Jim Kling

CHICAGO – Metastatic invasive lobular breast cancers (ILC) that are hormone receptor (HR)-positive and HER2-negative have therapeutic outcomes similar to those of invasive ductal cancer (IDC) following treatment with endocrine therapy combined with a CDK4/6 inhibitor, mTOR inhibitor, or PI3K inhibitor, according to a new retrospective analysis of patients treated at MD Anderson Cancer Center.

The two conditions have historically been lumped together when studying treatment outcomes, but more recent research has shown key differences between the two subtypes, according to Jason A. Mouabbi, MD, who presented the results at the annual meeting of the American Society of Clinical Oncology.

“All the studies that were done were driven by ductal patients, so you can never take conclusions for the lobular patients. We have a big database at MD Anderson, so we can really study a large number of patients and get some signals whether or not patients would benefit from that therapy or not,” said Dr. Mouabbi, a lobular breast cancer specialist at MD Anderson Cancer Center.

The results of the study are important since patients often come to physicians with sophisticated understanding of their disease, he said. Patients with lobular cancer naturally wonder if a therapeutic regimen tested primarily in IDC will benefit them. “For the longest time, we said, ‘we have no data,’ ” said Dr. Mouabbi.

The new study should offer patients and physicians some reassurance. “We found that all of them benefit from it and most importantly, they all benefit from it (with) the same magnitude,” Dr. Mouabbi said.

The researchers analyzed data from 2,971 patients (82% IDC, 14% ILC, 4% mixed) treated between 2010 and 2021. The median age was 50 in all groups. Eighty percent were White, 10% were Hispanic, and 5% were Black. Ninety-nine percent had estrogen receptor (ER) + tumors, and 88% had progesterone positive (PR) + tumors.

A total of 1,895 patients received CDK4/6 inhibitors, 1,027 received everolimus, and 49 received alpelisib. There was no statistically significant difference in overall survival or progression-free survival between the two cancer types in any of the treatment groups.

Despite the similar outcomes, the two conditions remain unique. IDC is a disease of cells from the ducts that deliver milk, while ILC arises in cells that produce milk. Nearly 95% of ILC cases are hormone-positive, compared to 50%-55% of IDC.

So, while existing treatments seem to benefit both groups, there are nonetheless plans to develop therapeutic strategies tailored to lobular cancer.

Dr. Mouabbi’s group has compared molecular profiles of ILC and IDC tumors to better understand how to target them individually. Almost all ILC cancers have a mutation in a gene called CDH1, which leads to loss of an anchoring protein. They believe this causes a unique growth pattern of thin tendrils, rather than the onion-like growths of IDC. A therapy targeting this mutation could provide a specific benefit for lobular breast cancer.

There are other differences: PI3 kinases are mutated in about 60% of ILC tumors, versus about 30% of IDC tumors, and other genes mutated at lower frequencies are also different between the two subtypes. “So there are a lot of (approaches) we are trying to initiate in lobular cancer because we have awareness now that they are different,” Dr. Mouabbi said.

The study received no external funding.

CHICAGO – Metastatic invasive lobular breast cancers (ILC) that are hormone receptor (HR)-positive and HER2-negative have therapeutic outcomes similar to those of invasive ductal cancer (IDC) following treatment with endocrine therapy combined with a CDK4/6 inhibitor, mTOR inhibitor, or PI3K inhibitor, according to a new retrospective analysis of patients treated at MD Anderson Cancer Center.

The two conditions have historically been lumped together when studying treatment outcomes, but more recent research has shown key differences between the two subtypes, according to Jason A. Mouabbi, MD, who presented the results at the annual meeting of the American Society of Clinical Oncology.

“All the studies that were done were driven by ductal patients, so you can never take conclusions for the lobular patients. We have a big database at MD Anderson, so we can really study a large number of patients and get some signals whether or not patients would benefit from that therapy or not,” said Dr. Mouabbi, a lobular breast cancer specialist at MD Anderson Cancer Center.

The results of the study are important since patients often come to physicians with sophisticated understanding of their disease, he said. Patients with lobular cancer naturally wonder if a therapeutic regimen tested primarily in IDC will benefit them. “For the longest time, we said, ‘we have no data,’ ” said Dr. Mouabbi.

The new study should offer patients and physicians some reassurance. “We found that all of them benefit from it and most importantly, they all benefit from it (with) the same magnitude,” Dr. Mouabbi said.

The researchers analyzed data from 2,971 patients (82% IDC, 14% ILC, 4% mixed) treated between 2010 and 2021. The median age was 50 in all groups. Eighty percent were White, 10% were Hispanic, and 5% were Black. Ninety-nine percent had estrogen receptor (ER) + tumors, and 88% had progesterone positive (PR) + tumors.

A total of 1,895 patients received CDK4/6 inhibitors, 1,027 received everolimus, and 49 received alpelisib. There was no statistically significant difference in overall survival or progression-free survival between the two cancer types in any of the treatment groups.

Despite the similar outcomes, the two conditions remain unique. IDC is a disease of cells from the ducts that deliver milk, while ILC arises in cells that produce milk. Nearly 95% of ILC cases are hormone-positive, compared to 50%-55% of IDC.

So, while existing treatments seem to benefit both groups, there are nonetheless plans to develop therapeutic strategies tailored to lobular cancer.

Dr. Mouabbi’s group has compared molecular profiles of ILC and IDC tumors to better understand how to target them individually. Almost all ILC cancers have a mutation in a gene called CDH1, which leads to loss of an anchoring protein. They believe this causes a unique growth pattern of thin tendrils, rather than the onion-like growths of IDC. A therapy targeting this mutation could provide a specific benefit for lobular breast cancer.

There are other differences: PI3 kinases are mutated in about 60% of ILC tumors, versus about 30% of IDC tumors, and other genes mutated at lower frequencies are also different between the two subtypes. “So there are a lot of (approaches) we are trying to initiate in lobular cancer because we have awareness now that they are different,” Dr. Mouabbi said.

The study received no external funding.

CHICAGO – Metastatic invasive lobular breast cancers (ILC) that are hormone receptor (HR)-positive and HER2-negative have therapeutic outcomes similar to those of invasive ductal cancer (IDC) following treatment with endocrine therapy combined with a CDK4/6 inhibitor, mTOR inhibitor, or PI3K inhibitor, according to a new retrospective analysis of patients treated at MD Anderson Cancer Center.

The two conditions have historically been lumped together when studying treatment outcomes, but more recent research has shown key differences between the two subtypes, according to Jason A. Mouabbi, MD, who presented the results at the annual meeting of the American Society of Clinical Oncology.

“All the studies that were done were driven by ductal patients, so you can never take conclusions for the lobular patients. We have a big database at MD Anderson, so we can really study a large number of patients and get some signals whether or not patients would benefit from that therapy or not,” said Dr. Mouabbi, a lobular breast cancer specialist at MD Anderson Cancer Center.

The results of the study are important since patients often come to physicians with sophisticated understanding of their disease, he said. Patients with lobular cancer naturally wonder if a therapeutic regimen tested primarily in IDC will benefit them. “For the longest time, we said, ‘we have no data,’ ” said Dr. Mouabbi.

The new study should offer patients and physicians some reassurance. “We found that all of them benefit from it and most importantly, they all benefit from it (with) the same magnitude,” Dr. Mouabbi said.

The researchers analyzed data from 2,971 patients (82% IDC, 14% ILC, 4% mixed) treated between 2010 and 2021. The median age was 50 in all groups. Eighty percent were White, 10% were Hispanic, and 5% were Black. Ninety-nine percent had estrogen receptor (ER) + tumors, and 88% had progesterone positive (PR) + tumors.

A total of 1,895 patients received CDK4/6 inhibitors, 1,027 received everolimus, and 49 received alpelisib. There was no statistically significant difference in overall survival or progression-free survival between the two cancer types in any of the treatment groups.

Despite the similar outcomes, the two conditions remain unique. IDC is a disease of cells from the ducts that deliver milk, while ILC arises in cells that produce milk. Nearly 95% of ILC cases are hormone-positive, compared to 50%-55% of IDC.

So, while existing treatments seem to benefit both groups, there are nonetheless plans to develop therapeutic strategies tailored to lobular cancer.

Dr. Mouabbi’s group has compared molecular profiles of ILC and IDC tumors to better understand how to target them individually. Almost all ILC cancers have a mutation in a gene called CDH1, which leads to loss of an anchoring protein. They believe this causes a unique growth pattern of thin tendrils, rather than the onion-like growths of IDC. A therapy targeting this mutation could provide a specific benefit for lobular breast cancer.

There are other differences: PI3 kinases are mutated in about 60% of ILC tumors, versus about 30% of IDC tumors, and other genes mutated at lower frequencies are also different between the two subtypes. “So there are a lot of (approaches) we are trying to initiate in lobular cancer because we have awareness now that they are different,” Dr. Mouabbi said.

The study received no external funding.

A neighborhood analysis of socioeconomic status conducted in the Pittsburgh area found worse metastatic breast cancer survival outcomes among patients of low socioeconomic status. The findings suggest that race is not a relevant factor in outcomes.

“This study demonstrates that metastatic breast cancer patients of low socioeconomic status have worse outcomes than those with higher socioeconomic status at our center. It also underscores the idea that race is not so much a biological construct but more a consequence of socioeconomic issues. The effect of race is likely mediated by lower socioeconomic status,” said Susrutha Puthanmadhom Narayanan, MD, who presented the results of her study earlier this month in Chicago at the annual meeting of the American Society of Clinical Oncology.

“The current study should make clinicians cognizant of the potential for biases in the management of metastatic breast cancer in terms of socioeconomic status and race. One should think of socioeconomic status as a predictor of bad outcomes, almost like a comorbidity, and think of [associations between race and outcomes], as a consequence of socioeconomic inequality,” said Dr. Puthanmadhom Narayanan, who is an internal medicine resident at University of Pittsburgh Medical Center.

She and her colleagues intend to dig deeper into the relationships. “We are interested in looking at utilization of different treatment options for metastatic breast cancer between the socioeconomic status groups. In the preliminary analysis, we saw that ER-positive metastatic breast cancer patients with lower socioeconomic status get treated with tamoxifen more often than aromatase inhibitors and newer agents. And, we have plans to study stress signaling and inflammation as mediators of bad outcomes in the low socioeconomic status population,” Dr. Puthanmadhom Narayanan said.

In fact, that tendency for lower socioeconomic status patients to receive older treatments should be a call to action for physicians. “This study should make clinicians cognizant of the potential for biases in management of metastatic breast cancer in terms of socioeconomic status and race,” she said.

The study is based on an analysis of data from the Neighborhood Atlas in which a Neighborhood Deprivation Index (NDI) score was calculated. An NDI score in the bottom tertile meant that patients were better off than patients with mid to high range NDI scores. In this study, socioeconomic status was described as “low deprivation” or “high depreviation.” Higher deprivation correlated with lower overall survival. And, there were more Black patients in the higher deprivation group (10.5%), compared with the low deprivation group (3.7%). In multivariate Cox proportional hazard model, socioeconomic status, but not race, had a significant effect on overall survival (HR for high deprivation was 1.19 [95% confidence interval; 1.04-1.37], P = 0.01).

It included 1,246 patients who were treated at the University of Pittsburgh Medical Center between 2000 and 2017. Of 1,246 patients, 414 patients considered in the bottom tertile of NDI as having low deprivation, while 832 patients in the middle or top tertiles were classified as having high deprivation.

The two socioeconomic status groups were similar in baseline characteristics, with the exception of race: 10.5% of the high deprivation group were African American, compared with 3.7% of the low deprivation group (P =.000093).

Univariate analyses showed worse survival in both Black women and women in the lower socioeconomic status group, but a multivariate analysis found only socioeconomic status was associated with overall survival (hazard ratio for lower socioeconomic status, 1.19; P = .01).

The study had several strengths, according to Rachel Freedman, MD, MPH, who served as a discussant for the abstract. “It included both de novo and recurrent metastatic breast cancer, unlike previous studies based on the Surveillance, Epidemiology, and End Results (SEER) database that only included de novo cases. It also employed a novel tool to define socioeconomic status in the form of the Neighborhood Atlas. The study “adds more evidence that socioeconomic status likely mediates much of what we see when it comes to racial disparities,” said Dr. Freedman, who is a senior physician at Dana Farber Cancer Institute.

Nevertheless, more work needs to be done. Dr. Freedman pointed out that the current study did not include information on treatment.

The findings underscore the failure to date to address disparities in breast cancer treatment, an effort that is hampered by difficulty in teasing out complex factors that may impact survival. “We need to standardize the way that we collect social determinants of health and act upon findings, and we need to standardize patient navigation, and we need to commit as a community to diverse clinical trial populations,” Dr. Freedman said.

Dr. Narayanan has no relevant financial disclosures. Dr. Freedman is an employee and stockholder of Firefly Health.

A neighborhood analysis of socioeconomic status conducted in the Pittsburgh area found worse metastatic breast cancer survival outcomes among patients of low socioeconomic status. The findings suggest that race is not a relevant factor in outcomes.

