TBD Meeting (3035-21)

A simple nasal swab may help in the diagnosis of lung cancer in smokers who have undergone CT screening and had lung nodules detected on the scan.  

Only about 5% of the nearly 1.6 million lung nodules identified as incidental findings on low-dose CT screening tests will turn out to be malignant. The new test helps to distinguish between benign and malignant nodules, say researchers reporting a validation study.  

The results show that the test identified those at low risk for cancer with a sensitivity of 96.3% and specificity of 41.7%, as well as identifying those as high risk, with a specificity of 90.4% and sensitivity of 58.2%.

The Percepta nasal swab is a first-of-its-kind genomic test, says the manufacturer Veracyte.

It is based on “field of injury” technology, which examines genomic changes in the lining of the respiratory tract for evidence of active cancer cells, coupled with a machine learning model that includes factors such as age, gender, and smoking history.

Veracyte hopes to begin to make the test available to a select number of sites in the second half of 2021. “The test is intended to be performed in the physician’s office on patients referred with suspicious lung nodules found on CT scans,” said Giulia C. Kennedy, PhD, chief scientific officer and chief medical officer at Veracyte. “This could include patients with nodules found through screening programs, as well as incidentally.”

“It will be made available as a laboratory developed test in the U.S. through Veracyte’s centralized CLIA laboratory,” she said in an interview. “In global markets, we will offer the test as an IVD product that can be performed on the nCounter instrument by laboratories locally. Outside of the United States, the test will require a CE mark, which we are equipped to support.”

Results with the test were presented during the American Society of Clinical Oncology (ASCO) 2021 Annual Meeting, which was held virtually this year.

It was first tested in a training set, which consisted of more than 1,100 patients. All were current or former smokers who had a lung nodule detected on chest CT scanning and were followed for up to 1 year or until a final diagnosis of lung cancer or benign disease.

Brushings of the nasal epithelium were prospectively collected in patients with lung nodules from multiple cohorts.

A total of 502 genes were used in the classifier, and performance was evaluated in an independent clinical validation set consisting of 249 patients.

The test identified true benign patients as low risk with 41.7% specificity and 96.3% sensitivity, resulting in a negative predictive value (NPV) of 97.1% in a population with a cancer prevalence of 25%. The risk of malignancy for patients in this low-risk group was less than 3% (1-NPV), and for this group, clinical guidelines recommend surveillance.  

Patients with true malignancies were identified as high risk, with 58.2% sensitivity and 90.4% specificity, resulting in a positive predictive value of 67.0% in a population with 25% cancer prevalence. The risk of malignancy for patients deemed to be high risk by the classifier was 67.0%, which exceeds the current guideline threshold for consideration of surgical resection or other ablative therapy if a staging evaluation confirms early stage disease, the authors point out.  

The remaining patients, who did not meet the stringent cut-offs for low or high risk, were identified as intermediate risk. In this population, the prevalence of malignancy for patients identified as intermediate risk was 20.7%, which is consistent with guidelines that provide a range for intermediate-risk patients as between 5% and 65% for whom diagnostic biopsy is recommended.
 

Help guide decisions, more data needed

Approached by this news organization for independent comment, Alexander Spira, MD, PhD, medical oncologist, Virginia Cancer Specialists, Fairfax, explained that the study provides an interesting way to look at a common finding and lung nodules and to predict whether further workup should be done.

“This could provide a role in reassurance that patients who fall into the low-risk category could be observed with serial imaging rather than proceeding to immediate biopsy,” he said. “It falls in under the ‘field of injury’ principle.”

Dr. Spira noted that although the low-risk group appears to have a negative predictive value of >90%, it doesn’t mean that the patient would require no further workup. “It would require CT surveillance rather than proceeding to immediate biopsy, and at this point it does appear promising, but I would want further follow-up in terms of outcomes,” he said.

“This does not apply to nonsmokers, which is of increasing prevalence, but with the increased use of CT screening for patients with a history of tobacco use, it may indeed have a role.”

He also pointed out that while the idea is to avoid biopsies, the smaller lesions are the ones that are concerning. “They are often tough to get at, and it would also depend on patient choice and anxiety as well, given the chance of being in that low percentage that the test misses,” said Dr. Spira. “Lastly, many pulmonologists are ordering PET scans in lieu of a biopsy, and this may also help.”

The bottom line is that this may help guide clinical decisions, but more data are needed. “Even in the low-risk category, 9.4% of patients had a malignancy, which is still a high miss rate,” he added.

The study was funded by Veracyte. Dr. Kennedy is employed by Veracyte. Dr. Spira has reported no relevant financial relationships.

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

A simple nasal swab may help in the diagnosis of lung cancer in smokers who have undergone CT screening and had lung nodules detected on the scan.  

Only about 5% of the nearly 1.6 million lung nodules identified as incidental findings on low-dose CT screening tests will turn out to be malignant. The new test helps to distinguish between benign and malignant nodules, say researchers reporting a validation study.  

The results show that the test identified those at low risk for cancer with a sensitivity of 96.3% and specificity of 41.7%, as well as identifying those as high risk, with a specificity of 90.4% and sensitivity of 58.2%.

The Percepta nasal swab is a first-of-its-kind genomic test, says the manufacturer Veracyte.

It is based on “field of injury” technology, which examines genomic changes in the lining of the respiratory tract for evidence of active cancer cells, coupled with a machine learning model that includes factors such as age, gender, and smoking history.

Veracyte hopes to begin to make the test available to a select number of sites in the second half of 2021. “The test is intended to be performed in the physician’s office on patients referred with suspicious lung nodules found on CT scans,” said Giulia C. Kennedy, PhD, chief scientific officer and chief medical officer at Veracyte. “This could include patients with nodules found through screening programs, as well as incidentally.”

“It will be made available as a laboratory developed test in the U.S. through Veracyte’s centralized CLIA laboratory,” she said in an interview. “In global markets, we will offer the test as an IVD product that can be performed on the nCounter instrument by laboratories locally. Outside of the United States, the test will require a CE mark, which we are equipped to support.”

Results with the test were presented during the American Society of Clinical Oncology (ASCO) 2021 Annual Meeting, which was held virtually this year.

It was first tested in a training set, which consisted of more than 1,100 patients. All were current or former smokers who had a lung nodule detected on chest CT scanning and were followed for up to 1 year or until a final diagnosis of lung cancer or benign disease.

Brushings of the nasal epithelium were prospectively collected in patients with lung nodules from multiple cohorts.

A total of 502 genes were used in the classifier, and performance was evaluated in an independent clinical validation set consisting of 249 patients.

The test identified true benign patients as low risk with 41.7% specificity and 96.3% sensitivity, resulting in a negative predictive value (NPV) of 97.1% in a population with a cancer prevalence of 25%. The risk of malignancy for patients in this low-risk group was less than 3% (1-NPV), and for this group, clinical guidelines recommend surveillance.  

Patients with true malignancies were identified as high risk, with 58.2% sensitivity and 90.4% specificity, resulting in a positive predictive value of 67.0% in a population with 25% cancer prevalence. The risk of malignancy for patients deemed to be high risk by the classifier was 67.0%, which exceeds the current guideline threshold for consideration of surgical resection or other ablative therapy if a staging evaluation confirms early stage disease, the authors point out.  

The remaining patients, who did not meet the stringent cut-offs for low or high risk, were identified as intermediate risk. In this population, the prevalence of malignancy for patients identified as intermediate risk was 20.7%, which is consistent with guidelines that provide a range for intermediate-risk patients as between 5% and 65% for whom diagnostic biopsy is recommended.
 

Help guide decisions, more data needed

Approached by this news organization for independent comment, Alexander Spira, MD, PhD, medical oncologist, Virginia Cancer Specialists, Fairfax, explained that the study provides an interesting way to look at a common finding and lung nodules and to predict whether further workup should be done.

“This could provide a role in reassurance that patients who fall into the low-risk category could be observed with serial imaging rather than proceeding to immediate biopsy,” he said. “It falls in under the ‘field of injury’ principle.”

Dr. Spira noted that although the low-risk group appears to have a negative predictive value of >90%, it doesn’t mean that the patient would require no further workup. “It would require CT surveillance rather than proceeding to immediate biopsy, and at this point it does appear promising, but I would want further follow-up in terms of outcomes,” he said.

“This does not apply to nonsmokers, which is of increasing prevalence, but with the increased use of CT screening for patients with a history of tobacco use, it may indeed have a role.”

He also pointed out that while the idea is to avoid biopsies, the smaller lesions are the ones that are concerning. “They are often tough to get at, and it would also depend on patient choice and anxiety as well, given the chance of being in that low percentage that the test misses,” said Dr. Spira. “Lastly, many pulmonologists are ordering PET scans in lieu of a biopsy, and this may also help.”

The bottom line is that this may help guide clinical decisions, but more data are needed. “Even in the low-risk category, 9.4% of patients had a malignancy, which is still a high miss rate,” he added.

The study was funded by Veracyte. Dr. Kennedy is employed by Veracyte. Dr. Spira has reported no relevant financial relationships.

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

A simple nasal swab may help in the diagnosis of lung cancer in smokers who have undergone CT screening and had lung nodules detected on the scan.  

Only about 5% of the nearly 1.6 million lung nodules identified as incidental findings on low-dose CT screening tests will turn out to be malignant. The new test helps to distinguish between benign and malignant nodules, say researchers reporting a validation study.  

The results show that the test identified those at low risk for cancer with a sensitivity of 96.3% and specificity of 41.7%, as well as identifying those as high risk, with a specificity of 90.4% and sensitivity of 58.2%.

The Percepta nasal swab is a first-of-its-kind genomic test, says the manufacturer Veracyte.

It is based on “field of injury” technology, which examines genomic changes in the lining of the respiratory tract for evidence of active cancer cells, coupled with a machine learning model that includes factors such as age, gender, and smoking history.

Veracyte hopes to begin to make the test available to a select number of sites in the second half of 2021. “The test is intended to be performed in the physician’s office on patients referred with suspicious lung nodules found on CT scans,” said Giulia C. Kennedy, PhD, chief scientific officer and chief medical officer at Veracyte. “This could include patients with nodules found through screening programs, as well as incidentally.”

“It will be made available as a laboratory developed test in the U.S. through Veracyte’s centralized CLIA laboratory,” she said in an interview. “In global markets, we will offer the test as an IVD product that can be performed on the nCounter instrument by laboratories locally. Outside of the United States, the test will require a CE mark, which we are equipped to support.”

Results with the test were presented during the American Society of Clinical Oncology (ASCO) 2021 Annual Meeting, which was held virtually this year.

It was first tested in a training set, which consisted of more than 1,100 patients. All were current or former smokers who had a lung nodule detected on chest CT scanning and were followed for up to 1 year or until a final diagnosis of lung cancer or benign disease.

Brushings of the nasal epithelium were prospectively collected in patients with lung nodules from multiple cohorts.

A total of 502 genes were used in the classifier, and performance was evaluated in an independent clinical validation set consisting of 249 patients.

The test identified true benign patients as low risk with 41.7% specificity and 96.3% sensitivity, resulting in a negative predictive value (NPV) of 97.1% in a population with a cancer prevalence of 25%. The risk of malignancy for patients in this low-risk group was less than 3% (1-NPV), and for this group, clinical guidelines recommend surveillance.  

Patients with true malignancies were identified as high risk, with 58.2% sensitivity and 90.4% specificity, resulting in a positive predictive value of 67.0% in a population with 25% cancer prevalence. The risk of malignancy for patients deemed to be high risk by the classifier was 67.0%, which exceeds the current guideline threshold for consideration of surgical resection or other ablative therapy if a staging evaluation confirms early stage disease, the authors point out.  

The remaining patients, who did not meet the stringent cut-offs for low or high risk, were identified as intermediate risk. In this population, the prevalence of malignancy for patients identified as intermediate risk was 20.7%, which is consistent with guidelines that provide a range for intermediate-risk patients as between 5% and 65% for whom diagnostic biopsy is recommended.
 

Help guide decisions, more data needed

Approached by this news organization for independent comment, Alexander Spira, MD, PhD, medical oncologist, Virginia Cancer Specialists, Fairfax, explained that the study provides an interesting way to look at a common finding and lung nodules and to predict whether further workup should be done.

“This could provide a role in reassurance that patients who fall into the low-risk category could be observed with serial imaging rather than proceeding to immediate biopsy,” he said. “It falls in under the ‘field of injury’ principle.”

Dr. Spira noted that although the low-risk group appears to have a negative predictive value of >90%, it doesn’t mean that the patient would require no further workup. “It would require CT surveillance rather than proceeding to immediate biopsy, and at this point it does appear promising, but I would want further follow-up in terms of outcomes,” he said.

“This does not apply to nonsmokers, which is of increasing prevalence, but with the increased use of CT screening for patients with a history of tobacco use, it may indeed have a role.”

He also pointed out that while the idea is to avoid biopsies, the smaller lesions are the ones that are concerning. “They are often tough to get at, and it would also depend on patient choice and anxiety as well, given the chance of being in that low percentage that the test misses,” said Dr. Spira. “Lastly, many pulmonologists are ordering PET scans in lieu of a biopsy, and this may also help.”

The bottom line is that this may help guide clinical decisions, but more data are needed. “Even in the low-risk category, 9.4% of patients had a malignancy, which is still a high miss rate,” he added.

The study was funded by Veracyte. Dr. Kennedy is employed by Veracyte. Dr. Spira has reported no relevant financial relationships.

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

Lung cancer patients could soon have their risk of dying over the following 3 months accurately predicted by analyzing their urine samples, allowing them to better prepare for their end of life, say U.K. researchers.

Dr. Seamus Coyle, consultant in palliative medicine, the Clatterbridge Cancer Centre, Liverpool, and colleagues studied urine samples from more than 100 lung cancer patients, deriving a model based on their metabolite profile.

This allowed patients to be divided into high- and low-risk groups for dying over the following 3 months, with an accuracy of 88%.

The model “predicts dying … for every single day for the last 3 months of life,” Dr. Coyle said.

“That’s an outstanding prediction,” Dr. Coyle added, “based on the fact that people actively die over 2 to 3 days on average,” while “some die over a day.”

He continued: “It’s the only test that predicts dying within the last 2 weeks of life, and that’s what I’m passionate about: The earlier recognition of dying.”

The research was presented at the 2021 American Society of Clinical Oncology Annual Meeting on June 4.
 

‘Promising and important pilot study’

Dr. Nathan Pennell, an ASCO expert, told this news organization that “predicting the actual ‘time’ someone has left is more of an art than a science.”

“For people who may be closer to death, this would potentially allow more focus on supportive care and allow families and patients to plan more accurately for supporting their loved one through the dying process.”

He continued that “while this is a promising and important pilot study, there is more work to be done before this could be used in practice.”

For example, the treatment status of the patients was not clear.

“Were these patients all in hospice, or were some undergoing treatment which, if effective, could ‘rescue’ them from their poor prognostic state?”

Dr. Pennell continued: “Would measuring kidney function be just as good? Is this something that could be intervened upon?

“For example, if someone has a high-risk score for dying, could medical intervention to treat an infection or some other modifiable action change that ‘fate’?”
 

Death ‘difficult to predict’

Dr. Coyle began by saying that, while for him recognizing that a patient is dying is the start of good end of life care, “recognizing dying accurately, when someone is in the last days of life, is difficult.”

He noted that the 2019 National Audit of Care at the End of Life found that people were recognized to be dying at median of 34 hours before death, with 20% recognized in the last 8 hours.

Moreover, 50% of people who are dying “are unconscious and unable to be involved in any conversation that [is] pertinent to them.”

In an attempt to better predict the onset of dying, the researchers conducted a prospective, longitudinal study in which 424 urine samples were collected from 162 lung cancer patients from six centers.

Of those, 63 patients gave a sample within the last 28 days of life, and 29 within the last week of life.

Urine samples were analyzed using a liquid chromatography quadrupole time-of-flight mass spectrometer for 112 patients, who had a median age of 71 years and a range of 47-89 years, and 40.2% were female. The most common diagnosis was non–small cell lung cancer, in 55.4%, while 19.6% had small cell lung cancer.

Performing Cox Lasso regression analysis on the “hundreds of metabolites” identified in the urine samples, the team developed an End of Life Metabolome (ELM) that predicted an individual’s risk of dying over the following 3 months.

Kaplan-Meier analysis allowed the patients to be divided into five risk groups based on their ELM (P < .001 for trend), which showed that all patients in the lowest-risk group were still alive after more than 2 months following the urine sample.

In contrast, more than 50% of patients in the highest-risk group died within 1 week of their urine sample being taken, and 100% had died within 3 weeks.

Calculating the area under the receiver operating characteristic curve revealed that the ELM was able to predict the risk of dying for every day for the last 3 months of life with an accuracy of 88%.

ELM is being validated in a new cohort of lung cancer patients and it is being assessed in multiple cancers.

The study was funded by the Wellcome Trust UK and North West Cancer Research UK.

No relevant financial relationships were declared.

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

Lung cancer patients could soon have their risk of dying over the following 3 months accurately predicted by analyzing their urine samples, allowing them to better prepare for their end of life, say U.K. researchers.

Dr. Seamus Coyle, consultant in palliative medicine, the Clatterbridge Cancer Centre, Liverpool, and colleagues studied urine samples from more than 100 lung cancer patients, deriving a model based on their metabolite profile.

