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ERBB2 expression predicts pCR in HER2+ breast cancer
SAN ANTONIO – Among patients receiving trastuzumab plus lapatinib neoadjuvant therapy for HER2-positive early breast cancer, amplification of ERBB2 was predictive of a pathologic complete response (pCR), according to findings presented at the San Antonio Breast Cancer Symposium.
However, ERBB2 mRNA expression and PAM50-enriched HER2 better predicted pCR, said lead study author Cristos Sotiriou, MD, of the Breast Cancer Translational Research Laboratory at the Institut Jules Bordet in Belgium
High genomic instability was associated with a higher pCR rate in patients with estrogen receptor–positive tumors, but copy number alterations (CNAs) were not associated with event-free survival (EFS).
In the large phase 3 NeoALTTO trial, lapatinib combined with trastuzumab in the neoadjuvant setting nearly doubled the pCR rate as compared with either agent used alone. The 3-year EFS was also improved with dual HER2 blockage versus single HER2 therapy (84% for the combination, hazard ratio, 0.78; P = .33 vs. 78% for lapatinib alone and 76% for trastuzumab alone, HR, 1.06; P = .81 for both).
The researchers of this trial also found that pCR was a surrogate for long-term outcome.
“Expression of ERBB2, ESR1, and immune signatures were the main drivers of pCR,” said Dr. Sotiriou.
The main goal of the current study was to investigate the relevance of CNAs for pCR and EFS in this population. A total of 455 patients were enrolled in the NeoALTTO study, and of this cohort, 270 had tumor content that was sufficient to assay for CNAs. Tumor-infiltrating lymphocytes and gene expression were also obtained and the genome instability index was calculated, and 184 samples were included in the final analysis.
Of the cancer genes, only ERBB2 was predictive of pCR.
A total of 159 recurrent CNA regions were identified. ERBB2 amplification was associated with high pCR (P = .0007), but less than ERBB2 expression, and it lost its significance after correcting for ERBB2 expression.
The genome instability index (GII) was defined as the “median absolute deviation of the normalized copy number” and independent of ERBB2 amplification, the pCR rate increased with the GII (P = .03.
Amplification of two regions on 6q23-24 was significantly associated with higher pCR (P = .00005 and P = .00087). One of the segments harbored 39 genes, some with an expression level that was also predictive of pCR. The 6q23-24 segment was associated with pCR in estrogen receptor–positive tumors only (interaction test P = .04).
After multiple testing correction, there were no amplified regions or genes found to be predictive of EFS.
“A novel amplified region on 6q23-24 was shown to be predictive of pCR, in particular for estrogen receptor–positive tumors,” said Dr. Sotiriou. “This may warrant further investigation.”
SOURCE: Sotiriou et al. SABCS Abstract GS1-04
SAN ANTONIO – Among patients receiving trastuzumab plus lapatinib neoadjuvant therapy for HER2-positive early breast cancer, amplification of ERBB2 was predictive of a pathologic complete response (pCR), according to findings presented at the San Antonio Breast Cancer Symposium.
However, ERBB2 mRNA expression and PAM50-enriched HER2 better predicted pCR, said lead study author Cristos Sotiriou, MD, of the Breast Cancer Translational Research Laboratory at the Institut Jules Bordet in Belgium
High genomic instability was associated with a higher pCR rate in patients with estrogen receptor–positive tumors, but copy number alterations (CNAs) were not associated with event-free survival (EFS).
In the large phase 3 NeoALTTO trial, lapatinib combined with trastuzumab in the neoadjuvant setting nearly doubled the pCR rate as compared with either agent used alone. The 3-year EFS was also improved with dual HER2 blockage versus single HER2 therapy (84% for the combination, hazard ratio, 0.78; P = .33 vs. 78% for lapatinib alone and 76% for trastuzumab alone, HR, 1.06; P = .81 for both).
The researchers of this trial also found that pCR was a surrogate for long-term outcome.
“Expression of ERBB2, ESR1, and immune signatures were the main drivers of pCR,” said Dr. Sotiriou.
The main goal of the current study was to investigate the relevance of CNAs for pCR and EFS in this population. A total of 455 patients were enrolled in the NeoALTTO study, and of this cohort, 270 had tumor content that was sufficient to assay for CNAs. Tumor-infiltrating lymphocytes and gene expression were also obtained and the genome instability index was calculated, and 184 samples were included in the final analysis.
Of the cancer genes, only ERBB2 was predictive of pCR.
A total of 159 recurrent CNA regions were identified. ERBB2 amplification was associated with high pCR (P = .0007), but less than ERBB2 expression, and it lost its significance after correcting for ERBB2 expression.
The genome instability index (GII) was defined as the “median absolute deviation of the normalized copy number” and independent of ERBB2 amplification, the pCR rate increased with the GII (P = .03.
Amplification of two regions on 6q23-24 was significantly associated with higher pCR (P = .00005 and P = .00087). One of the segments harbored 39 genes, some with an expression level that was also predictive of pCR. The 6q23-24 segment was associated with pCR in estrogen receptor–positive tumors only (interaction test P = .04).
After multiple testing correction, there were no amplified regions or genes found to be predictive of EFS.
“A novel amplified region on 6q23-24 was shown to be predictive of pCR, in particular for estrogen receptor–positive tumors,” said Dr. Sotiriou. “This may warrant further investigation.”
SOURCE: Sotiriou et al. SABCS Abstract GS1-04
SAN ANTONIO – Among patients receiving trastuzumab plus lapatinib neoadjuvant therapy for HER2-positive early breast cancer, amplification of ERBB2 was predictive of a pathologic complete response (pCR), according to findings presented at the San Antonio Breast Cancer Symposium.
However, ERBB2 mRNA expression and PAM50-enriched HER2 better predicted pCR, said lead study author Cristos Sotiriou, MD, of the Breast Cancer Translational Research Laboratory at the Institut Jules Bordet in Belgium
High genomic instability was associated with a higher pCR rate in patients with estrogen receptor–positive tumors, but copy number alterations (CNAs) were not associated with event-free survival (EFS).
In the large phase 3 NeoALTTO trial, lapatinib combined with trastuzumab in the neoadjuvant setting nearly doubled the pCR rate as compared with either agent used alone. The 3-year EFS was also improved with dual HER2 blockage versus single HER2 therapy (84% for the combination, hazard ratio, 0.78; P = .33 vs. 78% for lapatinib alone and 76% for trastuzumab alone, HR, 1.06; P = .81 for both).
The researchers of this trial also found that pCR was a surrogate for long-term outcome.
“Expression of ERBB2, ESR1, and immune signatures were the main drivers of pCR,” said Dr. Sotiriou.
The main goal of the current study was to investigate the relevance of CNAs for pCR and EFS in this population. A total of 455 patients were enrolled in the NeoALTTO study, and of this cohort, 270 had tumor content that was sufficient to assay for CNAs. Tumor-infiltrating lymphocytes and gene expression were also obtained and the genome instability index was calculated, and 184 samples were included in the final analysis.
Of the cancer genes, only ERBB2 was predictive of pCR.
A total of 159 recurrent CNA regions were identified. ERBB2 amplification was associated with high pCR (P = .0007), but less than ERBB2 expression, and it lost its significance after correcting for ERBB2 expression.
The genome instability index (GII) was defined as the “median absolute deviation of the normalized copy number” and independent of ERBB2 amplification, the pCR rate increased with the GII (P = .03.
Amplification of two regions on 6q23-24 was significantly associated with higher pCR (P = .00005 and P = .00087). One of the segments harbored 39 genes, some with an expression level that was also predictive of pCR. The 6q23-24 segment was associated with pCR in estrogen receptor–positive tumors only (interaction test P = .04).
After multiple testing correction, there were no amplified regions or genes found to be predictive of EFS.
“A novel amplified region on 6q23-24 was shown to be predictive of pCR, in particular for estrogen receptor–positive tumors,” said Dr. Sotiriou. “This may warrant further investigation.”
SOURCE: Sotiriou et al. SABCS Abstract GS1-04
REPORTING FROM SABCS 2017
Key clinical point: ERBB2 mRNA expression and PAM50-enriched HER2 better predicted pathologic complete response than did EEBB2 amplification.
Major finding: Of the cancer genes, only ERBB2 was predictive of pCR, and amplification of two regions on 6q23-24 was significantly associated with higher pCR (P = .00005 and P = .00087).
Data source: An analysis of the large phase 3 NeoALTTO trial, in which lapatinib was combined with trastuzumab in the neoadjuvant setting to investigate the relevance of copy number alterations on outcome.
Disclosures: The NeoALTTO trial was funded by GlaxoSmithKline. Dr. Sotiriou did not make any disclosures.
Source: Sotiriou et al. SABCS Abstract GS1-04
Zika RNA persists in blood components after clearance from plasma
SAN DIEGO – Zika virus can persist in blood components for several months, long after it is no longer detectable in plasma and other body fluids, based on data reported at the annual meeting of the American Association of Blood Banks.
The presence of Zika virus in plasma declined rapidly following donation, but could be detected in red blood cells (RBCs) and whole blood for up to 3 months. In addition, the virus was also detected intermittently in peripheral blood mononuclear cells (PBMCs) at low levels after clearance from plasma.
“There was longer persistence of Zika RNA in whole blood and RBC blood components than in plasma and other body fluids. It was detected at high levels and persists for about 6 weeks,” Mars Stone, PhD said in presenting the findings.
The findings were based on 2016 data collected in Puerto Rico, which began screening blood donations for Zika virus RNA under an investigational protocol by using a nucleic acid test; they began doing so as a result of guidance from the U.S. Food and Drug Administration. Approximately 350 confirmed infected – that is, nucleic acid test positive (NAT+) – donations were detected through December 2016.
The FDA approved the cobas Zika test used in the study on October 5. Intended for use by blood collection establishments to detect Zika virus in blood donations, the test is manufactured by Roche Molecular Systems. Dr. Stone is an employee of Blood Systems Research Institute, a confirmatory laboratory for Roche.
Of the 52,942 donations collected between April 3 and Dec. 31, 352 were reactive for ZIKV RNA. Plasma from blood donors was screened by individual donation NAT for the presence of ZIKV RNA with the cobas Zika test. At an interval of between 57 and 120 days, no Zika RNA was found in 350 samples of plasma, but it was found in 38.2% (34 samples) of RBCs and 40.0% (35 samples) of whole blood.
In urine and saliva, the virus was detected in high levels at 1-2 weeks, but then rapidly waned. In semen, it was detected at high levels and persisted for about 6 weeks.
“But despite the huge epidemics in Latin America, Puerto Rico, and the other Caribbean islands, there have been no cases of transfusion-related infections linked to RBC transfusions when plasma NAT screening was negative,” said Dr. Stone. “So we are tentatively confirming that red cell–associated virus is not infectious and that plasma NAT screening is likely sufficient.”
The authors point out that RNA persistence has been reported in whole blood long after the virus cleared from plasma and therefore have raised concerns about the risk of transfusion-related viral transmission. The goal of the current study was to characterize the dynamics of infection using donors who were infected with Zika virus.
To date there are 56 donors enrolled in the study, primarily male and from Puerto Rico. Most of them are also positive for dengue fever, Dr. Stone pointed out. “The epidemic in Puerto Rico reached peak in June 2016 but has very little activity this year.”
Plasma and RBCs were collected from index donations, while blood, urine, saliva, and semen samples were collected prospectively at weeks 1, 3, 6, 12, and 24 following index donations. Blood compartments and body fluids were tested for Zika RNA by real time reverse transcription polymerase chain reaction testing, and plasma samples were tested for Zika-specific immunoglobulin M and immunoglobulin G antibodies.
In plasma, Zika virus RNA rapidly decreased after index donations but persisted for up to 3 months in RBCs and whole blood. In peripheral blood mononuclear cells, Zika virus was detected intermittently at low levels but waned by 3 months. In peripheral blood mononuclear cells, Zika RNA was detected in 5.9% (17 samples) at 121-196 days.
Among donors who entered the study while in the acute preseroconversion stage of infection, 65% developed Zika virus symptoms at 1 week post index donation, compared with 30% of donors detected after seroconversion.
The study was funded by the U.S. Department of Health & Human Services.
SAN DIEGO – Zika virus can persist in blood components for several months, long after it is no longer detectable in plasma and other body fluids, based on data reported at the annual meeting of the American Association of Blood Banks.
The presence of Zika virus in plasma declined rapidly following donation, but could be detected in red blood cells (RBCs) and whole blood for up to 3 months. In addition, the virus was also detected intermittently in peripheral blood mononuclear cells (PBMCs) at low levels after clearance from plasma.
“There was longer persistence of Zika RNA in whole blood and RBC blood components than in plasma and other body fluids. It was detected at high levels and persists for about 6 weeks,” Mars Stone, PhD said in presenting the findings.
The findings were based on 2016 data collected in Puerto Rico, which began screening blood donations for Zika virus RNA under an investigational protocol by using a nucleic acid test; they began doing so as a result of guidance from the U.S. Food and Drug Administration. Approximately 350 confirmed infected – that is, nucleic acid test positive (NAT+) – donations were detected through December 2016.
The FDA approved the cobas Zika test used in the study on October 5. Intended for use by blood collection establishments to detect Zika virus in blood donations, the test is manufactured by Roche Molecular Systems. Dr. Stone is an employee of Blood Systems Research Institute, a confirmatory laboratory for Roche.
Of the 52,942 donations collected between April 3 and Dec. 31, 352 were reactive for ZIKV RNA. Plasma from blood donors was screened by individual donation NAT for the presence of ZIKV RNA with the cobas Zika test. At an interval of between 57 and 120 days, no Zika RNA was found in 350 samples of plasma, but it was found in 38.2% (34 samples) of RBCs and 40.0% (35 samples) of whole blood.
In urine and saliva, the virus was detected in high levels at 1-2 weeks, but then rapidly waned. In semen, it was detected at high levels and persisted for about 6 weeks.
“But despite the huge epidemics in Latin America, Puerto Rico, and the other Caribbean islands, there have been no cases of transfusion-related infections linked to RBC transfusions when plasma NAT screening was negative,” said Dr. Stone. “So we are tentatively confirming that red cell–associated virus is not infectious and that plasma NAT screening is likely sufficient.”
The authors point out that RNA persistence has been reported in whole blood long after the virus cleared from plasma and therefore have raised concerns about the risk of transfusion-related viral transmission. The goal of the current study was to characterize the dynamics of infection using donors who were infected with Zika virus.
To date there are 56 donors enrolled in the study, primarily male and from Puerto Rico. Most of them are also positive for dengue fever, Dr. Stone pointed out. “The epidemic in Puerto Rico reached peak in June 2016 but has very little activity this year.”
Plasma and RBCs were collected from index donations, while blood, urine, saliva, and semen samples were collected prospectively at weeks 1, 3, 6, 12, and 24 following index donations. Blood compartments and body fluids were tested for Zika RNA by real time reverse transcription polymerase chain reaction testing, and plasma samples were tested for Zika-specific immunoglobulin M and immunoglobulin G antibodies.