“This study demonstrates that metastatic breast cancer patients of low socioeconomic status have worse outcomes than those with higher socioeconomic status at our center. It also underscores the idea that race is not so much a biological construct but more a consequence of socioeconomic issues. The effect of race is likely mediated by lower socioeconomic status,” said Susrutha Puthanmadhom Narayanan, MD, who presented the results of her study earlier this month in Chicago at the annual meeting of the American Society of Clinical Oncology.

“The current study should make clinicians cognizant of the potential for biases in the management of metastatic breast cancer in terms of socioeconomic status and race. One should think of socioeconomic status as a predictor of bad outcomes, almost like a comorbidity, and think of [associations between race and outcomes], as a consequence of socioeconomic inequality,” said Dr. Puthanmadhom Narayanan, who is an internal medicine resident at University of Pittsburgh Medical Center.

She and her colleagues intend to dig deeper into the relationships. “We are interested in looking at utilization of different treatment options for metastatic breast cancer between the socioeconomic status groups. In the preliminary analysis, we saw that ER-positive metastatic breast cancer patients with lower socioeconomic status get treated with tamoxifen more often than aromatase inhibitors and newer agents. And, we have plans to study stress signaling and inflammation as mediators of bad outcomes in the low socioeconomic status population,” Dr. Puthanmadhom Narayanan said.

In fact, that tendency for lower socioeconomic status patients to receive older treatments should be a call to action for physicians. “This study should make clinicians cognizant of the potential for biases in management of metastatic breast cancer in terms of socioeconomic status and race,” she said.

The study is based on an analysis of data from the Neighborhood Atlas in which a Neighborhood Deprivation Index (NDI) score was calculated. An NDI score in the bottom tertile meant that patients were better off than patients with mid to high range NDI scores. In this study, socioeconomic status was described as “low deprivation” or “high depreviation.” Higher deprivation correlated with lower overall survival. And, there were more Black patients in the higher deprivation group (10.5%), compared with the low deprivation group (3.7%). In multivariate Cox proportional hazard model, socioeconomic status, but not race, had a significant effect on overall survival (HR for high deprivation was 1.19 [95% confidence interval; 1.04-1.37], P = 0.01).

It included 1,246 patients who were treated at the University of Pittsburgh Medical Center between 2000 and 2017. Of 1,246 patients, 414 patients considered in the bottom tertile of NDI as having low deprivation, while 832 patients in the middle or top tertiles were classified as having high deprivation.

The two socioeconomic status groups were similar in baseline characteristics, with the exception of race: 10.5% of the high deprivation group were African American, compared with 3.7% of the low deprivation group (P =.000093).

Univariate analyses showed worse survival in both Black women and women in the lower socioeconomic status group, but a multivariate analysis found only socioeconomic status was associated with overall survival (hazard ratio for lower socioeconomic status, 1.19; P = .01).

The study had several strengths, according to Rachel Freedman, MD, MPH, who served as a discussant for the abstract. “It included both de novo and recurrent metastatic breast cancer, unlike previous studies based on the Surveillance, Epidemiology, and End Results (SEER) database that only included de novo cases. It also employed a novel tool to define socioeconomic status in the form of the Neighborhood Atlas. The study “adds more evidence that socioeconomic status likely mediates much of what we see when it comes to racial disparities,” said Dr. Freedman, who is a senior physician at Dana Farber Cancer Institute.

Nevertheless, more work needs to be done. Dr. Freedman pointed out that the current study did not include information on treatment.

The findings underscore the failure to date to address disparities in breast cancer treatment, an effort that is hampered by difficulty in teasing out complex factors that may impact survival. “We need to standardize the way that we collect social determinants of health and act upon findings, and we need to standardize patient navigation, and we need to commit as a community to diverse clinical trial populations,” Dr. Freedman said.

Dr. Narayanan has no relevant financial disclosures. Dr. Freedman is an employee and stockholder of Firefly Health.

A neighborhood analysis of socioeconomic status conducted in the Pittsburgh area found worse metastatic breast cancer survival outcomes among patients of low socioeconomic status. The findings suggest that race is not a relevant factor in outcomes.

“This study demonstrates that metastatic breast cancer patients of low socioeconomic status have worse outcomes than those with higher socioeconomic status at our center. It also underscores the idea that race is not so much a biological construct but more a consequence of socioeconomic issues. The effect of race is likely mediated by lower socioeconomic status,” said Susrutha Puthanmadhom Narayanan, MD, who presented the results of her study earlier this month in Chicago at the annual meeting of the American Society of Clinical Oncology.

“The current study should make clinicians cognizant of the potential for biases in the management of metastatic breast cancer in terms of socioeconomic status and race. One should think of socioeconomic status as a predictor of bad outcomes, almost like a comorbidity, and think of [associations between race and outcomes], as a consequence of socioeconomic inequality,” said Dr. Puthanmadhom Narayanan, who is an internal medicine resident at University of Pittsburgh Medical Center.

She and her colleagues intend to dig deeper into the relationships. “We are interested in looking at utilization of different treatment options for metastatic breast cancer between the socioeconomic status groups. In the preliminary analysis, we saw that ER-positive metastatic breast cancer patients with lower socioeconomic status get treated with tamoxifen more often than aromatase inhibitors and newer agents. And, we have plans to study stress signaling and inflammation as mediators of bad outcomes in the low socioeconomic status population,” Dr. Puthanmadhom Narayanan said.

In fact, that tendency for lower socioeconomic status patients to receive older treatments should be a call to action for physicians. “This study should make clinicians cognizant of the potential for biases in management of metastatic breast cancer in terms of socioeconomic status and race,” she said.

The study is based on an analysis of data from the Neighborhood Atlas in which a Neighborhood Deprivation Index (NDI) score was calculated. An NDI score in the bottom tertile meant that patients were better off than patients with mid to high range NDI scores. In this study, socioeconomic status was described as “low deprivation” or “high depreviation.” Higher deprivation correlated with lower overall survival. And, there were more Black patients in the higher deprivation group (10.5%), compared with the low deprivation group (3.7%). In multivariate Cox proportional hazard model, socioeconomic status, but not race, had a significant effect on overall survival (HR for high deprivation was 1.19 [95% confidence interval; 1.04-1.37], P = 0.01).

It included 1,246 patients who were treated at the University of Pittsburgh Medical Center between 2000 and 2017. Of 1,246 patients, 414 patients considered in the bottom tertile of NDI as having low deprivation, while 832 patients in the middle or top tertiles were classified as having high deprivation.

The two socioeconomic status groups were similar in baseline characteristics, with the exception of race: 10.5% of the high deprivation group were African American, compared with 3.7% of the low deprivation group (P =.000093).

Univariate analyses showed worse survival in both Black women and women in the lower socioeconomic status group, but a multivariate analysis found only socioeconomic status was associated with overall survival (hazard ratio for lower socioeconomic status, 1.19; P = .01).

The study had several strengths, according to Rachel Freedman, MD, MPH, who served as a discussant for the abstract. “It included both de novo and recurrent metastatic breast cancer, unlike previous studies based on the Surveillance, Epidemiology, and End Results (SEER) database that only included de novo cases. It also employed a novel tool to define socioeconomic status in the form of the Neighborhood Atlas. The study “adds more evidence that socioeconomic status likely mediates much of what we see when it comes to racial disparities,” said Dr. Freedman, who is a senior physician at Dana Farber Cancer Institute.

Nevertheless, more work needs to be done. Dr. Freedman pointed out that the current study did not include information on treatment.

The findings underscore the failure to date to address disparities in breast cancer treatment, an effort that is hampered by difficulty in teasing out complex factors that may impact survival. “We need to standardize the way that we collect social determinants of health and act upon findings, and we need to standardize patient navigation, and we need to commit as a community to diverse clinical trial populations,” Dr. Freedman said.

Dr. Narayanan has no relevant financial disclosures. Dr. Freedman is an employee and stockholder of Firefly Health.

CHICAGO – Comorbid autoimmune disease is associated with a greater chance of survival among women with stage IV breast cancer, according to a retrospective study presented at the annual meeting of the American Society of Clinical Oncology.

“It’s counterintuitive that, if you have two diseases instead of one, that you live longer, so then we had to scratch our heads a little bit and think about why these people are living longer,” said lead author Demitrios Dedousis, MD, University Hospitals, Case Medical Center, Cleveland.

Dr. Dedousis and colleagues conducted a retrospective analysis of patients from Surveillance, Epidemiology, and End Results–Medicare databases between 2007 and 2014 with breast cancer. The study included data from 137,324 patients diagnosed between 2007 and 2012, before the widespread use of immunotherapy. 27% of patients had an autoimmune disease, most commonly rheumatoid arthritis (23%), psoriasis (2.4%), and systemic lupus erythematosus (1.1%).

When all patients were included in the analysis, those with autoimmune disorders had slightly longer survival times, but these weren’t clinically significant. A subanalysis found a greater difference in survival.

The association appears more pronounced in metastatic cancer. Patients with stage 4 breast cancer and autoimmune disease had a longer mean overall survival (36 months vs. 30 months; hazard ratio, 1.46; P < .0001. Cancer-specific survival: HR, 1.39; P < .0001). Patients with autoimmune disease and stage 1-3 breast cancer had lower overall survival (P < .0001, P < 0.0001, and P = 0.026 respectively), compared with patients without autoimmune disease.

“What we thought was happening is that the lack of increased survival in stages 1 through 3 was hiding the increase in survival among the stage IV patients when looking at the overall cohort,” Dr. Dedousis said.

The retrospective nature of the study makes it impossible to draw any firm conclusions about causation. It could be that patients who have already been diagnosed with an autoimmune disease are more vigilant about going to health checkups. “There are other possible explanations, but the one that’s most interesting to us is that their immune system is involved in fighting the cancer. Our study certainly didn’t prove that, but it’s suggesting that’s a possibility,” Dr. Dedousis said.

He and his coauthors anticipate conducting similar studies in other cancers to see if there are similar relationships. Some preliminary work has already suggested something similar in lung cancer. “I think demonstrating this in a few kinds of cancer goes part of the way towards showing that this is a real biological phenomenon,” he said.

Another research avenue is to examine the immune systems and pathology specimens in patients with both an autoimmune disease and cancer to see if there is a greater immune response within the tumor. If so, that could suggest new immunotherapy strategies.

Another possibility is to look at the specific immune pathways within “protective” autoimmune conditions. “For the sake of argument, if we find a particular autoimmune condition is improving survival across multiple kinds of cancers, we could look at those pathways that are specifically involved in that autoimmune condition. It might help us identify a target for drug development,” Dr. Dedousis said.

Asked why a potential benefit might be more apparent in late-stage disease, he suggested that, in early-stage breast cancer, surgery and other treatments may be so effective that the immune system’s role only rarely makes a difference. It could play a larger role in late-stage disease when there are less effective therapies. It could also be that the immune system doesn’t recognize the cancer until it has spread beyond the regional lymph nodes on its way to metastasizing.

According to the National Cancer Institute, 10%-30% of people with cancer also have an autoimmune disease.

Dr. Dedousis has no relevant financial disclosures.

CHICAGO – Comorbid autoimmune disease is associated with a greater chance of survival among women with stage IV breast cancer, according to a retrospective study presented at the annual meeting of the American Society of Clinical Oncology.

“It’s counterintuitive that, if you have two diseases instead of one, that you live longer, so then we had to scratch our heads a little bit and think about why these people are living longer,” said lead author Demitrios Dedousis, MD, University Hospitals, Case Medical Center, Cleveland.

Dr. Dedousis and colleagues conducted a retrospective analysis of patients from Surveillance, Epidemiology, and End Results–Medicare databases between 2007 and 2014 with breast cancer. The study included data from 137,324 patients diagnosed between 2007 and 2012, before the widespread use of immunotherapy. 27% of patients had an autoimmune disease, most commonly rheumatoid arthritis (23%), psoriasis (2.4%), and systemic lupus erythematosus (1.1%).

When all patients were included in the analysis, those with autoimmune disorders had slightly longer survival times, but these weren’t clinically significant. A subanalysis found a greater difference in survival.

The association appears more pronounced in metastatic cancer. Patients with stage 4 breast cancer and autoimmune disease had a longer mean overall survival (36 months vs. 30 months; hazard ratio, 1.46; P < .0001. Cancer-specific survival: HR, 1.39; P < .0001). Patients with autoimmune disease and stage 1-3 breast cancer had lower overall survival (P < .0001, P < 0.0001, and P = 0.026 respectively), compared with patients without autoimmune disease.

“What we thought was happening is that the lack of increased survival in stages 1 through 3 was hiding the increase in survival among the stage IV patients when looking at the overall cohort,” Dr. Dedousis said.

The retrospective nature of the study makes it impossible to draw any firm conclusions about causation. It could be that patients who have already been diagnosed with an autoimmune disease are more vigilant about going to health checkups. “There are other possible explanations, but the one that’s most interesting to us is that their immune system is involved in fighting the cancer. Our study certainly didn’t prove that, but it’s suggesting that’s a possibility,” Dr. Dedousis said.