This allowed patients to be divided into high- and low-risk groups for dying over the following 3 months, with an accuracy of 88%.

The model “predicts dying … for every single day for the last 3 months of life,” Dr. Coyle said.

“That’s an outstanding prediction,” Dr. Coyle added, “based on the fact that people actively die over 2 to 3 days on average,” while “some die over a day.”

He continued: “It’s the only test that predicts dying within the last 2 weeks of life, and that’s what I’m passionate about: The earlier recognition of dying.”

The research was presented at the 2021 American Society of Clinical Oncology Annual Meeting on June 4.
 

‘Promising and important pilot study’

Dr. Nathan Pennell, an ASCO expert, told this news organization that “predicting the actual ‘time’ someone has left is more of an art than a science.”

“For people who may be closer to death, this would potentially allow more focus on supportive care and allow families and patients to plan more accurately for supporting their loved one through the dying process.”

He continued that “while this is a promising and important pilot study, there is more work to be done before this could be used in practice.”

For example, the treatment status of the patients was not clear.

“Were these patients all in hospice, or were some undergoing treatment which, if effective, could ‘rescue’ them from their poor prognostic state?”

Dr. Pennell continued: “Would measuring kidney function be just as good? Is this something that could be intervened upon?

“For example, if someone has a high-risk score for dying, could medical intervention to treat an infection or some other modifiable action change that ‘fate’?”
 

Death ‘difficult to predict’

Dr. Coyle began by saying that, while for him recognizing that a patient is dying is the start of good end of life care, “recognizing dying accurately, when someone is in the last days of life, is difficult.”

He noted that the 2019 National Audit of Care at the End of Life found that people were recognized to be dying at median of 34 hours before death, with 20% recognized in the last 8 hours.

Moreover, 50% of people who are dying “are unconscious and unable to be involved in any conversation that [is] pertinent to them.”

In an attempt to better predict the onset of dying, the researchers conducted a prospective, longitudinal study in which 424 urine samples were collected from 162 lung cancer patients from six centers.

Of those, 63 patients gave a sample within the last 28 days of life, and 29 within the last week of life.

Urine samples were analyzed using a liquid chromatography quadrupole time-of-flight mass spectrometer for 112 patients, who had a median age of 71 years and a range of 47-89 years, and 40.2% were female. The most common diagnosis was non–small cell lung cancer, in 55.4%, while 19.6% had small cell lung cancer.

Performing Cox Lasso regression analysis on the “hundreds of metabolites” identified in the urine samples, the team developed an End of Life Metabolome (ELM) that predicted an individual’s risk of dying over the following 3 months.

Kaplan-Meier analysis allowed the patients to be divided into five risk groups based on their ELM (P < .001 for trend), which showed that all patients in the lowest-risk group were still alive after more than 2 months following the urine sample.

In contrast, more than 50% of patients in the highest-risk group died within 1 week of their urine sample being taken, and 100% had died within 3 weeks.

Calculating the area under the receiver operating characteristic curve revealed that the ELM was able to predict the risk of dying for every day for the last 3 months of life with an accuracy of 88%.

ELM is being validated in a new cohort of lung cancer patients and it is being assessed in multiple cancers.

The study was funded by the Wellcome Trust UK and North West Cancer Research UK.

No relevant financial relationships were declared.

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

Lung cancer patients could soon have their risk of dying over the following 3 months accurately predicted by analyzing their urine samples, allowing them to better prepare for their end of life, say U.K. researchers.

Dr. Seamus Coyle, consultant in palliative medicine, the Clatterbridge Cancer Centre, Liverpool, and colleagues studied urine samples from more than 100 lung cancer patients, deriving a model based on their metabolite profile.

This allowed patients to be divided into high- and low-risk groups for dying over the following 3 months, with an accuracy of 88%.

The model “predicts dying … for every single day for the last 3 months of life,” Dr. Coyle said.

“That’s an outstanding prediction,” Dr. Coyle added, “based on the fact that people actively die over 2 to 3 days on average,” while “some die over a day.”

He continued: “It’s the only test that predicts dying within the last 2 weeks of life, and that’s what I’m passionate about: The earlier recognition of dying.”

The research was presented at the 2021 American Society of Clinical Oncology Annual Meeting on June 4.
 

‘Promising and important pilot study’

Dr. Nathan Pennell, an ASCO expert, told this news organization that “predicting the actual ‘time’ someone has left is more of an art than a science.”

“For people who may be closer to death, this would potentially allow more focus on supportive care and allow families and patients to plan more accurately for supporting their loved one through the dying process.”

He continued that “while this is a promising and important pilot study, there is more work to be done before this could be used in practice.”

For example, the treatment status of the patients was not clear.

“Were these patients all in hospice, or were some undergoing treatment which, if effective, could ‘rescue’ them from their poor prognostic state?”

Dr. Pennell continued: “Would measuring kidney function be just as good? Is this something that could be intervened upon?

“For example, if someone has a high-risk score for dying, could medical intervention to treat an infection or some other modifiable action change that ‘fate’?”
 

Death ‘difficult to predict’

Dr. Coyle began by saying that, while for him recognizing that a patient is dying is the start of good end of life care, “recognizing dying accurately, when someone is in the last days of life, is difficult.”

He noted that the 2019 National Audit of Care at the End of Life found that people were recognized to be dying at median of 34 hours before death, with 20% recognized in the last 8 hours.

Moreover, 50% of people who are dying “are unconscious and unable to be involved in any conversation that [is] pertinent to them.”

In an attempt to better predict the onset of dying, the researchers conducted a prospective, longitudinal study in which 424 urine samples were collected from 162 lung cancer patients from six centers.

Of those, 63 patients gave a sample within the last 28 days of life, and 29 within the last week of life.

Urine samples were analyzed using a liquid chromatography quadrupole time-of-flight mass spectrometer for 112 patients, who had a median age of 71 years and a range of 47-89 years, and 40.2% were female. The most common diagnosis was non–small cell lung cancer, in 55.4%, while 19.6% had small cell lung cancer.

Performing Cox Lasso regression analysis on the “hundreds of metabolites” identified in the urine samples, the team developed an End of Life Metabolome (ELM) that predicted an individual’s risk of dying over the following 3 months.

Kaplan-Meier analysis allowed the patients to be divided into five risk groups based on their ELM (P < .001 for trend), which showed that all patients in the lowest-risk group were still alive after more than 2 months following the urine sample.

In contrast, more than 50% of patients in the highest-risk group died within 1 week of their urine sample being taken, and 100% had died within 3 weeks.

Calculating the area under the receiver operating characteristic curve revealed that the ELM was able to predict the risk of dying for every day for the last 3 months of life with an accuracy of 88%.

ELM is being validated in a new cohort of lung cancer patients and it is being assessed in multiple cancers.

The study was funded by the Wellcome Trust UK and North West Cancer Research UK.

No relevant financial relationships were declared.

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

After decades of off-label use, vinorelbine finally has a randomized clinical trial supporting its efficacy as a second-line treatment of mesothelioma, an investigator reported at the annual meeting of the American Society of Clinical Oncology.

However, the development of other treatment regimens, and notably immuno-oncology approaches, are pushing this classic chemotherapy option to later lines of therapy in patients with malignant pleural mesothelioma (MPM), a speaker said at the meeting.

Adding vinorelbine to active symptom control statistically improved progression-free survival (PFS), among patients with MPM who had prior platinum-based therapy, according to results of the randomized Vinorelbine in Mesothelioma (VIM) trial.

Median PFS reached 4.2 months in the vinorelbine arm, versus 2.8 months for active symptom control alone, study results show.

That finding , coupled with safety results, supports the off-label use of vinorelbine as a treatment option for patients with relapsed MPM, according to investigator Dean Anthony Fennell, FRCP, PhD, of the University of Leicester (England).

“Vinorelbine appears to be a safe and effective treatment and could be considered as a treatment option for patients with relapsed mesothelioma,” Prof. Fennell said in his presentation at ASCO (Abstract 8507).
 

Changing status

While that welcome pronouncement was a long time coming, there are now other promising treatment approaches that relegate vinorelbine to a “lower priority” in the treatment algorithm, said discussant Anna K. Nowak, MBBS, FRACP, PhD, of the University of Western Australia, Nedlands.

In October 2020, the U.S. Food and Drug Administration approved the combination of ipilimumab and nivolumab for the first-line treatment of unresectable malignant pleural mesothelioma, on the basis of results from CHECKMATE-743, a randomized, open-label trial.

“Certainly, we know now that first-line ipilimumab and nivolumab is of very substantial benefit to these patients, and we still have clinical trials open in this space as well,” Prof. Nowak said in her discussion at ASCO.

There is “no doubt” that many patients with mesothelioma should at some point receive an IO agent, particularly now with recently reported randomized clinical trial evidence of an overall survival benefit, she added.

“This really pushes vinorelbine out to be a third- or fourth-line treatment,” she added, “and we know that there are usually diminishing returns from using chemotherapies further down the treatment algorithm.”
 

Trial details

The VIM trial described at ASCO by Prof. Fennell was a randomized, controlled phase 2 including 154 patients with MPM that had progressed after first-line chemotherapy.

“Vinorelbine has shown useful clinical activity in single-arm phase two studies, however, the specific efficacy of vinorelbine has not been evaluated in an appropriately controlled randomized trial,” Prof. Fennell said in this presentation.

Patients in the trial were randomized 2:1 to either vinorelbine plus active supportive care or active supportive care alone. Vinorelbine was given initially at 60 mg/m² weekly every 21 days, escalated to 80 mg/m² from cycle 2.

The median age of patients in VIM was approximately 71 years, and about 80% were male.

More partial responses were seen in the vinorelbine arm, at 3.1% of patients, compared with 1.8% for active supportive care, according to Prof. Fennell. Likewise, the rate of stable disease was higher in the vinorelbine arm, at 62.2%, versus 46.4% in the control arm.

The primary outcome of the study, PFS, was significantly improved in the vinorelbine arm, according to Dr. Fennell. The median PFS was 4.2 months in the vinorelbine arm and 2.8 months in the supportive care arm (P = .002), translating into a hazard ratio of 0.60 (95% confidence interval, 0.41-0.86), Prof. Fennell reported.

The most common grade 3-4 adverse event was neutropenia, occurring in 12.5% of the vinorelbine-treated patients and no patients managed with supportive care alone, according to the report. Other grade 3-4 adverse events occurred in fewer than 10% of patients and included dyspnea, lower respiratory infection, lymphopenia, and fatigue, among others.

Overall survival (OS) was not statistically different between vinorelbine and supportive care arms, with median OS of 9.3 months and 9.1 months, respectively.

However, a number of patients in the control arm went on to receive subsequent therapy, including 15 (or about 27%) who went into CONFIRM, a randomized phase 3 trial that, as recently reported, met its coprimary endpoints of improve OS and PFS with nivolumab vs. placebo in relapsed malignant mesothelioma.

Investigators also sought to test the hypothesis that BRCA1-negative patients might be chemoresistant, based in part on preclinical models demonstrating that BRCA1 predicted sensitivity to vinorelbine. However, there was no difference in PFS by BRCA1 expression in the VIM study, according to Prof. Fennell.

Taken together, findings of the VIM trial suggest vinorelbine is a “modestly active” agent with low cost and acceptable toxicity, according to Prof. Nowak.

“It is incumbent on us to have clear discussions with our patients on the risks and benefits of trying this as a subsequent-line therapy, in the context of this evidence that was generated as a second-line therapy,” she said in her discussant remarks on the study.

“I would say that it is a lower priority in our algorithm than cisplatin and pemetrexed, or of course, immuno-oncology agents,” she added.

Dr. Fennell reported disclosures related to AstraZeneca, Astex Therapeutics, Bayer, and multiple other pharmaceutical companies. Dr. Nowak reported disclosures with AstraZeneca, Atara Biotherapeutics, Boehringer Ingelheim, and multiple other pharmaceutical companies.

After decades of off-label use, vinorelbine finally has a randomized clinical trial supporting its efficacy as a second-line treatment of mesothelioma, an investigator reported at the annual meeting of the American Society of Clinical Oncology.

However, the development of other treatment regimens, and notably immuno-oncology approaches, are pushing this classic chemotherapy option to later lines of therapy in patients with malignant pleural mesothelioma (MPM), a speaker said at the meeting.

Adding vinorelbine to active symptom control statistically improved progression-free survival (PFS), among patients with MPM who had prior platinum-based therapy, according to results of the randomized Vinorelbine in Mesothelioma (VIM) trial.

Median PFS reached 4.2 months in the vinorelbine arm, versus 2.8 months for active symptom control alone, study results show.

That finding , coupled with safety results, supports the off-label use of vinorelbine as a treatment option for patients with relapsed MPM, according to investigator Dean Anthony Fennell, FRCP, PhD, of the University of Leicester (England).

“Vinorelbine appears to be a safe and effective treatment and could be considered as a treatment option for patients with relapsed mesothelioma,” Prof. Fennell said in his presentation at ASCO (Abstract 8507).
 

Changing status

While that welcome pronouncement was a long time coming, there are now other promising treatment approaches that relegate vinorelbine to a “lower priority” in the treatment algorithm, said discussant Anna K. Nowak, MBBS, FRACP, PhD, of the University of Western Australia, Nedlands.

In October 2020, the U.S. Food and Drug Administration approved the combination of ipilimumab and nivolumab for the first-line treatment of unresectable malignant pleural mesothelioma, on the basis of results from CHECKMATE-743, a randomized, open-label trial.

“Certainly, we know now that first-line ipilimumab and nivolumab is of very substantial benefit to these patients, and we still have clinical trials open in this space as well,” Prof. Nowak said in her discussion at ASCO.

There is “no doubt” that many patients with mesothelioma should at some point receive an IO agent, particularly now with recently reported randomized clinical trial evidence of an overall survival benefit, she added.

“This really pushes vinorelbine out to be a third- or fourth-line treatment,” she added, “and we know that there are usually diminishing returns from using chemotherapies further down the treatment algorithm.”
 

Trial details

The VIM trial described at ASCO by Prof. Fennell was a randomized, controlled phase 2 including 154 patients with MPM that had progressed after first-line chemotherapy.

“Vinorelbine has shown useful clinical activity in single-arm phase two studies, however, the specific efficacy of vinorelbine has not been evaluated in an appropriately controlled randomized trial,” Prof. Fennell said in this presentation.

Patients in the trial were randomized 2:1 to either vinorelbine plus active supportive care or active supportive care alone. Vinorelbine was given initially at 60 mg/m² weekly every 21 days, escalated to 80 mg/m² from cycle 2.

The median age of patients in VIM was approximately 71 years, and about 80% were male.

More partial responses were seen in the vinorelbine arm, at 3.1% of patients, compared with 1.8% for active supportive care, according to Prof. Fennell. Likewise, the rate of stable disease was higher in the vinorelbine arm, at 62.2%, versus 46.4% in the control arm.

The primary outcome of the study, PFS, was significantly improved in the vinorelbine arm, according to Dr. Fennell. The median PFS was 4.2 months in the vinorelbine arm and 2.8 months in the supportive care arm (P = .002), translating into a hazard ratio of 0.60 (95% confidence interval, 0.41-0.86), Prof. Fennell reported.

The most common grade 3-4 adverse event was neutropenia, occurring in 12.5% of the vinorelbine-treated patients and no patients managed with supportive care alone, according to the report. Other grade 3-4 adverse events occurred in fewer than 10% of patients and included dyspnea, lower respiratory infection, lymphopenia, and fatigue, among others.

Overall survival (OS) was not statistically different between vinorelbine and supportive care arms, with median OS of 9.3 months and 9.1 months, respectively.

However, a number of patients in the control arm went on to receive subsequent therapy, including 15 (or about 27%) who went into CONFIRM, a randomized phase 3 trial that, as recently reported, met its coprimary endpoints of improve OS and PFS with nivolumab vs. placebo in relapsed malignant mesothelioma.

Investigators also sought to test the hypothesis that BRCA1-negative patients might be chemoresistant, based in part on preclinical models demonstrating that BRCA1 predicted sensitivity to vinorelbine. However, there was no difference in PFS by BRCA1 expression in the VIM study, according to Prof. Fennell.

Taken together, findings of the VIM trial suggest vinorelbine is a “modestly active” agent with low cost and acceptable toxicity, according to Prof. Nowak.

“It is incumbent on us to have clear discussions with our patients on the risks and benefits of trying this as a subsequent-line therapy, in the context of this evidence that was generated as a second-line therapy,” she said in her discussant remarks on the study.

“I would say that it is a lower priority in our algorithm than cisplatin and pemetrexed, or of course, immuno-oncology agents,” she added.

Dr. Fennell reported disclosures related to AstraZeneca, Astex Therapeutics, Bayer, and multiple other pharmaceutical companies. Dr. Nowak reported disclosures with AstraZeneca, Atara Biotherapeutics, Boehringer Ingelheim, and multiple other pharmaceutical companies.

After decades of off-label use, vinorelbine finally has a randomized clinical trial supporting its efficacy as a second-line treatment of mesothelioma, an investigator reported at the annual meeting of the American Society of Clinical Oncology.

However, the development of other treatment regimens, and notably immuno-oncology approaches, are pushing this classic chemotherapy option to later lines of therapy in patients with malignant pleural mesothelioma (MPM), a speaker said at the meeting.