In plasma, Zika virus RNA rapidly decreased after index donations but persisted for up to 3 months in RBCs and whole blood. In peripheral blood mononuclear cells, Zika virus was detected intermittently at low levels but waned by 3 months. In peripheral blood mononuclear cells, Zika RNA was detected in 5.9% (17 samples) at 121-196 days.
Among donors who entered the study while in the acute preseroconversion stage of infection, 65% developed Zika virus symptoms at 1 week post index donation, compared with 30% of donors detected after seroconversion.
The study was funded by the U.S. Department of Health & Human Services.
SAN DIEGO – Zika virus can persist in blood components for several months, long after it is no longer detectable in plasma and other body fluids, based on data reported at the annual meeting of the American Association of Blood Banks.
The presence of Zika virus in plasma declined rapidly following donation, but could be detected in red blood cells (RBCs) and whole blood for up to 3 months. In addition, the virus was also detected intermittently in peripheral blood mononuclear cells (PBMCs) at low levels after clearance from plasma.
“There was longer persistence of Zika RNA in whole blood and RBC blood components than in plasma and other body fluids. It was detected at high levels and persists for about 6 weeks,” Mars Stone, PhD said in presenting the findings.
The findings were based on 2016 data collected in Puerto Rico, which began screening blood donations for Zika virus RNA under an investigational protocol by using a nucleic acid test; they began doing so as a result of guidance from the U.S. Food and Drug Administration. Approximately 350 confirmed infected – that is, nucleic acid test positive (NAT+) – donations were detected through December 2016.
The FDA approved the cobas Zika test used in the study on October 5. Intended for use by blood collection establishments to detect Zika virus in blood donations, the test is manufactured by Roche Molecular Systems. Dr. Stone is an employee of Blood Systems Research Institute, a confirmatory laboratory for Roche.
Of the 52,942 donations collected between April 3 and Dec. 31, 352 were reactive for ZIKV RNA. Plasma from blood donors was screened by individual donation NAT for the presence of ZIKV RNA with the cobas Zika test. At an interval of between 57 and 120 days, no Zika RNA was found in 350 samples of plasma, but it was found in 38.2% (34 samples) of RBCs and 40.0% (35 samples) of whole blood.
In urine and saliva, the virus was detected in high levels at 1-2 weeks, but then rapidly waned. In semen, it was detected at high levels and persisted for about 6 weeks.
“But despite the huge epidemics in Latin America, Puerto Rico, and the other Caribbean islands, there have been no cases of transfusion-related infections linked to RBC transfusions when plasma NAT screening was negative,” said Dr. Stone. “So we are tentatively confirming that red cell–associated virus is not infectious and that plasma NAT screening is likely sufficient.”
The authors point out that RNA persistence has been reported in whole blood long after the virus cleared from plasma and therefore have raised concerns about the risk of transfusion-related viral transmission. The goal of the current study was to characterize the dynamics of infection using donors who were infected with Zika virus.
To date there are 56 donors enrolled in the study, primarily male and from Puerto Rico. Most of them are also positive for dengue fever, Dr. Stone pointed out. “The epidemic in Puerto Rico reached peak in June 2016 but has very little activity this year.”
Plasma and RBCs were collected from index donations, while blood, urine, saliva, and semen samples were collected prospectively at weeks 1, 3, 6, 12, and 24 following index donations. Blood compartments and body fluids were tested for Zika RNA by real time reverse transcription polymerase chain reaction testing, and plasma samples were tested for Zika-specific immunoglobulin M and immunoglobulin G antibodies.
In plasma, Zika virus RNA rapidly decreased after index donations but persisted for up to 3 months in RBCs and whole blood. In peripheral blood mononuclear cells, Zika virus was detected intermittently at low levels but waned by 3 months. In peripheral blood mononuclear cells, Zika RNA was detected in 5.9% (17 samples) at 121-196 days.
Among donors who entered the study while in the acute preseroconversion stage of infection, 65% developed Zika virus symptoms at 1 week post index donation, compared with 30% of donors detected after seroconversion.
The study was funded by the U.S. Department of Health & Human Services.
AT AABB17
Key clinical point: Zika virus can persist in cellular blood components for months after clearance from plasma.
Major finding: Plasma viremia rapidly declined after index donations, but
Data source: Zika RNA persistence in blood components after clearance of viremia in plasma was evaluated in 56 donors positive for Zika virus.
Disclosures: Dr. Stone is an employee of Blood Systems Research Institute in San Francisco, a confirmatory laboratory for Roche Molecular Systems, which manufactures the testing device used. The study was funded by the U.S. Department of Health & Human Services.
Source: Stone M et al. AABB 2017 Abstract C9-A01AC.
High rate of arm morbidity in young breast cancer survivors
SAN ANTONIO – as compared with having a sentinel lymph node biopsy (SLNB), according to new findings.
In a large prospective cohort study that included 1,302 breast cancer patients aged 40 or younger, the incidence of arm swelling 1 year after diagnosis among women who underwent breast-conserving surgery was 6% for the SLNB group versus 24% for those who had ALND. Among patients who had a mastectomy, the rates were similar; 6% versus 23% for SLNB or ALND, respectively.
“Young breast cancer survivors report high rates of arm morbidity in the first year of follow-up,” said lead author Anne Kuijer, MD, of Dana-Farber Cancer Institute/Brigham and Women’s Hospital in Boston. “Axillary node dissection, increased BMI [body mass index] and socioeconomic status were all independently associated with an increased risk of arm swelling,” she said at the San Antonio Breast Cancer Symposium.
She noted that patients who received mastectomy with radiation therapy were twice as likely to have decreased range of motion at 1 year, compared with patients treated with breast-conserving treatment.
In this study, the authors evaluated the incidence of arm morbidity associated with both ALND and SLNB in patients who were enrolled in the Young Women’s Breast Cancer Study. This multicenter prospective cohort study was designed to explore biological, medical, and psychosocial issues experienced by young breast cancer patients.
Within this large cohort, 55% had undergone an SLNB only, and 41% an ALND. The remaining patients did not undergo either procedure.
The primary endpoint of this study was to examine the incidence of patient-reported arm swelling or decreased range of motion at 1 year after their breast cancer diagnosis. Patients used the Cancer Rehabilitation Evaluation System (CARES-SF) to measure their symptoms.
Overall, at 1 year, 13% of the cohort reported arm swelling, and 40% reported decreased range of motion in the ipsilateral arm.
Several factors were associated with a higher risk of arm morbidity. Patients with a BMI of greater than 25 were more likely to report arm swelling vs. those with lower BMI (odds ratio, 1.7; P = .03) as well as have less range of motion (OR, 1.5; P = .05). Women who reported feeling financially comfortable were 40% less likely to report swelling (P = .02) and 90% less likely to report decreased range of motion (P = .67).
In addition, those who underwent ALND were 3.4 times more likely to report swelling, compared with women who had SLNB, but it was not associated with a reduction in range of motion.
One limitation of the study is that the cohort included patients who had received treatment at large cancer centers in the Northeast, suggesting that they may have been of higher socioeconomic status and may have led more active lifestyles, compared with the general population. Another limitation is that arm morbidity was self-reported and not objectively measured.
“I think our findings highlight opportunities for preoperative counseling, early referral of patients to physical therapy, and identification of resources for support of those at increased risk,” said Dr. Kuijer.
SOURCE: Kuijer et al. SABCS Abstract GS5-03
SAN ANTONIO – as compared with having a sentinel lymph node biopsy (SLNB), according to new findings.
In a large prospective cohort study that included 1,302 breast cancer patients aged 40 or younger, the incidence of arm swelling 1 year after diagnosis among women who underwent breast-conserving surgery was 6% for the SLNB group versus 24% for those who had ALND. Among patients who had a mastectomy, the rates were similar; 6% versus 23% for SLNB or ALND, respectively.
“Young breast cancer survivors report high rates of arm morbidity in the first year of follow-up,” said lead author Anne Kuijer, MD, of Dana-Farber Cancer Institute/Brigham and Women’s Hospital in Boston. “Axillary node dissection, increased BMI [body mass index] and socioeconomic status were all independently associated with an increased risk of arm swelling,” she said at the San Antonio Breast Cancer Symposium.
She noted that patients who received mastectomy with radiation therapy were twice as likely to have decreased range of motion at 1 year, compared with patients treated with breast-conserving treatment.
In this study, the authors evaluated the incidence of arm morbidity associated with both ALND and SLNB in patients who were enrolled in the Young Women’s Breast Cancer Study. This multicenter prospective cohort study was designed to explore biological, medical, and psychosocial issues experienced by young breast cancer patients.
Within this large cohort, 55% had undergone an SLNB only, and 41% an ALND. The remaining patients did not undergo either procedure.
The primary endpoint of this study was to examine the incidence of patient-reported arm swelling or decreased range of motion at 1 year after their breast cancer diagnosis. Patients used the Cancer Rehabilitation Evaluation System (CARES-SF) to measure their symptoms.
Overall, at 1 year, 13% of the cohort reported arm swelling, and 40% reported decreased range of motion in the ipsilateral arm.
Several factors were associated with a higher risk of arm morbidity. Patients with a BMI of greater than 25 were more likely to report arm swelling vs. those with lower BMI (odds ratio, 1.7; P = .03) as well as have less range of motion (OR, 1.5; P = .05). Women who reported feeling financially comfortable were 40% less likely to report swelling (P = .02) and 90% less likely to report decreased range of motion (P = .67).
In addition, those who underwent ALND were 3.4 times more likely to report swelling, compared with women who had SLNB, but it was not associated with a reduction in range of motion.
One limitation of the study is that the cohort included patients who had received treatment at large cancer centers in the Northeast, suggesting that they may have been of higher socioeconomic status and may have led more active lifestyles, compared with the general population. Another limitation is that arm morbidity was self-reported and not objectively measured.
“I think our findings highlight opportunities for preoperative counseling, early referral of patients to physical therapy, and identification of resources for support of those at increased risk,” said Dr. Kuijer.
SOURCE: Kuijer et al. SABCS Abstract GS5-03
SAN ANTONIO – as compared with having a sentinel lymph node biopsy (SLNB), according to new findings.
In a large prospective cohort study that included 1,302 breast cancer patients aged 40 or younger, the incidence of arm swelling 1 year after diagnosis among women who underwent breast-conserving surgery was 6% for the SLNB group versus 24% for those who had ALND. Among patients who had a mastectomy, the rates were similar; 6% versus 23% for SLNB or ALND, respectively.
“Young breast cancer survivors report high rates of arm morbidity in the first year of follow-up,” said lead author Anne Kuijer, MD, of Dana-Farber Cancer Institute/Brigham and Women’s Hospital in Boston. “Axillary node dissection, increased BMI [body mass index] and socioeconomic status were all independently associated with an increased risk of arm swelling,” she said at the San Antonio Breast Cancer Symposium.
She noted that patients who received mastectomy with radiation therapy were twice as likely to have decreased range of motion at 1 year, compared with patients treated with breast-conserving treatment.
In this study, the authors evaluated the incidence of arm morbidity associated with both ALND and SLNB in patients who were enrolled in the Young Women’s Breast Cancer Study. This multicenter prospective cohort study was designed to explore biological, medical, and psychosocial issues experienced by young breast cancer patients.
Within this large cohort, 55% had undergone an SLNB only, and 41% an ALND. The remaining patients did not undergo either procedure.
The primary endpoint of this study was to examine the incidence of patient-reported arm swelling or decreased range of motion at 1 year after their breast cancer diagnosis. Patients used the Cancer Rehabilitation Evaluation System (CARES-SF) to measure their symptoms.
Overall, at 1 year, 13% of the cohort reported arm swelling, and 40% reported decreased range of motion in the ipsilateral arm.
Several factors were associated with a higher risk of arm morbidity. Patients with a BMI of greater than 25 were more likely to report arm swelling vs. those with lower BMI (odds ratio, 1.7; P = .03) as well as have less range of motion (OR, 1.5; P = .05). Women who reported feeling financially comfortable were 40% less likely to report swelling (P = .02) and 90% less likely to report decreased range of motion (P = .67).
In addition, those who underwent ALND were 3.4 times more likely to report swelling, compared with women who had SLNB, but it was not associated with a reduction in range of motion.
One limitation of the study is that the cohort included patients who had received treatment at large cancer centers in the Northeast, suggesting that they may have been of higher socioeconomic status and may have led more active lifestyles, compared with the general population. Another limitation is that arm morbidity was self-reported and not objectively measured.
“I think our findings highlight opportunities for preoperative counseling, early referral of patients to physical therapy, and identification of resources for support of those at increased risk,” said Dr. Kuijer.
SOURCE: Kuijer et al. SABCS Abstract GS5-03
REPORTING FROM SABCS 2017
Key clinical point: A significant rate of arm swelling and decreased range of motion was seen in young breast cancer patients 1 year after undergoing surgery.
Major finding: At 1 year, 13% of a large cohort of breast cancer patients aged 40 years or younger reported arm swelling, and 40% reported decreased range of motion in the ipsilateral arm.
Data source: Large prospective cohort study that included 1,302 breast cancer patients aged 40 or younger.
Disclosures:. This study was funded by the National Institutes of Health, the Susan G. Komen Foundation, The Pink Agenda, and the Breast Cancer Research Foundation. Dr. Kuijer and her colleagues declare no conflicts of interest.
Source: Kuijer et al. SABCS 2017 Abstract GS5-03.
Zika virus testing shows low incidence in donor blood outside of high-infection areas
SAN DIEGO – The Zika virus is primarily transmitted via the Aedes mosquitoes, most commonly by A. aegypti, but recent outbreaks have revealed that nonvector transmission routes may also spread the infection. Some data suggest that blood transfusion can be a source of transmission.
While the number of contaminated blood donations remains very small, three studies presented at the American Association of Blood Banks annual meeting confirmed the ability of new investigational assays to detect Zika virus in donated blood.
There have been no confirmed transfusion-transmission cases of Zika virus in the United States, but as cases have now been documented in Brazil, the Food and Drug Administration issued revised guidance in August 2016 recommending that blood centers in all states and U.S. territories screen individual units of donated whole blood and blood components.
In the first report (C7-A01C), Paula Saá, PhD, and her colleagues at the American Red Cross initially investigated the use of mini-pool (MP)- nucleic acid testing (NAT) using the Procleix Zika Virus Assay (TMA). Testing was initially implemented on blood collections from Florida, Georgia, South Carolina, Mississippi, and Alabama – five states that were presumed to be at high risk of Zika virus infection. After the FDA revised its guidance, the protocol changed and testing was extended to all blood donations. The use of the MP-NAT was also converted to individual donation (ID)-NAT, and questions concerning travel history was also eventually discontinued.
However, even with the use of ID-NAT, the rate of confirmed positive donations was quite small but the associated cost was quite high, the researchers pointed out. “In the first year of testing at the American Red Cross, we identified nine confirmed positive donations,” said Dr. Saá.
The rate of confirmed positive donations was 1:354, 602 during the study period, but if the period up until September 2017 is taken into account (no additional cases were identified), the rate increases to 1:514,266. “This is a very low rate,” Dr. Saá said. “If there are no changes to the current guidelines, we have estimated that the yearly cost for the American Red Cross of testing will exceed $48 million.”
These figures extrapolate to approximately $6 million per confirmed case, according to the results of this study sponsored by the American Red Cross.
