about factors associated with higher likelihood of CRA,” they added, noting that the findings have several clinical implications.

For example, premenopausal women should be made aware of the risks associated with chemotherapy-related premature ovarian failure and persistent CRA, and should and receive systematic oncofertility counseling, they argue.

“In addition, in light of data showing possible late [menses] recoveries, contraceptive options should also be clearly discussed,” and “[d]edicated gynecological counseling may help patients who have an inaccurate perception of infertility due to previous exposure to chemotherapy and long-term absence of menses.”

Given that a late menses recovery pattern was also observed in older age groups in the cohort, the investigators noted that choosing the optimal adjuvant endocrine treatment can pose a challenge.

“The absence of menses after completion of chemotherapy should not be used as a proxy for permanent transition to menopause, because it does not represent a reliable surrogate of gonadotoxicity,” they warned. “Adjuvant endocrine treatment choices should be based on a more thorough and comprehensive evaluation, combining absence of menses, assessments of circulating hormone levels, and gynecological ultrasonographic imaging.”

These findings “can inform personalized care pathways targeting patients at higher risk of QOL deterioration associated with a permanent menopausal transition,” they noted, concluding that “[r]isk and duration of CRA, including potential late resumption of menses and its downstream implications for QOL, should be approached using a coordinated biopsychosocial model addressing multiple dimensions of physical, psychological, and social health.

“Proactive management of premenopausal women with early breast cancer undergoing chemotherapy should also include adapted strategies for risk communication, as well as personalized counseling and early supportive care referrals.”

The CANTO study is supported by the French government under the Investment for the Future program managed by the National Research Agency, the Prism project, and the MYPROBE Program. Dr. Kabirian reported having no disclosures.

Persistent chemotherapy-related amenorrhea (CRA) after treatment for breast cancer was common and associated with worse long-term quality of life among premenopausal women in a large multicenter French cohort study.

The findings, which showed a particularly increased risk of persistent CRA in older women and those who received adjuvant tamoxifen, can help inform communication, personalized counseling, and supportive care, according to the investigators.

At 1 year after treatment, CRA occurred in 1242 of 1497 women (83.0%) from the prospective, longitudinal Cancers Toxicity Study (CANTO). The rates at years 2 and 4 after treatment were 72.5% and 66.1%, respectively, Rayan Kabirian, MD, of Gustave Roussy, Villejuif, France, and Sorbonne University, Paris, and colleagues reported.

In a quality-of-life analysis conducted among 729 women from the cohort, 416 (57.1%) had persistent CRA, although 11 of 21 women aged 18-34 years who had no menses at year 2 had late menses recovery between years 2 and 4. Those with persistent CRA at year 4, compared with those who had menses recovery at any time, had significantly worse insomnia (mean difference, 9.9 points), worse systemic therapy-related adverse effects (mean difference, 3.0 points), and worse sexual functioning (mean difference, -9.2 points).

Factors associated with greater risk of persistent CRA included receipt versus non-receipt of adjuvant tamoxifen (adjusted odds ratio, 1.97), and hot flashes at diagnosis (aOR, 1.83, and older age versus age 18-34 (aORs, 1.84 for those aged 35-39 years; 5.90 for those aged 40-44 years, and 21.29 for those 45 or older).

The findings were published online November 16 in JAMA Network Open.

The study cohort included 1636 women under age 50 years (mean age of 42.2 years) at the time of diagnosis of stage I to III breast cancer. Outcomes at up to 4 years after diagnosis and enrollment between 2012 and 2017 were reported. QOL was assessed using the European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaires c30 and br23.

“Breast cancer is the most commonly diagnosed tumor in women, and approximately 20% of women with breast cancer are younger than 50 years at diagnosis,” the investigators note, explaining that younger survivors have higher risk of cancer-related symptoms and quality-of-life deterioration. “In particular, treatment-related symptoms linked to the menopausal transition (ie, vasomotor symptoms and sexual problems) represent an important source of distress during and after treatment, highlighting a need to monitor and address survivorship-related problems that are specific to this population.”

The current analysis “helps answer several clinical questions about long-term trajectories of CRA and menses recovery rates by age and about factors associated with higher likelihood of CRA,” they added, noting that the findings have several clinical implications.