He and his coauthors anticipate conducting similar studies in other cancers to see if there are similar relationships. Some preliminary work has already suggested something similar in lung cancer. “I think demonstrating this in a few kinds of cancer goes part of the way towards showing that this is a real biological phenomenon,” he said.

Another research avenue is to examine the immune systems and pathology specimens in patients with both an autoimmune disease and cancer to see if there is a greater immune response within the tumor. If so, that could suggest new immunotherapy strategies.

Another possibility is to look at the specific immune pathways within “protective” autoimmune conditions. “For the sake of argument, if we find a particular autoimmune condition is improving survival across multiple kinds of cancers, we could look at those pathways that are specifically involved in that autoimmune condition. It might help us identify a target for drug development,” Dr. Dedousis said.

Asked why a potential benefit might be more apparent in late-stage disease, he suggested that, in early-stage breast cancer, surgery and other treatments may be so effective that the immune system’s role only rarely makes a difference. It could play a larger role in late-stage disease when there are less effective therapies. It could also be that the immune system doesn’t recognize the cancer until it has spread beyond the regional lymph nodes on its way to metastasizing.

According to the National Cancer Institute, 10%-30% of people with cancer also have an autoimmune disease.

Dr. Dedousis has no relevant financial disclosures.

CHICAGO – Comorbid autoimmune disease is associated with a greater chance of survival among women with stage IV breast cancer, according to a retrospective study presented at the annual meeting of the American Society of Clinical Oncology.

“It’s counterintuitive that, if you have two diseases instead of one, that you live longer, so then we had to scratch our heads a little bit and think about why these people are living longer,” said lead author Demitrios Dedousis, MD, University Hospitals, Case Medical Center, Cleveland.

Dr. Dedousis and colleagues conducted a retrospective analysis of patients from Surveillance, Epidemiology, and End Results–Medicare databases between 2007 and 2014 with breast cancer. The study included data from 137,324 patients diagnosed between 2007 and 2012, before the widespread use of immunotherapy. 27% of patients had an autoimmune disease, most commonly rheumatoid arthritis (23%), psoriasis (2.4%), and systemic lupus erythematosus (1.1%).

When all patients were included in the analysis, those with autoimmune disorders had slightly longer survival times, but these weren’t clinically significant. A subanalysis found a greater difference in survival.

The association appears more pronounced in metastatic cancer. Patients with stage 4 breast cancer and autoimmune disease had a longer mean overall survival (36 months vs. 30 months; hazard ratio, 1.46; P < .0001. Cancer-specific survival: HR, 1.39; P < .0001). Patients with autoimmune disease and stage 1-3 breast cancer had lower overall survival (P < .0001, P < 0.0001, and P = 0.026 respectively), compared with patients without autoimmune disease.

“What we thought was happening is that the lack of increased survival in stages 1 through 3 was hiding the increase in survival among the stage IV patients when looking at the overall cohort,” Dr. Dedousis said.

The retrospective nature of the study makes it impossible to draw any firm conclusions about causation. It could be that patients who have already been diagnosed with an autoimmune disease are more vigilant about going to health checkups. “There are other possible explanations, but the one that’s most interesting to us is that their immune system is involved in fighting the cancer. Our study certainly didn’t prove that, but it’s suggesting that’s a possibility,” Dr. Dedousis said.

He and his coauthors anticipate conducting similar studies in other cancers to see if there are similar relationships. Some preliminary work has already suggested something similar in lung cancer. “I think demonstrating this in a few kinds of cancer goes part of the way towards showing that this is a real biological phenomenon,” he said.

Another research avenue is to examine the immune systems and pathology specimens in patients with both an autoimmune disease and cancer to see if there is a greater immune response within the tumor. If so, that could suggest new immunotherapy strategies.

Another possibility is to look at the specific immune pathways within “protective” autoimmune conditions. “For the sake of argument, if we find a particular autoimmune condition is improving survival across multiple kinds of cancers, we could look at those pathways that are specifically involved in that autoimmune condition. It might help us identify a target for drug development,” Dr. Dedousis said.

Asked why a potential benefit might be more apparent in late-stage disease, he suggested that, in early-stage breast cancer, surgery and other treatments may be so effective that the immune system’s role only rarely makes a difference. It could play a larger role in late-stage disease when there are less effective therapies. It could also be that the immune system doesn’t recognize the cancer until it has spread beyond the regional lymph nodes on its way to metastasizing.

According to the National Cancer Institute, 10%-30% of people with cancer also have an autoimmune disease.

Dr. Dedousis has no relevant financial disclosures.

CHICAGO – Progress in breast cancer treatment over the past 2 decades has reduced expected mortality from both early-stage and metastatic disease, according to a new model that looked at 10-year distant recurrence-free survival and survival time after metastatic diagnosis, among other factors.

“There has been an accelerating influx of new treatments for breast cancer starting around 1990. We wished to ask whether and to what extent decades of metastatic treatment advances may have affected population level breast cancer mortality,” said Jennifer Lee Caswell-Jin, MD, during a presentation of the study at the annual meeting of the American Society of Clinical Oncology.

“Our models find that metastatic treatments improved population-level survival in all breast cancer subtypes since 2000 with substantial variability by subtype," said Dr. Caswell-Jin, who is a medical oncologist with Stanford (Calif.) Medicine specializing in breast cancer.

The study is based on an analysis of four models from the Cancer Intervention and Surveillance Modeling Network (CISNET). The models simulated breast cancer mortality between 2000 and 2019 factoring in the use of mammography, efficacy and dissemination of estrogen receptor (ER) and HER2-specific treatments of early-stage (stages I-III) and metastatic (stage IV or distant recurrence) disease, but also non–cancer-related mortality. The models compared overall and ER/HER2-specific breast cancer mortality rates during this period with estimated rates with no screening or treatment, and then attributed mortality reductions to screening, early-stage, or metastatic treatment.

The results were compared with three clinical trials that tested therapies in different subtypes of metastatic disease. Dr. Caswell-Jin and colleagues adjusted the analysis to reflect expected differences between clinical trial populations and the broader population by sampling simulated patients who resembled the trial population.

The investigators found that, at 71%, the biggest drop in mortality rates were for women with ER+/HER2+ breast cancer, followed by 61% for women with ER-/HER2+ breast cancer and 59% for women with ER+/HER2– breast cancer. Triple-negative breast cancer – one of the most challenging breast cancers to treat – only saw a drop of 40% during this period. About 19% of the overall reduction in breast cancer mortality were caused by treatments after metastasis.

The median survival after a diagnosis of ER+/HER2– metastatic recurrence increased from 2 years in 2000 to 3.5 years in 2019. In triple-negative breast cancer, the increase was more modest, from 1.2 years in 2000 to 1.8 years in 2019. After a diagnosis of metastatic recurrence of ER+/HER2+ breast cancer, median survival increased from 2.3 years in 2000 to 4.8 years in 2019, and for ER–/HER2+ breast cancer, from 2.2 years in 2000 to 3.9 years in 2019.

“How much metastatic treatments contributed to the overall mortality reduction varied over time depending on what therapies were entering the metastatic setting at that time and what therapies were transitioning from the metastatic to early-stage setting,” Dr. Caswell-Jin said.

The study did not include sacituzumab govitecan for metastatic triple-negative breast cancer, or trastuzumab deruxtecan and tucatinib for HER2-positive disease, which were approved after 2020. “The numbers that we cite will be better today for triple-negative breast cancer because of those two drugs. And will be even better for HER2-positive breast cancer because of those two drugs,” she said.

During the Q&A portion of the presentation, Daniel Hayes, MD, the Stuart B. Padnos Professor of Breast Cancer Research at the University of Michigan Rogel Cancer Center, Ann Arbor, asked about the potential of CISNET as an in-practice diagnostic tool.

“We’ve traditionally told patients who have metastatic disease that they will not be cured. I told two patients that on Tuesday. Can CISNET modeling let us begin to see if there is indeed now, with the improved therapies we have, a group of patients who do appear to be cured, or is that not possible?” he asked.

Perhaps, Dr. Caswell-Jin said, in a very small population of older patients with HER2-positive breast cancer that did in fact occur, but to a very small degree.

CHICAGO – Progress in breast cancer treatment over the past 2 decades has reduced expected mortality from both early-stage and metastatic disease, according to a new model that looked at 10-year distant recurrence-free survival and survival time after metastatic diagnosis, among other factors.

“There has been an accelerating influx of new treatments for breast cancer starting around 1990. We wished to ask whether and to what extent decades of metastatic treatment advances may have affected population level breast cancer mortality,” said Jennifer Lee Caswell-Jin, MD, during a presentation of the study at the annual meeting of the American Society of Clinical Oncology.

“Our models find that metastatic treatments improved population-level survival in all breast cancer subtypes since 2000 with substantial variability by subtype," said Dr. Caswell-Jin, who is a medical oncologist with Stanford (Calif.) Medicine specializing in breast cancer.

The study is based on an analysis of four models from the Cancer Intervention and Surveillance Modeling Network (CISNET). The models simulated breast cancer mortality between 2000 and 2019 factoring in the use of mammography, efficacy and dissemination of estrogen receptor (ER) and HER2-specific treatments of early-stage (stages I-III) and metastatic (stage IV or distant recurrence) disease, but also non–cancer-related mortality. The models compared overall and ER/HER2-specific breast cancer mortality rates during this period with estimated rates with no screening or treatment, and then attributed mortality reductions to screening, early-stage, or metastatic treatment.

The results were compared with three clinical trials that tested therapies in different subtypes of metastatic disease. Dr. Caswell-Jin and colleagues adjusted the analysis to reflect expected differences between clinical trial populations and the broader population by sampling simulated patients who resembled the trial population.

The investigators found that, at 71%, the biggest drop in mortality rates were for women with ER+/HER2+ breast cancer, followed by 61% for women with ER-/HER2+ breast cancer and 59% for women with ER+/HER2– breast cancer. Triple-negative breast cancer – one of the most challenging breast cancers to treat – only saw a drop of 40% during this period. About 19% of the overall reduction in breast cancer mortality were caused by treatments after metastasis.

The median survival after a diagnosis of ER+/HER2– metastatic recurrence increased from 2 years in 2000 to 3.5 years in 2019. In triple-negative breast cancer, the increase was more modest, from 1.2 years in 2000 to 1.8 years in 2019. After a diagnosis of metastatic recurrence of ER+/HER2+ breast cancer, median survival increased from 2.3 years in 2000 to 4.8 years in 2019, and for ER–/HER2+ breast cancer, from 2.2 years in 2000 to 3.9 years in 2019.

“How much metastatic treatments contributed to the overall mortality reduction varied over time depending on what therapies were entering the metastatic setting at that time and what therapies were transitioning from the metastatic to early-stage setting,” Dr. Caswell-Jin said.

The study did not include sacituzumab govitecan for metastatic triple-negative breast cancer, or trastuzumab deruxtecan and tucatinib for HER2-positive disease, which were approved after 2020. “The numbers that we cite will be better today for triple-negative breast cancer because of those two drugs. And will be even better for HER2-positive breast cancer because of those two drugs,” she said.

During the Q&A portion of the presentation, Daniel Hayes, MD, the Stuart B. Padnos Professor of Breast Cancer Research at the University of Michigan Rogel Cancer Center, Ann Arbor, asked about the potential of CISNET as an in-practice diagnostic tool.

“We’ve traditionally told patients who have metastatic disease that they will not be cured. I told two patients that on Tuesday. Can CISNET modeling let us begin to see if there is indeed now, with the improved therapies we have, a group of patients who do appear to be cured, or is that not possible?” he asked.

Perhaps, Dr. Caswell-Jin said, in a very small population of older patients with HER2-positive breast cancer that did in fact occur, but to a very small degree.

CHICAGO – Progress in breast cancer treatment over the past 2 decades has reduced expected mortality from both early-stage and metastatic disease, according to a new model that looked at 10-year distant recurrence-free survival and survival time after metastatic diagnosis, among other factors.

“There has been an accelerating influx of new treatments for breast cancer starting around 1990. We wished to ask whether and to what extent decades of metastatic treatment advances may have affected population level breast cancer mortality,” said Jennifer Lee Caswell-Jin, MD, during a presentation of the study at the annual meeting of the American Society of Clinical Oncology.

“Our models find that metastatic treatments improved population-level survival in all breast cancer subtypes since 2000 with substantial variability by subtype," said Dr. Caswell-Jin, who is a medical oncologist with Stanford (Calif.) Medicine specializing in breast cancer.

The study is based on an analysis of four models from the Cancer Intervention and Surveillance Modeling Network (CISNET). The models simulated breast cancer mortality between 2000 and 2019 factoring in the use of mammography, efficacy and dissemination of estrogen receptor (ER) and HER2-specific treatments of early-stage (stages I-III) and metastatic (stage IV or distant recurrence) disease, but also non–cancer-related mortality. The models compared overall and ER/HER2-specific breast cancer mortality rates during this period with estimated rates with no screening or treatment, and then attributed mortality reductions to screening, early-stage, or metastatic treatment.