Confirmatory testing included repeat TMA; in addition, RT-PCR, serology and red blood cell count (RBC) TMA were performed. Estimates of viral loads were performed by endpoint TMA on plasma and RBCs.
A total of 2,288,855 blood donations had been tested as of April 2017, including 393,713 (17%) in 24,611 MPs, which did not detect any reactive donations.
Of the confirmed positive blood donors, three lived in Florida and two of those were from local transmission. Six individuals had traveled to a region highly active for Zika virus, and returned to the United States between 2 and 73 days before donating blood. Clinical symptoms were reported in two individuals with a travel risk; the other donors with a confirmed positive test (75%) remained asymptomatic. The longest period for detection in RBCs was 91 days thus far, but in the same person, detection in plasma was only 17 days.
“The data that we are showing here recommends a testing strategy with mini pool testing in areas at low risk of Zika transmission,” said Dr. Saá.
A second related study (C9-A01C), described the detection of ZIKV RNA in blood donations collected in U.S. states between April 3, 2016, and September 23, 2017, using the cobas Zika test, to be used on the cobas 6800/8800 Systems.
Although the test was investigational during the study period, it has just been approved by the FDA, said study author Lisa Pate, MD, who is with Roche Molecular Systems, the manufacturer of the cobas Zika test and cobas 6800/8800 systems. “This is now the first licensed test for screening blood donations for Zika virus.”
Overall, testing showed that Zika contamination in the U.S. blood supply was quite low. Only 0.001% of screened blood donations in United States were confirmed as true positives.
The development of this test came about after the first cases of Zika virus in the United States were detected in Puerto Rico in December 2015, explained Dr. Pate. Shortly after that, the FDA issued guidance prohibiting the use of blood collected in Zika active areas, unless the donations were screened.
“The impact was significant in Puerto Rico, as blood donations were halted, which then forced Puerto Rico to rely on imported blood,” she said.
About that time the FDA reached out to Roche and competitors to see if a test could be developed to screen for Zika.
The cobas Zika test was approved under an investigational new drug application on March 30, 2016, and although initially used to test blood samples in Puerto Rico, testing was expanded to include donor blood from all over the country.
Screening was conducted by individual donation testing, with all initial reactive results repeated in duplicate. Supplemental testing was also done, and included an alternative NAT (AltNAT) assay which was considered to be less sensitive than cobas Zika and serology testing for anti-Zika IgM and IgG. A donor confirmed Zika confirmed positive if at least one replicate of the repeat testing by cobas Zika was reactive on index donation or follow-up, reactive by AltNAT on the index donation, or positive for anti-Zika IgM on index or follow-up.
Screening was conducted at 12 testing labs in the United States, and more than 4 million donations were screened and 27 positive donations were confirmed. Overall, that amounted to less than 1 in 100,000.
“For donors in the U.S. with confirmed positive results, and for whom follow-up information is available, 84% of them report recent travel to Zika active areas,” noted Dr. Pate.
For Puerto Rico, 111,842 blood donations were screened and there were 356 confirmed positive results. The incidence is much higher than in United States, and was 1.27% during peak incidence in July 2016.
A third paper (C12-A01C), also reported on testing the blood supply in Singapore, which had reported its first locally transmitted Zika case last August, using the investigational Procleix ZIKV nucleic acid technology (NAT) assay.
The presence of Zika virus in screened blood was also quite low, with an incidence of only 0.0032%. The Procleix ZIKV assay was found to suitable for screening for Zika infection in an asymptomatic population, as it showed good analytical sensitivity and clinical performance.
The Zika virus came to Singapore in May 2016, imported by an individual who had recently traveled to Brazil, said Sally Lam, laboratory director, Blood Services Group, Health Sciences Authority, Singapore.
“Then in August we had 41 confirmed local Zika virus cases,” she said.
In 2016, there were 458 clinical Zika cases reported, with 8 clusters identified. This year, 63 cases have been reported to date, she said.
Mandatory Zika virus screening in donor blood with ID-NAT began after the onset of local outbreaks, and was implemented in January 2017. A total of 126,906 blood donations were screened.
Researchers in Singapore assessed the performance of the Procleix ZIKV NAT assay for universal blood donation screening. They screened all blood that was donated, beginning Oct. 1, 2016, a confirmed case was defined as having Zika RNA by PCR and/or Zika antibodies. Analytical sensitivity was assessed by use of 300 blinded frozen samples containing Zika virus and 25 negative controls. The performance of the Procleix ZIKV assay was also evaluated by use of samples from the local patient population.
Of four confirmed positive cases, only one was available for follow-up. “In the index donation, the viral load was quite high in the plasma but at 10 days, it was reduced to about 400 copies/mL in the plasma,” said Ms. Lam. “The donor did not develop any symptoms.”
The analytical sensitivity for the Procleix ZIKV assay was determined to be 2.1 copies/mL at 50% LOD and 10.0 copies/mL at 95% LOD, and it detected RNA in six out of nine patient samples for an 85.7% agreement with reference material, according to the researchers.
SAN DIEGO – The Zika virus is primarily transmitted via the Aedes mosquitoes, most commonly by A. aegypti, but recent outbreaks have revealed that nonvector transmission routes may also spread the infection. Some data suggest that blood transfusion can be a source of transmission.
While the number of contaminated blood donations remains very small, three studies presented at the American Association of Blood Banks annual meeting confirmed the ability of new investigational assays to detect Zika virus in donated blood.
There have been no confirmed transfusion-transmission cases of Zika virus in the United States, but as cases have now been documented in Brazil, the Food and Drug Administration issued revised guidance in August 2016 recommending that blood centers in all states and U.S. territories screen individual units of donated whole blood and blood components.
In the first report (C7-A01C), Paula Saá, PhD, and her colleagues at the American Red Cross initially investigated the use of mini-pool (MP)- nucleic acid testing (NAT) using the Procleix Zika Virus Assay (TMA). Testing was initially implemented on blood collections from Florida, Georgia, South Carolina, Mississippi, and Alabama – five states that were presumed to be at high risk of Zika virus infection. After the FDA revised its guidance, the protocol changed and testing was extended to all blood donations. The use of the MP-NAT was also converted to individual donation (ID)-NAT, and questions concerning travel history was also eventually discontinued.
However, even with the use of ID-NAT, the rate of confirmed positive donations was quite small but the associated cost was quite high, the researchers pointed out. “In the first year of testing at the American Red Cross, we identified nine confirmed positive donations,” said Dr. Saá.
The rate of confirmed positive donations was 1:354, 602 during the study period, but if the period up until September 2017 is taken into account (no additional cases were identified), the rate increases to 1:514,266. “This is a very low rate,” Dr. Saá said. “If there are no changes to the current guidelines, we have estimated that the yearly cost for the American Red Cross of testing will exceed $48 million.”
These figures extrapolate to approximately $6 million per confirmed case, according to the results of this study sponsored by the American Red Cross.
Confirmatory testing included repeat TMA; in addition, RT-PCR, serology and red blood cell count (RBC) TMA were performed. Estimates of viral loads were performed by endpoint TMA on plasma and RBCs.
A total of 2,288,855 blood donations had been tested as of April 2017, including 393,713 (17%) in 24,611 MPs, which did not detect any reactive donations.
Of the confirmed positive blood donors, three lived in Florida and two of those were from local transmission. Six individuals had traveled to a region highly active for Zika virus, and returned to the United States between 2 and 73 days before donating blood. Clinical symptoms were reported in two individuals with a travel risk; the other donors with a confirmed positive test (75%) remained asymptomatic. The longest period for detection in RBCs was 91 days thus far, but in the same person, detection in plasma was only 17 days.
“The data that we are showing here recommends a testing strategy with mini pool testing in areas at low risk of Zika transmission,” said Dr. Saá.
A second related study (C9-A01C), described the detection of ZIKV RNA in blood donations collected in U.S. states between April 3, 2016, and September 23, 2017, using the cobas Zika test, to be used on the cobas 6800/8800 Systems.
Although the test was investigational during the study period, it has just been approved by the FDA, said study author Lisa Pate, MD, who is with Roche Molecular Systems, the manufacturer of the cobas Zika test and cobas 6800/8800 systems. “This is now the first licensed test for screening blood donations for Zika virus.”
Overall, testing showed that Zika contamination in the U.S. blood supply was quite low. Only 0.001% of screened blood donations in United States were confirmed as true positives.
The development of this test came about after the first cases of Zika virus in the United States were detected in Puerto Rico in December 2015, explained Dr. Pate. Shortly after that, the FDA issued guidance prohibiting the use of blood collected in Zika active areas, unless the donations were screened.
“The impact was significant in Puerto Rico, as blood donations were halted, which then forced Puerto Rico to rely on imported blood,” she said.
About that time the FDA reached out to Roche and competitors to see if a test could be developed to screen for Zika.
The cobas Zika test was approved under an investigational new drug application on March 30, 2016, and although initially used to test blood samples in Puerto Rico, testing was expanded to include donor blood from all over the country.
Screening was conducted by individual donation testing, with all initial reactive results repeated in duplicate. Supplemental testing was also done, and included an alternative NAT (AltNAT) assay which was considered to be less sensitive than cobas Zika and serology testing for anti-Zika IgM and IgG. A donor confirmed Zika confirmed positive if at least one replicate of the repeat testing by cobas Zika was reactive on index donation or follow-up, reactive by AltNAT on the index donation, or positive for anti-Zika IgM on index or follow-up.
Screening was conducted at 12 testing labs in the United States, and more than 4 million donations were screened and 27 positive donations were confirmed. Overall, that amounted to less than 1 in 100,000.
“For donors in the U.S. with confirmed positive results, and for whom follow-up information is available, 84% of them report recent travel to Zika active areas,” noted Dr. Pate.
For Puerto Rico, 111,842 blood donations were screened and there were 356 confirmed positive results. The incidence is much higher than in United States, and was 1.27% during peak incidence in July 2016.
A third paper (C12-A01C), also reported on testing the blood supply in Singapore, which had reported its first locally transmitted Zika case last August, using the investigational Procleix ZIKV nucleic acid technology (NAT) assay.
The presence of Zika virus in screened blood was also quite low, with an incidence of only 0.0032%. The Procleix ZIKV assay was found to suitable for screening for Zika infection in an asymptomatic population, as it showed good analytical sensitivity and clinical performance.
The Zika virus came to Singapore in May 2016, imported by an individual who had recently traveled to Brazil, said Sally Lam, laboratory director, Blood Services Group, Health Sciences Authority, Singapore.
“Then in August we had 41 confirmed local Zika virus cases,” she said.
In 2016, there were 458 clinical Zika cases reported, with 8 clusters identified. This year, 63 cases have been reported to date, she said.
Mandatory Zika virus screening in donor blood with ID-NAT began after the onset of local outbreaks, and was implemented in January 2017. A total of 126,906 blood donations were screened.
Researchers in Singapore assessed the performance of the Procleix ZIKV NAT assay for universal blood donation screening. They screened all blood that was donated, beginning Oct. 1, 2016, a confirmed case was defined as having Zika RNA by PCR and/or Zika antibodies. Analytical sensitivity was assessed by use of 300 blinded frozen samples containing Zika virus and 25 negative controls. The performance of the Procleix ZIKV assay was also evaluated by use of samples from the local patient population.
Of four confirmed positive cases, only one was available for follow-up. “In the index donation, the viral load was quite high in the plasma but at 10 days, it was reduced to about 400 copies/mL in the plasma,” said Ms. Lam. “The donor did not develop any symptoms.”
The analytical sensitivity for the Procleix ZIKV assay was determined to be 2.1 copies/mL at 50% LOD and 10.0 copies/mL at 95% LOD, and it detected RNA in six out of nine patient samples for an 85.7% agreement with reference material, according to the researchers.
SAN DIEGO – The Zika virus is primarily transmitted via the Aedes mosquitoes, most commonly by A. aegypti, but recent outbreaks have revealed that nonvector transmission routes may also spread the infection. Some data suggest that blood transfusion can be a source of transmission.
While the number of contaminated blood donations remains very small, three studies presented at the American Association of Blood Banks annual meeting confirmed the ability of new investigational assays to detect Zika virus in donated blood.
There have been no confirmed transfusion-transmission cases of Zika virus in the United States, but as cases have now been documented in Brazil, the Food and Drug Administration issued revised guidance in August 2016 recommending that blood centers in all states and U.S. territories screen individual units of donated whole blood and blood components.
In the first report (C7-A01C), Paula Saá, PhD, and her colleagues at the American Red Cross initially investigated the use of mini-pool (MP)- nucleic acid testing (NAT) using the Procleix Zika Virus Assay (TMA). Testing was initially implemented on blood collections from Florida, Georgia, South Carolina, Mississippi, and Alabama – five states that were presumed to be at high risk of Zika virus infection. After the FDA revised its guidance, the protocol changed and testing was extended to all blood donations. The use of the MP-NAT was also converted to individual donation (ID)-NAT, and questions concerning travel history was also eventually discontinued.
However, even with the use of ID-NAT, the rate of confirmed positive donations was quite small but the associated cost was quite high, the researchers pointed out. “In the first year of testing at the American Red Cross, we identified nine confirmed positive donations,” said Dr. Saá.
The rate of confirmed positive donations was 1:354, 602 during the study period, but if the period up until September 2017 is taken into account (no additional cases were identified), the rate increases to 1:514,266. “This is a very low rate,” Dr. Saá said. “If there are no changes to the current guidelines, we have estimated that the yearly cost for the American Red Cross of testing will exceed $48 million.”
These figures extrapolate to approximately $6 million per confirmed case, according to the results of this study sponsored by the American Red Cross.
Confirmatory testing included repeat TMA; in addition, RT-PCR, serology and red blood cell count (RBC) TMA were performed. Estimates of viral loads were performed by endpoint TMA on plasma and RBCs.
A total of 2,288,855 blood donations had been tested as of April 2017, including 393,713 (17%) in 24,611 MPs, which did not detect any reactive donations.
Of the confirmed positive blood donors, three lived in Florida and two of those were from local transmission. Six individuals had traveled to a region highly active for Zika virus, and returned to the United States between 2 and 73 days before donating blood. Clinical symptoms were reported in two individuals with a travel risk; the other donors with a confirmed positive test (75%) remained asymptomatic. The longest period for detection in RBCs was 91 days thus far, but in the same person, detection in plasma was only 17 days.
“The data that we are showing here recommends a testing strategy with mini pool testing in areas at low risk of Zika transmission,” said Dr. Saá.
A second related study (C9-A01C), described the detection of ZIKV RNA in blood donations collected in U.S. states between April 3, 2016, and September 23, 2017, using the cobas Zika test, to be used on the cobas 6800/8800 Systems.
Although the test was investigational during the study period, it has just been approved by the FDA, said study author Lisa Pate, MD, who is with Roche Molecular Systems, the manufacturer of the cobas Zika test and cobas 6800/8800 systems. “This is now the first licensed test for screening blood donations for Zika virus.”
Overall, testing showed that Zika contamination in the U.S. blood supply was quite low. Only 0.001% of screened blood donations in United States were confirmed as true positives.