For example, premenopausal women should be made aware of the risks associated with chemotherapy-related premature ovarian failure and persistent CRA, and should and receive systematic oncofertility counseling, they argue.

“In addition, in light of data showing possible late [menses] recoveries, contraceptive options should also be clearly discussed,” and “[d]edicated gynecological counseling may help patients who have an inaccurate perception of infertility due to previous exposure to chemotherapy and long-term absence of menses.”

Given that a late menses recovery pattern was also observed in older age groups in the cohort, the investigators noted that choosing the optimal adjuvant endocrine treatment can pose a challenge.

“The absence of menses after completion of chemotherapy should not be used as a proxy for permanent transition to menopause, because it does not represent a reliable surrogate of gonadotoxicity,” they warned. “Adjuvant endocrine treatment choices should be based on a more thorough and comprehensive evaluation, combining absence of menses, assessments of circulating hormone levels, and gynecological ultrasonographic imaging.”

These findings “can inform personalized care pathways targeting patients at higher risk of QOL deterioration associated with a permanent menopausal transition,” they noted, concluding that “[r]isk and duration of CRA, including potential late resumption of menses and its downstream implications for QOL, should be approached using a coordinated biopsychosocial model addressing multiple dimensions of physical, psychological, and social health.

“Proactive management of premenopausal women with early breast cancer undergoing chemotherapy should also include adapted strategies for risk communication, as well as personalized counseling and early supportive care referrals.”

The CANTO study is supported by the French government under the Investment for the Future program managed by the National Research Agency, the Prism project, and the MYPROBE Program. Dr. Kabirian reported having no disclosures.

Persistent chemotherapy-related amenorrhea (CRA) after treatment for breast cancer was common and associated with worse long-term quality of life among premenopausal women in a large multicenter French cohort study.

The findings, which showed a particularly increased risk of persistent CRA in older women and those who received adjuvant tamoxifen, can help inform communication, personalized counseling, and supportive care, according to the investigators.

At 1 year after treatment, CRA occurred in 1242 of 1497 women (83.0%) from the prospective, longitudinal Cancers Toxicity Study (CANTO). The rates at years 2 and 4 after treatment were 72.5% and 66.1%, respectively, Rayan Kabirian, MD, of Gustave Roussy, Villejuif, France, and Sorbonne University, Paris, and colleagues reported.

In a quality-of-life analysis conducted among 729 women from the cohort, 416 (57.1%) had persistent CRA, although 11 of 21 women aged 18-34 years who had no menses at year 2 had late menses recovery between years 2 and 4. Those with persistent CRA at year 4, compared with those who had menses recovery at any time, had significantly worse insomnia (mean difference, 9.9 points), worse systemic therapy-related adverse effects (mean difference, 3.0 points), and worse sexual functioning (mean difference, -9.2 points).

Factors associated with greater risk of persistent CRA included receipt versus non-receipt of adjuvant tamoxifen (adjusted odds ratio, 1.97), and hot flashes at diagnosis (aOR, 1.83, and older age versus age 18-34 (aORs, 1.84 for those aged 35-39 years; 5.90 for those aged 40-44 years, and 21.29 for those 45 or older).

The findings were published online November 16 in JAMA Network Open.

The study cohort included 1636 women under age 50 years (mean age of 42.2 years) at the time of diagnosis of stage I to III breast cancer. Outcomes at up to 4 years after diagnosis and enrollment between 2012 and 2017 were reported. QOL was assessed using the European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaires c30 and br23.

“Breast cancer is the most commonly diagnosed tumor in women, and approximately 20% of women with breast cancer are younger than 50 years at diagnosis,” the investigators note, explaining that younger survivors have higher risk of cancer-related symptoms and quality-of-life deterioration. “In particular, treatment-related symptoms linked to the menopausal transition (ie, vasomotor symptoms and sexual problems) represent an important source of distress during and after treatment, highlighting a need to monitor and address survivorship-related problems that are specific to this population.”