The results were compared with three clinical trials that tested therapies in different subtypes of metastatic disease. Dr. Caswell-Jin and colleagues adjusted the analysis to reflect expected differences between clinical trial populations and the broader population by sampling simulated patients who resembled the trial population.

The investigators found that, at 71%, the biggest drop in mortality rates were for women with ER+/HER2+ breast cancer, followed by 61% for women with ER-/HER2+ breast cancer and 59% for women with ER+/HER2– breast cancer. Triple-negative breast cancer – one of the most challenging breast cancers to treat – only saw a drop of 40% during this period. About 19% of the overall reduction in breast cancer mortality were caused by treatments after metastasis.

The median survival after a diagnosis of ER+/HER2– metastatic recurrence increased from 2 years in 2000 to 3.5 years in 2019. In triple-negative breast cancer, the increase was more modest, from 1.2 years in 2000 to 1.8 years in 2019. After a diagnosis of metastatic recurrence of ER+/HER2+ breast cancer, median survival increased from 2.3 years in 2000 to 4.8 years in 2019, and for ER–/HER2+ breast cancer, from 2.2 years in 2000 to 3.9 years in 2019.

“How much metastatic treatments contributed to the overall mortality reduction varied over time depending on what therapies were entering the metastatic setting at that time and what therapies were transitioning from the metastatic to early-stage setting,” Dr. Caswell-Jin said.

The study did not include sacituzumab govitecan for metastatic triple-negative breast cancer, or trastuzumab deruxtecan and tucatinib for HER2-positive disease, which were approved after 2020. “The numbers that we cite will be better today for triple-negative breast cancer because of those two drugs. And will be even better for HER2-positive breast cancer because of those two drugs,” she said.

During the Q&A portion of the presentation, Daniel Hayes, MD, the Stuart B. Padnos Professor of Breast Cancer Research at the University of Michigan Rogel Cancer Center, Ann Arbor, asked about the potential of CISNET as an in-practice diagnostic tool.

“We’ve traditionally told patients who have metastatic disease that they will not be cured. I told two patients that on Tuesday. Can CISNET modeling let us begin to see if there is indeed now, with the improved therapies we have, a group of patients who do appear to be cured, or is that not possible?” he asked.

Perhaps, Dr. Caswell-Jin said, in a very small population of older patients with HER2-positive breast cancer that did in fact occur, but to a very small degree.

CHICAGO – In a large case series of metastatic breast cancer patients with pseudocirrhosis, researchers found that almost all such patients had hormone receptor–positive (HR+) disease as well as extensive liver metastases. Pseudocirrhosis appears radiographically similar to cirrhosis, but lacks its classic pathologic features.

The study is the largest cohort of patients with pseudocirrhosis studied to date. “It provides important clinical information about the natural history of this condition to help oncologists better understand which patients develop this condition and what complications are most common. Interestingly, we found that patients who developed ascites had a worse overall survival than patients who did not develop ascites, which was not previously reported,” said Laura Huppert, MD, who presented the findings during a poster session at the annual meeting of the American Society of Clinical Oncology.

Pseudocirrhosis is commonly found in patients with metastatic breast cancer and can lead to ascites and varices, among other complications. “These problems can be quite debilitating and even life-threatening for our patients. In order to better diagnose and treat our patients with pseudocirrhosis, we first wanted to understand the natural history of this condition, including which patients develop it, what treatments they have received, and what complications are most frequent,” said Dr. Huppert, MD, who is a hematology/oncology fellow at the University of California, San Francisco.

The study was retrospective, making it impossible to determine causality. “It is possible that the biology of HR+ disease predisposes patients to the development of pseudocirrhosis through mechanisms that are not yet elucidated. Alternatively, this may be due to the fact that patients with HR+ disease tend to have longer survival and are on systemic therapy for longer periods of time, allowing more time for pseudocirrhosis to develop in response to systemic therapy,” Dr. Huppert said.

In future work, Dr. Huppert plans to examine a control arm of patients with liver disease who do not develop pseudocirrhosis to gain a better understanding of factors that might cause the condition. She also hopes to work with hepatologists to determine if new antifibrosis agents might be applicable to pseudocirrhosis. “There may be interesting things we can learn from other disease states and apply to this condition,” she said.

The researchers analyzed data from 120 patients with pseudocirrhosis. 82.5% of patients were HR+/HER2–, 11.7% were HR+/HER2+, 2.5% were HR–/HER2+, and 3.3% were triple negative. Liver metastases were present in all patients, and 82.5% had more than 15 liver lesions.

A total of 92.5% of patients had previously undergone chemotherapy before pseudocirrhosis was identified, and the median time to diagnosis of pseudocirrhosis after diagnosis of liver metastases was 18.7 months. 50% of patients with pseudocirrhosis had stable or responding disease. After pseudocirrhosis diagnosis, patients underwent a median of 1.0 additional lines of therapy, and the median overall survival following pseudocirrhosis diagnosis was 7.9 months. A total of 80.8% of patients went on to be diagnosed with ascites, 17.5% with esophageal varices, 21.7% with splenomegaly, 10.0% with gastrointestinal bleeding, and 9.2% with hepatic encephalopathy.

Patients with radiographic evidence of ascites survived an average of 42.8 months after metastatic breast cancer diagnosis, while those without ascites survived an average of 76.2 months (P < .001).

Specialty care was rare: Just 7.5% of patients received a GI/hepatology consultation.

Dr. Huppert has no relevant financial disclosures.

CHICAGO – In a large case series of metastatic breast cancer patients with pseudocirrhosis, researchers found that almost all such patients had hormone receptor–positive (HR+) disease as well as extensive liver metastases. Pseudocirrhosis appears radiographically similar to cirrhosis, but lacks its classic pathologic features.

The study is the largest cohort of patients with pseudocirrhosis studied to date. “It provides important clinical information about the natural history of this condition to help oncologists better understand which patients develop this condition and what complications are most common. Interestingly, we found that patients who developed ascites had a worse overall survival than patients who did not develop ascites, which was not previously reported,” said Laura Huppert, MD, who presented the findings during a poster session at the annual meeting of the American Society of Clinical Oncology.

Pseudocirrhosis is commonly found in patients with metastatic breast cancer and can lead to ascites and varices, among other complications. “These problems can be quite debilitating and even life-threatening for our patients. In order to better diagnose and treat our patients with pseudocirrhosis, we first wanted to understand the natural history of this condition, including which patients develop it, what treatments they have received, and what complications are most frequent,” said Dr. Huppert, MD, who is a hematology/oncology fellow at the University of California, San Francisco.

The study was retrospective, making it impossible to determine causality. “It is possible that the biology of HR+ disease predisposes patients to the development of pseudocirrhosis through mechanisms that are not yet elucidated. Alternatively, this may be due to the fact that patients with HR+ disease tend to have longer survival and are on systemic therapy for longer periods of time, allowing more time for pseudocirrhosis to develop in response to systemic therapy,” Dr. Huppert said.

In future work, Dr. Huppert plans to examine a control arm of patients with liver disease who do not develop pseudocirrhosis to gain a better understanding of factors that might cause the condition. She also hopes to work with hepatologists to determine if new antifibrosis agents might be applicable to pseudocirrhosis. “There may be interesting things we can learn from other disease states and apply to this condition,” she said.

The researchers analyzed data from 120 patients with pseudocirrhosis. 82.5% of patients were HR+/HER2–, 11.7% were HR+/HER2+, 2.5% were HR–/HER2+, and 3.3% were triple negative. Liver metastases were present in all patients, and 82.5% had more than 15 liver lesions.

A total of 92.5% of patients had previously undergone chemotherapy before pseudocirrhosis was identified, and the median time to diagnosis of pseudocirrhosis after diagnosis of liver metastases was 18.7 months. 50% of patients with pseudocirrhosis had stable or responding disease. After pseudocirrhosis diagnosis, patients underwent a median of 1.0 additional lines of therapy, and the median overall survival following pseudocirrhosis diagnosis was 7.9 months. A total of 80.8% of patients went on to be diagnosed with ascites, 17.5% with esophageal varices, 21.7% with splenomegaly, 10.0% with gastrointestinal bleeding, and 9.2% with hepatic encephalopathy.

Patients with radiographic evidence of ascites survived an average of 42.8 months after metastatic breast cancer diagnosis, while those without ascites survived an average of 76.2 months (P < .001).

Specialty care was rare: Just 7.5% of patients received a GI/hepatology consultation.

Dr. Huppert has no relevant financial disclosures.

CHICAGO – In a large case series of metastatic breast cancer patients with pseudocirrhosis, researchers found that almost all such patients had hormone receptor–positive (HR+) disease as well as extensive liver metastases. Pseudocirrhosis appears radiographically similar to cirrhosis, but lacks its classic pathologic features.

The study is the largest cohort of patients with pseudocirrhosis studied to date. “It provides important clinical information about the natural history of this condition to help oncologists better understand which patients develop this condition and what complications are most common. Interestingly, we found that patients who developed ascites had a worse overall survival than patients who did not develop ascites, which was not previously reported,” said Laura Huppert, MD, who presented the findings during a poster session at the annual meeting of the American Society of Clinical Oncology.

Pseudocirrhosis is commonly found in patients with metastatic breast cancer and can lead to ascites and varices, among other complications. “These problems can be quite debilitating and even life-threatening for our patients. In order to better diagnose and treat our patients with pseudocirrhosis, we first wanted to understand the natural history of this condition, including which patients develop it, what treatments they have received, and what complications are most frequent,” said Dr. Huppert, MD, who is a hematology/oncology fellow at the University of California, San Francisco.

The study was retrospective, making it impossible to determine causality. “It is possible that the biology of HR+ disease predisposes patients to the development of pseudocirrhosis through mechanisms that are not yet elucidated. Alternatively, this may be due to the fact that patients with HR+ disease tend to have longer survival and are on systemic therapy for longer periods of time, allowing more time for pseudocirrhosis to develop in response to systemic therapy,” Dr. Huppert said.

In future work, Dr. Huppert plans to examine a control arm of patients with liver disease who do not develop pseudocirrhosis to gain a better understanding of factors that might cause the condition. She also hopes to work with hepatologists to determine if new antifibrosis agents might be applicable to pseudocirrhosis. “There may be interesting things we can learn from other disease states and apply to this condition,” she said.

The researchers analyzed data from 120 patients with pseudocirrhosis. 82.5% of patients were HR+/HER2–, 11.7% were HR+/HER2+, 2.5% were HR–/HER2+, and 3.3% were triple negative. Liver metastases were present in all patients, and 82.5% had more than 15 liver lesions.

A total of 92.5% of patients had previously undergone chemotherapy before pseudocirrhosis was identified, and the median time to diagnosis of pseudocirrhosis after diagnosis of liver metastases was 18.7 months. 50% of patients with pseudocirrhosis had stable or responding disease. After pseudocirrhosis diagnosis, patients underwent a median of 1.0 additional lines of therapy, and the median overall survival following pseudocirrhosis diagnosis was 7.9 months. A total of 80.8% of patients went on to be diagnosed with ascites, 17.5% with esophageal varices, 21.7% with splenomegaly, 10.0% with gastrointestinal bleeding, and 9.2% with hepatic encephalopathy.

Patients with radiographic evidence of ascites survived an average of 42.8 months after metastatic breast cancer diagnosis, while those without ascites survived an average of 76.2 months (P < .001).

Specialty care was rare: Just 7.5% of patients received a GI/hepatology consultation.

Dr. Huppert has no relevant financial disclosures.

CHICAGO -- Breast cancer patients with low levels of HER2 expression, previously considered untreatable with HER2-targeted therapies, benefited from the anti-HER2 antibody drug conjugate trastuzumab deruxtecan. The therapy doubled progression-free survival versus chemotherapy in patients with hormone receptor positive (HR+) and low levels of HER2.

“Overall, these results establish HER2 low metastatic breast cancer as a targetable population of breast cancer with trastuzumab deruxtecan as a new standard of care in this setting,” said Shanu Modi, MD, during a press conference held in Chicago at the annual meeting of the American Society of Clinical Oncology, where she presented the results.

“I think the results of this trial clearly will be practice changing,” said ASCO spokesperson and breast cancer expert Jane Lowe Meisel, MD, during the press conference. “I think what this trial does is really extend the benefits of this agent to a whole new group of patients that traditionally is really quite difficult to treat. I think this will offer a wonderful new option for patients and also will really fundamentally change the way we think about HER2 status and how we classify this in our metastatic patients,” Dr. Meisel added.

The conjugate includes the anti-HER2 antibody trastuzumab and the topoisomerase I inhibitor deruxtecan, which interferes with DNA replication. Trastuzumab has demonstrated efficacy in patients with high levels of HER2 expression, and trastuzumab-deruxtecan received FDA approval in May 2022 for the treatment of HER2-positive breast cancer in patients who had previously received an anti-HER2 regimen.

However, anti-HER2 agents had not been shown to benefit HER2-low patients, defined as immunohistochemistry (IHC) 1+ or 2+. About 60% of breast cancer patients traditionally thought of HER2 negative could be classified as HER2 low, according to Dr. Modi, who is a medical oncologist at Memorial Sloan Kettering Cancer Center, New York.