The development of this test came about after the first cases of Zika virus in the United States were detected in Puerto Rico in December 2015, explained Dr. Pate. Shortly after that, the FDA issued guidance prohibiting the use of blood collected in Zika active areas, unless the donations were screened.
“The impact was significant in Puerto Rico, as blood donations were halted, which then forced Puerto Rico to rely on imported blood,” she said.
About that time the FDA reached out to Roche and competitors to see if a test could be developed to screen for Zika.
The cobas Zika test was approved under an investigational new drug application on March 30, 2016, and although initially used to test blood samples in Puerto Rico, testing was expanded to include donor blood from all over the country.
Screening was conducted by individual donation testing, with all initial reactive results repeated in duplicate. Supplemental testing was also done, and included an alternative NAT (AltNAT) assay which was considered to be less sensitive than cobas Zika and serology testing for anti-Zika IgM and IgG. A donor confirmed Zika confirmed positive if at least one replicate of the repeat testing by cobas Zika was reactive on index donation or follow-up, reactive by AltNAT on the index donation, or positive for anti-Zika IgM on index or follow-up.
Screening was conducted at 12 testing labs in the United States, and more than 4 million donations were screened and 27 positive donations were confirmed. Overall, that amounted to less than 1 in 100,000.
“For donors in the U.S. with confirmed positive results, and for whom follow-up information is available, 84% of them report recent travel to Zika active areas,” noted Dr. Pate.
For Puerto Rico, 111,842 blood donations were screened and there were 356 confirmed positive results. The incidence is much higher than in United States, and was 1.27% during peak incidence in July 2016.
A third paper (C12-A01C), also reported on testing the blood supply in Singapore, which had reported its first locally transmitted Zika case last August, using the investigational Procleix ZIKV nucleic acid technology (NAT) assay.
The presence of Zika virus in screened blood was also quite low, with an incidence of only 0.0032%. The Procleix ZIKV assay was found to suitable for screening for Zika infection in an asymptomatic population, as it showed good analytical sensitivity and clinical performance.
The Zika virus came to Singapore in May 2016, imported by an individual who had recently traveled to Brazil, said Sally Lam, laboratory director, Blood Services Group, Health Sciences Authority, Singapore.
“Then in August we had 41 confirmed local Zika virus cases,” she said.
In 2016, there were 458 clinical Zika cases reported, with 8 clusters identified. This year, 63 cases have been reported to date, she said.
Mandatory Zika virus screening in donor blood with ID-NAT began after the onset of local outbreaks, and was implemented in January 2017. A total of 126,906 blood donations were screened.
Researchers in Singapore assessed the performance of the Procleix ZIKV NAT assay for universal blood donation screening. They screened all blood that was donated, beginning Oct. 1, 2016, a confirmed case was defined as having Zika RNA by PCR and/or Zika antibodies. Analytical sensitivity was assessed by use of 300 blinded frozen samples containing Zika virus and 25 negative controls. The performance of the Procleix ZIKV assay was also evaluated by use of samples from the local patient population.
Of four confirmed positive cases, only one was available for follow-up. “In the index donation, the viral load was quite high in the plasma but at 10 days, it was reduced to about 400 copies/mL in the plasma,” said Ms. Lam. “The donor did not develop any symptoms.”
The analytical sensitivity for the Procleix ZIKV assay was determined to be 2.1 copies/mL at 50% LOD and 10.0 copies/mL at 95% LOD, and it detected RNA in six out of nine patient samples for an 85.7% agreement with reference material, according to the researchers.
AT AABB17
Denmark reinstates ID NAT screening for blood donations
SAN DIEGO – After funding was discontinued for individual donation (ID) nucleic acid testing (NAT) of blood donations, the risk of transfusion-related infections in Denmark increased. But according to new findings presented here at the American Association of Blood Banks annual meeting, that policy was short lived.
When ID NAT was removed from the screening process, the estimated increase in the risk for transfusion-transmitted HIV went from one in 80 years to one in 18 years; for hepatitis B virus (HBV), it went from one in 34 years to one in 17 years; and for hepatitis C virus (HCV), the risk increased from one in 250 years to one in 8 years.
“Between 2009 and 2016, we had 14 NAT reactive/seronegative cases among the repeat donors, and one was due to an acute hepatitis C infection,” said study author Leen Baudewijn, MD, of Odense (Denmark) University Hospital. “This would have been missed without NAT testing.”
Dr. Baudewijn explained that Denmark has since reversed this new policy. “The Danish government decided not to discontinue NAT because there were almost no savings,” she said during her presentation. “We had the extra costs for anti-HBc [anti-Hepatitis B core] testing for repeat donors, and extra cost due to mandatory NAT testing for plasma for manufacturing medicinal products. So it was not possible to abrogate NAT testing because of contracts with the industry.”
However, she added that “one of the most important reasons was that one of the vendors for NAT screening reduced the price substantially by 45%.”
The majority of industrialized countries have implemented the use of increasingly sensitive assays for screening donated blood, although to date, there is no technology that can guarantee zero-risk blood products. However, the risk for transmission of a viral infection via transfusion is low in Northern Europe.
But after a case of HIV infection linked to a blood transfusion occurred, Denmark mandated ID NAT in 2009 for serologic-based screening assays for HIV, HBV, and HCV. In July 2017, the government changed its policy and discontinued funding for ID NAT screening and, instead, mandated anti-Hepatitis B core screening be added to the serologic screening assays for repeat donors.
In this study, Dr. Baudewijn and her colleagues used an incidence/window model to estimate the residual risk (RR) of transfusion-transmitted viral infections after ID NAT was halted in Denmark. They estimated incidence rates for blood and plasma donations obtained from repeat donors during 2006-2016 based on the number of positive tests after a negative donation. The residual risk was estimated as the incidence rate multiplied by the average window period for HIV, HBV, and HCV, with and without ID NAT testing.
A total of 3.5 million donations were screened during the study’s time period, with donors averaging two blood donations per year. The researchers estimated the RR for each donation with and without ID NAT.
For HIV, the RR without ID NAT was 1/3,647,888 and with ID NAT it was 1/16,436,213; for HBV, those numbers were 1/3,352,628 without and 1/6,806,407 with; and for HCV, 1/1,573,213 without and 1/50,429,289, with.
The overall probability of missing an infectious red blood cell unit was 35/1,000 in a population of 6 million, Dr. Baudewijn noted.
The authors had no relevant financial disclosures
SOURCE: Baudewijn L et al. AABB 2017. Abstract P4-A03A.
SAN DIEGO – After funding was discontinued for individual donation (ID) nucleic acid testing (NAT) of blood donations, the risk of transfusion-related infections in Denmark increased. But according to new findings presented here at the American Association of Blood Banks annual meeting, that policy was short lived.
When ID NAT was removed from the screening process, the estimated increase in the risk for transfusion-transmitted HIV went from one in 80 years to one in 18 years; for hepatitis B virus (HBV), it went from one in 34 years to one in 17 years; and for hepatitis C virus (HCV), the risk increased from one in 250 years to one in 8 years.
“Between 2009 and 2016, we had 14 NAT reactive/seronegative cases among the repeat donors, and one was due to an acute hepatitis C infection,” said study author Leen Baudewijn, MD, of Odense (Denmark) University Hospital. “This would have been missed without NAT testing.”
Dr. Baudewijn explained that Denmark has since reversed this new policy. “The Danish government decided not to discontinue NAT because there were almost no savings,” she said during her presentation. “We had the extra costs for anti-HBc [anti-Hepatitis B core] testing for repeat donors, and extra cost due to mandatory NAT testing for plasma for manufacturing medicinal products. So it was not possible to abrogate NAT testing because of contracts with the industry.”
However, she added that “one of the most important reasons was that one of the vendors for NAT screening reduced the price substantially by 45%.”
The majority of industrialized countries have implemented the use of increasingly sensitive assays for screening donated blood, although to date, there is no technology that can guarantee zero-risk blood products. However, the risk for transmission of a viral infection via transfusion is low in Northern Europe.
But after a case of HIV infection linked to a blood transfusion occurred, Denmark mandated ID NAT in 2009 for serologic-based screening assays for HIV, HBV, and HCV. In July 2017, the government changed its policy and discontinued funding for ID NAT screening and, instead, mandated anti-Hepatitis B core screening be added to the serologic screening assays for repeat donors.
In this study, Dr. Baudewijn and her colleagues used an incidence/window model to estimate the residual risk (RR) of transfusion-transmitted viral infections after ID NAT was halted in Denmark. They estimated incidence rates for blood and plasma donations obtained from repeat donors during 2006-2016 based on the number of positive tests after a negative donation. The residual risk was estimated as the incidence rate multiplied by the average window period for HIV, HBV, and HCV, with and without ID NAT testing.
A total of 3.5 million donations were screened during the study’s time period, with donors averaging two blood donations per year. The researchers estimated the RR for each donation with and without ID NAT.
For HIV, the RR without ID NAT was 1/3,647,888 and with ID NAT it was 1/16,436,213; for HBV, those numbers were 1/3,352,628 without and 1/6,806,407 with; and for HCV, 1/1,573,213 without and 1/50,429,289, with.
The overall probability of missing an infectious red blood cell unit was 35/1,000 in a population of 6 million, Dr. Baudewijn noted.
The authors had no relevant financial disclosures
SOURCE: Baudewijn L et al. AABB 2017. Abstract P4-A03A.
SAN DIEGO – After funding was discontinued for individual donation (ID) nucleic acid testing (NAT) of blood donations, the risk of transfusion-related infections in Denmark increased. But according to new findings presented here at the American Association of Blood Banks annual meeting, that policy was short lived.
When ID NAT was removed from the screening process, the estimated increase in the risk for transfusion-transmitted HIV went from one in 80 years to one in 18 years; for hepatitis B virus (HBV), it went from one in 34 years to one in 17 years; and for hepatitis C virus (HCV), the risk increased from one in 250 years to one in 8 years.
“Between 2009 and 2016, we had 14 NAT reactive/seronegative cases among the repeat donors, and one was due to an acute hepatitis C infection,” said study author Leen Baudewijn, MD, of Odense (Denmark) University Hospital. “This would have been missed without NAT testing.”
Dr. Baudewijn explained that Denmark has since reversed this new policy. “The Danish government decided not to discontinue NAT because there were almost no savings,” she said during her presentation. “We had the extra costs for anti-HBc [anti-Hepatitis B core] testing for repeat donors, and extra cost due to mandatory NAT testing for plasma for manufacturing medicinal products. So it was not possible to abrogate NAT testing because of contracts with the industry.”
However, she added that “one of the most important reasons was that one of the vendors for NAT screening reduced the price substantially by 45%.”
The majority of industrialized countries have implemented the use of increasingly sensitive assays for screening donated blood, although to date, there is no technology that can guarantee zero-risk blood products. However, the risk for transmission of a viral infection via transfusion is low in Northern Europe.
But after a case of HIV infection linked to a blood transfusion occurred, Denmark mandated ID NAT in 2009 for serologic-based screening assays for HIV, HBV, and HCV. In July 2017, the government changed its policy and discontinued funding for ID NAT screening and, instead, mandated anti-Hepatitis B core screening be added to the serologic screening assays for repeat donors.
In this study, Dr. Baudewijn and her colleagues used an incidence/window model to estimate the residual risk (RR) of transfusion-transmitted viral infections after ID NAT was halted in Denmark. They estimated incidence rates for blood and plasma donations obtained from repeat donors during 2006-2016 based on the number of positive tests after a negative donation. The residual risk was estimated as the incidence rate multiplied by the average window period for HIV, HBV, and HCV, with and without ID NAT testing.
A total of 3.5 million donations were screened during the study’s time period, with donors averaging two blood donations per year. The researchers estimated the RR for each donation with and without ID NAT.
For HIV, the RR without ID NAT was 1/3,647,888 and with ID NAT it was 1/16,436,213; for HBV, those numbers were 1/3,352,628 without and 1/6,806,407 with; and for HCV, 1/1,573,213 without and 1/50,429,289, with.
The overall probability of missing an infectious red blood cell unit was 35/1,000 in a population of 6 million, Dr. Baudewijn noted.
The authors had no relevant financial disclosures
SOURCE: Baudewijn L et al. AABB 2017. Abstract P4-A03A.
AT AABB17
Key clinical point:
Major finding: Without ID NAT, the estimated increase in the risk for transfusion-transmitted HIV went from 1 patient per 80 years to 1 per 18; for HBV, from 1 per 34 to 1 per 17; and for HCV, the risk increased from 1 per 250 to 1 per 8.
Data source: An incidence/window model estimating the residual risk of transfusion-transmitted viral infections following Denmark’s decision not to fund ID NAT testing.
Disclosures: The authors had no relevant financial disclosures.
SOURCE: Baudewijn L et al. AABB 2017. Abstract P4-A03A.
CDK4/6 inhibitors have similar efficacy in older breast cancer patients
SAN ANTONIO – Treatment with cyclin-dependent kinase 4/6 inhibitors (CDK4/6) appears to have the same efficacy in older breast cancer patients, as compared to younger ones, according to new findings presented at the San Antonio Breast Cancer Symposium.
Women aged 65 years and older with hormone receptor (HR)–positive, HER2-negative metastatic breast cancer who received CDK4/6 inhibitors achieved a rate of progression-free survival (PFS) similar to that which has been reported in younger patients. Importantly, combining a CDK4/6 inhibitor with endocrine therapy led to superior PFS as compared to endocrine therapy alone.
However, older patients appeared to be less tolerant of associated adverse events and were more likely to discontinue treatment for that reason.
“Older patients with breast cancer benefit from treatment with CDK4/6 inhibitors ... for HR-positive, HER2-negative, metastatic breast cancer,” said the study’s lead author, Harpreet Singh, MD, scientific liaison for the FDA’s Cancer in Older Adults and a medical officer in the Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, at the Food and Drug Administration.
“The severity of adverse events and rates of dose modifications and interruptions were higher in those 65 years of age and older and those 70 years and older,” Dr. Singh said. “Rates of selected adverse events were similar across pooled trials.”
Breast cancer is a disease of aging, and 72,000 breast cancers occur annually in women aged 70 years or older, she explained. “Most cancers in older women are lower risk tumors and most older patients will die of other causes, but approximately 40% of breast cancer related deaths are in women over the age of 70.
“But the accrual of older individuals in trials has been a persistent challenge,” said Dr. Singh. “Older patients traditionally have been underrepresented in oncology clinical trials, so pooling outcomes of older patients across clinical trials in the same drug class allows us to gain insight into how these patients may benefit.”
In the current study, which was an FDA-conducted review of FDA registration trials over a 10 year period, the authors found that fewer than 60% of new cases of breast cancer are diagnosed in women under the age of 65 years.
“But these women make up about 80% of the clinical trial populations even though they are only 57% of cases,” said Dr. Singh.
Only 17% of clinical trial populations comprised individuals aged 65-74 years – even though patients aged 75 years and older make up about 20% of new cases, they comprise only 4% of the clinical trial population.
The FDA has issued several guidances that encourage investigators to enroll older women into trials but does not require them to. Only 22% of patients over 70 received adjuvant or neoadjuvant therapy compared to close to 50% of younger patients, and as a result, very little is known about the safety and efficacy of these agents in older adults.