Adding vinorelbine to active symptom control statistically improved progression-free survival (PFS), among patients with MPM who had prior platinum-based therapy, according to results of the randomized Vinorelbine in Mesothelioma (VIM) trial.

Median PFS reached 4.2 months in the vinorelbine arm, versus 2.8 months for active symptom control alone, study results show.

That finding , coupled with safety results, supports the off-label use of vinorelbine as a treatment option for patients with relapsed MPM, according to investigator Dean Anthony Fennell, FRCP, PhD, of the University of Leicester (England).

“Vinorelbine appears to be a safe and effective treatment and could be considered as a treatment option for patients with relapsed mesothelioma,” Prof. Fennell said in his presentation at ASCO (Abstract 8507).
 

Changing status

While that welcome pronouncement was a long time coming, there are now other promising treatment approaches that relegate vinorelbine to a “lower priority” in the treatment algorithm, said discussant Anna K. Nowak, MBBS, FRACP, PhD, of the University of Western Australia, Nedlands.

In October 2020, the U.S. Food and Drug Administration approved the combination of ipilimumab and nivolumab for the first-line treatment of unresectable malignant pleural mesothelioma, on the basis of results from CHECKMATE-743, a randomized, open-label trial.

“Certainly, we know now that first-line ipilimumab and nivolumab is of very substantial benefit to these patients, and we still have clinical trials open in this space as well,” Prof. Nowak said in her discussion at ASCO.

There is “no doubt” that many patients with mesothelioma should at some point receive an IO agent, particularly now with recently reported randomized clinical trial evidence of an overall survival benefit, she added.

“This really pushes vinorelbine out to be a third- or fourth-line treatment,” she added, “and we know that there are usually diminishing returns from using chemotherapies further down the treatment algorithm.”
 

Trial details

The VIM trial described at ASCO by Prof. Fennell was a randomized, controlled phase 2 including 154 patients with MPM that had progressed after first-line chemotherapy.

“Vinorelbine has shown useful clinical activity in single-arm phase two studies, however, the specific efficacy of vinorelbine has not been evaluated in an appropriately controlled randomized trial,” Prof. Fennell said in this presentation.

Patients in the trial were randomized 2:1 to either vinorelbine plus active supportive care or active supportive care alone. Vinorelbine was given initially at 60 mg/m² weekly every 21 days, escalated to 80 mg/m² from cycle 2.

The median age of patients in VIM was approximately 71 years, and about 80% were male.

More partial responses were seen in the vinorelbine arm, at 3.1% of patients, compared with 1.8% for active supportive care, according to Prof. Fennell. Likewise, the rate of stable disease was higher in the vinorelbine arm, at 62.2%, versus 46.4% in the control arm.

The primary outcome of the study, PFS, was significantly improved in the vinorelbine arm, according to Dr. Fennell. The median PFS was 4.2 months in the vinorelbine arm and 2.8 months in the supportive care arm (P = .002), translating into a hazard ratio of 0.60 (95% confidence interval, 0.41-0.86), Prof. Fennell reported.

The most common grade 3-4 adverse event was neutropenia, occurring in 12.5% of the vinorelbine-treated patients and no patients managed with supportive care alone, according to the report. Other grade 3-4 adverse events occurred in fewer than 10% of patients and included dyspnea, lower respiratory infection, lymphopenia, and fatigue, among others.

Overall survival (OS) was not statistically different between vinorelbine and supportive care arms, with median OS of 9.3 months and 9.1 months, respectively.

However, a number of patients in the control arm went on to receive subsequent therapy, including 15 (or about 27%) who went into CONFIRM, a randomized phase 3 trial that, as recently reported, met its coprimary endpoints of improve OS and PFS with nivolumab vs. placebo in relapsed malignant mesothelioma.

Investigators also sought to test the hypothesis that BRCA1-negative patients might be chemoresistant, based in part on preclinical models demonstrating that BRCA1 predicted sensitivity to vinorelbine. However, there was no difference in PFS by BRCA1 expression in the VIM study, according to Prof. Fennell.

Taken together, findings of the VIM trial suggest vinorelbine is a “modestly active” agent with low cost and acceptable toxicity, according to Prof. Nowak.

“It is incumbent on us to have clear discussions with our patients on the risks and benefits of trying this as a subsequent-line therapy, in the context of this evidence that was generated as a second-line therapy,” she said in her discussant remarks on the study.

“I would say that it is a lower priority in our algorithm than cisplatin and pemetrexed, or of course, immuno-oncology agents,” she added.

Dr. Fennell reported disclosures related to AstraZeneca, Astex Therapeutics, Bayer, and multiple other pharmaceutical companies. Dr. Nowak reported disclosures with AstraZeneca, Atara Biotherapeutics, Boehringer Ingelheim, and multiple other pharmaceutical companies.

An online support tool for health care professionals that recommends whether to admit or discharge a cancer patient with COVID-19, based on their risk of a severe complication, has been developed by researchers from Manchester.

The team used machine learning on data from more than 900 cancer patients with COVID-19, conducting multiple analyses to arrive at a set of features that could accurately predict the need for admission or oxygen therapy, as well as the risk of death.

Dr. Rebecca Lee, The Christie NHS Foundation Trust, Manchester, and colleagues then developed thresholds to derive a score that recommended admission in 95% of patients who went on to need oxygen and an even greater proportion of those who later died.

The research was presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting on June 4.
 

CORONET

The resulting COVID-19 Risk in Oncology Evaluation Tool (CORONET) model “performs very well at predicting admission and severity of COVID-19 in patients with cancer,” Dr. Lee said. “We have set pragmatic and clinically relevant thresholds that focus on the safety regarding an admission versus discharge decision.”

To help health care professionals, the researchers have built a free online support tool that allows them to enter data and receive a recommendation “as to whether their patient should be considered for discharge, considered for admission, or is at high risk of having a severe outcome of coronavirus,” Dr. Lee explained.

“The health care professional can then explore the recommendation by seeing how their patient … compares with the rest of the cohort.”

The tool also includes a “diagram showing which features are most important to recommend a discharge decision versus an admission decision for each individual patient.”
 

Clinically intuitive

Dr. Alexi Wright, associate professor, Dana-Faber Cancer Institute, Boston, who was not involved in the study, commented that there were many things that were “really nice about the study.”

“First and foremost that they were establishing a tool to efficiently triage [patients] presenting with COVID,” she said, adding that it was “clinically intuitive” that the team made “pragmatic choices,” and the use of a random forest algorithm means the results are “very interpretable.”

However, Dr. Wright wondered whether the results can be replicated.

Alongside a lack of information on the deaths in the cohort, she pointed out that “ideally you have three data sets, with a training set, a testing set, and a validation set.”

The CORONET model was, however, trained and evaluated on the same dataset, “so it really needs external validation before it would be ready for direct clinical application.”

She continued that there is a “critical need to establish that studies can both be reproduced and replicated,” noting that a recent review showed that 85% of machine-learning studies that were used to detect COVID-19 using chest radiographs “failed fundamental reproducibility and quality checks.” 

Risk factors

Dr. Lee began her presentation by reminding the audience that cancer patients are at increased risk of severe COVID-19 and death, with older age, male sex, nosocomial infection, higher ECOG performance status, and active cancer among the risk factors for mortality.

“However, outcomes are very heterogeneous, ranging from patients without symptoms at all to cases with multi-organ failure and death,” she said.

It is consequently “very important for the treating clinician to determine which patients could be safely discharged to the community versus those who need additional support in being admitted to hospital.”

To develop a tool that could distinguish between those two groups of patients, the researchers collected data on 1,743 cancer patients, which was reduced down to 920 patients after excluding those without laboratory confirmed COVID-19 and those with missing data.

Using recursive feature elimination, they selected 10 key patient features associated with prognosis, then compared a lasso regression model with a random forest model, with the latter performing the best.

The team then divided their patients into four cohorts, with the model trained on three cohorts and tested on the fourth. This resulted in the CORONET score, with the final model determined by testing it against the entire patient population.

Next, thresholds were determined for assessing patients for admission versus discharge, as well as for severity of illness, giving the final CORONET model, from which the online tool was developed.
 

Checking performance

The results showed that the model was able to predict admission with an area under the receiver operating characteristics curve (AUROC) of 0.82 for admission, 0.85 for oxygen requirement, and 0.79 for death.

Further analysis revealed that the most important feature at the time of presentation for determining outcome was the National Early Warning Score 2 (NEWS2), “which is a composite score of heart rate, respiratory rate, saturations and confusion level,” Dr. Lee said.

In addition, C-reactive protein levels, albumin, age, and platelet counts “were also very important features,” she continued, “and these have also been shown in a number of different studies to be important at determining the outcome from coronavirus.”

To examine the performance of the CORONET score further, they applied it to a European hospital dataset, ESMO-CoCARE registry data, and a U.S. cohort, the COVID-19 and Cancer Consortium Registry (CCC19). They found that the score discriminated between patients, but it did so with some degree of heterogeneity.

This was largely driven by higher patient age among the U.S. patients, a higher NEWS2 score, and lower albumin levels, Dr. Lee said.

To ensure the score’s applicability to clinical practice, the team set pragmatic thresholds to determine whether or not a patient required admission or whether they were at risk of dying.

For admission, they set a sensitivity of 85% and a specificity of 56%, while for mortality they set a sensitivity of 43% and a specificity of 92%.

When this was converted into a decision support tool, the model recommended hospital admission for 95% of patients who eventually required oxygen and 97% of patients who died.

The study was funded by The Christie Charitable Foundation. Dr. Lee declares relationships with AstraZeneca and Bristol-Myers Squibb (Inst). Dr. Wright declares relationships with NCCN/AstraZeneca (Inst).

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

An online support tool for health care professionals that recommends whether to admit or discharge a cancer patient with COVID-19, based on their risk of a severe complication, has been developed by researchers from Manchester.

The team used machine learning on data from more than 900 cancer patients with COVID-19, conducting multiple analyses to arrive at a set of features that could accurately predict the need for admission or oxygen therapy, as well as the risk of death.

Dr. Rebecca Lee, The Christie NHS Foundation Trust, Manchester, and colleagues then developed thresholds to derive a score that recommended admission in 95% of patients who went on to need oxygen and an even greater proportion of those who later died.

The research was presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting on June 4.
 

CORONET

The resulting COVID-19 Risk in Oncology Evaluation Tool (CORONET) model “performs very well at predicting admission and severity of COVID-19 in patients with cancer,” Dr. Lee said. “We have set pragmatic and clinically relevant thresholds that focus on the safety regarding an admission versus discharge decision.”

To help health care professionals, the researchers have built a free online support tool that allows them to enter data and receive a recommendation “as to whether their patient should be considered for discharge, considered for admission, or is at high risk of having a severe outcome of coronavirus,” Dr. Lee explained.

“The health care professional can then explore the recommendation by seeing how their patient … compares with the rest of the cohort.”

The tool also includes a “diagram showing which features are most important to recommend a discharge decision versus an admission decision for each individual patient.”
 

Clinically intuitive

Dr. Alexi Wright, associate professor, Dana-Faber Cancer Institute, Boston, who was not involved in the study, commented that there were many things that were “really nice about the study.”

“First and foremost that they were establishing a tool to efficiently triage [patients] presenting with COVID,” she said, adding that it was “clinically intuitive” that the team made “pragmatic choices,” and the use of a random forest algorithm means the results are “very interpretable.”

However, Dr. Wright wondered whether the results can be replicated.

Alongside a lack of information on the deaths in the cohort, she pointed out that “ideally you have three data sets, with a training set, a testing set, and a validation set.”

The CORONET model was, however, trained and evaluated on the same dataset, “so it really needs external validation before it would be ready for direct clinical application.”

She continued that there is a “critical need to establish that studies can both be reproduced and replicated,” noting that a recent review showed that 85% of machine-learning studies that were used to detect COVID-19 using chest radiographs “failed fundamental reproducibility and quality checks.” 

Risk factors

Dr. Lee began her presentation by reminding the audience that cancer patients are at increased risk of severe COVID-19 and death, with older age, male sex, nosocomial infection, higher ECOG performance status, and active cancer among the risk factors for mortality.

“However, outcomes are very heterogeneous, ranging from patients without symptoms at all to cases with multi-organ failure and death,” she said.

It is consequently “very important for the treating clinician to determine which patients could be safely discharged to the community versus those who need additional support in being admitted to hospital.”

To develop a tool that could distinguish between those two groups of patients, the researchers collected data on 1,743 cancer patients, which was reduced down to 920 patients after excluding those without laboratory confirmed COVID-19 and those with missing data.

Using recursive feature elimination, they selected 10 key patient features associated with prognosis, then compared a lasso regression model with a random forest model, with the latter performing the best.

The team then divided their patients into four cohorts, with the model trained on three cohorts and tested on the fourth. This resulted in the CORONET score, with the final model determined by testing it against the entire patient population.

Next, thresholds were determined for assessing patients for admission versus discharge, as well as for severity of illness, giving the final CORONET model, from which the online tool was developed.
 

Checking performance

The results showed that the model was able to predict admission with an area under the receiver operating characteristics curve (AUROC) of 0.82 for admission, 0.85 for oxygen requirement, and 0.79 for death.

Further analysis revealed that the most important feature at the time of presentation for determining outcome was the National Early Warning Score 2 (NEWS2), “which is a composite score of heart rate, respiratory rate, saturations and confusion level,” Dr. Lee said.

In addition, C-reactive protein levels, albumin, age, and platelet counts “were also very important features,” she continued, “and these have also been shown in a number of different studies to be important at determining the outcome from coronavirus.”

To examine the performance of the CORONET score further, they applied it to a European hospital dataset, ESMO-CoCARE registry data, and a U.S. cohort, the COVID-19 and Cancer Consortium Registry (CCC19). They found that the score discriminated between patients, but it did so with some degree of heterogeneity.

This was largely driven by higher patient age among the U.S. patients, a higher NEWS2 score, and lower albumin levels, Dr. Lee said.

To ensure the score’s applicability to clinical practice, the team set pragmatic thresholds to determine whether or not a patient required admission or whether they were at risk of dying.

For admission, they set a sensitivity of 85% and a specificity of 56%, while for mortality they set a sensitivity of 43% and a specificity of 92%.

When this was converted into a decision support tool, the model recommended hospital admission for 95% of patients who eventually required oxygen and 97% of patients who died.

The study was funded by The Christie Charitable Foundation. Dr. Lee declares relationships with AstraZeneca and Bristol-Myers Squibb (Inst). Dr. Wright declares relationships with NCCN/AstraZeneca (Inst).

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

An online support tool for health care professionals that recommends whether to admit or discharge a cancer patient with COVID-19, based on their risk of a severe complication, has been developed by researchers from Manchester.

The team used machine learning on data from more than 900 cancer patients with COVID-19, conducting multiple analyses to arrive at a set of features that could accurately predict the need for admission or oxygen therapy, as well as the risk of death.

Dr. Rebecca Lee, The Christie NHS Foundation Trust, Manchester, and colleagues then developed thresholds to derive a score that recommended admission in 95% of patients who went on to need oxygen and an even greater proportion of those who later died.

The research was presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting on June 4.
 

CORONET

The resulting COVID-19 Risk in Oncology Evaluation Tool (CORONET) model “performs very well at predicting admission and severity of COVID-19 in patients with cancer,” Dr. Lee said. “We have set pragmatic and clinically relevant thresholds that focus on the safety regarding an admission versus discharge decision.”

To help health care professionals, the researchers have built a free online support tool that allows them to enter data and receive a recommendation “as to whether their patient should be considered for discharge, considered for admission, or is at high risk of having a severe outcome of coronavirus,” Dr. Lee explained.

“The health care professional can then explore the recommendation by seeing how their patient … compares with the rest of the cohort.”

The tool also includes a “diagram showing which features are most important to recommend a discharge decision versus an admission decision for each individual patient.”
 

Clinically intuitive

Dr. Alexi Wright, associate professor, Dana-Faber Cancer Institute, Boston, who was not involved in the study, commented that there were many things that were “really nice about the study.”

“First and foremost that they were establishing a tool to efficiently triage [patients] presenting with COVID,” she said, adding that it was “clinically intuitive” that the team made “pragmatic choices,” and the use of a random forest algorithm means the results are “very interpretable.”

However, Dr. Wright wondered whether the results can be replicated.

Alongside a lack of information on the deaths in the cohort, she pointed out that “ideally you have three data sets, with a training set, a testing set, and a validation set.”

The CORONET model was, however, trained and evaluated on the same dataset, “so it really needs external validation before it would be ready for direct clinical application.”

She continued that there is a “critical need to establish that studies can both be reproduced and replicated,” noting that a recent review showed that 85% of machine-learning studies that were used to detect COVID-19 using chest radiographs “failed fundamental reproducibility and quality checks.” 

Risk factors

Dr. Lee began her presentation by reminding the audience that cancer patients are at increased risk of severe COVID-19 and death, with older age, male sex, nosocomial infection, higher ECOG performance status, and active cancer among the risk factors for mortality.

“However, outcomes are very heterogeneous, ranging from patients without symptoms at all to cases with multi-organ failure and death,” she said.

It is consequently “very important for the treating clinician to determine which patients could be safely discharged to the community versus those who need additional support in being admitted to hospital.”

To develop a tool that could distinguish between those two groups of patients, the researchers collected data on 1,743 cancer patients, which was reduced down to 920 patients after excluding those without laboratory confirmed COVID-19 and those with missing data.