Asked why she thought trastuzumab deruxtecan succeeded where other anti-HER2 therapies failed in this population, Dr. Modi highlighted the nature of the drug conjugate, including a high drug payload and the use of a topoisomerase inhibitor, which is rarely employed against breast cancer. Once released from the antibody, the drug retains its ability to cross cell membranes and enter the tumor microenvironment. That ‘knock on’ effect might allow it to reach neighboring cells that don’t express HER2. “We know HER2 expression is very heterogeneous. I think that’s why, for the first time, we’re seeing activity for a targeted agent,” Dr. Modi said.

The DESTINY-Breast04 study included 557 patients in Asia, Europe, and North America with HR-negative or HR-positive, HER2-low, unresectable, and/or metastatic breast cancer. Patients were randomized to trastuzumab deruxtecan or physician’s choice of several standard chemotherapy drugs. After a median follow-up of 18.4 months, compared with the chemotherapy group, patients in the trastuzumab deruxtecan arm had a 49% reduction in risk of progression and a 36% reduction in mortality. The group also had longer progression-free survival (10.1 months vs. 5.4 months) and overall survival (23.9 months vs. 17.5 months).

Although adverse events were similar between the two groups (52.6% in trastuzumab deruxtecan, 67.4% in chemotherapy), lung toxicity occurred in 12% of the group, and there were 3 fatalities as a result (0.8%). Interstitial lung disease/pneumonitis has been linked to trastuzumab treatment in the past, with one meta-analysis finding a frequency of 2.4% and fatality rate of 0.2%.

Additional studies are in progress to determine the minimum threshold of HER2 expression needed to gain a benefit from trastuzumab deruxtecan treatment.

The study was funded by Daiichi Sankyo, and AstraZeneca. Dr. Modi has advised, consulted for, or received honoraria from Daiichi Sankyo, and AstraZeneca. Dr. Meisel has advised or consulted for Medscape and AstraZeneca.

CHICAGO -- Breast cancer patients with low levels of HER2 expression, previously considered untreatable with HER2-targeted therapies, benefited from the anti-HER2 antibody drug conjugate trastuzumab deruxtecan. The therapy doubled progression-free survival versus chemotherapy in patients with hormone receptor positive (HR+) and low levels of HER2.

“Overall, these results establish HER2 low metastatic breast cancer as a targetable population of breast cancer with trastuzumab deruxtecan as a new standard of care in this setting,” said Shanu Modi, MD, during a press conference held in Chicago at the annual meeting of the American Society of Clinical Oncology, where she presented the results.

“I think the results of this trial clearly will be practice changing,” said ASCO spokesperson and breast cancer expert Jane Lowe Meisel, MD, during the press conference. “I think what this trial does is really extend the benefits of this agent to a whole new group of patients that traditionally is really quite difficult to treat. I think this will offer a wonderful new option for patients and also will really fundamentally change the way we think about HER2 status and how we classify this in our metastatic patients,” Dr. Meisel added.

The conjugate includes the anti-HER2 antibody trastuzumab and the topoisomerase I inhibitor deruxtecan, which interferes with DNA replication. Trastuzumab has demonstrated efficacy in patients with high levels of HER2 expression, and trastuzumab-deruxtecan received FDA approval in May 2022 for the treatment of HER2-positive breast cancer in patients who had previously received an anti-HER2 regimen.

However, anti-HER2 agents had not been shown to benefit HER2-low patients, defined as immunohistochemistry (IHC) 1+ or 2+. About 60% of breast cancer patients traditionally thought of HER2 negative could be classified as HER2 low, according to Dr. Modi, who is a medical oncologist at Memorial Sloan Kettering Cancer Center, New York.

Asked why she thought trastuzumab deruxtecan succeeded where other anti-HER2 therapies failed in this population, Dr. Modi highlighted the nature of the drug conjugate, including a high drug payload and the use of a topoisomerase inhibitor, which is rarely employed against breast cancer. Once released from the antibody, the drug retains its ability to cross cell membranes and enter the tumor microenvironment. That ‘knock on’ effect might allow it to reach neighboring cells that don’t express HER2. “We know HER2 expression is very heterogeneous. I think that’s why, for the first time, we’re seeing activity for a targeted agent,” Dr. Modi said.

The DESTINY-Breast04 study included 557 patients in Asia, Europe, and North America with HR-negative or HR-positive, HER2-low, unresectable, and/or metastatic breast cancer. Patients were randomized to trastuzumab deruxtecan or physician’s choice of several standard chemotherapy drugs. After a median follow-up of 18.4 months, compared with the chemotherapy group, patients in the trastuzumab deruxtecan arm had a 49% reduction in risk of progression and a 36% reduction in mortality. The group also had longer progression-free survival (10.1 months vs. 5.4 months) and overall survival (23.9 months vs. 17.5 months).

Although adverse events were similar between the two groups (52.6% in trastuzumab deruxtecan, 67.4% in chemotherapy), lung toxicity occurred in 12% of the group, and there were 3 fatalities as a result (0.8%). Interstitial lung disease/pneumonitis has been linked to trastuzumab treatment in the past, with one meta-analysis finding a frequency of 2.4% and fatality rate of 0.2%.

Additional studies are in progress to determine the minimum threshold of HER2 expression needed to gain a benefit from trastuzumab deruxtecan treatment.

The study was funded by Daiichi Sankyo, and AstraZeneca. Dr. Modi has advised, consulted for, or received honoraria from Daiichi Sankyo, and AstraZeneca. Dr. Meisel has advised or consulted for Medscape and AstraZeneca.

CHICAGO -- Breast cancer patients with low levels of HER2 expression, previously considered untreatable with HER2-targeted therapies, benefited from the anti-HER2 antibody drug conjugate trastuzumab deruxtecan. The therapy doubled progression-free survival versus chemotherapy in patients with hormone receptor positive (HR+) and low levels of HER2.

“Overall, these results establish HER2 low metastatic breast cancer as a targetable population of breast cancer with trastuzumab deruxtecan as a new standard of care in this setting,” said Shanu Modi, MD, during a press conference held in Chicago at the annual meeting of the American Society of Clinical Oncology, where she presented the results.

“I think the results of this trial clearly will be practice changing,” said ASCO spokesperson and breast cancer expert Jane Lowe Meisel, MD, during the press conference. “I think what this trial does is really extend the benefits of this agent to a whole new group of patients that traditionally is really quite difficult to treat. I think this will offer a wonderful new option for patients and also will really fundamentally change the way we think about HER2 status and how we classify this in our metastatic patients,” Dr. Meisel added.

The conjugate includes the anti-HER2 antibody trastuzumab and the topoisomerase I inhibitor deruxtecan, which interferes with DNA replication. Trastuzumab has demonstrated efficacy in patients with high levels of HER2 expression, and trastuzumab-deruxtecan received FDA approval in May 2022 for the treatment of HER2-positive breast cancer in patients who had previously received an anti-HER2 regimen.

However, anti-HER2 agents had not been shown to benefit HER2-low patients, defined as immunohistochemistry (IHC) 1+ or 2+. About 60% of breast cancer patients traditionally thought of HER2 negative could be classified as HER2 low, according to Dr. Modi, who is a medical oncologist at Memorial Sloan Kettering Cancer Center, New York.

Asked why she thought trastuzumab deruxtecan succeeded where other anti-HER2 therapies failed in this population, Dr. Modi highlighted the nature of the drug conjugate, including a high drug payload and the use of a topoisomerase inhibitor, which is rarely employed against breast cancer. Once released from the antibody, the drug retains its ability to cross cell membranes and enter the tumor microenvironment. That ‘knock on’ effect might allow it to reach neighboring cells that don’t express HER2. “We know HER2 expression is very heterogeneous. I think that’s why, for the first time, we’re seeing activity for a targeted agent,” Dr. Modi said.

The DESTINY-Breast04 study included 557 patients in Asia, Europe, and North America with HR-negative or HR-positive, HER2-low, unresectable, and/or metastatic breast cancer. Patients were randomized to trastuzumab deruxtecan or physician’s choice of several standard chemotherapy drugs. After a median follow-up of 18.4 months, compared with the chemotherapy group, patients in the trastuzumab deruxtecan arm had a 49% reduction in risk of progression and a 36% reduction in mortality. The group also had longer progression-free survival (10.1 months vs. 5.4 months) and overall survival (23.9 months vs. 17.5 months).

Although adverse events were similar between the two groups (52.6% in trastuzumab deruxtecan, 67.4% in chemotherapy), lung toxicity occurred in 12% of the group, and there were 3 fatalities as a result (0.8%). Interstitial lung disease/pneumonitis has been linked to trastuzumab treatment in the past, with one meta-analysis finding a frequency of 2.4% and fatality rate of 0.2%.

Additional studies are in progress to determine the minimum threshold of HER2 expression needed to gain a benefit from trastuzumab deruxtecan treatment.

The study was funded by Daiichi Sankyo, and AstraZeneca. Dr. Modi has advised, consulted for, or received honoraria from Daiichi Sankyo, and AstraZeneca. Dr. Meisel has advised or consulted for Medscape and AstraZeneca.

CHICAGO -- An antibody drug conjugate that targets a cell-surface antigen found on most breast and bladder cancers demonstrated improved progression-free survival over standard chemotherapy in patients with endocrine-resistant hormone receptor positive/HER2 negative metastatic breast cancer.

The agent, called sacituzumab govitecan (Trodelvy, Gilead), was approved on an accelerated basis in 2020 by the Food and Drug Administration for patients with unresectable locally advanced or metastatic triple-negative breast cancer. It received regular approval in 2021.

The conjugate includes an antibody that targets the Trop-2 protein. The antibody is bound to govitecan, which is the active metabolite of the topoisomerase inhibitor 1 irinotecan.

“Sacituzumab demonstrated significant and clinically meaningful benefit, compared with chemotherapy in patients with heavily pretreated endocrine resistant hormone receptor positive, HER2 negative, advanced breast cancer and should be considered a potential treatment in this heavily pretreated patient population,” said lead author Hope S. Rugo, MD, during a press conference held June 4 in Chicago at the annual meeting of the American Society of Clinical Oncology. Dr. Rugo is director of Breast Oncology and Clinical Trials Education at the University of California, San Francisco comprehensive cancer center.

The results drew praise from ASCO spokesperson and breast cancer expert Jane Lowe Meisel, MD, since patients with HR+/HER2- metastatic breast cancer who become resistant to endocrine therapy are left with only sequential, single-agent chemotherapy. “We’ve all been eagerly awaiting the results of this trial. These estrogen positive endocrine negative resistant patients really are an area of great unmet clinical need, and their cancers can be very difficult to treat,” Dr. Meisel said during the press conference.

Approximately, 74% of all breast cancers are HR positive/HER2 negative. And, of these, 92% of patients live beyond five years, according to the American Cancer Society.

The study found a relatively small 1.5 months difference in median progression-free survival, but the results are nevertheless clinically important, especially given that 21% of patients were progression-free at one year, compared with 7% in the chemotherapy arm. “When you look at the patients who do respond on sacituzumab govitecan, it seems that they tend to respond better and longer. The idea that someone with such heavily pretreated disease could walk into your clinic and you could offer them an option that would allow them a one in five chance of still not having progressed at one year is really huge from a clinical standpoint,” Dr. Meisel said.

“This is what we need, incremental options that may be different or better than chemotherapy, so I think this really represents a step forward for the field,” he said.

Two other antibody-drug conjugates that are FDA approved for HER2-positive breast cancer include ado-trastuzumab emtansine (Kadcyla, Genentech) and fam-trastuzumab deruxtecan (Enhertu, AstraZeneca, and Daiichi Sankyo). This new wave of therapies is exciting, according to Julie Gralow, MD, who is chief medical officer and executive vice president of ASCO. “I think this way of delivering chemotherapy inside the cancer cell by having an antibody directed to something on the cell surface and then internalization is really, really very interesting,” Dr. Gralow said during the press conference.

The study included 543 patients from 113 international centers who had previously received endocrine therapy, CDK4/6 inhibitors, and at least two previous regimens of chemotherapy. Median progression-free survival (PFS) was 5.5 months in the sacituzumab govitecan group and 4.0 months in the chemotherapy group (hazard ratio, 0.66; P <.001). PFS was more frequent at 6 months (46% vs. 30%) and 12 months (21% vs. 7%). There was no significant improvement in overall survival (13.9 months vs. 12.3 months). The sacituzumab govitecan group had higher rates of overall response (21% vs. 14%) and clinical benefit (34% vs. 22%), as well as a longer median duration of response (7.4 vs. 5.6 months).

Adverse events were more common with sacituzumab govitecan (74% vs. 60%), including low white blood cell counts (51% vs. 39%) and diarrhea (10% vs. 1%). Both groups had low rates of treatment discontinuation due to adverse events (6% in sacituzumab govitecan vs. 4% in chemotherapy).