To assess the efficacy and safety of CDK4/6 inhibitors in an older population, Dr. Singh and her colleagues pooled and analyzed data from prospective, randomized, controlled trials that evaluated three different CDK4/6 inhibitors in combination with an aromatase inhibitor, as the first-line treatment for postmenopausal patients with HR-positive metastatic breast cancer. The cohort included 1,334 patients, (intention-to-treat population, 1,992), of whom 42% were aged 65 years or older, and 24% were 70 years or older.
The primary endpoint was PFS in patients aged 70 years and older, and in control groups.
For patients 70 years or older who received a CDK4/6 inhibitor in combination with an aromatase inhibitor, the estimated PFS was not reached (25.1 months, not reached), versus 16.8 months (13.7, 21.9) for those who received an aromatase inhibitor only.
For patients younger than 70 years of age, PFS also was superior among those who received a CDK4/6 inhibitor, compared with treatment with an aromatase inhibitor alone: 23.75(21.9, 25.4) months versus an estimated 13.8 months (12.9, 14.7).
There were no treatment differences across age subgroups and similar results with alternate age cut-offs (greater than 65 years, greater than 75 years, etc.).
When looking at safety, the authors found that older patients were more likely to stop treatment because of adverse events. Among those 70 years and older, 20% discontinued treatment as compared with 17% of those 65 years or older, and 8% of those under the age of 65 years. Virtually all patients in the three age groups experienced grade 1-2 events (younger than 65, 98%; greater than or equal to 65 years, 98%; greater than or equal to 70 years, 99%), and the majority experienced grade 3-4 events (76%, 83%, 85%, respectively), with the rate higher in the older age groups. More than three quarters of all patients experienced neutropenia (76%, 77%, 80%), and two-thirds or higher grade 3-4 neutropenia (65%, 69%, 72%). Adverse events leading to dose interruption and/or reduction were also higher in the older age groups (66%, 75%, 77%).
“But there are many signs of progress,” said Dr. Singh, referring to efforts in enrolling more older breast cancer patients in clinical trials. “There are ongoing efforts to modernize eligibility criteria which will include greater inclusion of older adults, and specifically, taking a rational approach to organ dysfunction and prior malignancies.”
The increased use of patient-reported outcomes will provide further information on the tolerability of therapy. “Also the acquisition of real-world data from more diverse oncology practices will help inform data on efficacy and safety of novel therapies in older adults,” concluded Dr. Singh.
SOURCE: Singh et al., SABCS 2017 Abstract GS5-06.
SAN ANTONIO – Treatment with cyclin-dependent kinase 4/6 inhibitors (CDK4/6) appears to have the same efficacy in older breast cancer patients, as compared to younger ones, according to new findings presented at the San Antonio Breast Cancer Symposium.
Women aged 65 years and older with hormone receptor (HR)–positive, HER2-negative metastatic breast cancer who received CDK4/6 inhibitors achieved a rate of progression-free survival (PFS) similar to that which has been reported in younger patients. Importantly, combining a CDK4/6 inhibitor with endocrine therapy led to superior PFS as compared to endocrine therapy alone.
However, older patients appeared to be less tolerant of associated adverse events and were more likely to discontinue treatment for that reason.
“Older patients with breast cancer benefit from treatment with CDK4/6 inhibitors ... for HR-positive, HER2-negative, metastatic breast cancer,” said the study’s lead author, Harpreet Singh, MD, scientific liaison for the FDA’s Cancer in Older Adults and a medical officer in the Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, at the Food and Drug Administration.
“The severity of adverse events and rates of dose modifications and interruptions were higher in those 65 years of age and older and those 70 years and older,” Dr. Singh said. “Rates of selected adverse events were similar across pooled trials.”
Breast cancer is a disease of aging, and 72,000 breast cancers occur annually in women aged 70 years or older, she explained. “Most cancers in older women are lower risk tumors and most older patients will die of other causes, but approximately 40% of breast cancer related deaths are in women over the age of 70.
“But the accrual of older individuals in trials has been a persistent challenge,” said Dr. Singh. “Older patients traditionally have been underrepresented in oncology clinical trials, so pooling outcomes of older patients across clinical trials in the same drug class allows us to gain insight into how these patients may benefit.”
In the current study, which was an FDA-conducted review of FDA registration trials over a 10 year period, the authors found that fewer than 60% of new cases of breast cancer are diagnosed in women under the age of 65 years.
“But these women make up about 80% of the clinical trial populations even though they are only 57% of cases,” said Dr. Singh.
Only 17% of clinical trial populations comprised individuals aged 65-74 years – even though patients aged 75 years and older make up about 20% of new cases, they comprise only 4% of the clinical trial population.
The FDA has issued several guidances that encourage investigators to enroll older women into trials but does not require them to. Only 22% of patients over 70 received adjuvant or neoadjuvant therapy compared to close to 50% of younger patients, and as a result, very little is known about the safety and efficacy of these agents in older adults.
To assess the efficacy and safety of CDK4/6 inhibitors in an older population, Dr. Singh and her colleagues pooled and analyzed data from prospective, randomized, controlled trials that evaluated three different CDK4/6 inhibitors in combination with an aromatase inhibitor, as the first-line treatment for postmenopausal patients with HR-positive metastatic breast cancer. The cohort included 1,334 patients, (intention-to-treat population, 1,992), of whom 42% were aged 65 years or older, and 24% were 70 years or older.
The primary endpoint was PFS in patients aged 70 years and older, and in control groups.
For patients 70 years or older who received a CDK4/6 inhibitor in combination with an aromatase inhibitor, the estimated PFS was not reached (25.1 months, not reached), versus 16.8 months (13.7, 21.9) for those who received an aromatase inhibitor only.
For patients younger than 70 years of age, PFS also was superior among those who received a CDK4/6 inhibitor, compared with treatment with an aromatase inhibitor alone: 23.75(21.9, 25.4) months versus an estimated 13.8 months (12.9, 14.7).
There were no treatment differences across age subgroups and similar results with alternate age cut-offs (greater than 65 years, greater than 75 years, etc.).
When looking at safety, the authors found that older patients were more likely to stop treatment because of adverse events. Among those 70 years and older, 20% discontinued treatment as compared with 17% of those 65 years or older, and 8% of those under the age of 65 years. Virtually all patients in the three age groups experienced grade 1-2 events (younger than 65, 98%; greater than or equal to 65 years, 98%; greater than or equal to 70 years, 99%), and the majority experienced grade 3-4 events (76%, 83%, 85%, respectively), with the rate higher in the older age groups. More than three quarters of all patients experienced neutropenia (76%, 77%, 80%), and two-thirds or higher grade 3-4 neutropenia (65%, 69%, 72%). Adverse events leading to dose interruption and/or reduction were also higher in the older age groups (66%, 75%, 77%).
“But there are many signs of progress,” said Dr. Singh, referring to efforts in enrolling more older breast cancer patients in clinical trials. “There are ongoing efforts to modernize eligibility criteria which will include greater inclusion of older adults, and specifically, taking a rational approach to organ dysfunction and prior malignancies.”
The increased use of patient-reported outcomes will provide further information on the tolerability of therapy. “Also the acquisition of real-world data from more diverse oncology practices will help inform data on efficacy and safety of novel therapies in older adults,” concluded Dr. Singh.
SOURCE: Singh et al., SABCS 2017 Abstract GS5-06.
SAN ANTONIO – Treatment with cyclin-dependent kinase 4/6 inhibitors (CDK4/6) appears to have the same efficacy in older breast cancer patients, as compared to younger ones, according to new findings presented at the San Antonio Breast Cancer Symposium.
Women aged 65 years and older with hormone receptor (HR)–positive, HER2-negative metastatic breast cancer who received CDK4/6 inhibitors achieved a rate of progression-free survival (PFS) similar to that which has been reported in younger patients. Importantly, combining a CDK4/6 inhibitor with endocrine therapy led to superior PFS as compared to endocrine therapy alone.
However, older patients appeared to be less tolerant of associated adverse events and were more likely to discontinue treatment for that reason.
“Older patients with breast cancer benefit from treatment with CDK4/6 inhibitors ... for HR-positive, HER2-negative, metastatic breast cancer,” said the study’s lead author, Harpreet Singh, MD, scientific liaison for the FDA’s Cancer in Older Adults and a medical officer in the Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, at the Food and Drug Administration.
“The severity of adverse events and rates of dose modifications and interruptions were higher in those 65 years of age and older and those 70 years and older,” Dr. Singh said. “Rates of selected adverse events were similar across pooled trials.”
Breast cancer is a disease of aging, and 72,000 breast cancers occur annually in women aged 70 years or older, she explained. “Most cancers in older women are lower risk tumors and most older patients will die of other causes, but approximately 40% of breast cancer related deaths are in women over the age of 70.
“But the accrual of older individuals in trials has been a persistent challenge,” said Dr. Singh. “Older patients traditionally have been underrepresented in oncology clinical trials, so pooling outcomes of older patients across clinical trials in the same drug class allows us to gain insight into how these patients may benefit.”
In the current study, which was an FDA-conducted review of FDA registration trials over a 10 year period, the authors found that fewer than 60% of new cases of breast cancer are diagnosed in women under the age of 65 years.
“But these women make up about 80% of the clinical trial populations even though they are only 57% of cases,” said Dr. Singh.
Only 17% of clinical trial populations comprised individuals aged 65-74 years – even though patients aged 75 years and older make up about 20% of new cases, they comprise only 4% of the clinical trial population.
The FDA has issued several guidances that encourage investigators to enroll older women into trials but does not require them to. Only 22% of patients over 70 received adjuvant or neoadjuvant therapy compared to close to 50% of younger patients, and as a result, very little is known about the safety and efficacy of these agents in older adults.
To assess the efficacy and safety of CDK4/6 inhibitors in an older population, Dr. Singh and her colleagues pooled and analyzed data from prospective, randomized, controlled trials that evaluated three different CDK4/6 inhibitors in combination with an aromatase inhibitor, as the first-line treatment for postmenopausal patients with HR-positive metastatic breast cancer. The cohort included 1,334 patients, (intention-to-treat population, 1,992), of whom 42% were aged 65 years or older, and 24% were 70 years or older.
The primary endpoint was PFS in patients aged 70 years and older, and in control groups.
For patients 70 years or older who received a CDK4/6 inhibitor in combination with an aromatase inhibitor, the estimated PFS was not reached (25.1 months, not reached), versus 16.8 months (13.7, 21.9) for those who received an aromatase inhibitor only.
For patients younger than 70 years of age, PFS also was superior among those who received a CDK4/6 inhibitor, compared with treatment with an aromatase inhibitor alone: 23.75(21.9, 25.4) months versus an estimated 13.8 months (12.9, 14.7).
There were no treatment differences across age subgroups and similar results with alternate age cut-offs (greater than 65 years, greater than 75 years, etc.).
When looking at safety, the authors found that older patients were more likely to stop treatment because of adverse events. Among those 70 years and older, 20% discontinued treatment as compared with 17% of those 65 years or older, and 8% of those under the age of 65 years. Virtually all patients in the three age groups experienced grade 1-2 events (younger than 65, 98%; greater than or equal to 65 years, 98%; greater than or equal to 70 years, 99%), and the majority experienced grade 3-4 events (76%, 83%, 85%, respectively), with the rate higher in the older age groups. More than three quarters of all patients experienced neutropenia (76%, 77%, 80%), and two-thirds or higher grade 3-4 neutropenia (65%, 69%, 72%). Adverse events leading to dose interruption and/or reduction were also higher in the older age groups (66%, 75%, 77%).
“But there are many signs of progress,” said Dr. Singh, referring to efforts in enrolling more older breast cancer patients in clinical trials. “There are ongoing efforts to modernize eligibility criteria which will include greater inclusion of older adults, and specifically, taking a rational approach to organ dysfunction and prior malignancies.”
The increased use of patient-reported outcomes will provide further information on the tolerability of therapy. “Also the acquisition of real-world data from more diverse oncology practices will help inform data on efficacy and safety of novel therapies in older adults,” concluded Dr. Singh.
SOURCE: Singh et al., SABCS 2017 Abstract GS5-06.
REPORTING FROM SABCS 2017
Key clinical point: Cyclin-dependent kinase 4 and 6 inhibitors are as effective in older breast cancer patients, as compared with younger ones.
Major finding: The PFS in patients aged 70 years or older treated with a CDK4/6 inhibitor plus an aromatase inhibitor was not reached vs. 16.8 months for those who received an aromatase inhibitor only.
Data source: Pooled retrospective subgroup analysis that included 1,334 breast cancer patients treated with CDK4/6 inhibitors and aromatase inhibitors.
Disclosures:. The study was run by the FDA. Dr. Singh and coauthors have no disclosures.
Source: Singh H et al., SABCS 2017 Abstract GS5-06.
Adjuvant trastuzumab for 1 year remains standard of care for early HER2+ breast cancer
SAN ANTONIO – The phase 3 SOLD trial failed to show a 9-week course of trastuzumab as noninferior to the standard 12-month course when combined with chemotherapy for women with early-stage HER2-positive breast cancer.
Disease-free survival (DFS) with a 9-week course of adjuvant trastuzumab (Herceptin)did not pass muster as noninferior to the standard 12 months, reported Dr. Heikki Joensuu, professor in the department of oncology at the Helsinki University Hospital and University of Helsinki.
“The non-inferiority of 9 week administration of trastuzumab plus docetaxel could not be demonstrated in terms of disease free survival, as compared to chemotherapy and one year duration of adjuvant trastuzumab.”
Based on these findings, he noted that chemotherapy plus one year of anti-HER2 therapy should remain the standard of care.
However, the dose of docetaxel administered along with trastuzumab could influence survival outcomes. Patients who received a higher dose of docetaxel in the 9 week cohort had similar DFS as those who received 12 months of trastuzumab.
Dr. Joensuu explained that the regimen of giving trastuzumab for one year is an arbitrary one and is not based on research data. In the four large randomized trials that established the current standard treatment for this population of breast cancer patients, trastuzumab was administered for one year and that eventually became the standard of care, he said at the San Antonio Breast Cancer Symposium.
But in two randomized trials that had relatively limited statistical power, a statistically significant difference in DFS or overall survival was not observed between patients who received only nine weeks of trastuzumab compared with those who received the one year regimen.
In addition, the one year treatment course is costly and has been associated with cardiac-related adverse events, although it is relatively uncommon (less than 3% of patients).
The phase 3 SOLD (Synergism or Long Duration) clinical trial was conducted by Dr. Joensuu and his colleagues to compare DFS between women treated with 9 weeks of concomitant trastuzumab plus docetaxel followed by 5-FU, epirubicin, and cyclophosphamide (FEC) to that of women treated with the same regimen followed by single-agent trastuzumab for a one year duration.
The cohort included 2,176 patients with early-stage HER2-positive breast cancer who were randomized to either the 9-week or the 12-month trastuzumab arm. In addition, cardiac function among women enrolled in the trial had to be normal, Dr. Joensuu said, as determined by left ventricular ejection fraction of 50% or greater.