The current analysis “helps answer several clinical questions about long-term trajectories of CRA and menses recovery rates by age and about factors associated with higher likelihood of CRA,” they added, noting that the findings have several clinical implications.

For example, premenopausal women should be made aware of the risks associated with chemotherapy-related premature ovarian failure and persistent CRA, and should and receive systematic oncofertility counseling, they argue.

“In addition, in light of data showing possible late [menses] recoveries, contraceptive options should also be clearly discussed,” and “[d]edicated gynecological counseling may help patients who have an inaccurate perception of infertility due to previous exposure to chemotherapy and long-term absence of menses.”

Given that a late menses recovery pattern was also observed in older age groups in the cohort, the investigators noted that choosing the optimal adjuvant endocrine treatment can pose a challenge.

“The absence of menses after completion of chemotherapy should not be used as a proxy for permanent transition to menopause, because it does not represent a reliable surrogate of gonadotoxicity,” they warned. “Adjuvant endocrine treatment choices should be based on a more thorough and comprehensive evaluation, combining absence of menses, assessments of circulating hormone levels, and gynecological ultrasonographic imaging.”

These findings “can inform personalized care pathways targeting patients at higher risk of QOL deterioration associated with a permanent menopausal transition,” they noted, concluding that “[r]isk and duration of CRA, including potential late resumption of menses and its downstream implications for QOL, should be approached using a coordinated biopsychosocial model addressing multiple dimensions of physical, psychological, and social health.

“Proactive management of premenopausal women with early breast cancer undergoing chemotherapy should also include adapted strategies for risk communication, as well as personalized counseling and early supportive care referrals.”

The CANTO study is supported by the French government under the Investment for the Future program managed by the National Research Agency, the Prism project, and the MYPROBE Program. Dr. Kabirian reported having no disclosures.

The American Society of Clinical Oncology (ASCO) has released guidance on how to prioritize use of key oncology drugs amid ongoing shortages.

As of November 30, the US Food and Drug Administration lists 16 commonly used oncology drugs currently in shortage, including methotrexate, capecitabine, vinblastine, carboplatin, and cisplatin, along with another 13 discontinued agents.

The ASCO guidance, which is updated regularly on ASCO’s drug shortage website, covers dozens of clinical situations involving breast, gastrointestinal, genitourinary, gynecologic, thoracic, and head & neck cancers, as well as Hodgkin lymphoma.

The recommendations, published earlier in JCO Oncology Practice, represent the work of a Drug Shortages Advisory Group with over 40 oncologists, ethicists, and patient advocates brought together by ASCO in collaboration with the Society for Gynecologic Oncology. 

In the guidance, the advisory group also provides some context about why these shortage issues have persisted, including a paucity of generic options, quality control issues, and reluctance among manufacturers to produce older drugs with slim profit margins.

And “while ASCO continues to work to address the root causes of the shortages, this guidance document aims to support clinicians, as they navigate the complexities of treatment planning amid the drug shortage, and patients with cancer who are already enduring physical and emotional hardships,” the advisory group writes.

The overall message in the guidance: conserve oncology drugs in limited supply to use when needed most.

The recommendations highlight alternative regimens, when available, and what to do in situations when there are no alternatives, advice that has become particularly relevant for the oncology workhorses cisplatin and carboplatin.

More generally, when ranges of acceptable doses and dose frequencies exist for drugs in short supply, clinicians should opt for the lowest dose at the longest interval. Dose rounding and multi-use vials should also be used to eliminate waste, and alternatives should be used whenever possible. If an alternative agent with similar efficacy and safety is available, the agent in limited supply should not be ordered.

In certain settings where no reasonable alternatives to platinum regimens exist, the advisory group recommends patients travel to where platinum agents are available. The group noted this strategy specifically for patients with non–small cell lung cancer or testicular germ cell cancers, but also acknowledged that this option “may cause additional financial toxicity, hardship, and distress.”

Other, more granular advice includes holding carboplatin in reserve for patients with early-stage triple-negative breast cancer on neoadjuvant therapy who don’t respond well to upfront doxorubicin, cyclophosphamide, and pembrolizumab.

In addition to providing strategies to manage the ongoing cancer drug shortages, ASCO advises counseling for patients and clinicians struggling with the “psychological or moral distress” from the ongoing shortages.