Using recursive feature elimination, they selected 10 key patient features associated with prognosis, then compared a lasso regression model with a random forest model, with the latter performing the best.

The team then divided their patients into four cohorts, with the model trained on three cohorts and tested on the fourth. This resulted in the CORONET score, with the final model determined by testing it against the entire patient population.

Next, thresholds were determined for assessing patients for admission versus discharge, as well as for severity of illness, giving the final CORONET model, from which the online tool was developed.
 

Checking performance

The results showed that the model was able to predict admission with an area under the receiver operating characteristics curve (AUROC) of 0.82 for admission, 0.85 for oxygen requirement, and 0.79 for death.

Further analysis revealed that the most important feature at the time of presentation for determining outcome was the National Early Warning Score 2 (NEWS2), “which is a composite score of heart rate, respiratory rate, saturations and confusion level,” Dr. Lee said.

In addition, C-reactive protein levels, albumin, age, and platelet counts “were also very important features,” she continued, “and these have also been shown in a number of different studies to be important at determining the outcome from coronavirus.”

To examine the performance of the CORONET score further, they applied it to a European hospital dataset, ESMO-CoCARE registry data, and a U.S. cohort, the COVID-19 and Cancer Consortium Registry (CCC19). They found that the score discriminated between patients, but it did so with some degree of heterogeneity.

This was largely driven by higher patient age among the U.S. patients, a higher NEWS2 score, and lower albumin levels, Dr. Lee said.

To ensure the score’s applicability to clinical practice, the team set pragmatic thresholds to determine whether or not a patient required admission or whether they were at risk of dying.

For admission, they set a sensitivity of 85% and a specificity of 56%, while for mortality they set a sensitivity of 43% and a specificity of 92%.

When this was converted into a decision support tool, the model recommended hospital admission for 95% of patients who eventually required oxygen and 97% of patients who died.

The study was funded by The Christie Charitable Foundation. Dr. Lee declares relationships with AstraZeneca and Bristol-Myers Squibb (Inst). Dr. Wright declares relationships with NCCN/AstraZeneca (Inst).

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

For patients with HER2-negative metastatic breast cancer, first line chemotherapy with cabazitaxel (Jevtana) every 3 weeks offers efficacy comparable to that of once-weekly paclitaxel, but with lower risk for peripheral neuropathy and better patient-reported quality of life, investigators in the multicenter CONCERT trial found.

In an open-label clinical trial of 158 patients from 14 hospitals in the United Kingdom, there was no difference in the primary endpoint of progression-free survival (PFS) or a secondary overall survival endpoint between patients randomly assigned to initial chemotherapy with cabazitaxel every 3 weeks or weekly paclitaxel, reported Amit Bahl, MD, of University Hospital Bristol, England, and colleagues.

“Cabazitaxel is safe and well tolerated for metastatic breast cancer and requires fewer hospital visits than weekly paclitaxel, which is very important for patients and health care providers, but more so in the current situation,” he said in an oral abstract session at the American Society of Clinical Oncology annual meeting (Abstract 1008).

Cabazitaxel is currently approved in the United States and Europe in combination with prednisone for treatment of patients with metastatic castration-resistant prostate cancer previously treated with a docetaxel-containing treatment regimen. It is not currently approved for the treatment of metastatic breast cancer, but has been explored for this indication in clinical trials.

“In the metastatic setting, where patients continue on treatment pretty much indefinitely until disease progression or unacceptable toxicity, the use of an every-3-week regimen could be attractive, because it means less visits for the patients, and it appears that this drug has lower toxicity in terms of peripheral neuropathy,” said breast cancer specialist Aditya Bardia, MD, MPH, who was not involved in the study.

Dr. Bardia, of Mass General Cancer Center in Boston, commented on the study in an interview.

Although paclitaxel is commonly used as first-line chemotherapy for HER2-negative metastatic breast cancer, it is associated with only modest response rates, ranging from 21.5% to 53.7% and carries significant risk of peripheral neuropathy, Dr. Bahl and colleagues noted.

“There is an unmet need for an alternative first-line cytotoxic chemotherapy agent, and cabazitaxel is a taxoid agent which has showed promising results in phase 2 trial of metastatic breast cancer patients in the second-line setting, even those with taxane resistance,” he said.
 

Open-label trial

To see whether cabazitaxel could meet those requirements, the investigators conducted a phase 2 randomized trial in which patients with HER2-negative metastatic breast cancer not previously treated with cytotoxic chemotherapy were assigned, 79 in each arm, to receive cabazitaxel 25 mg/m² every 3 weeks, or paclitaxel 80 mg/m² weekly.

The median patient age was 56 years in the cabazitaxel group and 61 years in the paclitaxel group. Roughly two-thirds of patients in each arm had Eastern Cooperative Oncology Group performance status 0, and the remainder had ECOG performance status 1.

In each arm, the median time on treatment was 15 weeks, but treatment delays and dose reductions were more common among patients on paclitaxel than cabazitaxel (61% vs. 39%, and 37% vs. 24%, respectively).

There were 149 PFS events at the time of the analysis. The median PFS with cabazitaxel was 6.7 months vs. 5.8 months with paclitaxel. This difference was not statistically significant. Median overall survival was 20.6 months in the cabazitaxel arm, vs. 18.2 months 20.0 months, respectively.

Similarly, there were no significant differences in either the overall response rates (42% vs. 37%), or time to response.

There were no complete responses with cabazitaxel vs. two (2.5%) with paclitaxel. The respective partial response rates were 41.8% vs. 34.2%.

In a subgroup analysis of PFS, there were no significant between-arm differences, except for an improved PFS in patients 65 and older with cabazitaxel (hazard ratio 0.45, 95% confidence interval, 0.25-0.80).
 

Quality of life favors cabazitaxel

Grade 3 or greater adverse events occurred in 42% of patients on cabazitaxel vs. 51% on paclitaxel. Diarrhea, febrile neutropenia, and nausea were the most common grade 3 or greater events in the cabazitaxel arm, whereas grade 3 or greater lung infection and peripheral neuropathy were more common with paclitaxel.

Sensory peripheral neuropathy of any grade occurred in 16% of patients assigned to cabazitaxel, compared with 54% assigned to paclitaxel. The respective rates of alopecia were 27% and 42%.

Over the course of treatment, the mean EuroQuol EQ-5D-5L single index utility score and visual analogue scale score were higher with cabazitaxel arm compared to paclitaxel, suggesting better patient quality of life with cabazitaxel.

In addition, throughout treatment patients in the cabazitaxel arm reported significantly better scores on The Functional Assessment of Cancer Therapy – Breast (FACT-B) breast cancer subscale, Dr. Bahl said.
 

Second-line may be better

ASCO invited discussant Marleen Kok, MD, PhD, from the Netherlands Cancer Institute in Amsterdam, pointed out that in the phase 2 GENEVIEVE trial comparing the efficacy and safety of cabazitaxel versus weekly paclitaxel as neoadjuvant treatment in patients with triple negative or luminal B/HER2 normal breast cancer the pathologic complete response rate with cabazitaxel was 1.2%, compared with 11% with paclitaxel.

“This GENEVIEVE trial, together with the CONCERT trial, suggests that there is not a big role for cabazitaxel to be used upfront before other taxanes,” she said.

However, in a phase 2 study of cabazitaxel as second-line therapy in patients with HER2-negative metastatic breast cancer who had previously been treated with taxanes, the overall response rate was 23%, “which is still of interest and importance for our patients,” she added.

Dr. Kok did not address quality of life differences between the regimens, however.

In a side note, Dr. Bardia said that “if there were an oral form of paclitaxel, that would certainly be very welcome, in that an oral drug is more convenient for patients, and would require fewer visits to the hospital.”

The CONCERT trial was funded by an investigator-sponsored study grant from Sanofi. Dr. Bahl disclosed honoraria and institutional research funding from Sanofi/Aventis and others, and travel expenses from Bayer and Roche. Dr. Kok disclosed a consulting or advisory role for Bristol Myers Squibb/Medarex, and institutional research funding from that company and others. Dr. Bardia disclosed a consulting or advisory role and research funding to his institution from multiple companies.

For patients with HER2-negative metastatic breast cancer, first line chemotherapy with cabazitaxel (Jevtana) every 3 weeks offers efficacy comparable to that of once-weekly paclitaxel, but with lower risk for peripheral neuropathy and better patient-reported quality of life, investigators in the multicenter CONCERT trial found.

In an open-label clinical trial of 158 patients from 14 hospitals in the United Kingdom, there was no difference in the primary endpoint of progression-free survival (PFS) or a secondary overall survival endpoint between patients randomly assigned to initial chemotherapy with cabazitaxel every 3 weeks or weekly paclitaxel, reported Amit Bahl, MD, of University Hospital Bristol, England, and colleagues.

“Cabazitaxel is safe and well tolerated for metastatic breast cancer and requires fewer hospital visits than weekly paclitaxel, which is very important for patients and health care providers, but more so in the current situation,” he said in an oral abstract session at the American Society of Clinical Oncology annual meeting (Abstract 1008).

Cabazitaxel is currently approved in the United States and Europe in combination with prednisone for treatment of patients with metastatic castration-resistant prostate cancer previously treated with a docetaxel-containing treatment regimen. It is not currently approved for the treatment of metastatic breast cancer, but has been explored for this indication in clinical trials.

“In the metastatic setting, where patients continue on treatment pretty much indefinitely until disease progression or unacceptable toxicity, the use of an every-3-week regimen could be attractive, because it means less visits for the patients, and it appears that this drug has lower toxicity in terms of peripheral neuropathy,” said breast cancer specialist Aditya Bardia, MD, MPH, who was not involved in the study.

Dr. Bardia, of Mass General Cancer Center in Boston, commented on the study in an interview.

Although paclitaxel is commonly used as first-line chemotherapy for HER2-negative metastatic breast cancer, it is associated with only modest response rates, ranging from 21.5% to 53.7% and carries significant risk of peripheral neuropathy, Dr. Bahl and colleagues noted.

“There is an unmet need for an alternative first-line cytotoxic chemotherapy agent, and cabazitaxel is a taxoid agent which has showed promising results in phase 2 trial of metastatic breast cancer patients in the second-line setting, even those with taxane resistance,” he said.
 

Open-label trial

To see whether cabazitaxel could meet those requirements, the investigators conducted a phase 2 randomized trial in which patients with HER2-negative metastatic breast cancer not previously treated with cytotoxic chemotherapy were assigned, 79 in each arm, to receive cabazitaxel 25 mg/m² every 3 weeks, or paclitaxel 80 mg/m² weekly.

The median patient age was 56 years in the cabazitaxel group and 61 years in the paclitaxel group. Roughly two-thirds of patients in each arm had Eastern Cooperative Oncology Group performance status 0, and the remainder had ECOG performance status 1.

In each arm, the median time on treatment was 15 weeks, but treatment delays and dose reductions were more common among patients on paclitaxel than cabazitaxel (61% vs. 39%, and 37% vs. 24%, respectively).

There were 149 PFS events at the time of the analysis. The median PFS with cabazitaxel was 6.7 months vs. 5.8 months with paclitaxel. This difference was not statistically significant. Median overall survival was 20.6 months in the cabazitaxel arm, vs. 18.2 months 20.0 months, respectively.

Similarly, there were no significant differences in either the overall response rates (42% vs. 37%), or time to response.

There were no complete responses with cabazitaxel vs. two (2.5%) with paclitaxel. The respective partial response rates were 41.8% vs. 34.2%.

In a subgroup analysis of PFS, there were no significant between-arm differences, except for an improved PFS in patients 65 and older with cabazitaxel (hazard ratio 0.45, 95% confidence interval, 0.25-0.80).
 

Quality of life favors cabazitaxel

Grade 3 or greater adverse events occurred in 42% of patients on cabazitaxel vs. 51% on paclitaxel. Diarrhea, febrile neutropenia, and nausea were the most common grade 3 or greater events in the cabazitaxel arm, whereas grade 3 or greater lung infection and peripheral neuropathy were more common with paclitaxel.

Sensory peripheral neuropathy of any grade occurred in 16% of patients assigned to cabazitaxel, compared with 54% assigned to paclitaxel. The respective rates of alopecia were 27% and 42%.

Over the course of treatment, the mean EuroQuol EQ-5D-5L single index utility score and visual analogue scale score were higher with cabazitaxel arm compared to paclitaxel, suggesting better patient quality of life with cabazitaxel.

In addition, throughout treatment patients in the cabazitaxel arm reported significantly better scores on The Functional Assessment of Cancer Therapy – Breast (FACT-B) breast cancer subscale, Dr. Bahl said.
 

Second-line may be better

ASCO invited discussant Marleen Kok, MD, PhD, from the Netherlands Cancer Institute in Amsterdam, pointed out that in the phase 2 GENEVIEVE trial comparing the efficacy and safety of cabazitaxel versus weekly paclitaxel as neoadjuvant treatment in patients with triple negative or luminal B/HER2 normal breast cancer the pathologic complete response rate with cabazitaxel was 1.2%, compared with 11% with paclitaxel.

“This GENEVIEVE trial, together with the CONCERT trial, suggests that there is not a big role for cabazitaxel to be used upfront before other taxanes,” she said.

However, in a phase 2 study of cabazitaxel as second-line therapy in patients with HER2-negative metastatic breast cancer who had previously been treated with taxanes, the overall response rate was 23%, “which is still of interest and importance for our patients,” she added.

Dr. Kok did not address quality of life differences between the regimens, however.

In a side note, Dr. Bardia said that “if there were an oral form of paclitaxel, that would certainly be very welcome, in that an oral drug is more convenient for patients, and would require fewer visits to the hospital.”

The CONCERT trial was funded by an investigator-sponsored study grant from Sanofi. Dr. Bahl disclosed honoraria and institutional research funding from Sanofi/Aventis and others, and travel expenses from Bayer and Roche. Dr. Kok disclosed a consulting or advisory role for Bristol Myers Squibb/Medarex, and institutional research funding from that company and others. Dr. Bardia disclosed a consulting or advisory role and research funding to his institution from multiple companies.

For patients with HER2-negative metastatic breast cancer, first line chemotherapy with cabazitaxel (Jevtana) every 3 weeks offers efficacy comparable to that of once-weekly paclitaxel, but with lower risk for peripheral neuropathy and better patient-reported quality of life, investigators in the multicenter CONCERT trial found.

In an open-label clinical trial of 158 patients from 14 hospitals in the United Kingdom, there was no difference in the primary endpoint of progression-free survival (PFS) or a secondary overall survival endpoint between patients randomly assigned to initial chemotherapy with cabazitaxel every 3 weeks or weekly paclitaxel, reported Amit Bahl, MD, of University Hospital Bristol, England, and colleagues.

“Cabazitaxel is safe and well tolerated for metastatic breast cancer and requires fewer hospital visits than weekly paclitaxel, which is very important for patients and health care providers, but more so in the current situation,” he said in an oral abstract session at the American Society of Clinical Oncology annual meeting (Abstract 1008).

Cabazitaxel is currently approved in the United States and Europe in combination with prednisone for treatment of patients with metastatic castration-resistant prostate cancer previously treated with a docetaxel-containing treatment regimen. It is not currently approved for the treatment of metastatic breast cancer, but has been explored for this indication in clinical trials.

“In the metastatic setting, where patients continue on treatment pretty much indefinitely until disease progression or unacceptable toxicity, the use of an every-3-week regimen could be attractive, because it means less visits for the patients, and it appears that this drug has lower toxicity in terms of peripheral neuropathy,” said breast cancer specialist Aditya Bardia, MD, MPH, who was not involved in the study.

Dr. Bardia, of Mass General Cancer Center in Boston, commented on the study in an interview.

Although paclitaxel is commonly used as first-line chemotherapy for HER2-negative metastatic breast cancer, it is associated with only modest response rates, ranging from 21.5% to 53.7% and carries significant risk of peripheral neuropathy, Dr. Bahl and colleagues noted.

“There is an unmet need for an alternative first-line cytotoxic chemotherapy agent, and cabazitaxel is a taxoid agent which has showed promising results in phase 2 trial of metastatic breast cancer patients in the second-line setting, even those with taxane resistance,” he said.
 

Open-label trial

To see whether cabazitaxel could meet those requirements, the investigators conducted a phase 2 randomized trial in which patients with HER2-negative metastatic breast cancer not previously treated with cytotoxic chemotherapy were assigned, 79 in each arm, to receive cabazitaxel 25 mg/m² every 3 weeks, or paclitaxel 80 mg/m² weekly.

The median patient age was 56 years in the cabazitaxel group and 61 years in the paclitaxel group. Roughly two-thirds of patients in each arm had Eastern Cooperative Oncology Group performance status 0, and the remainder had ECOG performance status 1.

In each arm, the median time on treatment was 15 weeks, but treatment delays and dose reductions were more common among patients on paclitaxel than cabazitaxel (61% vs. 39%, and 37% vs. 24%, respectively).

There were 149 PFS events at the time of the analysis. The median PFS with cabazitaxel was 6.7 months vs. 5.8 months with paclitaxel. This difference was not statistically significant. Median overall survival was 20.6 months in the cabazitaxel arm, vs. 18.2 months 20.0 months, respectively.

Similarly, there were no significant differences in either the overall response rates (42% vs. 37%), or time to response.