Dr. Rugo has received honoraria from Puma Biotechnology and Samsung Bioepis, has consulted for Napo Pharmaceuticals, and has received funding from Astellas Pharma, AstraZeneca, Ayala Pharmaceuticals, Daiichi Sankyo, Genentech, Gilead Sciences, Lilly, Merck, Novartis, OBI Pharma, Odonate Therapeutics, Pfizer, and Sermonix Pharmaceuticals. Dr. Meisel has advised or consulted for Medscape and Total Health Conferencing. She has advised or consulted for AstraZeneca, Curio Science, Genentech, GlaxoSmithKline, Novartis, and SeaGen. She has received research funding from Pfizer and Seattle Genetics. She has received travel, accommodation, or expenses from Pfizer, Puma Biotechnology, and Total Health Conferencing.

CHICAGO -- An antibody drug conjugate that targets a cell-surface antigen found on most breast and bladder cancers demonstrated improved progression-free survival over standard chemotherapy in patients with endocrine-resistant hormone receptor positive/HER2 negative metastatic breast cancer.

The agent, called sacituzumab govitecan (Trodelvy, Gilead), was approved on an accelerated basis in 2020 by the Food and Drug Administration for patients with unresectable locally advanced or metastatic triple-negative breast cancer. It received regular approval in 2021.

The conjugate includes an antibody that targets the Trop-2 protein. The antibody is bound to govitecan, which is the active metabolite of the topoisomerase inhibitor 1 irinotecan.

“Sacituzumab demonstrated significant and clinically meaningful benefit, compared with chemotherapy in patients with heavily pretreated endocrine resistant hormone receptor positive, HER2 negative, advanced breast cancer and should be considered a potential treatment in this heavily pretreated patient population,” said lead author Hope S. Rugo, MD, during a press conference held June 4 in Chicago at the annual meeting of the American Society of Clinical Oncology. Dr. Rugo is director of Breast Oncology and Clinical Trials Education at the University of California, San Francisco comprehensive cancer center.

The results drew praise from ASCO spokesperson and breast cancer expert Jane Lowe Meisel, MD, since patients with HR+/HER2- metastatic breast cancer who become resistant to endocrine therapy are left with only sequential, single-agent chemotherapy. “We’ve all been eagerly awaiting the results of this trial. These estrogen positive endocrine negative resistant patients really are an area of great unmet clinical need, and their cancers can be very difficult to treat,” Dr. Meisel said during the press conference.

Approximately, 74% of all breast cancers are HR positive/HER2 negative. And, of these, 92% of patients live beyond five years, according to the American Cancer Society.

The study found a relatively small 1.5 months difference in median progression-free survival, but the results are nevertheless clinically important, especially given that 21% of patients were progression-free at one year, compared with 7% in the chemotherapy arm. “When you look at the patients who do respond on sacituzumab govitecan, it seems that they tend to respond better and longer. The idea that someone with such heavily pretreated disease could walk into your clinic and you could offer them an option that would allow them a one in five chance of still not having progressed at one year is really huge from a clinical standpoint,” Dr. Meisel said.

“This is what we need, incremental options that may be different or better than chemotherapy, so I think this really represents a step forward for the field,” he said.

Two other antibody-drug conjugates that are FDA approved for HER2-positive breast cancer include ado-trastuzumab emtansine (Kadcyla, Genentech) and fam-trastuzumab deruxtecan (Enhertu, AstraZeneca, and Daiichi Sankyo). This new wave of therapies is exciting, according to Julie Gralow, MD, who is chief medical officer and executive vice president of ASCO. “I think this way of delivering chemotherapy inside the cancer cell by having an antibody directed to something on the cell surface and then internalization is really, really very interesting,” Dr. Gralow said during the press conference.

The study included 543 patients from 113 international centers who had previously received endocrine therapy, CDK4/6 inhibitors, and at least two previous regimens of chemotherapy. Median progression-free survival (PFS) was 5.5 months in the sacituzumab govitecan group and 4.0 months in the chemotherapy group (hazard ratio, 0.66; P <.001). PFS was more frequent at 6 months (46% vs. 30%) and 12 months (21% vs. 7%). There was no significant improvement in overall survival (13.9 months vs. 12.3 months). The sacituzumab govitecan group had higher rates of overall response (21% vs. 14%) and clinical benefit (34% vs. 22%), as well as a longer median duration of response (7.4 vs. 5.6 months).

Adverse events were more common with sacituzumab govitecan (74% vs. 60%), including low white blood cell counts (51% vs. 39%) and diarrhea (10% vs. 1%). Both groups had low rates of treatment discontinuation due to adverse events (6% in sacituzumab govitecan vs. 4% in chemotherapy).

Dr. Rugo has received honoraria from Puma Biotechnology and Samsung Bioepis, has consulted for Napo Pharmaceuticals, and has received funding from Astellas Pharma, AstraZeneca, Ayala Pharmaceuticals, Daiichi Sankyo, Genentech, Gilead Sciences, Lilly, Merck, Novartis, OBI Pharma, Odonate Therapeutics, Pfizer, and Sermonix Pharmaceuticals. Dr. Meisel has advised or consulted for Medscape and Total Health Conferencing. She has advised or consulted for AstraZeneca, Curio Science, Genentech, GlaxoSmithKline, Novartis, and SeaGen. She has received research funding from Pfizer and Seattle Genetics. She has received travel, accommodation, or expenses from Pfizer, Puma Biotechnology, and Total Health Conferencing.

CHICAGO -- An antibody drug conjugate that targets a cell-surface antigen found on most breast and bladder cancers demonstrated improved progression-free survival over standard chemotherapy in patients with endocrine-resistant hormone receptor positive/HER2 negative metastatic breast cancer.

The agent, called sacituzumab govitecan (Trodelvy, Gilead), was approved on an accelerated basis in 2020 by the Food and Drug Administration for patients with unresectable locally advanced or metastatic triple-negative breast cancer. It received regular approval in 2021.

The conjugate includes an antibody that targets the Trop-2 protein. The antibody is bound to govitecan, which is the active metabolite of the topoisomerase inhibitor 1 irinotecan.

“Sacituzumab demonstrated significant and clinically meaningful benefit, compared with chemotherapy in patients with heavily pretreated endocrine resistant hormone receptor positive, HER2 negative, advanced breast cancer and should be considered a potential treatment in this heavily pretreated patient population,” said lead author Hope S. Rugo, MD, during a press conference held June 4 in Chicago at the annual meeting of the American Society of Clinical Oncology. Dr. Rugo is director of Breast Oncology and Clinical Trials Education at the University of California, San Francisco comprehensive cancer center.

The results drew praise from ASCO spokesperson and breast cancer expert Jane Lowe Meisel, MD, since patients with HR+/HER2- metastatic breast cancer who become resistant to endocrine therapy are left with only sequential, single-agent chemotherapy. “We’ve all been eagerly awaiting the results of this trial. These estrogen positive endocrine negative resistant patients really are an area of great unmet clinical need, and their cancers can be very difficult to treat,” Dr. Meisel said during the press conference.

Approximately, 74% of all breast cancers are HR positive/HER2 negative. And, of these, 92% of patients live beyond five years, according to the American Cancer Society.

The study found a relatively small 1.5 months difference in median progression-free survival, but the results are nevertheless clinically important, especially given that 21% of patients were progression-free at one year, compared with 7% in the chemotherapy arm. “When you look at the patients who do respond on sacituzumab govitecan, it seems that they tend to respond better and longer. The idea that someone with such heavily pretreated disease could walk into your clinic and you could offer them an option that would allow them a one in five chance of still not having progressed at one year is really huge from a clinical standpoint,” Dr. Meisel said.

“This is what we need, incremental options that may be different or better than chemotherapy, so I think this really represents a step forward for the field,” he said.

Two other antibody-drug conjugates that are FDA approved for HER2-positive breast cancer include ado-trastuzumab emtansine (Kadcyla, Genentech) and fam-trastuzumab deruxtecan (Enhertu, AstraZeneca, and Daiichi Sankyo). This new wave of therapies is exciting, according to Julie Gralow, MD, who is chief medical officer and executive vice president of ASCO. “I think this way of delivering chemotherapy inside the cancer cell by having an antibody directed to something on the cell surface and then internalization is really, really very interesting,” Dr. Gralow said during the press conference.

The study included 543 patients from 113 international centers who had previously received endocrine therapy, CDK4/6 inhibitors, and at least two previous regimens of chemotherapy. Median progression-free survival (PFS) was 5.5 months in the sacituzumab govitecan group and 4.0 months in the chemotherapy group (hazard ratio, 0.66; P <.001). PFS was more frequent at 6 months (46% vs. 30%) and 12 months (21% vs. 7%). There was no significant improvement in overall survival (13.9 months vs. 12.3 months). The sacituzumab govitecan group had higher rates of overall response (21% vs. 14%) and clinical benefit (34% vs. 22%), as well as a longer median duration of response (7.4 vs. 5.6 months).

Adverse events were more common with sacituzumab govitecan (74% vs. 60%), including low white blood cell counts (51% vs. 39%) and diarrhea (10% vs. 1%). Both groups had low rates of treatment discontinuation due to adverse events (6% in sacituzumab govitecan vs. 4% in chemotherapy).

Dr. Rugo has received honoraria from Puma Biotechnology and Samsung Bioepis, has consulted for Napo Pharmaceuticals, and has received funding from Astellas Pharma, AstraZeneca, Ayala Pharmaceuticals, Daiichi Sankyo, Genentech, Gilead Sciences, Lilly, Merck, Novartis, OBI Pharma, Odonate Therapeutics, Pfizer, and Sermonix Pharmaceuticals. Dr. Meisel has advised or consulted for Medscape and Total Health Conferencing. She has advised or consulted for AstraZeneca, Curio Science, Genentech, GlaxoSmithKline, Novartis, and SeaGen. She has received research funding from Pfizer and Seattle Genetics. She has received travel, accommodation, or expenses from Pfizer, Puma Biotechnology, and Total Health Conferencing.

CHICAGO -- Circulating tumor DNA successfully identified minimal residual disease in patients with hormone receptor-positive (HR+) breast cancer who are at high risk for recurrence – generally years before metastases occurs. The findings come from the CHiRP study, which included patients who were at least 5 years post diagnosis.

The researchers and other groups previously showed that minimal residual disease (MRD) status is associated with distant-recurrence free survival, “yet little is known about ctDNA in the late adjuvant setting in hormone receptor-positive breast cancer,” said Marla Lipsyc-Sharf, MD, a clinical fellow in medicine at Dana-Farber Cancer Institute, Boston. Dr. Lipsyc-Sharf presented her findings June 4 in Chicago at the annual meeting of the American Society of Clinical Oncology.

The study was simultaneously published online in the Journal of Clinical Oncology.

Plasma samples were collected at follow-up visits every 6-12 months, and a personalized version of the RaDaR assay was used to detect ctDNA associated with MRD. Although the technology is currently only useful for research, the team hopes it can soon provide clinical guidance. “The CHiRP study is an important first step toward an understanding of the baseline prevalence and role of ctDNA in this setting. Multiple prospective clinical trials are underway or beginning to establish the clinical utility of ctDNA assays in this setting and understand whether intervention after MRD detection improves patient outcomes, such as survival or quality of life,” she said.

Ben Ho Park, MD, PhD, an oncologist with Vanderbilt University Medical Center, Nashville, Tenn., described the findings as encouraging.

“I think most of us saw this very striking data that you could actually predict who’s going to recur and that all patients who did recur were ctDNA positive. The numbers are really, indeed very encouraging that we can develop assays now that detect minimal residual disease with serum monitoring. It really opens up the floodgates for designing studies [to determine] who to treat with additional adjuvant therapies while they’re still in the adjuvant phase of breast cancer therapy,” Dr. Park said during a discussion that followed the presentation.

The study included 83 patients with high-risk HR+ breast cancer and no evidence of recurrence within 5 years of diagnosis. High risk was defined as T3/T4 and/or N2/N3 disease; T1/N1 disease with 3 or more lymph nodes involved; or T2N1 disease with Ki67 ≥ 20%, grade 3, or oncotype DX score ≥ 26.

For each patient, clinicians designed a tumor-informed liquid biopsy assay to detect plasma ctDNA. A total of 68.7% of participants had stage 3 disease. A total of 90.4% received curative-intent chemotherapy, and all received endocrine therapy. A total of 47% remained on endocrine therapy at their last follow-up.

A total of 93.2% of patients who completed adjuvant endocrine therapy had at least 5 years of treatment. A median of 8.4 years elapsed between diagnosis and first ctDNA sample, and the median follow-up was 10.4 years from diagnosis and 1.8 years from the first sample.

A total of 5% of patients had MRD when they entered the study, and 10% were found to have MRD at any time. Of 6 patients (7.2%) who experienced a metastatic recurrence, all were MRD+, and ctDNA evidence appeared as soon as 37.6 months before diagnosis (median 12.4 months). Of eight patients who were MRD+ at some point, two of them had not had a recurrence at the latest follow-up, and one patient had no follow-up at all, and the other had a follow-up 15.4 months after ctDNA detection.

Limitations of the study included a limited follow-up period and low rate of recurrence, as well as infrequent plasma sampling.