Patients in both groups received three cycles of docetaxel (80 mg/m2 or 100 mg/m2) and trastuzumab three times a week, followed by three cycles of FEC. The dose of docetaxel was determined by the individual center. Patients in the 12-month arm continued to receive trastuzumab every 3 weeks for 14 cycles and in both groups, those with estrogen receptor–positive cancer received appropriate endocrine treatment per guidelines.
“SOLD was initially designed as a superiority trial,” he said, “But, we redesigned the study and the size during the study because we noticed that the assumptions we made for 5-year disease-free survival were too low.”
“We also realized that the shorter arm cannot be better than the longer arm because less drug is given,” said Dr. Joensuu. “So we changed it from a superiority trial to a noninferiority design, where the shorter arm would be at least equal to the longer arm.”
When looking at results, the DFS favored the longer arm: 90.5% in the 12-month arm vs. 88% in the 9-week arm (hazard ratio, 1.39; 90% confidence interval, 1.12-1.72). However, there were no substantial differences in secondary endpoints. Five-year distant DFS was 93.2% in the 9-week arm vs. 94.2% in the 12-month arm (HR, 1.24; 90% CI, 0.93-1.65), and similarly, 5-year overall survival was 94.7% vs. 95.9% (HR, 1.39; 90% CI, 0.98-1.89).
There was an interaction between the dose of docetaxel given concomitantly with trastuzumab. For patients who received 100 mg/m2 docetaxel, DFS was similar in both groups: 92.2% (long arm) vs. 87.8% (short arm) (HR 0.71, 90% CI 0,44-1.14). But among those who received 80 mg/m2 docetaxel, DFS was superior in the group who received 12 months of trastuzumab, compared with the 9-week group (91.3% vs. 86.8%; HR, 1.66; 90% CI, 1.30-2.11).
Less cardiac toxicity was observed in the 9-week group, for any protocol-defined cardiac adverse event (n = 22 [2%] vs. n = 42 [3.9%]; P = .012) and for heart failure (n = 21 [1.9%] vs. n = 36 [3.3%]; P = .046).
“Docetaxel dosing with trastuzumab requires further study,” Dr. Joensuu said.
SOURCE: Joensuu H et al., Abstract GS3-04
SAN ANTONIO – The phase 3 SOLD trial failed to show a 9-week course of trastuzumab as noninferior to the standard 12-month course when combined with chemotherapy for women with early-stage HER2-positive breast cancer.
Disease-free survival (DFS) with a 9-week course of adjuvant trastuzumab (Herceptin)did not pass muster as noninferior to the standard 12 months, reported Dr. Heikki Joensuu, professor in the department of oncology at the Helsinki University Hospital and University of Helsinki.
“The non-inferiority of 9 week administration of trastuzumab plus docetaxel could not be demonstrated in terms of disease free survival, as compared to chemotherapy and one year duration of adjuvant trastuzumab.”
Based on these findings, he noted that chemotherapy plus one year of anti-HER2 therapy should remain the standard of care.
However, the dose of docetaxel administered along with trastuzumab could influence survival outcomes. Patients who received a higher dose of docetaxel in the 9 week cohort had similar DFS as those who received 12 months of trastuzumab.
Dr. Joensuu explained that the regimen of giving trastuzumab for one year is an arbitrary one and is not based on research data. In the four large randomized trials that established the current standard treatment for this population of breast cancer patients, trastuzumab was administered for one year and that eventually became the standard of care, he said at the San Antonio Breast Cancer Symposium.
But in two randomized trials that had relatively limited statistical power, a statistically significant difference in DFS or overall survival was not observed between patients who received only nine weeks of trastuzumab compared with those who received the one year regimen.
In addition, the one year treatment course is costly and has been associated with cardiac-related adverse events, although it is relatively uncommon (less than 3% of patients).
The phase 3 SOLD (Synergism or Long Duration) clinical trial was conducted by Dr. Joensuu and his colleagues to compare DFS between women treated with 9 weeks of concomitant trastuzumab plus docetaxel followed by 5-FU, epirubicin, and cyclophosphamide (FEC) to that of women treated with the same regimen followed by single-agent trastuzumab for a one year duration.
The cohort included 2,176 patients with early-stage HER2-positive breast cancer who were randomized to either the 9-week or the 12-month trastuzumab arm. In addition, cardiac function among women enrolled in the trial had to be normal, Dr. Joensuu said, as determined by left ventricular ejection fraction of 50% or greater.
Patients in both groups received three cycles of docetaxel (80 mg/m2 or 100 mg/m2) and trastuzumab three times a week, followed by three cycles of FEC. The dose of docetaxel was determined by the individual center. Patients in the 12-month arm continued to receive trastuzumab every 3 weeks for 14 cycles and in both groups, those with estrogen receptor–positive cancer received appropriate endocrine treatment per guidelines.
“SOLD was initially designed as a superiority trial,” he said, “But, we redesigned the study and the size during the study because we noticed that the assumptions we made for 5-year disease-free survival were too low.”
“We also realized that the shorter arm cannot be better than the longer arm because less drug is given,” said Dr. Joensuu. “So we changed it from a superiority trial to a noninferiority design, where the shorter arm would be at least equal to the longer arm.”
When looking at results, the DFS favored the longer arm: 90.5% in the 12-month arm vs. 88% in the 9-week arm (hazard ratio, 1.39; 90% confidence interval, 1.12-1.72). However, there were no substantial differences in secondary endpoints. Five-year distant DFS was 93.2% in the 9-week arm vs. 94.2% in the 12-month arm (HR, 1.24; 90% CI, 0.93-1.65), and similarly, 5-year overall survival was 94.7% vs. 95.9% (HR, 1.39; 90% CI, 0.98-1.89).
There was an interaction between the dose of docetaxel given concomitantly with trastuzumab. For patients who received 100 mg/m2 docetaxel, DFS was similar in both groups: 92.2% (long arm) vs. 87.8% (short arm) (HR 0.71, 90% CI 0,44-1.14). But among those who received 80 mg/m2 docetaxel, DFS was superior in the group who received 12 months of trastuzumab, compared with the 9-week group (91.3% vs. 86.8%; HR, 1.66; 90% CI, 1.30-2.11).
Less cardiac toxicity was observed in the 9-week group, for any protocol-defined cardiac adverse event (n = 22 [2%] vs. n = 42 [3.9%]; P = .012) and for heart failure (n = 21 [1.9%] vs. n = 36 [3.3%]; P = .046).
“Docetaxel dosing with trastuzumab requires further study,” Dr. Joensuu said.
SOURCE: Joensuu H et al., Abstract GS3-04
SAN ANTONIO – The phase 3 SOLD trial failed to show a 9-week course of trastuzumab as noninferior to the standard 12-month course when combined with chemotherapy for women with early-stage HER2-positive breast cancer.
Disease-free survival (DFS) with a 9-week course of adjuvant trastuzumab (Herceptin)did not pass muster as noninferior to the standard 12 months, reported Dr. Heikki Joensuu, professor in the department of oncology at the Helsinki University Hospital and University of Helsinki.
“The non-inferiority of 9 week administration of trastuzumab plus docetaxel could not be demonstrated in terms of disease free survival, as compared to chemotherapy and one year duration of adjuvant trastuzumab.”
Based on these findings, he noted that chemotherapy plus one year of anti-HER2 therapy should remain the standard of care.
However, the dose of docetaxel administered along with trastuzumab could influence survival outcomes. Patients who received a higher dose of docetaxel in the 9 week cohort had similar DFS as those who received 12 months of trastuzumab.
Dr. Joensuu explained that the regimen of giving trastuzumab for one year is an arbitrary one and is not based on research data. In the four large randomized trials that established the current standard treatment for this population of breast cancer patients, trastuzumab was administered for one year and that eventually became the standard of care, he said at the San Antonio Breast Cancer Symposium.
But in two randomized trials that had relatively limited statistical power, a statistically significant difference in DFS or overall survival was not observed between patients who received only nine weeks of trastuzumab compared with those who received the one year regimen.
In addition, the one year treatment course is costly and has been associated with cardiac-related adverse events, although it is relatively uncommon (less than 3% of patients).
The phase 3 SOLD (Synergism or Long Duration) clinical trial was conducted by Dr. Joensuu and his colleagues to compare DFS between women treated with 9 weeks of concomitant trastuzumab plus docetaxel followed by 5-FU, epirubicin, and cyclophosphamide (FEC) to that of women treated with the same regimen followed by single-agent trastuzumab for a one year duration.
The cohort included 2,176 patients with early-stage HER2-positive breast cancer who were randomized to either the 9-week or the 12-month trastuzumab arm. In addition, cardiac function among women enrolled in the trial had to be normal, Dr. Joensuu said, as determined by left ventricular ejection fraction of 50% or greater.
Patients in both groups received three cycles of docetaxel (80 mg/m2 or 100 mg/m2) and trastuzumab three times a week, followed by three cycles of FEC. The dose of docetaxel was determined by the individual center. Patients in the 12-month arm continued to receive trastuzumab every 3 weeks for 14 cycles and in both groups, those with estrogen receptor–positive cancer received appropriate endocrine treatment per guidelines.
“SOLD was initially designed as a superiority trial,” he said, “But, we redesigned the study and the size during the study because we noticed that the assumptions we made for 5-year disease-free survival were too low.”
“We also realized that the shorter arm cannot be better than the longer arm because less drug is given,” said Dr. Joensuu. “So we changed it from a superiority trial to a noninferiority design, where the shorter arm would be at least equal to the longer arm.”
When looking at results, the DFS favored the longer arm: 90.5% in the 12-month arm vs. 88% in the 9-week arm (hazard ratio, 1.39; 90% confidence interval, 1.12-1.72). However, there were no substantial differences in secondary endpoints. Five-year distant DFS was 93.2% in the 9-week arm vs. 94.2% in the 12-month arm (HR, 1.24; 90% CI, 0.93-1.65), and similarly, 5-year overall survival was 94.7% vs. 95.9% (HR, 1.39; 90% CI, 0.98-1.89).
There was an interaction between the dose of docetaxel given concomitantly with trastuzumab. For patients who received 100 mg/m2 docetaxel, DFS was similar in both groups: 92.2% (long arm) vs. 87.8% (short arm) (HR 0.71, 90% CI 0,44-1.14). But among those who received 80 mg/m2 docetaxel, DFS was superior in the group who received 12 months of trastuzumab, compared with the 9-week group (91.3% vs. 86.8%; HR, 1.66; 90% CI, 1.30-2.11).
Less cardiac toxicity was observed in the 9-week group, for any protocol-defined cardiac adverse event (n = 22 [2%] vs. n = 42 [3.9%]; P = .012) and for heart failure (n = 21 [1.9%] vs. n = 36 [3.3%]; P = .046).
“Docetaxel dosing with trastuzumab requires further study,” Dr. Joensuu said.
SOURCE: Joensuu H et al., Abstract GS3-04
REPORTING FROM SABCS 2017
Key clinical point: Disease-free survival with a 9-week course of adjuvant trastuzumab did not pass muster as noninferior to the standard 12 months.
Major finding: DFS favored the longer arm: 90.5% in the 12 month arm vs. 88% in the 9-week arm (HR, 1.39; 90% CI 1.12-1.72), but no substantial differences were observed in secondary endpoints.
Data source: Randomized phase 3 trial that included 2,176 patients with early-stage HER2-positive breast cancer
Disclosures:. The study was funded by Pharmac, Sanofi, Novartis, the Academy of Finland, the Cancer Society of Finland, Helsinki University Hospital research funds, Sigrid Juselius Foundation, and Jane and Aatos Erkko Foundation. Dr. Joensuu is a scientific adviser for Neutron Therapeutics, has received consultation fees from Orion Pharma, and has stock ownership interest in Orion, Faron Pharmaceuticals, and Sartar Therapeutics.
Source: Joensuu H et al., GS3-04
Acupuncture significantly reduces AI-associated arthralgias
SAN ANTONIO – Acupuncture significantly reduced joint pain that was associated with the use of aromatase inhibitors (AIs) in women with early breast cancer, according to new findings reported at the San Antonio Breast Cancer Symposium.
The randomized, phase 3 SWOG S1200 clinical trial found that, compared with sham acupuncture and a control group receiving no therapy, women receiving acupuncture reported significantly lower scores on the Brief Pain Inventory–Short Form (BPI).
“We have shown consistently, with multiple measures assessing pain and stiffness, that true acupuncture generated better outcomes than either control group in a large multicenter trial,” said lead author Dawn L. Hershman, MD, leader of the Breast Cancer Program at the Herbert Irving Comprehensive Cancer Center at NewYork-Presbyterian/Columbia University Medical Center. “Acupuncture provides a nonpharmacologic option that can improve symptoms and possibly increase AI adherence and subsequent breast cancer outcomes.”
AIs can reduce both early breast cancer recurrence and mortality. Dr. Hershman noted that these agents are effective in the adjuvant setting and for prevention “but we know that it doesn’t work if you don’t take it. Noncompliance is a major problem among women taking hormonal therapy.”
Noncompliance is multifactorial and one of the main reasons women discontinue their therapy early is because of arthralgias or joint discomfort. “We were interested in a nonpharmacologic intervention, to assess whether or not we could control these symptoms.”
Dr. Hershman pointed out acupuncture provides a safe and effective alternative for patients reluctant to take a prescription medication that can result in other side effects. “Identification of nonopioid options for pain control is a public health priority,” she said.
Acupuncture is a popular nonpharmacologic modality and widely used for a number of indications. Several single-institution studies have suggested that it may be useful for controlling AI-associated arthralgias, while other studies have not demonstrated a benefit.
In this trial, the authors evaluated the efficacy of acupuncture, compared with sham acupuncture or waitlist control, in the treatment of AI associated arthralgia in a large population of patients. The study was conducted at 11 centers.
The cohort comprised 226 postmenopausal women diagnosed with early-stage, hormone receptor–positive breast cancer who were receiving treatment with AIs. The primary endpoint was the decline in joint pain as measured by BPI-SF at 6 weeks, and to assess the duration of the effect, the women were followed for an additional 12 weeks.
Within this group, 110 were randomized to true acupuncture; 59 to sham acupuncture, and 57 to waitlist control (no treatment). Patients receiving true or sham acupuncture had sessions three times a week for 6 weeks followed by one session per week for 6 more weeks. Pain status was reported at baseline, during treatment, and then afterwards, using a variety of measurement tools including the BPI-SF, which is a self-administered 14-item questionnaire that evaluates pain severity on a 0-10 scale, and the impact of pain on activities of daily living.
At 6 weeks, the true acupuncture treatment arm reported significantly lower BPI worst pain scores than those in the sham acupuncture and the waitlist control arms. The mean BPI worst pain for the true acupuncture arm was 0.92 points lower than the sham acupuncture arm (P = .01) and 0.96 points lower than the waitlist control arm (P = .01). The proportion of patients experiencing a large reduction in BPI worst pain (greater than 2) was significantly greater in the true acupuncture arm, compared with the other groups: 58% versus 33% percent and 31%, respectively. The differences continued to remain statistically significant at 24 weeks, even though the treatment only continued for 12 weeks.
Associated adverse effects were minimal with true and sham acupuncture and limited to grade 1 bruising.
The cost of the 12-week intervention was about $1,250 or $65-$75 a session. “We feel that there is now sufficient evidence to support insurance coverage of acupuncture of AI arthralgia.”