There were no complete responses with cabazitaxel vs. two (2.5%) with paclitaxel. The respective partial response rates were 41.8% vs. 34.2%.

In a subgroup analysis of PFS, there were no significant between-arm differences, except for an improved PFS in patients 65 and older with cabazitaxel (hazard ratio 0.45, 95% confidence interval, 0.25-0.80).
 

Quality of life favors cabazitaxel

Grade 3 or greater adverse events occurred in 42% of patients on cabazitaxel vs. 51% on paclitaxel. Diarrhea, febrile neutropenia, and nausea were the most common grade 3 or greater events in the cabazitaxel arm, whereas grade 3 or greater lung infection and peripheral neuropathy were more common with paclitaxel.

Sensory peripheral neuropathy of any grade occurred in 16% of patients assigned to cabazitaxel, compared with 54% assigned to paclitaxel. The respective rates of alopecia were 27% and 42%.

Over the course of treatment, the mean EuroQuol EQ-5D-5L single index utility score and visual analogue scale score were higher with cabazitaxel arm compared to paclitaxel, suggesting better patient quality of life with cabazitaxel.

In addition, throughout treatment patients in the cabazitaxel arm reported significantly better scores on The Functional Assessment of Cancer Therapy – Breast (FACT-B) breast cancer subscale, Dr. Bahl said.
 

Second-line may be better

ASCO invited discussant Marleen Kok, MD, PhD, from the Netherlands Cancer Institute in Amsterdam, pointed out that in the phase 2 GENEVIEVE trial comparing the efficacy and safety of cabazitaxel versus weekly paclitaxel as neoadjuvant treatment in patients with triple negative or luminal B/HER2 normal breast cancer the pathologic complete response rate with cabazitaxel was 1.2%, compared with 11% with paclitaxel.

“This GENEVIEVE trial, together with the CONCERT trial, suggests that there is not a big role for cabazitaxel to be used upfront before other taxanes,” she said.

However, in a phase 2 study of cabazitaxel as second-line therapy in patients with HER2-negative metastatic breast cancer who had previously been treated with taxanes, the overall response rate was 23%, “which is still of interest and importance for our patients,” she added.

Dr. Kok did not address quality of life differences between the regimens, however.

In a side note, Dr. Bardia said that “if there were an oral form of paclitaxel, that would certainly be very welcome, in that an oral drug is more convenient for patients, and would require fewer visits to the hospital.”

The CONCERT trial was funded by an investigator-sponsored study grant from Sanofi. Dr. Bahl disclosed honoraria and institutional research funding from Sanofi/Aventis and others, and travel expenses from Bayer and Roche. Dr. Kok disclosed a consulting or advisory role for Bristol Myers Squibb/Medarex, and institutional research funding from that company and others. Dr. Bardia disclosed a consulting or advisory role and research funding to his institution from multiple companies.

A novel 16-gene panel based on the biology of locoregional recurrence in early invasive breast cancer can both identify patients with a low risk of recurrence if they were to skip postsurgery radiation therapy, and predict which patients would be unlikely to benefit from adjuvant radiation, investigators reported.

Among 354 patients with stage I or II invasive estrogen receptor–positive (ER+), HER2-negative breast cancers who did not receive adjuvant systemic therapy, the genomic signature, dubbed POLAR (Profile for the Omission of Local Adjuvant Radiation) was prognostic for locoregional recurrence in patients who did not undergo radiation therapy, reported Martin Sjöström, MD, PhD, of the University of California, San Francisco, and colleagues.

They reported their findings in a poster presented during the American Society of Clinical Oncology (ASCO) annual meeting (Abstract 512).

“This is to our knowledge the first radiation-omission signature that is both prognostic and predictive: prognostic for outcomes in the absence of radiation, and predictive of benefits,” coauthor Corey Speers MD, PhD, of the University of Michigan, Ann Arbor, said in an interview.

The investigators conducted a retrospective analysis of data on patients enrolled in the SweBCG 91 RT trial, in which 1,187 patients with T1-2N0M0 breast cancer underwent a standardized radical sector resection and were then randomly assigned to either postoperative radiotherapy or no further treatment.

As the investigators reported in a long-term follow-up study presented in 2010 at the San Antonio Breast Cancer Symposium, the addition of postoperative radiation did not significantly affect overall survival, but was associated with a significant improvement in recurrence-free survival.

In the study presented at ASCO 2021, Dr. Sjöström and colleagues in Sweden, the United States, and Canada sought to determine whether they could identify a genomic signature that would identify women at very low risk for recurrence who could safely be spared from radiotherapy.

They focused on those patients in the study with ER+, HER2-negative tumors who did not receive adjuvant systemic therapy. The patients were divided into a training cohort of 243, and a validation cohort of 354 patients.

The investigators performed transcriptome-wide profiling of tumors, and identified both biological gene sets and individuals genes associated with locoregional recurrence among patients in the training set who did not receive radiotherapy.

The final POLAR genomic signature, containing 16 genes, was locked prior to testing in the validation cohort.

In a multivariable Cox model adjusting for age, grade, tumor size and luminal A vs. luminal B subtype, the POLAR gene set was prognostic for locoregional recurrence, with a hazard ratio (HR) of 1.7 (P < .001).

The 10-year locoregional recurrence rate for patients in the POLAR low-risk category who had not received radiation was 7%, and there was no significant benefit for POLAR low-risk patients who did receive radiation (HR 1.1, P = ns).

In contrast, patients classified as POLAR high risk who received radiotherapy had significantly lower risk for locoregional recurrence than high-risk patients who did not receive radiotherapy (HR 0.43, P = .0053).

Dr. Speers said that the POLAR signature appears to be unique in its ability to discriminate radiation-omission risk.

“At least looking in this cohort in the Swedish trial, none of other previously derived signatures – Mammaprint, ProSigna, Oncotype – were prognostic or predictive of locoregional recurrence events with radiation,” he said.

The investigators are currently exploring the POLAR signature in other clinical trials in which patients were randomized to receive radiation or no radiation.
 

­‘A true victory’

Invited discussant Benjamin D. Smith, MD, of the University of Texas MD Anderson Cancer Center in Houston, pointed out that in randomized clinical trials, approximately 60% of patients treated for early breast cancer did not experience recurrence in the absence of radiation, and that radiation prevented recurrence in about 30%, while about 10% experienced recurrence despite receiving radiation.

He said that the study by Dr. Sjöström and colleagues asks the question “can we use molecular factors to help identify patients who will not recur with lumpectomy alone without radiation therapy?”

The 60% of patients who will not experience recurrence in the absence of radiation can be categorized into two subpopulations: those with no residual malignant clonogens – the population included in this study by Dr. Sjöström and colleagues – and those with residual clonogens in the breast or elsewhere in the body that are sensitive to adjuvant endocrine therapy.

He said that the 7% 10-year risk of recurrence among patients in the POLAR low-risk group, who had neither radiation nor endocrine therapy, “is an exceptional outcome, which should be applauded, and I would point out that this risk of local recurrence of only 7% is at least in the same ballpark as the risk of recurrence that we accept every day when we treat early stage breast cancer patients with mastectomy alone, so this is a true victory.

“When we reflect on these provocative results from Dr. Sjöström and colleagues, it prompts in mind the question, could there be a group of patients with early breast cancer for whom a true ‘one-and-done’ strategy could be effective and safe?” Dr. Smith said.

Getting there will require a multidisciplinary, multimodality approach, involving imaging features of the primary tumor, clinical and pathologic features, and molecular information such as that provided by the POLAR genomic signature, he said.

The study was supported by PFS Genomics. Dr. Sjöström reported institutional funding from PFS Genomics. Dr. Speers disclosed stock and other ownership interests in the company, and he has applied for a patent on methods and genomic classifiers for prognosis of breast cancer and predicting benefit from adjuvant radiotherapy. Dr. Smith reported an equity interest in Oncora Medical, and an uncompensated relationship with the American Society for Radiation Oncology.

A novel 16-gene panel based on the biology of locoregional recurrence in early invasive breast cancer can both identify patients with a low risk of recurrence if they were to skip postsurgery radiation therapy, and predict which patients would be unlikely to benefit from adjuvant radiation, investigators reported.

Among 354 patients with stage I or II invasive estrogen receptor–positive (ER+), HER2-negative breast cancers who did not receive adjuvant systemic therapy, the genomic signature, dubbed POLAR (Profile for the Omission of Local Adjuvant Radiation) was prognostic for locoregional recurrence in patients who did not undergo radiation therapy, reported Martin Sjöström, MD, PhD, of the University of California, San Francisco, and colleagues.

They reported their findings in a poster presented during the American Society of Clinical Oncology (ASCO) annual meeting (Abstract 512).

“This is to our knowledge the first radiation-omission signature that is both prognostic and predictive: prognostic for outcomes in the absence of radiation, and predictive of benefits,” coauthor Corey Speers MD, PhD, of the University of Michigan, Ann Arbor, said in an interview.

The investigators conducted a retrospective analysis of data on patients enrolled in the SweBCG 91 RT trial, in which 1,187 patients with T1-2N0M0 breast cancer underwent a standardized radical sector resection and were then randomly assigned to either postoperative radiotherapy or no further treatment.

As the investigators reported in a long-term follow-up study presented in 2010 at the San Antonio Breast Cancer Symposium, the addition of postoperative radiation did not significantly affect overall survival, but was associated with a significant improvement in recurrence-free survival.

In the study presented at ASCO 2021, Dr. Sjöström and colleagues in Sweden, the United States, and Canada sought to determine whether they could identify a genomic signature that would identify women at very low risk for recurrence who could safely be spared from radiotherapy.

They focused on those patients in the study with ER+, HER2-negative tumors who did not receive adjuvant systemic therapy. The patients were divided into a training cohort of 243, and a validation cohort of 354 patients.

The investigators performed transcriptome-wide profiling of tumors, and identified both biological gene sets and individuals genes associated with locoregional recurrence among patients in the training set who did not receive radiotherapy.

The final POLAR genomic signature, containing 16 genes, was locked prior to testing in the validation cohort.

In a multivariable Cox model adjusting for age, grade, tumor size and luminal A vs. luminal B subtype, the POLAR gene set was prognostic for locoregional recurrence, with a hazard ratio (HR) of 1.7 (P < .001).

The 10-year locoregional recurrence rate for patients in the POLAR low-risk category who had not received radiation was 7%, and there was no significant benefit for POLAR low-risk patients who did receive radiation (HR 1.1, P = ns).

In contrast, patients classified as POLAR high risk who received radiotherapy had significantly lower risk for locoregional recurrence than high-risk patients who did not receive radiotherapy (HR 0.43, P = .0053).

Dr. Speers said that the POLAR signature appears to be unique in its ability to discriminate radiation-omission risk.

“At least looking in this cohort in the Swedish trial, none of other previously derived signatures – Mammaprint, ProSigna, Oncotype – were prognostic or predictive of locoregional recurrence events with radiation,” he said.

The investigators are currently exploring the POLAR signature in other clinical trials in which patients were randomized to receive radiation or no radiation.
 

­‘A true victory’

Invited discussant Benjamin D. Smith, MD, of the University of Texas MD Anderson Cancer Center in Houston, pointed out that in randomized clinical trials, approximately 60% of patients treated for early breast cancer did not experience recurrence in the absence of radiation, and that radiation prevented recurrence in about 30%, while about 10% experienced recurrence despite receiving radiation.

He said that the study by Dr. Sjöström and colleagues asks the question “can we use molecular factors to help identify patients who will not recur with lumpectomy alone without radiation therapy?”

The 60% of patients who will not experience recurrence in the absence of radiation can be categorized into two subpopulations: those with no residual malignant clonogens – the population included in this study by Dr. Sjöström and colleagues – and those with residual clonogens in the breast or elsewhere in the body that are sensitive to adjuvant endocrine therapy.

He said that the 7% 10-year risk of recurrence among patients in the POLAR low-risk group, who had neither radiation nor endocrine therapy, “is an exceptional outcome, which should be applauded, and I would point out that this risk of local recurrence of only 7% is at least in the same ballpark as the risk of recurrence that we accept every day when we treat early stage breast cancer patients with mastectomy alone, so this is a true victory.

“When we reflect on these provocative results from Dr. Sjöström and colleagues, it prompts in mind the question, could there be a group of patients with early breast cancer for whom a true ‘one-and-done’ strategy could be effective and safe?” Dr. Smith said.

Getting there will require a multidisciplinary, multimodality approach, involving imaging features of the primary tumor, clinical and pathologic features, and molecular information such as that provided by the POLAR genomic signature, he said.

The study was supported by PFS Genomics. Dr. Sjöström reported institutional funding from PFS Genomics. Dr. Speers disclosed stock and other ownership interests in the company, and he has applied for a patent on methods and genomic classifiers for prognosis of breast cancer and predicting benefit from adjuvant radiotherapy. Dr. Smith reported an equity interest in Oncora Medical, and an uncompensated relationship with the American Society for Radiation Oncology.

A novel 16-gene panel based on the biology of locoregional recurrence in early invasive breast cancer can both identify patients with a low risk of recurrence if they were to skip postsurgery radiation therapy, and predict which patients would be unlikely to benefit from adjuvant radiation, investigators reported.

Among 354 patients with stage I or II invasive estrogen receptor–positive (ER+), HER2-negative breast cancers who did not receive adjuvant systemic therapy, the genomic signature, dubbed POLAR (Profile for the Omission of Local Adjuvant Radiation) was prognostic for locoregional recurrence in patients who did not undergo radiation therapy, reported Martin Sjöström, MD, PhD, of the University of California, San Francisco, and colleagues.

They reported their findings in a poster presented during the American Society of Clinical Oncology (ASCO) annual meeting (Abstract 512).

“This is to our knowledge the first radiation-omission signature that is both prognostic and predictive: prognostic for outcomes in the absence of radiation, and predictive of benefits,” coauthor Corey Speers MD, PhD, of the University of Michigan, Ann Arbor, said in an interview.

The investigators conducted a retrospective analysis of data on patients enrolled in the SweBCG 91 RT trial, in which 1,187 patients with T1-2N0M0 breast cancer underwent a standardized radical sector resection and were then randomly assigned to either postoperative radiotherapy or no further treatment.

As the investigators reported in a long-term follow-up study presented in 2010 at the San Antonio Breast Cancer Symposium, the addition of postoperative radiation did not significantly affect overall survival, but was associated with a significant improvement in recurrence-free survival.

In the study presented at ASCO 2021, Dr. Sjöström and colleagues in Sweden, the United States, and Canada sought to determine whether they could identify a genomic signature that would identify women at very low risk for recurrence who could safely be spared from radiotherapy.

They focused on those patients in the study with ER+, HER2-negative tumors who did not receive adjuvant systemic therapy. The patients were divided into a training cohort of 243, and a validation cohort of 354 patients.

The investigators performed transcriptome-wide profiling of tumors, and identified both biological gene sets and individuals genes associated with locoregional recurrence among patients in the training set who did not receive radiotherapy.

The final POLAR genomic signature, containing 16 genes, was locked prior to testing in the validation cohort.

In a multivariable Cox model adjusting for age, grade, tumor size and luminal A vs. luminal B subtype, the POLAR gene set was prognostic for locoregional recurrence, with a hazard ratio (HR) of 1.7 (P < .001).

The 10-year locoregional recurrence rate for patients in the POLAR low-risk category who had not received radiation was 7%, and there was no significant benefit for POLAR low-risk patients who did receive radiation (HR 1.1, P = ns).

In contrast, patients classified as POLAR high risk who received radiotherapy had significantly lower risk for locoregional recurrence than high-risk patients who did not receive radiotherapy (HR 0.43, P = .0053).

Dr. Speers said that the POLAR signature appears to be unique in its ability to discriminate radiation-omission risk.

“At least looking in this cohort in the Swedish trial, none of other previously derived signatures – Mammaprint, ProSigna, Oncotype – were prognostic or predictive of locoregional recurrence events with radiation,” he said.

The investigators are currently exploring the POLAR signature in other clinical trials in which patients were randomized to receive radiation or no radiation.
 

­‘A true victory’

Invited discussant Benjamin D. Smith, MD, of the University of Texas MD Anderson Cancer Center in Houston, pointed out that in randomized clinical trials, approximately 60% of patients treated for early breast cancer did not experience recurrence in the absence of radiation, and that radiation prevented recurrence in about 30%, while about 10% experienced recurrence despite receiving radiation.

He said that the study by Dr. Sjöström and colleagues asks the question “can we use molecular factors to help identify patients who will not recur with lumpectomy alone without radiation therapy?”

The 60% of patients who will not experience recurrence in the absence of radiation can be categorized into two subpopulations: those with no residual malignant clonogens – the population included in this study by Dr. Sjöström and colleagues – and those with residual clonogens in the breast or elsewhere in the body that are sensitive to adjuvant endocrine therapy.

He said that the 7% 10-year risk of recurrence among patients in the POLAR low-risk group, who had neither radiation nor endocrine therapy, “is an exceptional outcome, which should be applauded, and I would point out that this risk of local recurrence of only 7% is at least in the same ballpark as the risk of recurrence that we accept every day when we treat early stage breast cancer patients with mastectomy alone, so this is a true victory.

“When we reflect on these provocative results from Dr. Sjöström and colleagues, it prompts in mind the question, could there be a group of patients with early breast cancer for whom a true ‘one-and-done’ strategy could be effective and safe?” Dr. Smith said.