Dr. Lipsyc-Sharf has no relevant financial disclosures. Dr. Park has financial relationships and/or has received funding from Celcuity, Loxo, Casdin Capital, EQRx, Guardant Health, Hologic, Horizon Discovery, Jackson Laboratory for Genomic Medicine, Sermonix Pharmaceuticals, Abbvie, GE Healthcare, Lilly, Pfizer, Horizon Discovery, and Tempus.

CHICAGO -- Circulating tumor DNA successfully identified minimal residual disease in patients with hormone receptor-positive (HR+) breast cancer who are at high risk for recurrence – generally years before metastases occurs. The findings come from the CHiRP study, which included patients who were at least 5 years post diagnosis.

The researchers and other groups previously showed that minimal residual disease (MRD) status is associated with distant-recurrence free survival, “yet little is known about ctDNA in the late adjuvant setting in hormone receptor-positive breast cancer,” said Marla Lipsyc-Sharf, MD, a clinical fellow in medicine at Dana-Farber Cancer Institute, Boston. Dr. Lipsyc-Sharf presented her findings June 4 in Chicago at the annual meeting of the American Society of Clinical Oncology.

The study was simultaneously published online in the Journal of Clinical Oncology.

Plasma samples were collected at follow-up visits every 6-12 months, and a personalized version of the RaDaR assay was used to detect ctDNA associated with MRD. Although the technology is currently only useful for research, the team hopes it can soon provide clinical guidance. “The CHiRP study is an important first step toward an understanding of the baseline prevalence and role of ctDNA in this setting. Multiple prospective clinical trials are underway or beginning to establish the clinical utility of ctDNA assays in this setting and understand whether intervention after MRD detection improves patient outcomes, such as survival or quality of life,” she said.

Ben Ho Park, MD, PhD, an oncologist with Vanderbilt University Medical Center, Nashville, Tenn., described the findings as encouraging.

“I think most of us saw this very striking data that you could actually predict who’s going to recur and that all patients who did recur were ctDNA positive. The numbers are really, indeed very encouraging that we can develop assays now that detect minimal residual disease with serum monitoring. It really opens up the floodgates for designing studies [to determine] who to treat with additional adjuvant therapies while they’re still in the adjuvant phase of breast cancer therapy,” Dr. Park said during a discussion that followed the presentation.

The study included 83 patients with high-risk HR+ breast cancer and no evidence of recurrence within 5 years of diagnosis. High risk was defined as T3/T4 and/or N2/N3 disease; T1/N1 disease with 3 or more lymph nodes involved; or T2N1 disease with Ki67 ≥ 20%, grade 3, or oncotype DX score ≥ 26.

For each patient, clinicians designed a tumor-informed liquid biopsy assay to detect plasma ctDNA. A total of 68.7% of participants had stage 3 disease. A total of 90.4% received curative-intent chemotherapy, and all received endocrine therapy. A total of 47% remained on endocrine therapy at their last follow-up.

A total of 93.2% of patients who completed adjuvant endocrine therapy had at least 5 years of treatment. A median of 8.4 years elapsed between diagnosis and first ctDNA sample, and the median follow-up was 10.4 years from diagnosis and 1.8 years from the first sample.

A total of 5% of patients had MRD when they entered the study, and 10% were found to have MRD at any time. Of 6 patients (7.2%) who experienced a metastatic recurrence, all were MRD+, and ctDNA evidence appeared as soon as 37.6 months before diagnosis (median 12.4 months). Of eight patients who were MRD+ at some point, two of them had not had a recurrence at the latest follow-up, and one patient had no follow-up at all, and the other had a follow-up 15.4 months after ctDNA detection.

Limitations of the study included a limited follow-up period and low rate of recurrence, as well as infrequent plasma sampling.

Dr. Lipsyc-Sharf has no relevant financial disclosures. Dr. Park has financial relationships and/or has received funding from Celcuity, Loxo, Casdin Capital, EQRx, Guardant Health, Hologic, Horizon Discovery, Jackson Laboratory for Genomic Medicine, Sermonix Pharmaceuticals, Abbvie, GE Healthcare, Lilly, Pfizer, Horizon Discovery, and Tempus.

CHICAGO -- Circulating tumor DNA successfully identified minimal residual disease in patients with hormone receptor-positive (HR+) breast cancer who are at high risk for recurrence – generally years before metastases occurs. The findings come from the CHiRP study, which included patients who were at least 5 years post diagnosis.

The researchers and other groups previously showed that minimal residual disease (MRD) status is associated with distant-recurrence free survival, “yet little is known about ctDNA in the late adjuvant setting in hormone receptor-positive breast cancer,” said Marla Lipsyc-Sharf, MD, a clinical fellow in medicine at Dana-Farber Cancer Institute, Boston. Dr. Lipsyc-Sharf presented her findings June 4 in Chicago at the annual meeting of the American Society of Clinical Oncology.

The study was simultaneously published online in the Journal of Clinical Oncology.

Plasma samples were collected at follow-up visits every 6-12 months, and a personalized version of the RaDaR assay was used to detect ctDNA associated with MRD. Although the technology is currently only useful for research, the team hopes it can soon provide clinical guidance. “The CHiRP study is an important first step toward an understanding of the baseline prevalence and role of ctDNA in this setting. Multiple prospective clinical trials are underway or beginning to establish the clinical utility of ctDNA assays in this setting and understand whether intervention after MRD detection improves patient outcomes, such as survival or quality of life,” she said.

Ben Ho Park, MD, PhD, an oncologist with Vanderbilt University Medical Center, Nashville, Tenn., described the findings as encouraging.

“I think most of us saw this very striking data that you could actually predict who’s going to recur and that all patients who did recur were ctDNA positive. The numbers are really, indeed very encouraging that we can develop assays now that detect minimal residual disease with serum monitoring. It really opens up the floodgates for designing studies [to determine] who to treat with additional adjuvant therapies while they’re still in the adjuvant phase of breast cancer therapy,” Dr. Park said during a discussion that followed the presentation.

The study included 83 patients with high-risk HR+ breast cancer and no evidence of recurrence within 5 years of diagnosis. High risk was defined as T3/T4 and/or N2/N3 disease; T1/N1 disease with 3 or more lymph nodes involved; or T2N1 disease with Ki67 ≥ 20%, grade 3, or oncotype DX score ≥ 26.

For each patient, clinicians designed a tumor-informed liquid biopsy assay to detect plasma ctDNA. A total of 68.7% of participants had stage 3 disease. A total of 90.4% received curative-intent chemotherapy, and all received endocrine therapy. A total of 47% remained on endocrine therapy at their last follow-up.

A total of 93.2% of patients who completed adjuvant endocrine therapy had at least 5 years of treatment. A median of 8.4 years elapsed between diagnosis and first ctDNA sample, and the median follow-up was 10.4 years from diagnosis and 1.8 years from the first sample.

A total of 5% of patients had MRD when they entered the study, and 10% were found to have MRD at any time. Of 6 patients (7.2%) who experienced a metastatic recurrence, all were MRD+, and ctDNA evidence appeared as soon as 37.6 months before diagnosis (median 12.4 months). Of eight patients who were MRD+ at some point, two of them had not had a recurrence at the latest follow-up, and one patient had no follow-up at all, and the other had a follow-up 15.4 months after ctDNA detection.

Limitations of the study included a limited follow-up period and low rate of recurrence, as well as infrequent plasma sampling.

Dr. Lipsyc-Sharf has no relevant financial disclosures. Dr. Park has financial relationships and/or has received funding from Celcuity, Loxo, Casdin Capital, EQRx, Guardant Health, Hologic, Horizon Discovery, Jackson Laboratory for Genomic Medicine, Sermonix Pharmaceuticals, Abbvie, GE Healthcare, Lilly, Pfizer, Horizon Discovery, and Tempus.

In an open-label, phase 1/2, randomized clinical trial (VICTORIA) performed at 12 cancer centers in France, the combination of the mammalian target of rapamycin inhibitor vistusertib with anastrozole led to reduced progression in hormone receptor–positive (HR+) endometrial cancer with good tolerability.

The study was published in JAMA Oncology.

Treatment of endometrial cancer involves a combination of surgery, radiation, and chemotherapy, but about 20% of patients relapse, usually within 5 years. HR+ endometrial cancer represents about 65% of endometrial cancers. It is usually endometrioid, and about 80% have phosphatase and tensin homologue (PTEN) mutations, while 36-52% have a mutation in the phosphoinositide 3-kinases/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway.

Endocrine therapy alone elicits a response rate of 15%-30% in HR+ endometrial cancer, generally in low-grade endometrioid subtypes. Most responses are short in duration. Aromatase inhibitors like anastrozole are used for more often than progestogens because they are better tolerated and they have a lower thromboembolic risk in this patient population. Previously, the phase 2 PARAGON trial showed a response rate of just 7% with anastrozole monotherapy, but 44% in women with recurrent HR+ endometrial cancer gained a clinical benefit.

Deregulation in the PI3K/AKT/mTOR pathway can also lead to hormone resistance, suggesting that combination of an mTOR inhibitor with endocrine therapy might have a synergistic effect.

mTOR inhibition alone or in combination with endocrine treatment has been investigated in some single-arm studies, with some encouraging progression-free survival results, but no clear objective response rate or overall survival benefit.

The new study included just 73 patients with a median age of 69.5 years: 49 received 125 mg vistusertib 2 days per week and 1 mg anastrozole daily and 24 received anastrozole only. The 8-week progression-free rate was 67.3% (unilateral 95% confidence interval, 54.7%) in the combination arm versus 39.1% (unilateral 95% CI, 22.2%) in the anastrozole-only arm.

Among 6 patients in the safety run-in period of the combination arm, there were no serious adverse events. Overall response rate was 24.5% (95% CI, 13.3-38.9%) in the combination arm and 17.4% (95% CI, 5.0-38.8%) in the anastrozole-only arm.

Over a median follow-up of 27.7 months, progression-free survival was 5.2 months in the combination arm (95% CI, 3.4-8.9 months) and 1.9 months (95% CI, 1.6-8.9) In the anastrozole-only arm. Common grade 2 or higher side effects linked to vistusertib included fatigue, lymphopenia, hyperglycemia, and diarrhea.

Although low tumor grade, endometrioid subtype, and HR+ status are associated with response to endocrine therapy, the low overall response and progression-free survival in the anastrozole arm suggest that better patient selection is needed. “The choice of treatment according to the histologic characteristics is not sufficient, and highly selected molecular criteria are necessary,” the authors wrote.

The study is limited by its small size and a lack of data on expression level of hormone receptors.

The study was funded by the National Cancer Institute of France.

In an open-label, phase 1/2, randomized clinical trial (VICTORIA) performed at 12 cancer centers in France, the combination of the mammalian target of rapamycin inhibitor vistusertib with anastrozole led to reduced progression in hormone receptor–positive (HR+) endometrial cancer with good tolerability.

The study was published in JAMA Oncology.

Treatment of endometrial cancer involves a combination of surgery, radiation, and chemotherapy, but about 20% of patients relapse, usually within 5 years. HR+ endometrial cancer represents about 65% of endometrial cancers. It is usually endometrioid, and about 80% have phosphatase and tensin homologue (PTEN) mutations, while 36-52% have a mutation in the phosphoinositide 3-kinases/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway.

Endocrine therapy alone elicits a response rate of 15%-30% in HR+ endometrial cancer, generally in low-grade endometrioid subtypes. Most responses are short in duration. Aromatase inhibitors like anastrozole are used for more often than progestogens because they are better tolerated and they have a lower thromboembolic risk in this patient population. Previously, the phase 2 PARAGON trial showed a response rate of just 7% with anastrozole monotherapy, but 44% in women with recurrent HR+ endometrial cancer gained a clinical benefit.

Deregulation in the PI3K/AKT/mTOR pathway can also lead to hormone resistance, suggesting that combination of an mTOR inhibitor with endocrine therapy might have a synergistic effect.

mTOR inhibition alone or in combination with endocrine treatment has been investigated in some single-arm studies, with some encouraging progression-free survival results, but no clear objective response rate or overall survival benefit.

The new study included just 73 patients with a median age of 69.5 years: 49 received 125 mg vistusertib 2 days per week and 1 mg anastrozole daily and 24 received anastrozole only. The 8-week progression-free rate was 67.3% (unilateral 95% confidence interval, 54.7%) in the combination arm versus 39.1% (unilateral 95% CI, 22.2%) in the anastrozole-only arm.

Among 6 patients in the safety run-in period of the combination arm, there were no serious adverse events. Overall response rate was 24.5% (95% CI, 13.3-38.9%) in the combination arm and 17.4% (95% CI, 5.0-38.8%) in the anastrozole-only arm.

Over a median follow-up of 27.7 months, progression-free survival was 5.2 months in the combination arm (95% CI, 3.4-8.9 months) and 1.9 months (95% CI, 1.6-8.9) In the anastrozole-only arm. Common grade 2 or higher side effects linked to vistusertib included fatigue, lymphopenia, hyperglycemia, and diarrhea.