In a discussion of the paper, Dr. Anne Partridge, from the Dana Farber Cancer Center, noted that it is imperative to seek new ways to improve outcomes in breast cancer, and AIs are contributing to that. However, she echoed the concern that nonadherence to treatment is a “tremendous problem” and hampers the clinical effectiveness of AI therapy.
The rate of discontinuation during the first year of therapy is 20% within the first year and up to 40% of patients do not take them daily. Both early discontinuation and nonadherence contribute to mortality.
Based on these results from the largest randomized controlled trial looking at acupuncture in this setting, should physicians be recommending acupuncture to patients prescribed AI therapy?
“The short answer is, why not?” said Dr. Partridge, “And that we should be recommending it for some of our patients.”
However, there are a number of issues that need to be addressed, she added. The duration of treatment is not known, and the need for follow-up treatment or the frequency of it is not known. The generalizability of it is also unclear when looking at a larger population, and acupuncture is highly operator dependent.
“There are cost and access issues, and insurance right now offers very limited coverage,” she said.
Importantly, Dr. Partridge emphasized, “We know that it will help symptoms, but will it improve adherence to AI?”
It may improve adherence for some patients, but “side effects are only one factor,” she said. “Adherence behavior is complicated. We need to figure out how to optimize these therapies in our patients.”
This study was supported by the National Institutes of Health National Center for Complementary and Integrative Health and the Office of Research on Women’s Health, and grants from the NIH/National Cancer Institute Division of Cancer Prevention. Dr. Hershman declared no conflicts of interest. Dr. Partridge had no disclosures.
SOURCE: Hershman et al. Abstract GS4-04
SAN ANTONIO – Acupuncture significantly reduced joint pain that was associated with the use of aromatase inhibitors (AIs) in women with early breast cancer, according to new findings reported at the San Antonio Breast Cancer Symposium.
The randomized, phase 3 SWOG S1200 clinical trial found that, compared with sham acupuncture and a control group receiving no therapy, women receiving acupuncture reported significantly lower scores on the Brief Pain Inventory–Short Form (BPI).
“We have shown consistently, with multiple measures assessing pain and stiffness, that true acupuncture generated better outcomes than either control group in a large multicenter trial,” said lead author Dawn L. Hershman, MD, leader of the Breast Cancer Program at the Herbert Irving Comprehensive Cancer Center at NewYork-Presbyterian/Columbia University Medical Center. “Acupuncture provides a nonpharmacologic option that can improve symptoms and possibly increase AI adherence and subsequent breast cancer outcomes.”
AIs can reduce both early breast cancer recurrence and mortality. Dr. Hershman noted that these agents are effective in the adjuvant setting and for prevention “but we know that it doesn’t work if you don’t take it. Noncompliance is a major problem among women taking hormonal therapy.”
Noncompliance is multifactorial and one of the main reasons women discontinue their therapy early is because of arthralgias or joint discomfort. “We were interested in a nonpharmacologic intervention, to assess whether or not we could control these symptoms.”
Dr. Hershman pointed out acupuncture provides a safe and effective alternative for patients reluctant to take a prescription medication that can result in other side effects. “Identification of nonopioid options for pain control is a public health priority,” she said.
Acupuncture is a popular nonpharmacologic modality and widely used for a number of indications. Several single-institution studies have suggested that it may be useful for controlling AI-associated arthralgias, while other studies have not demonstrated a benefit.
In this trial, the authors evaluated the efficacy of acupuncture, compared with sham acupuncture or waitlist control, in the treatment of AI associated arthralgia in a large population of patients. The study was conducted at 11 centers.
The cohort comprised 226 postmenopausal women diagnosed with early-stage, hormone receptor–positive breast cancer who were receiving treatment with AIs. The primary endpoint was the decline in joint pain as measured by BPI-SF at 6 weeks, and to assess the duration of the effect, the women were followed for an additional 12 weeks.
Within this group, 110 were randomized to true acupuncture; 59 to sham acupuncture, and 57 to waitlist control (no treatment). Patients receiving true or sham acupuncture had sessions three times a week for 6 weeks followed by one session per week for 6 more weeks. Pain status was reported at baseline, during treatment, and then afterwards, using a variety of measurement tools including the BPI-SF, which is a self-administered 14-item questionnaire that evaluates pain severity on a 0-10 scale, and the impact of pain on activities of daily living.
At 6 weeks, the true acupuncture treatment arm reported significantly lower BPI worst pain scores than those in the sham acupuncture and the waitlist control arms. The mean BPI worst pain for the true acupuncture arm was 0.92 points lower than the sham acupuncture arm (P = .01) and 0.96 points lower than the waitlist control arm (P = .01). The proportion of patients experiencing a large reduction in BPI worst pain (greater than 2) was significantly greater in the true acupuncture arm, compared with the other groups: 58% versus 33% percent and 31%, respectively. The differences continued to remain statistically significant at 24 weeks, even though the treatment only continued for 12 weeks.
Associated adverse effects were minimal with true and sham acupuncture and limited to grade 1 bruising.
The cost of the 12-week intervention was about $1,250 or $65-$75 a session. “We feel that there is now sufficient evidence to support insurance coverage of acupuncture of AI arthralgia.”
In a discussion of the paper, Dr. Anne Partridge, from the Dana Farber Cancer Center, noted that it is imperative to seek new ways to improve outcomes in breast cancer, and AIs are contributing to that. However, she echoed the concern that nonadherence to treatment is a “tremendous problem” and hampers the clinical effectiveness of AI therapy.
The rate of discontinuation during the first year of therapy is 20% within the first year and up to 40% of patients do not take them daily. Both early discontinuation and nonadherence contribute to mortality.
Based on these results from the largest randomized controlled trial looking at acupuncture in this setting, should physicians be recommending acupuncture to patients prescribed AI therapy?
“The short answer is, why not?” said Dr. Partridge, “And that we should be recommending it for some of our patients.”
However, there are a number of issues that need to be addressed, she added. The duration of treatment is not known, and the need for follow-up treatment or the frequency of it is not known. The generalizability of it is also unclear when looking at a larger population, and acupuncture is highly operator dependent.
“There are cost and access issues, and insurance right now offers very limited coverage,” she said.
Importantly, Dr. Partridge emphasized, “We know that it will help symptoms, but will it improve adherence to AI?”
It may improve adherence for some patients, but “side effects are only one factor,” she said. “Adherence behavior is complicated. We need to figure out how to optimize these therapies in our patients.”
This study was supported by the National Institutes of Health National Center for Complementary and Integrative Health and the Office of Research on Women’s Health, and grants from the NIH/National Cancer Institute Division of Cancer Prevention. Dr. Hershman declared no conflicts of interest. Dr. Partridge had no disclosures.
SOURCE: Hershman et al. Abstract GS4-04
SAN ANTONIO – Acupuncture significantly reduced joint pain that was associated with the use of aromatase inhibitors (AIs) in women with early breast cancer, according to new findings reported at the San Antonio Breast Cancer Symposium.
The randomized, phase 3 SWOG S1200 clinical trial found that, compared with sham acupuncture and a control group receiving no therapy, women receiving acupuncture reported significantly lower scores on the Brief Pain Inventory–Short Form (BPI).
“We have shown consistently, with multiple measures assessing pain and stiffness, that true acupuncture generated better outcomes than either control group in a large multicenter trial,” said lead author Dawn L. Hershman, MD, leader of the Breast Cancer Program at the Herbert Irving Comprehensive Cancer Center at NewYork-Presbyterian/Columbia University Medical Center. “Acupuncture provides a nonpharmacologic option that can improve symptoms and possibly increase AI adherence and subsequent breast cancer outcomes.”
AIs can reduce both early breast cancer recurrence and mortality. Dr. Hershman noted that these agents are effective in the adjuvant setting and for prevention “but we know that it doesn’t work if you don’t take it. Noncompliance is a major problem among women taking hormonal therapy.”
Noncompliance is multifactorial and one of the main reasons women discontinue their therapy early is because of arthralgias or joint discomfort. “We were interested in a nonpharmacologic intervention, to assess whether or not we could control these symptoms.”
Dr. Hershman pointed out acupuncture provides a safe and effective alternative for patients reluctant to take a prescription medication that can result in other side effects. “Identification of nonopioid options for pain control is a public health priority,” she said.
Acupuncture is a popular nonpharmacologic modality and widely used for a number of indications. Several single-institution studies have suggested that it may be useful for controlling AI-associated arthralgias, while other studies have not demonstrated a benefit.
In this trial, the authors evaluated the efficacy of acupuncture, compared with sham acupuncture or waitlist control, in the treatment of AI associated arthralgia in a large population of patients. The study was conducted at 11 centers.
The cohort comprised 226 postmenopausal women diagnosed with early-stage, hormone receptor–positive breast cancer who were receiving treatment with AIs. The primary endpoint was the decline in joint pain as measured by BPI-SF at 6 weeks, and to assess the duration of the effect, the women were followed for an additional 12 weeks.
Within this group, 110 were randomized to true acupuncture; 59 to sham acupuncture, and 57 to waitlist control (no treatment). Patients receiving true or sham acupuncture had sessions three times a week for 6 weeks followed by one session per week for 6 more weeks. Pain status was reported at baseline, during treatment, and then afterwards, using a variety of measurement tools including the BPI-SF, which is a self-administered 14-item questionnaire that evaluates pain severity on a 0-10 scale, and the impact of pain on activities of daily living.
At 6 weeks, the true acupuncture treatment arm reported significantly lower BPI worst pain scores than those in the sham acupuncture and the waitlist control arms. The mean BPI worst pain for the true acupuncture arm was 0.92 points lower than the sham acupuncture arm (P = .01) and 0.96 points lower than the waitlist control arm (P = .01). The proportion of patients experiencing a large reduction in BPI worst pain (greater than 2) was significantly greater in the true acupuncture arm, compared with the other groups: 58% versus 33% percent and 31%, respectively. The differences continued to remain statistically significant at 24 weeks, even though the treatment only continued for 12 weeks.
Associated adverse effects were minimal with true and sham acupuncture and limited to grade 1 bruising.
The cost of the 12-week intervention was about $1,250 or $65-$75 a session. “We feel that there is now sufficient evidence to support insurance coverage of acupuncture of AI arthralgia.”
In a discussion of the paper, Dr. Anne Partridge, from the Dana Farber Cancer Center, noted that it is imperative to seek new ways to improve outcomes in breast cancer, and AIs are contributing to that. However, she echoed the concern that nonadherence to treatment is a “tremendous problem” and hampers the clinical effectiveness of AI therapy.
The rate of discontinuation during the first year of therapy is 20% within the first year and up to 40% of patients do not take them daily. Both early discontinuation and nonadherence contribute to mortality.
Based on these results from the largest randomized controlled trial looking at acupuncture in this setting, should physicians be recommending acupuncture to patients prescribed AI therapy?
“The short answer is, why not?” said Dr. Partridge, “And that we should be recommending it for some of our patients.”
However, there are a number of issues that need to be addressed, she added. The duration of treatment is not known, and the need for follow-up treatment or the frequency of it is not known. The generalizability of it is also unclear when looking at a larger population, and acupuncture is highly operator dependent.
“There are cost and access issues, and insurance right now offers very limited coverage,” she said.
Importantly, Dr. Partridge emphasized, “We know that it will help symptoms, but will it improve adherence to AI?”
It may improve adherence for some patients, but “side effects are only one factor,” she said. “Adherence behavior is complicated. We need to figure out how to optimize these therapies in our patients.”
This study was supported by the National Institutes of Health National Center for Complementary and Integrative Health and the Office of Research on Women’s Health, and grants from the NIH/National Cancer Institute Division of Cancer Prevention. Dr. Hershman declared no conflicts of interest. Dr. Partridge had no disclosures.
SOURCE: Hershman et al. Abstract GS4-04
REPORTING FROM SABCS 2017
Key clinical point: Acupuncture significantly reduced joint pain associated with the use of aromatase inhibitors, compared with sham acupuncture and untreated controls.
Major finding: The proportion of patients who experienced a large reduction in BPI worst pain (less than 2) was significantly greater in the true acupuncture arm, compared with the other groups: 58% versus 33% percent and 31%, respectively.
Data source: Three-arm randomized phase 3 trial that included 226 patients with early-stage hormone receptor–positive breast cancer who were receiving treatment with AIs.
Disclosures: This study was supported by the National Institutes of Health National Center for Complementary and Integrative Health and the Office of Research on Women’s Health, and grants from the NIH/National Cancer Institute Division of Cancer Prevention. Dr. Hershman declared no conflicts of interest. Dr. Partridge had no disclosures.
Source: Hershman et al. Abstract GS4-04
Novel ADC shows promise in metastatic triple-negative breast cancer
SAN ANTONIO – A novel antibody drug conjugate has shown promise in metastatic triple-negative breast cancer (TNBC), according to new findings presented at the San Antonio Breast Cancer Symposium.
Sacituzumab govitecan, a novel antibody-drug conjugate, demonstrated significant clinical activity when used as a single agent among patients with relapsed/refractory disease who had already received multiple lines of therapy. The objective response rate in a cohort of more than 100 patients was 34%, and that included 3 complete responses and 34 partial responses.
“Sacituzumab govitecan demonstrated significant single-agent activity in this population,” said lead author Aditya Bardia, MD, of Harvard Medical School and Massachusetts General Hospital Cancer Center.
“Metastatic triple-negative breast cancer is an aggressive disease with a poor prognosis that tends to affect young women,” said Dr. Bardia. “Visceral and brain metastases are very common. Currently there is no single standard chemotherapy for relapsed or refractory metastatic triple-negative breast cancer.”
He noted that the response rates to standard chemotherapy are low and that median progression-free survival is in the range of 2-3 months. The response rate to standard chemotherapy first line and beyond, based on available data, is in the range of 6-15%.
“Consequently, there is a large unmet need in the breast cancer community,” said Dr. Bardia.
Sacituzumab govitecan (IMMU-132) is an antitrophoblastic cell-surface antigen (anti–Trop-2) and humanized antibody-SN-38 conjugate, which is the active metabolite of the topoisomerase I inhibitor irinotecan. Trop-2 is highly expressed in most epithelial cancers, including TNBC. A phase 1/2 basket trial was previously conducted in a cohort with multiple, advanced epithelial cancers and showed encouraging activity.
Dr. Bardia and his group also published preliminary results earlier this year in patients with metastatic TNBC, which showed an objective response rate of 30%, and last year, sacituzumab govitecan was granted Breakthrough Designation by the Food and Drug Administration. In the current study, the authors expanded the cohort and looked at a more defined population (third-line setting or greater in metastatic TNBC).
In this study, 110 patients who had metastatic TNBC (109 female, 1 male) and had received two or more lines of therapy for metastatic disease were enrolled between July 2013 and February 2017. The cohort included 53 patients from the investigators’ previously reported study in metastatic TNBC (n=69 total). As of this study’s cutoff date (June 30, 2017), 66 patients had died, 30 were in long term follow up, and 14 were still on treatment.
All patients were treated at the 10 mg/kg dose level, receiving 14.5 median doses (range, 1-88) over a median duration of 4.9 months. Treatment was administered on day 1 and 8 in a 21 day cycle, until progression or unacceptable toxicity.