“Unfortunately, drug shortages place the patient and the provider in a challenging situation, possibly resulting in inferior outcomes, delayed or denied care, and increased adverse events,” the advisory group writes. “ASCO will continue to respond to the oncology drug shortage crisis through policy and advocacy efforts, provide ethical guidance for allocation and prioritization decisions, and maintain shortage-specific clinical guidance as long as necessary.”
 

A version of this article appeared on Medscape.com.

The American Society of Clinical Oncology (ASCO) has released guidance on how to prioritize use of key oncology drugs amid ongoing shortages.

As of November 30, the US Food and Drug Administration lists 16 commonly used oncology drugs currently in shortage, including methotrexate, capecitabine, vinblastine, carboplatin, and cisplatin, along with another 13 discontinued agents.

The ASCO guidance, which is updated regularly on ASCO’s drug shortage website, covers dozens of clinical situations involving breast, gastrointestinal, genitourinary, gynecologic, thoracic, and head & neck cancers, as well as Hodgkin lymphoma.

The recommendations, published earlier in JCO Oncology Practice, represent the work of a Drug Shortages Advisory Group with over 40 oncologists, ethicists, and patient advocates brought together by ASCO in collaboration with the Society for Gynecologic Oncology. 

In the guidance, the advisory group also provides some context about why these shortage issues have persisted, including a paucity of generic options, quality control issues, and reluctance among manufacturers to produce older drugs with slim profit margins.

And “while ASCO continues to work to address the root causes of the shortages, this guidance document aims to support clinicians, as they navigate the complexities of treatment planning amid the drug shortage, and patients with cancer who are already enduring physical and emotional hardships,” the advisory group writes.

The overall message in the guidance: conserve oncology drugs in limited supply to use when needed most.

The recommendations highlight alternative regimens, when available, and what to do in situations when there are no alternatives, advice that has become particularly relevant for the oncology workhorses cisplatin and carboplatin.

More generally, when ranges of acceptable doses and dose frequencies exist for drugs in short supply, clinicians should opt for the lowest dose at the longest interval. Dose rounding and multi-use vials should also be used to eliminate waste, and alternatives should be used whenever possible. If an alternative agent with similar efficacy and safety is available, the agent in limited supply should not be ordered.

In certain settings where no reasonable alternatives to platinum regimens exist, the advisory group recommends patients travel to where platinum agents are available. The group noted this strategy specifically for patients with non–small cell lung cancer or testicular germ cell cancers, but also acknowledged that this option “may cause additional financial toxicity, hardship, and distress.”

Other, more granular advice includes holding carboplatin in reserve for patients with early-stage triple-negative breast cancer on neoadjuvant therapy who don’t respond well to upfront doxorubicin, cyclophosphamide, and pembrolizumab.

In addition to providing strategies to manage the ongoing cancer drug shortages, ASCO advises counseling for patients and clinicians struggling with the “psychological or moral distress” from the ongoing shortages.

“Unfortunately, drug shortages place the patient and the provider in a challenging situation, possibly resulting in inferior outcomes, delayed or denied care, and increased adverse events,” the advisory group writes. “ASCO will continue to respond to the oncology drug shortage crisis through policy and advocacy efforts, provide ethical guidance for allocation and prioritization decisions, and maintain shortage-specific clinical guidance as long as necessary.”
 

A version of this article appeared on Medscape.com.

The American Society of Clinical Oncology (ASCO) has released guidance on how to prioritize use of key oncology drugs amid ongoing shortages.

As of November 30, the US Food and Drug Administration lists 16 commonly used oncology drugs currently in shortage, including methotrexate, capecitabine, vinblastine, carboplatin, and cisplatin, along with another 13 discontinued agents.

The ASCO guidance, which is updated regularly on ASCO’s drug shortage website, covers dozens of clinical situations involving breast, gastrointestinal, genitourinary, gynecologic, thoracic, and head & neck cancers, as well as Hodgkin lymphoma.

The recommendations, published earlier in JCO Oncology Practice, represent the work of a Drug Shortages Advisory Group with over 40 oncologists, ethicists, and patient advocates brought together by ASCO in collaboration with the Society for Gynecologic Oncology. 