Getting there will require a multidisciplinary, multimodality approach, involving imaging features of the primary tumor, clinical and pathologic features, and molecular information such as that provided by the POLAR genomic signature, he said.

The study was supported by PFS Genomics. Dr. Sjöström reported institutional funding from PFS Genomics. Dr. Speers disclosed stock and other ownership interests in the company, and he has applied for a patent on methods and genomic classifiers for prognosis of breast cancer and predicting benefit from adjuvant radiotherapy. Dr. Smith reported an equity interest in Oncora Medical, and an uncompensated relationship with the American Society for Radiation Oncology.

For women with HER2-positive early breast cancer treated with an anthracycline-based regimen followed by trastuzumab (Herceptin), concurrent therapy with the angiotensin-converting enzyme (ACE) inhibitor lisinopril can help to prevent a decline in left-ventricular ejection fraction (LVEF) below 50%, investigators in a community-based study found.

Among 424 women with HER2-positive early-stage breast cancer, the rate of LVEF decline to below 50% was 21.4% among patients randomized to receive an anthracycline-based regimen, compared with 4.1% for patients who were treated with a non–anthracycline-based regimen.

Among patients in the anthracycline arm, treatment with lisinopril, but not carvedilol or placebo, was associated with significant protection against LVEF decline, reported Pamela N. Munster, MD, of the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco.

“The findings of this study suggested that the drop in left ventricular ejection fraction to below 50% or to below normal was much larger than previously reported in the anthracycline group,” she said in a video presentation during a poster discussion session at the American Society of Clinical Oncology annual meeting. (Abstract 509).

Although HER2 inhibition is a highly effective treatment strategy for patients with HER2-positive tumors, trastuzumab-associated decline in LVEF and clinical heart failure can result in treatment interruption or discontinuation of therapy, the authors noted.

They conducted the prospective randomized trial to see whether trastuzumab-associated cardiotoxicity could be mitigated by concurrent use of either an ACE inhibitor or beta-blocker.

They enrolled women with early HER2-positive breast cancer from 127 community-based oncology centers.

The patients were randomly assigned to receive either an anthracycline- or non–anthracycline-containing regimen, followed by a year of trastuzumab, and were then randomized again to receive either lisinopril, carvedilol, or placebo concurrently with trastuzumab.

The patients were assessed for cardiotoxicity every 12 weeks with a multiple-gated acquisition (MUGA) scan and echocardiogram. Cardiotoxicity was defined as an absolute decrease in LVEF of 10% or more, or at least 5% decrease in LVEF below 50% at baseline.
 

Small LVEF declines in all

The investigators observed that all patients in the study experienced a small but not clinically relevant decrease in LVEF during trastuzumab therapy, and that this decline was not significantly ameliorated by any of the interventions.

However, as noted before, among patients assigned to anthracycline-based regimens the rate of decline to LVEF below 50% was 21.4%, compared with 4.1 for patients assigned to non–anthracycline regimens.

LVEF declines of at least 10% occurred in 5.5% of patients who received anthracyclines, and in 14.4% of those who received a non-anthracycline regimen.

Among patients who received anthracycline, only 10.8% randomized to receive lisinopril prophylaxis experienced a decline in LVEF, compared with 30.5% assigned to placebo (P = .045).

“In contrast, while carvedilol showed a numerical prevention of LVEF below 50% to 22.8%, this was not statistically significant,” Dr. Munster said.

Decreases in LVEF of 10% or greater within the normal LVEF range were similar in both chemotherapy arms and were not affected by either lisinopril or carvedilol.

“Lisinopril was well tolerated in this group, even in patients without hypertension,” she said.

“In women treated in a community-based environment who could benefit from anthracyclines or where anthracyclines are indicated, one should anticipate the decrease in left ventricular ejection fraction to below normal to be larger than is reported by other groups. However, this could be prevented by lisinopril,” she concluded.
 

Low numbers overall

Invited discussant Fatima Cardoso, MD, of Champalimaud Clinical Center in Lisbon, noted that the overall number of cardiotoxicity events and the rate of important decreases in LVEF were comparatively low.

She also pointed out that the findings are in line with another recent analysis of the same cohort by the same authors, although in the earlier analysis the investigators found that the effect on cardiotoxicity-free survival was good with both agents compared with placebo, but slightly better with carvedilol (hazard ratio 0.49, P = .009) than with lisinopril (HR 0.53, P = .015).

“Lisinopril has the most important effect regarding preventing decrease of LVEF below 50%. When we look at the curves of LVEF drops above 10%, carvedilol seems to have a slightly bigger effect,” she said.

The trial was cosponsored by the SunCoast Community Clinical Oncology Programs Research Base at University of South Florida, Tampa, and by the National Cancer Institute. Dr. Munster disclosed leadership positions, stock ownership, and consulting or advisory roles with several companies. Dr. Cardoso disclosed consulting or advisory roles and travel support from multiple companies.

For women with HER2-positive early breast cancer treated with an anthracycline-based regimen followed by trastuzumab (Herceptin), concurrent therapy with the angiotensin-converting enzyme (ACE) inhibitor lisinopril can help to prevent a decline in left-ventricular ejection fraction (LVEF) below 50%, investigators in a community-based study found.

Among 424 women with HER2-positive early-stage breast cancer, the rate of LVEF decline to below 50% was 21.4% among patients randomized to receive an anthracycline-based regimen, compared with 4.1% for patients who were treated with a non–anthracycline-based regimen.

Among patients in the anthracycline arm, treatment with lisinopril, but not carvedilol or placebo, was associated with significant protection against LVEF decline, reported Pamela N. Munster, MD, of the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco.

“The findings of this study suggested that the drop in left ventricular ejection fraction to below 50% or to below normal was much larger than previously reported in the anthracycline group,” she said in a video presentation during a poster discussion session at the American Society of Clinical Oncology annual meeting. (Abstract 509).

Although HER2 inhibition is a highly effective treatment strategy for patients with HER2-positive tumors, trastuzumab-associated decline in LVEF and clinical heart failure can result in treatment interruption or discontinuation of therapy, the authors noted.

They conducted the prospective randomized trial to see whether trastuzumab-associated cardiotoxicity could be mitigated by concurrent use of either an ACE inhibitor or beta-blocker.

They enrolled women with early HER2-positive breast cancer from 127 community-based oncology centers.

The patients were randomly assigned to receive either an anthracycline- or non–anthracycline-containing regimen, followed by a year of trastuzumab, and were then randomized again to receive either lisinopril, carvedilol, or placebo concurrently with trastuzumab.

The patients were assessed for cardiotoxicity every 12 weeks with a multiple-gated acquisition (MUGA) scan and echocardiogram. Cardiotoxicity was defined as an absolute decrease in LVEF of 10% or more, or at least 5% decrease in LVEF below 50% at baseline.
 

Small LVEF declines in all

The investigators observed that all patients in the study experienced a small but not clinically relevant decrease in LVEF during trastuzumab therapy, and that this decline was not significantly ameliorated by any of the interventions.

However, as noted before, among patients assigned to anthracycline-based regimens the rate of decline to LVEF below 50% was 21.4%, compared with 4.1 for patients assigned to non–anthracycline regimens.

LVEF declines of at least 10% occurred in 5.5% of patients who received anthracyclines, and in 14.4% of those who received a non-anthracycline regimen.

Among patients who received anthracycline, only 10.8% randomized to receive lisinopril prophylaxis experienced a decline in LVEF, compared with 30.5% assigned to placebo (P = .045).

“In contrast, while carvedilol showed a numerical prevention of LVEF below 50% to 22.8%, this was not statistically significant,” Dr. Munster said.

Decreases in LVEF of 10% or greater within the normal LVEF range were similar in both chemotherapy arms and were not affected by either lisinopril or carvedilol.

“Lisinopril was well tolerated in this group, even in patients without hypertension,” she said.

“In women treated in a community-based environment who could benefit from anthracyclines or where anthracyclines are indicated, one should anticipate the decrease in left ventricular ejection fraction to below normal to be larger than is reported by other groups. However, this could be prevented by lisinopril,” she concluded.
 

Low numbers overall

Invited discussant Fatima Cardoso, MD, of Champalimaud Clinical Center in Lisbon, noted that the overall number of cardiotoxicity events and the rate of important decreases in LVEF were comparatively low.

She also pointed out that the findings are in line with another recent analysis of the same cohort by the same authors, although in the earlier analysis the investigators found that the effect on cardiotoxicity-free survival was good with both agents compared with placebo, but slightly better with carvedilol (hazard ratio 0.49, P = .009) than with lisinopril (HR 0.53, P = .015).

“Lisinopril has the most important effect regarding preventing decrease of LVEF below 50%. When we look at the curves of LVEF drops above 10%, carvedilol seems to have a slightly bigger effect,” she said.

The trial was cosponsored by the SunCoast Community Clinical Oncology Programs Research Base at University of South Florida, Tampa, and by the National Cancer Institute. Dr. Munster disclosed leadership positions, stock ownership, and consulting or advisory roles with several companies. Dr. Cardoso disclosed consulting or advisory roles and travel support from multiple companies.

For women with HER2-positive early breast cancer treated with an anthracycline-based regimen followed by trastuzumab (Herceptin), concurrent therapy with the angiotensin-converting enzyme (ACE) inhibitor lisinopril can help to prevent a decline in left-ventricular ejection fraction (LVEF) below 50%, investigators in a community-based study found.

Among 424 women with HER2-positive early-stage breast cancer, the rate of LVEF decline to below 50% was 21.4% among patients randomized to receive an anthracycline-based regimen, compared with 4.1% for patients who were treated with a non–anthracycline-based regimen.

Among patients in the anthracycline arm, treatment with lisinopril, but not carvedilol or placebo, was associated with significant protection against LVEF decline, reported Pamela N. Munster, MD, of the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco.

“The findings of this study suggested that the drop in left ventricular ejection fraction to below 50% or to below normal was much larger than previously reported in the anthracycline group,” she said in a video presentation during a poster discussion session at the American Society of Clinical Oncology annual meeting. (Abstract 509).

Although HER2 inhibition is a highly effective treatment strategy for patients with HER2-positive tumors, trastuzumab-associated decline in LVEF and clinical heart failure can result in treatment interruption or discontinuation of therapy, the authors noted.

They conducted the prospective randomized trial to see whether trastuzumab-associated cardiotoxicity could be mitigated by concurrent use of either an ACE inhibitor or beta-blocker.

They enrolled women with early HER2-positive breast cancer from 127 community-based oncology centers.

The patients were randomly assigned to receive either an anthracycline- or non–anthracycline-containing regimen, followed by a year of trastuzumab, and were then randomized again to receive either lisinopril, carvedilol, or placebo concurrently with trastuzumab.

The patients were assessed for cardiotoxicity every 12 weeks with a multiple-gated acquisition (MUGA) scan and echocardiogram. Cardiotoxicity was defined as an absolute decrease in LVEF of 10% or more, or at least 5% decrease in LVEF below 50% at baseline.
 

Small LVEF declines in all

The investigators observed that all patients in the study experienced a small but not clinically relevant decrease in LVEF during trastuzumab therapy, and that this decline was not significantly ameliorated by any of the interventions.

However, as noted before, among patients assigned to anthracycline-based regimens the rate of decline to LVEF below 50% was 21.4%, compared with 4.1 for patients assigned to non–anthracycline regimens.

LVEF declines of at least 10% occurred in 5.5% of patients who received anthracyclines, and in 14.4% of those who received a non-anthracycline regimen.

Among patients who received anthracycline, only 10.8% randomized to receive lisinopril prophylaxis experienced a decline in LVEF, compared with 30.5% assigned to placebo (P = .045).

“In contrast, while carvedilol showed a numerical prevention of LVEF below 50% to 22.8%, this was not statistically significant,” Dr. Munster said.

Decreases in LVEF of 10% or greater within the normal LVEF range were similar in both chemotherapy arms and were not affected by either lisinopril or carvedilol.

“Lisinopril was well tolerated in this group, even in patients without hypertension,” she said.

“In women treated in a community-based environment who could benefit from anthracyclines or where anthracyclines are indicated, one should anticipate the decrease in left ventricular ejection fraction to below normal to be larger than is reported by other groups. However, this could be prevented by lisinopril,” she concluded.
 

Low numbers overall

Invited discussant Fatima Cardoso, MD, of Champalimaud Clinical Center in Lisbon, noted that the overall number of cardiotoxicity events and the rate of important decreases in LVEF were comparatively low.

She also pointed out that the findings are in line with another recent analysis of the same cohort by the same authors, although in the earlier analysis the investigators found that the effect on cardiotoxicity-free survival was good with both agents compared with placebo, but slightly better with carvedilol (hazard ratio 0.49, P = .009) than with lisinopril (HR 0.53, P = .015).

“Lisinopril has the most important effect regarding preventing decrease of LVEF below 50%. When we look at the curves of LVEF drops above 10%, carvedilol seems to have a slightly bigger effect,” she said.

The trial was cosponsored by the SunCoast Community Clinical Oncology Programs Research Base at University of South Florida, Tampa, and by the National Cancer Institute. Dr. Munster disclosed leadership positions, stock ownership, and consulting or advisory roles with several companies. Dr. Cardoso disclosed consulting or advisory roles and travel support from multiple companies.

Reassuring news for women who receive a diagnosis of breast cancer during pregnancy: Pregnancy-induced alterations in the pharmacokinetics of chemotherapy do not appear to compromise outcomes for the mother.

That’s according to investigators who reviewed registry data on 662 pregnant women and 2,081 nonpregnant women with a diagnosis of breast cancer. After a median follow-up of 66 months, there were no significant differences in either disease-free survival (DFS) or overall survival (OS), and women who received more than 60% of their chemotherapy doses during pregnancy had survival comparable to that of nonpregnant women, reported Frédéric Amant, MD, PhD, of University Hospitals Leuven (Belgium).

“These results support initiation of chemotherapy for breast cancer during pregnancy where indicated for oncological reasons,” they reported in a poster discussion session at the American Society of Clinical Oncology annual meeting. (Abstract 515).

Although in general a diagnosis of breast cancer during pregnancy does not appear to affect the mother’s prognosis when standard therapy is used, “caution is warranted as gestational changes in pharmacokinetics with respect to the distribution, metabolism, and excretion of drugs may lead to reduced chemotherapy concentration in pregnant patients,” the authors wrote.

To get a better picture of the prognosis for women diagnosed with breast cancer during pregnancy, the investigators created a cohort of patients from two multicenter registries: the International Network of Cancer, Infertility, and Pregnancy and the German Breast Group. Both registries collect data retrospectively and prospectively,

They used propensity scoring to smooth out differences in the baseline characteristics of pregnant women and nonpregnant controls.

The median age at diagnosis was 34 year for pregnant women, and 38 years for controls. Pregnant women were more likely than were controls to have stage II disease (60.1% vs. 56, 1%, P = .035), grade 3 tumors (74% vs. 62.2%, P < .001), hormone receptor–negative breast tumors (48.4% vs. 30%), and triple-negative breast cancer (38.9% vs. 26.9%, P < .001).

In Cox proportional hazard regression analysis controlling for age, stage, grade, hormone receptor status, HER2 status and histology, there were no significant differences between pregnant women and controls in either DFS (hazard ratio [HR] 1.02, P = .83) or OS (HR 1.08, P = .57).

As noted before, a subgroup analysis of 339 women who received more than 60% of their assigned chemotherapy doses during pregnancy also showed that survival was not significantly different from that of nonpregnant women (HR for DFS 0,71, P = .13; HR for OS 0.85, P = .39).
 

Termination does not benefit the mother

“Thanks to the important work of Dr. Amant in the INCIP [International Network on Cancer, Infertility, and Pregnancy] network and others around the world, we now have sufficient data to know that it’s safe to treat breast cancer during pregnancy, and that the prognosis of breast cancer during pregnancy is comparable to nonpregnant controls if we adjust for certain characteristics such as age and others,” said Fatima Cardoso, MD, of Champalimaud Clinical Center in Lisbon, Portugal, the invited discussant.

­­“With this and other studies, we can come to the conclusion that pregnancy-induced alterations in the chemotherapy concentration due to altered pharmacokinetics does not seem to affect maternal prognosis, and therefore we should initiate treatment of breast cancer during wherever it’s indicated for oncological reasons, knowing that you can only use chemotherapy during the second or third trimester,” she said.

Dr. Cardoso emphasized that breast cancer during pregnancy is a rare situation requiring that treatment be given in a specialized center by an experienced multidisciplinary team, and that interrupting the pregnancy does not improve the mother’s prognosis.

“We have to spread the word to all health professionals who come across these women to stop advising them to immediately terminate pregnancy. For the children, the most important take-home message is avoid prematurely delivery,” she said.

Treatment for women with a diagnosis of breast cancer during pregnancy should be similar to that for nonpregnant women, with the exception of endocrine therapy and anti-HER2 agents, which should be withheld until after delivery, she added.

The study was supported by the European Research Council, Research Foundation Flanders, and Kom op tegen kanker (Stand Up to Cancer). Dr. Amant disclosed a consulting or advisory role for AstraZeneca and Clovis Oncology. Dr. Cardoso disclosed consulting or advisory roles and travel support from multiple companies.

Reassuring news for women who receive a diagnosis of breast cancer during pregnancy: Pregnancy-induced alterations in the pharmacokinetics of chemotherapy do not appear to compromise outcomes for the mother.