Although low tumor grade, endometrioid subtype, and HR+ status are associated with response to endocrine therapy, the low overall response and progression-free survival in the anastrozole arm suggest that better patient selection is needed. “The choice of treatment according to the histologic characteristics is not sufficient, and highly selected molecular criteria are necessary,” the authors wrote.

The study is limited by its small size and a lack of data on expression level of hormone receptors.

The study was funded by the National Cancer Institute of France.

In an open-label, phase 1/2, randomized clinical trial (VICTORIA) performed at 12 cancer centers in France, the combination of the mammalian target of rapamycin inhibitor vistusertib with anastrozole led to reduced progression in hormone receptor–positive (HR+) endometrial cancer with good tolerability.

The study was published in JAMA Oncology.

Treatment of endometrial cancer involves a combination of surgery, radiation, and chemotherapy, but about 20% of patients relapse, usually within 5 years. HR+ endometrial cancer represents about 65% of endometrial cancers. It is usually endometrioid, and about 80% have phosphatase and tensin homologue (PTEN) mutations, while 36-52% have a mutation in the phosphoinositide 3-kinases/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway.

Endocrine therapy alone elicits a response rate of 15%-30% in HR+ endometrial cancer, generally in low-grade endometrioid subtypes. Most responses are short in duration. Aromatase inhibitors like anastrozole are used for more often than progestogens because they are better tolerated and they have a lower thromboembolic risk in this patient population. Previously, the phase 2 PARAGON trial showed a response rate of just 7% with anastrozole monotherapy, but 44% in women with recurrent HR+ endometrial cancer gained a clinical benefit.

Deregulation in the PI3K/AKT/mTOR pathway can also lead to hormone resistance, suggesting that combination of an mTOR inhibitor with endocrine therapy might have a synergistic effect.

mTOR inhibition alone or in combination with endocrine treatment has been investigated in some single-arm studies, with some encouraging progression-free survival results, but no clear objective response rate or overall survival benefit.

The new study included just 73 patients with a median age of 69.5 years: 49 received 125 mg vistusertib 2 days per week and 1 mg anastrozole daily and 24 received anastrozole only. The 8-week progression-free rate was 67.3% (unilateral 95% confidence interval, 54.7%) in the combination arm versus 39.1% (unilateral 95% CI, 22.2%) in the anastrozole-only arm.

Among 6 patients in the safety run-in period of the combination arm, there were no serious adverse events. Overall response rate was 24.5% (95% CI, 13.3-38.9%) in the combination arm and 17.4% (95% CI, 5.0-38.8%) in the anastrozole-only arm.

Over a median follow-up of 27.7 months, progression-free survival was 5.2 months in the combination arm (95% CI, 3.4-8.9 months) and 1.9 months (95% CI, 1.6-8.9) In the anastrozole-only arm. Common grade 2 or higher side effects linked to vistusertib included fatigue, lymphopenia, hyperglycemia, and diarrhea.

Although low tumor grade, endometrioid subtype, and HR+ status are associated with response to endocrine therapy, the low overall response and progression-free survival in the anastrozole arm suggest that better patient selection is needed. “The choice of treatment according to the histologic characteristics is not sufficient, and highly selected molecular criteria are necessary,” the authors wrote.

The study is limited by its small size and a lack of data on expression level of hormone receptors.

The study was funded by the National Cancer Institute of France.

Among patients with resectable non–small cell lung cancer (NSCLC), neoadjuvant nivolumab combined with chemotherapy led to significantly longer event-free survival and more frequent pathological complete response in patients than chemotherapy alone.

“Our data show that three cycles of neoadjuvant nivolumab plus chemotherapy improved long-term clinical outcomes in patients with resectable stage IB-IIIA NSCLC without impeding the feasibility of surgery or increasing the incidence of adverse events as compared with chemotherapy alone,” wrote the investigators, who were led by Patrick M. Forde, MB, BCh, Johns Hopkins Kimmel Cancer Center, Baltimore. The study was published online in the New England Journal of Medicine.

Nivolumab (Opdivo, Bristol-Myers Squibb), in combination with platinum-doublet chemotherapy, was approved in March by the Food and Drug Administration as a treatment for adults with early-stage, resectable NSCLC. It is the first approval of a neoadjuvant therapy for this patient population. The results of the study, called CheckMate 816, formed the basis of the approval.

About one in four NSCLC patients have resectable disease at diagnosis, but their mortality rate is 30%-55% even after surgery. Neoadjuvant chemotherapy improves survival in this group, but 5-year recurrence rates improve by just 5%-6%, and rates of pathological complete response are low.

In the neoadjuvant setting, the anti–programmed death 1 (PD-1) antibody nivolumab could reduce micrometastases and boost immune response against bulk tumor and tumor antigens. A phase 2 study published in the Journal of Thoracic Oncology showed that neoadjuvant nivolumab combined with chemotherapy conferred good 3-year overall survival (81.9%) and progression-free survival (69.6%) among patients with stage IIIA NSCLC.
 

Results from CheckMate 816

CheckMate 816 is an open-label, phase 3 trial in which 358 patients were randomized to a neoadjuvant course of 360 mg nivolumab and platinum-doublet chemotherapy or platinum-doublet chemotherapy alone. Treatments occurred every 3 weeks for three cycles.

Definitive surgery was performed in 83.2% of the combination group (R0, 83.2%) and 75.4% in the chemotherapy-only group (R0, 77.8%). 93.8% in the combined group and 84.7% in the chemotherapy-only group completed neoadjuvant treatment. 11.9% of the combination group and 22.2% in the chemotherapy-only group underwent adjuvant therapy. A total of 21.2% in the combination group had cancer therapy versus 43.6% of the chemotherapy-only group.

After a minimum follow-up of 21 months, the combination group had a median event-free survival of 31.6 months versus 20.8 months in the chemotherapy-only group (hazard ratio for disease progression, disease recurrence, or death, 0.63; P = .005). The interim analysis for overall survival showed a possible trend towards improved overall survival in the combination group (HR, 0.57; 99.67% confidence interval, 0.30-1.07; P = .0008).

A total of 24.0% of the combination therapy achieved a pathological complete response versus 2.2% in the chemotherapy-only group (odds ratio, 13.94; P < .001).

Grade 3 or 4 treatment-related adverse events occurred in 33.5% of the combination group and 36.9% of the chemotherapy-only group.

The researchers noted that 63.1% of patients in the study had stage IIIA tumors, which has a poor prognosis.

There were benefits to the combination treatment across PD-1–status subgroups, but event-free survival was higher where PD-L1 expression level was 1% or more.

The study is limited by its open-label nature. It was funded by Bristol-Myers Squibb.

Among patients with resectable non–small cell lung cancer (NSCLC), neoadjuvant nivolumab combined with chemotherapy led to significantly longer event-free survival and more frequent pathological complete response in patients than chemotherapy alone.

“Our data show that three cycles of neoadjuvant nivolumab plus chemotherapy improved long-term clinical outcomes in patients with resectable stage IB-IIIA NSCLC without impeding the feasibility of surgery or increasing the incidence of adverse events as compared with chemotherapy alone,” wrote the investigators, who were led by Patrick M. Forde, MB, BCh, Johns Hopkins Kimmel Cancer Center, Baltimore. The study was published online in the New England Journal of Medicine.

Nivolumab (Opdivo, Bristol-Myers Squibb), in combination with platinum-doublet chemotherapy, was approved in March by the Food and Drug Administration as a treatment for adults with early-stage, resectable NSCLC. It is the first approval of a neoadjuvant therapy for this patient population. The results of the study, called CheckMate 816, formed the basis of the approval.

About one in four NSCLC patients have resectable disease at diagnosis, but their mortality rate is 30%-55% even after surgery. Neoadjuvant chemotherapy improves survival in this group, but 5-year recurrence rates improve by just 5%-6%, and rates of pathological complete response are low.

In the neoadjuvant setting, the anti–programmed death 1 (PD-1) antibody nivolumab could reduce micrometastases and boost immune response against bulk tumor and tumor antigens. A phase 2 study published in the Journal of Thoracic Oncology showed that neoadjuvant nivolumab combined with chemotherapy conferred good 3-year overall survival (81.9%) and progression-free survival (69.6%) among patients with stage IIIA NSCLC.
 

Results from CheckMate 816

CheckMate 816 is an open-label, phase 3 trial in which 358 patients were randomized to a neoadjuvant course of 360 mg nivolumab and platinum-doublet chemotherapy or platinum-doublet chemotherapy alone. Treatments occurred every 3 weeks for three cycles.

Definitive surgery was performed in 83.2% of the combination group (R0, 83.2%) and 75.4% in the chemotherapy-only group (R0, 77.8%). 93.8% in the combined group and 84.7% in the chemotherapy-only group completed neoadjuvant treatment. 11.9% of the combination group and 22.2% in the chemotherapy-only group underwent adjuvant therapy. A total of 21.2% in the combination group had cancer therapy versus 43.6% of the chemotherapy-only group.

After a minimum follow-up of 21 months, the combination group had a median event-free survival of 31.6 months versus 20.8 months in the chemotherapy-only group (hazard ratio for disease progression, disease recurrence, or death, 0.63; P = .005). The interim analysis for overall survival showed a possible trend towards improved overall survival in the combination group (HR, 0.57; 99.67% confidence interval, 0.30-1.07; P = .0008).

A total of 24.0% of the combination therapy achieved a pathological complete response versus 2.2% in the chemotherapy-only group (odds ratio, 13.94; P < .001).

Grade 3 or 4 treatment-related adverse events occurred in 33.5% of the combination group and 36.9% of the chemotherapy-only group.

The researchers noted that 63.1% of patients in the study had stage IIIA tumors, which has a poor prognosis.

There were benefits to the combination treatment across PD-1–status subgroups, but event-free survival was higher where PD-L1 expression level was 1% or more.

The study is limited by its open-label nature. It was funded by Bristol-Myers Squibb.

Among patients with resectable non–small cell lung cancer (NSCLC), neoadjuvant nivolumab combined with chemotherapy led to significantly longer event-free survival and more frequent pathological complete response in patients than chemotherapy alone.

“Our data show that three cycles of neoadjuvant nivolumab plus chemotherapy improved long-term clinical outcomes in patients with resectable stage IB-IIIA NSCLC without impeding the feasibility of surgery or increasing the incidence of adverse events as compared with chemotherapy alone,” wrote the investigators, who were led by Patrick M. Forde, MB, BCh, Johns Hopkins Kimmel Cancer Center, Baltimore. The study was published online in the New England Journal of Medicine.

Nivolumab (Opdivo, Bristol-Myers Squibb), in combination with platinum-doublet chemotherapy, was approved in March by the Food and Drug Administration as a treatment for adults with early-stage, resectable NSCLC. It is the first approval of a neoadjuvant therapy for this patient population. The results of the study, called CheckMate 816, formed the basis of the approval.

About one in four NSCLC patients have resectable disease at diagnosis, but their mortality rate is 30%-55% even after surgery. Neoadjuvant chemotherapy improves survival in this group, but 5-year recurrence rates improve by just 5%-6%, and rates of pathological complete response are low.

In the neoadjuvant setting, the anti–programmed death 1 (PD-1) antibody nivolumab could reduce micrometastases and boost immune response against bulk tumor and tumor antigens. A phase 2 study published in the Journal of Thoracic Oncology showed that neoadjuvant nivolumab combined with chemotherapy conferred good 3-year overall survival (81.9%) and progression-free survival (69.6%) among patients with stage IIIA NSCLC.
 

Results from CheckMate 816

CheckMate 816 is an open-label, phase 3 trial in which 358 patients were randomized to a neoadjuvant course of 360 mg nivolumab and platinum-doublet chemotherapy or platinum-doublet chemotherapy alone. Treatments occurred every 3 weeks for three cycles.

Definitive surgery was performed in 83.2% of the combination group (R0, 83.2%) and 75.4% in the chemotherapy-only group (R0, 77.8%). 93.8% in the combined group and 84.7% in the chemotherapy-only group completed neoadjuvant treatment. 11.9% of the combination group and 22.2% in the chemotherapy-only group underwent adjuvant therapy. A total of 21.2% in the combination group had cancer therapy versus 43.6% of the chemotherapy-only group.

After a minimum follow-up of 21 months, the combination group had a median event-free survival of 31.6 months versus 20.8 months in the chemotherapy-only group (hazard ratio for disease progression, disease recurrence, or death, 0.63; P = .005). The interim analysis for overall survival showed a possible trend towards improved overall survival in the combination group (HR, 0.57; 99.67% confidence interval, 0.30-1.07; P = .0008).

A total of 24.0% of the combination therapy achieved a pathological complete response versus 2.2% in the chemotherapy-only group (odds ratio, 13.94; P < .001).

Grade 3 or 4 treatment-related adverse events occurred in 33.5% of the combination group and 36.9% of the chemotherapy-only group.

The researchers noted that 63.1% of patients in the study had stage IIIA tumors, which has a poor prognosis.

There were benefits to the combination treatment across PD-1–status subgroups, but event-free survival was higher where PD-L1 expression level was 1% or more.

The study is limited by its open-label nature. It was funded by Bristol-Myers Squibb.