In the guidance, the advisory group also provides some context about why these shortage issues have persisted, including a paucity of generic options, quality control issues, and reluctance among manufacturers to produce older drugs with slim profit margins.

And “while ASCO continues to work to address the root causes of the shortages, this guidance document aims to support clinicians, as they navigate the complexities of treatment planning amid the drug shortage, and patients with cancer who are already enduring physical and emotional hardships,” the advisory group writes.

The overall message in the guidance: conserve oncology drugs in limited supply to use when needed most.

The recommendations highlight alternative regimens, when available, and what to do in situations when there are no alternatives, advice that has become particularly relevant for the oncology workhorses cisplatin and carboplatin.

More generally, when ranges of acceptable doses and dose frequencies exist for drugs in short supply, clinicians should opt for the lowest dose at the longest interval. Dose rounding and multi-use vials should also be used to eliminate waste, and alternatives should be used whenever possible. If an alternative agent with similar efficacy and safety is available, the agent in limited supply should not be ordered.

In certain settings where no reasonable alternatives to platinum regimens exist, the advisory group recommends patients travel to where platinum agents are available. The group noted this strategy specifically for patients with non–small cell lung cancer or testicular germ cell cancers, but also acknowledged that this option “may cause additional financial toxicity, hardship, and distress.”

Other, more granular advice includes holding carboplatin in reserve for patients with early-stage triple-negative breast cancer on neoadjuvant therapy who don’t respond well to upfront doxorubicin, cyclophosphamide, and pembrolizumab.

In addition to providing strategies to manage the ongoing cancer drug shortages, ASCO advises counseling for patients and clinicians struggling with the “psychological or moral distress” from the ongoing shortages.

“Unfortunately, drug shortages place the patient and the provider in a challenging situation, possibly resulting in inferior outcomes, delayed or denied care, and increased adverse events,” the advisory group writes. “ASCO will continue to respond to the oncology drug shortage crisis through policy and advocacy efforts, provide ethical guidance for allocation and prioritization decisions, and maintain shortage-specific clinical guidance as long as necessary.”
 

A version of this article appeared on Medscape.com.

TOPLINE:

For pregnant women with breast cancer, exposure to HER2-targeted therapies increases the risk of severe adverse outcomes to the fetus or newborn, according to a recent analysis.

METHODOLOGY:

• Current guidelines do not recommend treating pregnant women with trastuzumab, given documented safety concerns. Other anti-HER2 agents are also discouraged in this setting because of a lack of safety data. However, when considering the efficacy of these drugs in HER2-positive breast cancer, having a better understanding of the potential toxicities in pregnant patients is important.
• In the current case-control analysis, the team explored the risk for adverse effects among pregnant women exposed to anti-HER2 agents vs other anticancer drugs.
• The researchers leveraged the World Health Organization’s pharmacovigilance database, VigiBase, to identify reports with at least one pregnancy-related complication and one suspected anticancer drug.
• The researchers classified exposure to the drugs as occurring before pregnancy, during pregnancy, or via breast milk, semen, or skin. The team then examined 30 maternal and fetal or neonatal adverse outcomes and grouped them into seven categories: abortions, stillbirths, congenital malformations, pregnancy complications, preterm birth, neonatal complications, and delivery complications.
• The most used anti-HER2 agent was trastuzumab (n = 302), followed by pertuzumab (n = 55), trastuzumab-emtansine (n = 20), and lapatinib (n = 18).

TAKEAWAY:

• Among 3,558 reports included in the analysis, 328 patients were exposed to anti-HER2 drugs compared with 3,230 patients who received other anticancer agents.
• Pregnancy, fetal, or newborn adverse outcomes were reported in 61.3% of women treated with anti-HER2 agents and 56.3% of those receiving other anticancer drugs.
• The five most frequently reported complications in the anti-HER2 group were oligohydramnios (23.8%), preterm birth (17.4%), intrauterine growth restriction (9.8%), neonatal respiratory disorder (7.3%), and spontaneous abortion (7.3%).
• Adverse outcomes overreported in women who received anti-HER2 agents included oligohydramnios (reporting odds ratio [ROR], 17.68), congenital tract disorders (ROR, 9.98), and neonatal kidney failure (ROR, 9.15). Cardiovascular malformations were also overreported among women receiving trastuzumab-emtansine (ROR, 4.46), as were intrauterine growth restrictions for those treated with lapatinib (ROR, 7.68).