That’s according to investigators who reviewed registry data on 662 pregnant women and 2,081 nonpregnant women with a diagnosis of breast cancer. After a median follow-up of 66 months, there were no significant differences in either disease-free survival (DFS) or overall survival (OS), and women who received more than 60% of their chemotherapy doses during pregnancy had survival comparable to that of nonpregnant women, reported Frédéric Amant, MD, PhD, of University Hospitals Leuven (Belgium).

“These results support initiation of chemotherapy for breast cancer during pregnancy where indicated for oncological reasons,” they reported in a poster discussion session at the American Society of Clinical Oncology annual meeting. (Abstract 515).

Although in general a diagnosis of breast cancer during pregnancy does not appear to affect the mother’s prognosis when standard therapy is used, “caution is warranted as gestational changes in pharmacokinetics with respect to the distribution, metabolism, and excretion of drugs may lead to reduced chemotherapy concentration in pregnant patients,” the authors wrote.

To get a better picture of the prognosis for women diagnosed with breast cancer during pregnancy, the investigators created a cohort of patients from two multicenter registries: the International Network of Cancer, Infertility, and Pregnancy and the German Breast Group. Both registries collect data retrospectively and prospectively,

They used propensity scoring to smooth out differences in the baseline characteristics of pregnant women and nonpregnant controls.

The median age at diagnosis was 34 year for pregnant women, and 38 years for controls. Pregnant women were more likely than were controls to have stage II disease (60.1% vs. 56, 1%, P = .035), grade 3 tumors (74% vs. 62.2%, P < .001), hormone receptor–negative breast tumors (48.4% vs. 30%), and triple-negative breast cancer (38.9% vs. 26.9%, P < .001).

In Cox proportional hazard regression analysis controlling for age, stage, grade, hormone receptor status, HER2 status and histology, there were no significant differences between pregnant women and controls in either DFS (hazard ratio [HR] 1.02, P = .83) or OS (HR 1.08, P = .57).

As noted before, a subgroup analysis of 339 women who received more than 60% of their assigned chemotherapy doses during pregnancy also showed that survival was not significantly different from that of nonpregnant women (HR for DFS 0,71, P = .13; HR for OS 0.85, P = .39).
 

Termination does not benefit the mother

“Thanks to the important work of Dr. Amant in the INCIP [International Network on Cancer, Infertility, and Pregnancy] network and others around the world, we now have sufficient data to know that it’s safe to treat breast cancer during pregnancy, and that the prognosis of breast cancer during pregnancy is comparable to nonpregnant controls if we adjust for certain characteristics such as age and others,” said Fatima Cardoso, MD, of Champalimaud Clinical Center in Lisbon, Portugal, the invited discussant.

­­“With this and other studies, we can come to the conclusion that pregnancy-induced alterations in the chemotherapy concentration due to altered pharmacokinetics does not seem to affect maternal prognosis, and therefore we should initiate treatment of breast cancer during wherever it’s indicated for oncological reasons, knowing that you can only use chemotherapy during the second or third trimester,” she said.

Dr. Cardoso emphasized that breast cancer during pregnancy is a rare situation requiring that treatment be given in a specialized center by an experienced multidisciplinary team, and that interrupting the pregnancy does not improve the mother’s prognosis.

“We have to spread the word to all health professionals who come across these women to stop advising them to immediately terminate pregnancy. For the children, the most important take-home message is avoid prematurely delivery,” she said.

Treatment for women with a diagnosis of breast cancer during pregnancy should be similar to that for nonpregnant women, with the exception of endocrine therapy and anti-HER2 agents, which should be withheld until after delivery, she added.

The study was supported by the European Research Council, Research Foundation Flanders, and Kom op tegen kanker (Stand Up to Cancer). Dr. Amant disclosed a consulting or advisory role for AstraZeneca and Clovis Oncology. Dr. Cardoso disclosed consulting or advisory roles and travel support from multiple companies.

Reassuring news for women who receive a diagnosis of breast cancer during pregnancy: Pregnancy-induced alterations in the pharmacokinetics of chemotherapy do not appear to compromise outcomes for the mother.

That’s according to investigators who reviewed registry data on 662 pregnant women and 2,081 nonpregnant women with a diagnosis of breast cancer. After a median follow-up of 66 months, there were no significant differences in either disease-free survival (DFS) or overall survival (OS), and women who received more than 60% of their chemotherapy doses during pregnancy had survival comparable to that of nonpregnant women, reported Frédéric Amant, MD, PhD, of University Hospitals Leuven (Belgium).

“These results support initiation of chemotherapy for breast cancer during pregnancy where indicated for oncological reasons,” they reported in a poster discussion session at the American Society of Clinical Oncology annual meeting. (Abstract 515).

Although in general a diagnosis of breast cancer during pregnancy does not appear to affect the mother’s prognosis when standard therapy is used, “caution is warranted as gestational changes in pharmacokinetics with respect to the distribution, metabolism, and excretion of drugs may lead to reduced chemotherapy concentration in pregnant patients,” the authors wrote.

To get a better picture of the prognosis for women diagnosed with breast cancer during pregnancy, the investigators created a cohort of patients from two multicenter registries: the International Network of Cancer, Infertility, and Pregnancy and the German Breast Group. Both registries collect data retrospectively and prospectively,

They used propensity scoring to smooth out differences in the baseline characteristics of pregnant women and nonpregnant controls.

The median age at diagnosis was 34 year for pregnant women, and 38 years for controls. Pregnant women were more likely than were controls to have stage II disease (60.1% vs. 56, 1%, P = .035), grade 3 tumors (74% vs. 62.2%, P < .001), hormone receptor–negative breast tumors (48.4% vs. 30%), and triple-negative breast cancer (38.9% vs. 26.9%, P < .001).

In Cox proportional hazard regression analysis controlling for age, stage, grade, hormone receptor status, HER2 status and histology, there were no significant differences between pregnant women and controls in either DFS (hazard ratio [HR] 1.02, P = .83) or OS (HR 1.08, P = .57).

As noted before, a subgroup analysis of 339 women who received more than 60% of their assigned chemotherapy doses during pregnancy also showed that survival was not significantly different from that of nonpregnant women (HR for DFS 0,71, P = .13; HR for OS 0.85, P = .39).
 

Termination does not benefit the mother

“Thanks to the important work of Dr. Amant in the INCIP [International Network on Cancer, Infertility, and Pregnancy] network and others around the world, we now have sufficient data to know that it’s safe to treat breast cancer during pregnancy, and that the prognosis of breast cancer during pregnancy is comparable to nonpregnant controls if we adjust for certain characteristics such as age and others,” said Fatima Cardoso, MD, of Champalimaud Clinical Center in Lisbon, Portugal, the invited discussant.

­­“With this and other studies, we can come to the conclusion that pregnancy-induced alterations in the chemotherapy concentration due to altered pharmacokinetics does not seem to affect maternal prognosis, and therefore we should initiate treatment of breast cancer during wherever it’s indicated for oncological reasons, knowing that you can only use chemotherapy during the second or third trimester,” she said.

Dr. Cardoso emphasized that breast cancer during pregnancy is a rare situation requiring that treatment be given in a specialized center by an experienced multidisciplinary team, and that interrupting the pregnancy does not improve the mother’s prognosis.

“We have to spread the word to all health professionals who come across these women to stop advising them to immediately terminate pregnancy. For the children, the most important take-home message is avoid prematurely delivery,” she said.

Treatment for women with a diagnosis of breast cancer during pregnancy should be similar to that for nonpregnant women, with the exception of endocrine therapy and anti-HER2 agents, which should be withheld until after delivery, she added.

The study was supported by the European Research Council, Research Foundation Flanders, and Kom op tegen kanker (Stand Up to Cancer). Dr. Amant disclosed a consulting or advisory role for AstraZeneca and Clovis Oncology. Dr. Cardoso disclosed consulting or advisory roles and travel support from multiple companies.

Chemotherapy and local excision led to organ preservation in over half of early-stage rectal cancer patients in a small study, but follow-up was only a median of 15.4 months.

Even so, “we believe that subsequent trials ... are warranted,” said lead investigator Hagen F. Kennecke, MD, medical director of GI oncology at Providence Cancer Institute, Portland, Ore., who presented the findings at the American Society of Clinical Oncology annual meeting.

“The results are quite promising,” said study discussant Karyn Stitzenberg, MD, a surgical oncologist at the University of North Carolina, Chapel Hill.

“The reported organ preservation rates of 57% to 79% compare favorably with the rates previously demonstrated in studies of neoadjuvant chemoradiation followed by local excision,” but longer-term follow up is needed “to know the true organ preservation rate,” she said.

Organ preservation – sparing the rectum during treatment – is a hot topic in rectal cancer. Total mesorectal excision (TME) is still the go-to option, but it’s fraught with bad GI, urinary, sexual, and other complications for patients. “Consequently, the concept of organ preservation ... is very appealing,” Dr. Stitzenberg explained.

The chemoradiation/local excision approach she referenced is gaining traction as an alternative, but the radiation component is itself associated with substantial short- and long-term problems, including sphincter dysfunction and wound healing complications.

The goal of Dr. Kennecke’s study, dubbed NEO [Neoadjuvant, Excision, Observation], was to see if the radiation could be left out altogether.

Recruited at eight centers in Canada and one in the United States, the 58 subjects had clinical stage T1-T3 A/B node-negative tumors with no pathologic high-risk features.

They received neoadjuvant FOLFOX (six cycles in 32 patients, 91% completion rate) or CAPOX (four cycles in 26 patients, 89% completion); 56 of the 58 subjects then went on to transanal endoscopic tumor excision; one of the other two patients wasn’t eligible because of tumor progression and the other one declined.

The 33 patients who were stage T0/T1N0 after treatment were spared organ removal and underwent observation every 3-6 months. TME was recommended for the 23 others who were stage 2 or higher or had nodal metastases following chemotherapy and excision.

The numbers translated to a per-protocol organ preservation rate of 57% over a median follow-up of 15.4 months; when the 13 patients who declined TME were added, the rate climbed to 79%.

Although “organ preservation in rectal cancer is becoming an increasingly promising and realistic option for a subset of patients,” Dr. Stitzenberg said, there are more reasons to be cautious beyond the short follow-up.

“The standard of care treatment for these patients would have been proctectomy ... Most would not have [had] systemic chemotherapy. As a result, the added morbidity of FOLFOX or CAPOX needs to be considered.” The study reported that there were no unexpected toxicities, but “what were the expected toxicities? How many patients experienced grade 3 to 5 complications?” she wondered.

Also, how realistic is it to expect patients to report for surveillance every few months outside of a trial? And how can they best be watched to make sure recurrence is caught “while salvage TME is still feasible? There are many longer-term follow-up questions that remain to be answered,” Dr. Stitzenberg said.

Even with short follow-up, there were two locoregional recurrences across the cohort (3.5%), both treated by TME to R0/1 resection. There were no distant relapses.

Subjects were a median of 67 years old, and over two-thirds were men. The majority had stage 2 disease at baseline. Tumors were well to moderately differentiated nonmucinous rectal adenocarcinomas with a median height of 6 cm.

The work was funded by the Canadian Cancer Trials Group. Dr. Kennecke disclosed relationships with Advanced Accelerator Applications, Ipsen, and Taiho Pharmaceutical. Dr. Stitzenberg had no relevant disclosures.

aotto@mdedge.com

Chemotherapy and local excision led to organ preservation in over half of early-stage rectal cancer patients in a small study, but follow-up was only a median of 15.4 months.

Even so, “we believe that subsequent trials ... are warranted,” said lead investigator Hagen F. Kennecke, MD, medical director of GI oncology at Providence Cancer Institute, Portland, Ore., who presented the findings at the American Society of Clinical Oncology annual meeting.

“The results are quite promising,” said study discussant Karyn Stitzenberg, MD, a surgical oncologist at the University of North Carolina, Chapel Hill.

“The reported organ preservation rates of 57% to 79% compare favorably with the rates previously demonstrated in studies of neoadjuvant chemoradiation followed by local excision,” but longer-term follow up is needed “to know the true organ preservation rate,” she said.

Organ preservation – sparing the rectum during treatment – is a hot topic in rectal cancer. Total mesorectal excision (TME) is still the go-to option, but it’s fraught with bad GI, urinary, sexual, and other complications for patients. “Consequently, the concept of organ preservation ... is very appealing,” Dr. Stitzenberg explained.

The chemoradiation/local excision approach she referenced is gaining traction as an alternative, but the radiation component is itself associated with substantial short- and long-term problems, including sphincter dysfunction and wound healing complications.

The goal of Dr. Kennecke’s study, dubbed NEO [Neoadjuvant, Excision, Observation], was to see if the radiation could be left out altogether.

Recruited at eight centers in Canada and one in the United States, the 58 subjects had clinical stage T1-T3 A/B node-negative tumors with no pathologic high-risk features.

They received neoadjuvant FOLFOX (six cycles in 32 patients, 91% completion rate) or CAPOX (four cycles in 26 patients, 89% completion); 56 of the 58 subjects then went on to transanal endoscopic tumor excision; one of the other two patients wasn’t eligible because of tumor progression and the other one declined.

The 33 patients who were stage T0/T1N0 after treatment were spared organ removal and underwent observation every 3-6 months. TME was recommended for the 23 others who were stage 2 or higher or had nodal metastases following chemotherapy and excision.

The numbers translated to a per-protocol organ preservation rate of 57% over a median follow-up of 15.4 months; when the 13 patients who declined TME were added, the rate climbed to 79%.

Although “organ preservation in rectal cancer is becoming an increasingly promising and realistic option for a subset of patients,” Dr. Stitzenberg said, there are more reasons to be cautious beyond the short follow-up.

“The standard of care treatment for these patients would have been proctectomy ... Most would not have [had] systemic chemotherapy. As a result, the added morbidity of FOLFOX or CAPOX needs to be considered.” The study reported that there were no unexpected toxicities, but “what were the expected toxicities? How many patients experienced grade 3 to 5 complications?” she wondered.

Also, how realistic is it to expect patients to report for surveillance every few months outside of a trial? And how can they best be watched to make sure recurrence is caught “while salvage TME is still feasible? There are many longer-term follow-up questions that remain to be answered,” Dr. Stitzenberg said.

Even with short follow-up, there were two locoregional recurrences across the cohort (3.5%), both treated by TME to R0/1 resection. There were no distant relapses.

Subjects were a median of 67 years old, and over two-thirds were men. The majority had stage 2 disease at baseline. Tumors were well to moderately differentiated nonmucinous rectal adenocarcinomas with a median height of 6 cm.

The work was funded by the Canadian Cancer Trials Group. Dr. Kennecke disclosed relationships with Advanced Accelerator Applications, Ipsen, and Taiho Pharmaceutical. Dr. Stitzenberg had no relevant disclosures.

aotto@mdedge.com

Chemotherapy and local excision led to organ preservation in over half of early-stage rectal cancer patients in a small study, but follow-up was only a median of 15.4 months.

Even so, “we believe that subsequent trials ... are warranted,” said lead investigator Hagen F. Kennecke, MD, medical director of GI oncology at Providence Cancer Institute, Portland, Ore., who presented the findings at the American Society of Clinical Oncology annual meeting.

“The results are quite promising,” said study discussant Karyn Stitzenberg, MD, a surgical oncologist at the University of North Carolina, Chapel Hill.

“The reported organ preservation rates of 57% to 79% compare favorably with the rates previously demonstrated in studies of neoadjuvant chemoradiation followed by local excision,” but longer-term follow up is needed “to know the true organ preservation rate,” she said.

Organ preservation – sparing the rectum during treatment – is a hot topic in rectal cancer. Total mesorectal excision (TME) is still the go-to option, but it’s fraught with bad GI, urinary, sexual, and other complications for patients. “Consequently, the concept of organ preservation ... is very appealing,” Dr. Stitzenberg explained.

The chemoradiation/local excision approach she referenced is gaining traction as an alternative, but the radiation component is itself associated with substantial short- and long-term problems, including sphincter dysfunction and wound healing complications.

The goal of Dr. Kennecke’s study, dubbed NEO [Neoadjuvant, Excision, Observation], was to see if the radiation could be left out altogether.

Recruited at eight centers in Canada and one in the United States, the 58 subjects had clinical stage T1-T3 A/B node-negative tumors with no pathologic high-risk features.

They received neoadjuvant FOLFOX (six cycles in 32 patients, 91% completion rate) or CAPOX (four cycles in 26 patients, 89% completion); 56 of the 58 subjects then went on to transanal endoscopic tumor excision; one of the other two patients wasn’t eligible because of tumor progression and the other one declined.

The 33 patients who were stage T0/T1N0 after treatment were spared organ removal and underwent observation every 3-6 months. TME was recommended for the 23 others who were stage 2 or higher or had nodal metastases following chemotherapy and excision.

The numbers translated to a per-protocol organ preservation rate of 57% over a median follow-up of 15.4 months; when the 13 patients who declined TME were added, the rate climbed to 79%.

Although “organ preservation in rectal cancer is becoming an increasingly promising and realistic option for a subset of patients,” Dr. Stitzenberg said, there are more reasons to be cautious beyond the short follow-up.

“The standard of care treatment for these patients would have been proctectomy ... Most would not have [had] systemic chemotherapy. As a result, the added morbidity of FOLFOX or CAPOX needs to be considered.” The study reported that there were no unexpected toxicities, but “what were the expected toxicities? How many patients experienced grade 3 to 5 complications?” she wondered.