IN PRACTICE:

Exposure to anti-HER2 agents was associated with “severe specific adverse pregnancy and fetal or newborn outcomes compared with exposure to other anticancer treatments,” with a “strong, highly significant overreporting of congenital respiratory tract disorders and neonatal kidney failure,” which can lead to oligohydramnios, the authors wrote. The authors also noted that when delaying anti-HER2 therapy is not possible, it’s imperative to monitor patients closely for oligohydramnios.

SOURCE:

The study, led by Paul Gougis, MD, Institut Curie Centre de Recherche, Paris, , was published online in JAMA Network Open.

LIMITATIONS:

Potential inconsistencies in the collection of pharmacovigilance data could limit the generalizability of the results in the general population. The group of women exposed to other anticancer therapies may also constitute a different patient population from that given anti-HER2 therapies.

DISCLOSURES:

Coauthor Jean-Philippe Spano, MD, PhD, declared relationships Gilead, AstraZeneca, Lilly, Pfizer, Novartis, Daiichi Sankyo, and GSK.
 

A version of this article appeared on Medscape.com.

TOPLINE:

For pregnant women with breast cancer, exposure to HER2-targeted therapies increases the risk of severe adverse outcomes to the fetus or newborn, according to a recent analysis.

METHODOLOGY:

• Current guidelines do not recommend treating pregnant women with trastuzumab, given documented safety concerns. Other anti-HER2 agents are also discouraged in this setting because of a lack of safety data. However, when considering the efficacy of these drugs in HER2-positive breast cancer, having a better understanding of the potential toxicities in pregnant patients is important.
• In the current case-control analysis, the team explored the risk for adverse effects among pregnant women exposed to anti-HER2 agents vs other anticancer drugs.
• The researchers leveraged the World Health Organization’s pharmacovigilance database, VigiBase, to identify reports with at least one pregnancy-related complication and one suspected anticancer drug.
• The researchers classified exposure to the drugs as occurring before pregnancy, during pregnancy, or via breast milk, semen, or skin. The team then examined 30 maternal and fetal or neonatal adverse outcomes and grouped them into seven categories: abortions, stillbirths, congenital malformations, pregnancy complications, preterm birth, neonatal complications, and delivery complications.
• The most used anti-HER2 agent was trastuzumab (n = 302), followed by pertuzumab (n = 55), trastuzumab-emtansine (n = 20), and lapatinib (n = 18).

TAKEAWAY:

• Among 3,558 reports included in the analysis, 328 patients were exposed to anti-HER2 drugs compared with 3,230 patients who received other anticancer agents.
• Pregnancy, fetal, or newborn adverse outcomes were reported in 61.3% of women treated with anti-HER2 agents and 56.3% of those receiving other anticancer drugs.
• The five most frequently reported complications in the anti-HER2 group were oligohydramnios (23.8%), preterm birth (17.4%), intrauterine growth restriction (9.8%), neonatal respiratory disorder (7.3%), and spontaneous abortion (7.3%).
• Adverse outcomes overreported in women who received anti-HER2 agents included oligohydramnios (reporting odds ratio [ROR], 17.68), congenital tract disorders (ROR, 9.98), and neonatal kidney failure (ROR, 9.15). Cardiovascular malformations were also overreported among women receiving trastuzumab-emtansine (ROR, 4.46), as were intrauterine growth restrictions for those treated with lapatinib (ROR, 7.68).

IN PRACTICE:

Exposure to anti-HER2 agents was associated with “severe specific adverse pregnancy and fetal or newborn outcomes compared with exposure to other anticancer treatments,” with a “strong, highly significant overreporting of congenital respiratory tract disorders and neonatal kidney failure,” which can lead to oligohydramnios, the authors wrote. The authors also noted that when delaying anti-HER2 therapy is not possible, it’s imperative to monitor patients closely for oligohydramnios.