Also, how realistic is it to expect patients to report for surveillance every few months outside of a trial? And how can they best be watched to make sure recurrence is caught “while salvage TME is still feasible? There are many longer-term follow-up questions that remain to be answered,” Dr. Stitzenberg said.

Even with short follow-up, there were two locoregional recurrences across the cohort (3.5%), both treated by TME to R0/1 resection. There were no distant relapses.

Subjects were a median of 67 years old, and over two-thirds were men. The majority had stage 2 disease at baseline. Tumors were well to moderately differentiated nonmucinous rectal adenocarcinomas with a median height of 6 cm.

The work was funded by the Canadian Cancer Trials Group. Dr. Kennecke disclosed relationships with Advanced Accelerator Applications, Ipsen, and Taiho Pharmaceutical. Dr. Stitzenberg had no relevant disclosures.

aotto@mdedge.com

The first KRAS inhibitor approved for the treatment of lung cancer provided a clinically meaningful overall survival benefit in an updated analysis of a phase 2 study.

Treatment with sotorasib yielded a median overall survival (OS) of 12.5 months in patients with previously treated KRAS p.G12C-mutated non-small cell lung cancer (NSCLC), according to an analysis of the phase 2 CodeBreaK 100 trial data presented at the American Society of Clinical Oncology Annual Meeting.

Median progression-free survival (PFS) was 6.8 months in this update, which included a median follow-up of more than 15 months, according to investigator Ferdinandos Skoulidis, MD, PhD, assistant professor of thoracic/head and neck medical oncology at the University of Texas MD Anderson Cancer Center in Houston.

Efficacy responses

The confirmed objective response rate was 37.1%, including a 3.2% complete response rate and a median duration of response of 11.1 months, according to the report by Dr. Skoulidis.

In exploratory analyses, the benefit of sotorasib was consistent across patient subgroups, Dr. Skoulidis said in his presentation (Abstract 9003).

In particular, efficacy was observed in subgroups with co-occurring mutations in TP53, STK11, and KEAP1, which are molecular indicators of suboptimal outcomes on standard systemic treatments, according to Dr. Skoulidis.

This update on the registrational phase 2 CodeBreaK100 trial, published concurrently in the New England Journal of Medicine , came just one week after the U.S. Food and Drug Administration (FDA) granted accelerated approval to sotorasib.

Sotorasib was approved for the treatment of patients with previously treated KRAS G12C‑mutated locally advanced or metastatic NSCLC on the basis of previously reported results from CodeBreaK100.

This sotorasib indication represents a “historic milestone,” Dr. Skoulidis said in an interview.

No previously studied selective KRAS inhibitor has been approved despite scientific research efforts that stretch back nearly four decades, he explained.

“In a way, one can say that we have dealt KRAS-mutant lung cancer a knockdown blow, however, I should point out that the fight is not over,” he added.

“These clinical results will no doubt spearhead and galvanize further efforts to develop even more effective therapeutic combinations in the future, as well as identify and either forestall or overcome the eventual development of acquired resistance,” he said.
 

Only 1 out of 8 patients

The KRAS p.G12C mutation is present in about 13% of lung adenocarcinomas, or about one in every eight patients with nonsquamous NSCLC, Dr. Skoulidis said in the interview.

“We are estimating that this is in the region of 13,000 patients newly diagnosed every year in the U.S., and approximately 13,000 patients or so that are currently being treated in the second- or third-line setting,” he said.

The CodeBreaK100 trial included 126 patients with locally advanced or metastatic NSCLC and KRAS p.G12C mutation who had progressed on prior systemic therapies. About 43% had one prior line of treatment, while 35% had two lines, and 22% had three lines. A total of 81% had previously received both platinum-based chemotherapy and PD-1/PD-L1 axis inhibitors.

Most treatment-related adverse events in the study were grade 1-2 and generally manageable, according to Dr. Skoulidis. About 20% of patients experienced grade 3 treatment-related adverse events, which were mostly diarrhea or increases in aspartate aminotransferase and alanine aminotransferase levels. A grade 4 treatment-related adverse event, pneumonitis and dyspnea, was reported in one patient or approximately 1%.
 

Confirmatory trial

Although CodeBreak100 is not a randomized trial, the median OS of 12.5 months compares favorably to median OS times in the range of 7.9-10.3 months reported in randomized phase 3 clinical trials and subgroup analysis of randomized phase 3 trials of docetaxel for patients with KRAS-mutant lung adenocarcinoma, Dr. Skoulidis said in a question-and-answer session.

A confirmatory phase 3 CodeBreaK200 trial of sotorasib versus docetaxel in patients with previously treated KRAS p.G12C-mutated NSCLC is underway. That trial is evaluating PFS as a primary endpoint and OS as a secondary endpoint.

“If the same magnitude of benefit, 12.5 months median overall survival, is confirmed in the larger phase 3 clinical trial, as a clinician I would consider that beneficial for patients, compared to the standard of care,” Dr. Skoulidis said during the session.
 

Mature data

The updated analysis of the phase 2 CodeBreaK100 study is notable for its mature OS data, updated safety and the first molecular subgroup analyses, according to discussant Christine Marie Lovly, MD, PhD, of the division of hematology-oncology at Vanderbilt University Medical Center in Nashville.

“The objective response rate was 37.1%,” she added. “This is a little bit lower than we’re used to for targeted therapies, but remember, this is a different mutation and a very different class of drugs.”

The KRAS G12C inhibitors, several of which are under clinical development, are not tyrosine kinase inhibitors (TKIs), but rather allele-specific inhibitors that target mutant KRAS, trapping it in an inactive conformation, she explained.

Dr. Lovly referenced the exploratory analyses demonstrating efficacy in molecularly defined subgroups, calling it “interesting” that there was no difference in objective response rate between TP53 wild type and mutant tumors.

“We do have data that mutant TP53 seems to confer inferior outcomes for EGFR TKI-directed therapy in patients with EGFR-mutant lung cancer,” she said.

CodeBreaK100 was supported by Amgen, Inc. and partly by a National Institutes of Health Cancer Center Support Grant at Memorial Sloan Kettering Cancer Center.

Dr. Skoulidis reported honoraria from Bristol-Myers Squibb; research funding from AIMM Therapeutics and Amgen; and travel, accommodations, or expenses from Tango Therapeutics. Dr. Lovly reported disclosures related to Amgen, AstraZeneca, Genentech, Novartis, and Pfizer, among others.

The first KRAS inhibitor approved for the treatment of lung cancer provided a clinically meaningful overall survival benefit in an updated analysis of a phase 2 study.

Treatment with sotorasib yielded a median overall survival (OS) of 12.5 months in patients with previously treated KRAS p.G12C-mutated non-small cell lung cancer (NSCLC), according to an analysis of the phase 2 CodeBreaK 100 trial data presented at the American Society of Clinical Oncology Annual Meeting.

Median progression-free survival (PFS) was 6.8 months in this update, which included a median follow-up of more than 15 months, according to investigator Ferdinandos Skoulidis, MD, PhD, assistant professor of thoracic/head and neck medical oncology at the University of Texas MD Anderson Cancer Center in Houston.

Efficacy responses

The confirmed objective response rate was 37.1%, including a 3.2% complete response rate and a median duration of response of 11.1 months, according to the report by Dr. Skoulidis.

In exploratory analyses, the benefit of sotorasib was consistent across patient subgroups, Dr. Skoulidis said in his presentation (Abstract 9003).

In particular, efficacy was observed in subgroups with co-occurring mutations in TP53, STK11, and KEAP1, which are molecular indicators of suboptimal outcomes on standard systemic treatments, according to Dr. Skoulidis.

This update on the registrational phase 2 CodeBreaK100 trial, published concurrently in the New England Journal of Medicine , came just one week after the U.S. Food and Drug Administration (FDA) granted accelerated approval to sotorasib.

Sotorasib was approved for the treatment of patients with previously treated KRAS G12C‑mutated locally advanced or metastatic NSCLC on the basis of previously reported results from CodeBreaK100.

This sotorasib indication represents a “historic milestone,” Dr. Skoulidis said in an interview.

No previously studied selective KRAS inhibitor has been approved despite scientific research efforts that stretch back nearly four decades, he explained.

“In a way, one can say that we have dealt KRAS-mutant lung cancer a knockdown blow, however, I should point out that the fight is not over,” he added.

“These clinical results will no doubt spearhead and galvanize further efforts to develop even more effective therapeutic combinations in the future, as well as identify and either forestall or overcome the eventual development of acquired resistance,” he said.
 

Only 1 out of 8 patients

The KRAS p.G12C mutation is present in about 13% of lung adenocarcinomas, or about one in every eight patients with nonsquamous NSCLC, Dr. Skoulidis said in the interview.

“We are estimating that this is in the region of 13,000 patients newly diagnosed every year in the U.S., and approximately 13,000 patients or so that are currently being treated in the second- or third-line setting,” he said.

The CodeBreaK100 trial included 126 patients with locally advanced or metastatic NSCLC and KRAS p.G12C mutation who had progressed on prior systemic therapies. About 43% had one prior line of treatment, while 35% had two lines, and 22% had three lines. A total of 81% had previously received both platinum-based chemotherapy and PD-1/PD-L1 axis inhibitors.

Most treatment-related adverse events in the study were grade 1-2 and generally manageable, according to Dr. Skoulidis. About 20% of patients experienced grade 3 treatment-related adverse events, which were mostly diarrhea or increases in aspartate aminotransferase and alanine aminotransferase levels. A grade 4 treatment-related adverse event, pneumonitis and dyspnea, was reported in one patient or approximately 1%.
 

Confirmatory trial

Although CodeBreak100 is not a randomized trial, the median OS of 12.5 months compares favorably to median OS times in the range of 7.9-10.3 months reported in randomized phase 3 clinical trials and subgroup analysis of randomized phase 3 trials of docetaxel for patients with KRAS-mutant lung adenocarcinoma, Dr. Skoulidis said in a question-and-answer session.

A confirmatory phase 3 CodeBreaK200 trial of sotorasib versus docetaxel in patients with previously treated KRAS p.G12C-mutated NSCLC is underway. That trial is evaluating PFS as a primary endpoint and OS as a secondary endpoint.

“If the same magnitude of benefit, 12.5 months median overall survival, is confirmed in the larger phase 3 clinical trial, as a clinician I would consider that beneficial for patients, compared to the standard of care,” Dr. Skoulidis said during the session.
 

Mature data

The updated analysis of the phase 2 CodeBreaK100 study is notable for its mature OS data, updated safety and the first molecular subgroup analyses, according to discussant Christine Marie Lovly, MD, PhD, of the division of hematology-oncology at Vanderbilt University Medical Center in Nashville.

“The objective response rate was 37.1%,” she added. “This is a little bit lower than we’re used to for targeted therapies, but remember, this is a different mutation and a very different class of drugs.”

The KRAS G12C inhibitors, several of which are under clinical development, are not tyrosine kinase inhibitors (TKIs), but rather allele-specific inhibitors that target mutant KRAS, trapping it in an inactive conformation, she explained.

Dr. Lovly referenced the exploratory analyses demonstrating efficacy in molecularly defined subgroups, calling it “interesting” that there was no difference in objective response rate between TP53 wild type and mutant tumors.

“We do have data that mutant TP53 seems to confer inferior outcomes for EGFR TKI-directed therapy in patients with EGFR-mutant lung cancer,” she said.

CodeBreaK100 was supported by Amgen, Inc. and partly by a National Institutes of Health Cancer Center Support Grant at Memorial Sloan Kettering Cancer Center.

Dr. Skoulidis reported honoraria from Bristol-Myers Squibb; research funding from AIMM Therapeutics and Amgen; and travel, accommodations, or expenses from Tango Therapeutics. Dr. Lovly reported disclosures related to Amgen, AstraZeneca, Genentech, Novartis, and Pfizer, among others.

The first KRAS inhibitor approved for the treatment of lung cancer provided a clinically meaningful overall survival benefit in an updated analysis of a phase 2 study.

Treatment with sotorasib yielded a median overall survival (OS) of 12.5 months in patients with previously treated KRAS p.G12C-mutated non-small cell lung cancer (NSCLC), according to an analysis of the phase 2 CodeBreaK 100 trial data presented at the American Society of Clinical Oncology Annual Meeting.

Median progression-free survival (PFS) was 6.8 months in this update, which included a median follow-up of more than 15 months, according to investigator Ferdinandos Skoulidis, MD, PhD, assistant professor of thoracic/head and neck medical oncology at the University of Texas MD Anderson Cancer Center in Houston.

Efficacy responses

The confirmed objective response rate was 37.1%, including a 3.2% complete response rate and a median duration of response of 11.1 months, according to the report by Dr. Skoulidis.

In exploratory analyses, the benefit of sotorasib was consistent across patient subgroups, Dr. Skoulidis said in his presentation (Abstract 9003).

In particular, efficacy was observed in subgroups with co-occurring mutations in TP53, STK11, and KEAP1, which are molecular indicators of suboptimal outcomes on standard systemic treatments, according to Dr. Skoulidis.

This update on the registrational phase 2 CodeBreaK100 trial, published concurrently in the New England Journal of Medicine , came just one week after the U.S. Food and Drug Administration (FDA) granted accelerated approval to sotorasib.

Sotorasib was approved for the treatment of patients with previously treated KRAS G12C‑mutated locally advanced or metastatic NSCLC on the basis of previously reported results from CodeBreaK100.

This sotorasib indication represents a “historic milestone,” Dr. Skoulidis said in an interview.

No previously studied selective KRAS inhibitor has been approved despite scientific research efforts that stretch back nearly four decades, he explained.

“In a way, one can say that we have dealt KRAS-mutant lung cancer a knockdown blow, however, I should point out that the fight is not over,” he added.

“These clinical results will no doubt spearhead and galvanize further efforts to develop even more effective therapeutic combinations in the future, as well as identify and either forestall or overcome the eventual development of acquired resistance,” he said.
 

Only 1 out of 8 patients

The KRAS p.G12C mutation is present in about 13% of lung adenocarcinomas, or about one in every eight patients with nonsquamous NSCLC, Dr. Skoulidis said in the interview.

“We are estimating that this is in the region of 13,000 patients newly diagnosed every year in the U.S., and approximately 13,000 patients or so that are currently being treated in the second- or third-line setting,” he said.

The CodeBreaK100 trial included 126 patients with locally advanced or metastatic NSCLC and KRAS p.G12C mutation who had progressed on prior systemic therapies. About 43% had one prior line of treatment, while 35% had two lines, and 22% had three lines. A total of 81% had previously received both platinum-based chemotherapy and PD-1/PD-L1 axis inhibitors.

Most treatment-related adverse events in the study were grade 1-2 and generally manageable, according to Dr. Skoulidis. About 20% of patients experienced grade 3 treatment-related adverse events, which were mostly diarrhea or increases in aspartate aminotransferase and alanine aminotransferase levels. A grade 4 treatment-related adverse event, pneumonitis and dyspnea, was reported in one patient or approximately 1%.
 

Confirmatory trial

Although CodeBreak100 is not a randomized trial, the median OS of 12.5 months compares favorably to median OS times in the range of 7.9-10.3 months reported in randomized phase 3 clinical trials and subgroup analysis of randomized phase 3 trials of docetaxel for patients with KRAS-mutant lung adenocarcinoma, Dr. Skoulidis said in a question-and-answer session.

A confirmatory phase 3 CodeBreaK200 trial of sotorasib versus docetaxel in patients with previously treated KRAS p.G12C-mutated NSCLC is underway. That trial is evaluating PFS as a primary endpoint and OS as a secondary endpoint.

“If the same magnitude of benefit, 12.5 months median overall survival, is confirmed in the larger phase 3 clinical trial, as a clinician I would consider that beneficial for patients, compared to the standard of care,” Dr. Skoulidis said during the session.
 

Mature data

The updated analysis of the phase 2 CodeBreaK100 study is notable for its mature OS data, updated safety and the first molecular subgroup analyses, according to discussant Christine Marie Lovly, MD, PhD, of the division of hematology-oncology at Vanderbilt University Medical Center in Nashville.

“The objective response rate was 37.1%,” she added. “This is a little bit lower than we’re used to for targeted therapies, but remember, this is a different mutation and a very different class of drugs.”

The KRAS G12C inhibitors, several of which are under clinical development, are not tyrosine kinase inhibitors (TKIs), but rather allele-specific inhibitors that target mutant KRAS, trapping it in an inactive conformation, she explained.

Dr. Lovly referenced the exploratory analyses demonstrating efficacy in molecularly defined subgroups, calling it “interesting” that there was no difference in objective response rate between TP53 wild type and mutant tumors.

“We do have data that mutant TP53 seems to confer inferior outcomes for EGFR TKI-directed therapy in patients with EGFR-mutant lung cancer,” she said.

CodeBreaK100 was supported by Amgen, Inc. and partly by a National Institutes of Health Cancer Center Support Grant at Memorial Sloan Kettering Cancer Center.

Dr. Skoulidis reported honoraria from Bristol-Myers Squibb; research funding from AIMM Therapeutics and Amgen; and travel, accommodations, or expenses from Tango Therapeutics. Dr. Lovly reported disclosures related to Amgen, AstraZeneca, Genentech, Novartis, and Pfizer, among others.