SOURCE:

The study, led by Paul Gougis, MD, Institut Curie Centre de Recherche, Paris, , was published online in JAMA Network Open.

LIMITATIONS:

Potential inconsistencies in the collection of pharmacovigilance data could limit the generalizability of the results in the general population. The group of women exposed to other anticancer therapies may also constitute a different patient population from that given anti-HER2 therapies.

DISCLOSURES:

Coauthor Jean-Philippe Spano, MD, PhD, declared relationships Gilead, AstraZeneca, Lilly, Pfizer, Novartis, Daiichi Sankyo, and GSK.
 

A version of this article appeared on Medscape.com.

TOPLINE:

For pregnant women with breast cancer, exposure to HER2-targeted therapies increases the risk of severe adverse outcomes to the fetus or newborn, according to a recent analysis.

METHODOLOGY:

• Current guidelines do not recommend treating pregnant women with trastuzumab, given documented safety concerns. Other anti-HER2 agents are also discouraged in this setting because of a lack of safety data. However, when considering the efficacy of these drugs in HER2-positive breast cancer, having a better understanding of the potential toxicities in pregnant patients is important.
• In the current case-control analysis, the team explored the risk for adverse effects among pregnant women exposed to anti-HER2 agents vs other anticancer drugs.
• The researchers leveraged the World Health Organization’s pharmacovigilance database, VigiBase, to identify reports with at least one pregnancy-related complication and one suspected anticancer drug.
• The researchers classified exposure to the drugs as occurring before pregnancy, during pregnancy, or via breast milk, semen, or skin. The team then examined 30 maternal and fetal or neonatal adverse outcomes and grouped them into seven categories: abortions, stillbirths, congenital malformations, pregnancy complications, preterm birth, neonatal complications, and delivery complications.
• The most used anti-HER2 agent was trastuzumab (n = 302), followed by pertuzumab (n = 55), trastuzumab-emtansine (n = 20), and lapatinib (n = 18).

TAKEAWAY:

• Among 3,558 reports included in the analysis, 328 patients were exposed to anti-HER2 drugs compared with 3,230 patients who received other anticancer agents.
• Pregnancy, fetal, or newborn adverse outcomes were reported in 61.3% of women treated with anti-HER2 agents and 56.3% of those receiving other anticancer drugs.
• The five most frequently reported complications in the anti-HER2 group were oligohydramnios (23.8%), preterm birth (17.4%), intrauterine growth restriction (9.8%), neonatal respiratory disorder (7.3%), and spontaneous abortion (7.3%).
• Adverse outcomes overreported in women who received anti-HER2 agents included oligohydramnios (reporting odds ratio [ROR], 17.68), congenital tract disorders (ROR, 9.98), and neonatal kidney failure (ROR, 9.15). Cardiovascular malformations were also overreported among women receiving trastuzumab-emtansine (ROR, 4.46), as were intrauterine growth restrictions for those treated with lapatinib (ROR, 7.68).

IN PRACTICE:

Exposure to anti-HER2 agents was associated with “severe specific adverse pregnancy and fetal or newborn outcomes compared with exposure to other anticancer treatments,” with a “strong, highly significant overreporting of congenital respiratory tract disorders and neonatal kidney failure,” which can lead to oligohydramnios, the authors wrote. The authors also noted that when delaying anti-HER2 therapy is not possible, it’s imperative to monitor patients closely for oligohydramnios.

SOURCE:

The study, led by Paul Gougis, MD, Institut Curie Centre de Recherche, Paris, , was published online in JAMA Network Open.

LIMITATIONS:

Potential inconsistencies in the collection of pharmacovigilance data could limit the generalizability of the results in the general population. The group of women exposed to other anticancer therapies may also constitute a different patient population from that given anti-HER2 therapies.

DISCLOSURES:

Coauthor Jean-Philippe Spano, MD, PhD, declared relationships Gilead, AstraZeneca, Lilly, Pfizer, Novartis, Daiichi Sankyo, and GSK.
 

A version of this article appeared on Medscape.com.