Within the cohort of this heavily pretreated group, 41% received sacituzumab govitecan as third-line therapy while 59% received it at fourth line or more. The majority of patients had previously received taxanes or anthracyclines, and of note, 75% had previously received prior platinum, and 17% had previously received checkpoint inhibitors.
The clinical benefit rate, calculated using the rate of complete and partial response and stable disease greater than 6 months, was 45%. Responses were durable, with a median duration of 7.6 months by local assessment and 9.1 months by central review.
The median progression-free survival was 5.5 months (95% confidence interval, 4.8-6.6) and median overall survival was 12.7 months (95% CI, 10.8-13.6). Of the long term responders, nine have been progression free for more than a year, and four for more than 2 years. At the time of data cutoff, 12 responders were still receiving treatment.
Of note, Dr. Bardia said, patients stayed on sacituzumab govitecan longer than they had stayed on their most recent previous therapy.
The authors also conducted an exploratory subset analysis but found no difference in response when looking at age, prior regimens, onset of metastasis, the presence of visceral involvement at study entry, or Trop-2 expression.
Response among patients who had previously received checkpoint inhibitors was 47%, but Dr. Bardia cautions that “these numbers are small.”
Treatment with sacituzumab govitecan was well tolerated overall, with 2 patients discontinuing the drug because of related toxicity, and no antidrug antibodies detected. Grade 3 or greater toxicity included neutropenia (39%), leukopenia (14%), and anemia (10%); the incidence of febrile neutropenia was low (7%). There was a high rate of gastrointestinal related toxicity, but the majority were grade 1-2, and the rate of grade 3-4 “was in the single digits, ranging from 5-8%,” said Dr. Bardia. There were no drug-related deaths.
Given the high unmet medical need among patients with metastatic TNBC, data from this trial is being sent to the FDA to be considered for accelerated approval, and a global confirmatory randomized Phase 3 is now underway. “The ASCENT trial is recruiting in the United States right now,” said Dr. Bardia; this trial will include patients with metastatic TNBC who will receive either sacituzumab govitecan or physician’s choice of standard therapy.
Additional studies including rational combinations are currently being evaluated for metastatic TNBC and other breast cancer subsets.
SOURCE: Bardia A et al. Abstract GS1-07.
SAN ANTONIO – A novel antibody drug conjugate has shown promise in metastatic triple-negative breast cancer (TNBC), according to new findings presented at the San Antonio Breast Cancer Symposium.
Sacituzumab govitecan, a novel antibody-drug conjugate, demonstrated significant clinical activity when used as a single agent among patients with relapsed/refractory disease who had already received multiple lines of therapy. The objective response rate in a cohort of more than 100 patients was 34%, and that included 3 complete responses and 34 partial responses.
“Sacituzumab govitecan demonstrated significant single-agent activity in this population,” said lead author Aditya Bardia, MD, of Harvard Medical School and Massachusetts General Hospital Cancer Center.
“Metastatic triple-negative breast cancer is an aggressive disease with a poor prognosis that tends to affect young women,” said Dr. Bardia. “Visceral and brain metastases are very common. Currently there is no single standard chemotherapy for relapsed or refractory metastatic triple-negative breast cancer.”
He noted that the response rates to standard chemotherapy are low and that median progression-free survival is in the range of 2-3 months. The response rate to standard chemotherapy first line and beyond, based on available data, is in the range of 6-15%.
“Consequently, there is a large unmet need in the breast cancer community,” said Dr. Bardia.
Sacituzumab govitecan (IMMU-132) is an antitrophoblastic cell-surface antigen (anti–Trop-2) and humanized antibody-SN-38 conjugate, which is the active metabolite of the topoisomerase I inhibitor irinotecan. Trop-2 is highly expressed in most epithelial cancers, including TNBC. A phase 1/2 basket trial was previously conducted in a cohort with multiple, advanced epithelial cancers and showed encouraging activity.
Dr. Bardia and his group also published preliminary results earlier this year in patients with metastatic TNBC, which showed an objective response rate of 30%, and last year, sacituzumab govitecan was granted Breakthrough Designation by the Food and Drug Administration. In the current study, the authors expanded the cohort and looked at a more defined population (third-line setting or greater in metastatic TNBC).
In this study, 110 patients who had metastatic TNBC (109 female, 1 male) and had received two or more lines of therapy for metastatic disease were enrolled between July 2013 and February 2017. The cohort included 53 patients from the investigators’ previously reported study in metastatic TNBC (n=69 total). As of this study’s cutoff date (June 30, 2017), 66 patients had died, 30 were in long term follow up, and 14 were still on treatment.
All patients were treated at the 10 mg/kg dose level, receiving 14.5 median doses (range, 1-88) over a median duration of 4.9 months. Treatment was administered on day 1 and 8 in a 21 day cycle, until progression or unacceptable toxicity.
Within the cohort of this heavily pretreated group, 41% received sacituzumab govitecan as third-line therapy while 59% received it at fourth line or more. The majority of patients had previously received taxanes or anthracyclines, and of note, 75% had previously received prior platinum, and 17% had previously received checkpoint inhibitors.
The clinical benefit rate, calculated using the rate of complete and partial response and stable disease greater than 6 months, was 45%. Responses were durable, with a median duration of 7.6 months by local assessment and 9.1 months by central review.
The median progression-free survival was 5.5 months (95% confidence interval, 4.8-6.6) and median overall survival was 12.7 months (95% CI, 10.8-13.6). Of the long term responders, nine have been progression free for more than a year, and four for more than 2 years. At the time of data cutoff, 12 responders were still receiving treatment.
Of note, Dr. Bardia said, patients stayed on sacituzumab govitecan longer than they had stayed on their most recent previous therapy.
The authors also conducted an exploratory subset analysis but found no difference in response when looking at age, prior regimens, onset of metastasis, the presence of visceral involvement at study entry, or Trop-2 expression.
Response among patients who had previously received checkpoint inhibitors was 47%, but Dr. Bardia cautions that “these numbers are small.”
Treatment with sacituzumab govitecan was well tolerated overall, with 2 patients discontinuing the drug because of related toxicity, and no antidrug antibodies detected. Grade 3 or greater toxicity included neutropenia (39%), leukopenia (14%), and anemia (10%); the incidence of febrile neutropenia was low (7%). There was a high rate of gastrointestinal related toxicity, but the majority were grade 1-2, and the rate of grade 3-4 “was in the single digits, ranging from 5-8%,” said Dr. Bardia. There were no drug-related deaths.
Given the high unmet medical need among patients with metastatic TNBC, data from this trial is being sent to the FDA to be considered for accelerated approval, and a global confirmatory randomized Phase 3 is now underway. “The ASCENT trial is recruiting in the United States right now,” said Dr. Bardia; this trial will include patients with metastatic TNBC who will receive either sacituzumab govitecan or physician’s choice of standard therapy.
Additional studies including rational combinations are currently being evaluated for metastatic TNBC and other breast cancer subsets.
SOURCE: Bardia A et al. Abstract GS1-07.
SAN ANTONIO – A novel antibody drug conjugate has shown promise in metastatic triple-negative breast cancer (TNBC), according to new findings presented at the San Antonio Breast Cancer Symposium.
Sacituzumab govitecan, a novel antibody-drug conjugate, demonstrated significant clinical activity when used as a single agent among patients with relapsed/refractory disease who had already received multiple lines of therapy. The objective response rate in a cohort of more than 100 patients was 34%, and that included 3 complete responses and 34 partial responses.
“Sacituzumab govitecan demonstrated significant single-agent activity in this population,” said lead author Aditya Bardia, MD, of Harvard Medical School and Massachusetts General Hospital Cancer Center.
“Metastatic triple-negative breast cancer is an aggressive disease with a poor prognosis that tends to affect young women,” said Dr. Bardia. “Visceral and brain metastases are very common. Currently there is no single standard chemotherapy for relapsed or refractory metastatic triple-negative breast cancer.”
He noted that the response rates to standard chemotherapy are low and that median progression-free survival is in the range of 2-3 months. The response rate to standard chemotherapy first line and beyond, based on available data, is in the range of 6-15%.
“Consequently, there is a large unmet need in the breast cancer community,” said Dr. Bardia.
Sacituzumab govitecan (IMMU-132) is an antitrophoblastic cell-surface antigen (anti–Trop-2) and humanized antibody-SN-38 conjugate, which is the active metabolite of the topoisomerase I inhibitor irinotecan. Trop-2 is highly expressed in most epithelial cancers, including TNBC. A phase 1/2 basket trial was previously conducted in a cohort with multiple, advanced epithelial cancers and showed encouraging activity.
Dr. Bardia and his group also published preliminary results earlier this year in patients with metastatic TNBC, which showed an objective response rate of 30%, and last year, sacituzumab govitecan was granted Breakthrough Designation by the Food and Drug Administration. In the current study, the authors expanded the cohort and looked at a more defined population (third-line setting or greater in metastatic TNBC).
In this study, 110 patients who had metastatic TNBC (109 female, 1 male) and had received two or more lines of therapy for metastatic disease were enrolled between July 2013 and February 2017. The cohort included 53 patients from the investigators’ previously reported study in metastatic TNBC (n=69 total). As of this study’s cutoff date (June 30, 2017), 66 patients had died, 30 were in long term follow up, and 14 were still on treatment.
All patients were treated at the 10 mg/kg dose level, receiving 14.5 median doses (range, 1-88) over a median duration of 4.9 months. Treatment was administered on day 1 and 8 in a 21 day cycle, until progression or unacceptable toxicity.
Within the cohort of this heavily pretreated group, 41% received sacituzumab govitecan as third-line therapy while 59% received it at fourth line or more. The majority of patients had previously received taxanes or anthracyclines, and of note, 75% had previously received prior platinum, and 17% had previously received checkpoint inhibitors.
The clinical benefit rate, calculated using the rate of complete and partial response and stable disease greater than 6 months, was 45%. Responses were durable, with a median duration of 7.6 months by local assessment and 9.1 months by central review.
The median progression-free survival was 5.5 months (95% confidence interval, 4.8-6.6) and median overall survival was 12.7 months (95% CI, 10.8-13.6). Of the long term responders, nine have been progression free for more than a year, and four for more than 2 years. At the time of data cutoff, 12 responders were still receiving treatment.
Of note, Dr. Bardia said, patients stayed on sacituzumab govitecan longer than they had stayed on their most recent previous therapy.
The authors also conducted an exploratory subset analysis but found no difference in response when looking at age, prior regimens, onset of metastasis, the presence of visceral involvement at study entry, or Trop-2 expression.
Response among patients who had previously received checkpoint inhibitors was 47%, but Dr. Bardia cautions that “these numbers are small.”
Treatment with sacituzumab govitecan was well tolerated overall, with 2 patients discontinuing the drug because of related toxicity, and no antidrug antibodies detected. Grade 3 or greater toxicity included neutropenia (39%), leukopenia (14%), and anemia (10%); the incidence of febrile neutropenia was low (7%). There was a high rate of gastrointestinal related toxicity, but the majority were grade 1-2, and the rate of grade 3-4 “was in the single digits, ranging from 5-8%,” said Dr. Bardia. There were no drug-related deaths.
Given the high unmet medical need among patients with metastatic TNBC, data from this trial is being sent to the FDA to be considered for accelerated approval, and a global confirmatory randomized Phase 3 is now underway. “The ASCENT trial is recruiting in the United States right now,” said Dr. Bardia; this trial will include patients with metastatic TNBC who will receive either sacituzumab govitecan or physician’s choice of standard therapy.
Additional studies including rational combinations are currently being evaluated for metastatic TNBC and other breast cancer subsets.
SOURCE: Bardia A et al. Abstract GS1-07.
REPORTING FROM SABCS 2017
Key clinical point: Sacituzumab govitecan demonstrated significant clinical activity when used as a single agent among heavily pretreated patients with relapsed/refractory metastatic TNBC.
Major finding: The objective response rate was 34% and clinical benefit was 45%.
Data source: Single-arm, open-label trial that included 110 patients with relapsed/refractory metastatic TNBC who had received two or more lines of therapy.
Disclosures:. Immunomedics, which makes sacituzumab govitecan, funded the study. Dr. Bardia reported institutional funding but had no other disclosures.
Source: Bardia A et al. Abstract GS1-07.
No benefit to trastuzumab in low HER2 breast cancer
SAN ANTONIO – Adding trastuzumab to the standard regimen for patients with early-stage breast cancer and low levels of HER2 does not improve outcomes, according to new findings presented at the San Antonio Breast Cancer Symposium.
In a randomized trial of more than 3,000 patients, the
Patients in both arms did well, explained lead study author Louis Fehrenbacher, MD, medical director of Kaiser Permanente Oncology Clinical Trials and an oncologist with the Kaiser Permanente Vallejo (Calif.) Medical Center. “But the primary endpoint of IDFS was not met and none of the secondary endpoints were met. No trends of efficacy were seen.”
Current guidelines classify a breast cancer as HER2 positive if immunohistochemistry testing shows high levels of HER2 protein, defined as IHC 3+, or increased copies of the HER2 gene in situ hybridization. Adding 1 year of treatment with trastuzumab to standard adjuvant chemotherapy has been found to significantly reduce cancer recurrence and to improve survival for patients with early-stage HER2-positive breast cancer.
However, data from some of the early trastuzumab clinical trials suggested that patients with HER2-low breast cancer may benefit from the HER2-targeted treatment as well.
In 2005, the “stunning” results from the NSABP B-31 trial, of trastuzumab used in HER2+ breast cancer, were presented at the annual meeting of the American Society of Clinical Oncology. The study criteria included having a FISH+ test greater than 2.0 or IHC 3+, and testing was initially performed at a local laboratory site. When testing was conducted by the NSABP, submitted tissue samples showed that 9.7% of patients were not HER2 IHC 3+ or FISH+ greater than 2.0.
There were 174 patients defined as HER2 low, and not HER2 +.
“When the analysis was performed looking at the benefit of using trastuzumab in these patients considered low, it was found that the result was essentially identical, the benefit was equal, and statistically there was no interaction between FISH testing of IHC testing,” said Dr. Fehrenbacher. “These results were bewildering as the hypothesis was that only the HER2 amplified patients would benefit.
Because of these results, the NCI [National Cancer Institute] and the NSABP [National Surgical Adjuvant Breast and Bowel Project] initiated another trial, the N9831, which also found the same benefit in patients who were HER2 low.
About 15% of breast cancers are HER2 positive and another 45% have low levels of HER2, but these patients are not currently treated with adjuvant trastuzumab. Therefore, the current study, the NSABP-B-47, was designed and conducted to see if these early results could be validated in a large, prospective, randomized trial.
The study included 3,270 patients with early-stage breast cancer that was either IHC 1+, IHC 2+, and/or ISH negative in the trial. The patients were randomized 1:1 to standard adjuvant chemotherapy with or without a year of trastuzumab.
The standard regimen consisted of either one of the two chemotherapy regimens, per physician choice: The non-anthracycline regimen is TC (docetaxel 75 mg/m2, cyclophosphamide 600 mg/m2) administered intravenously every 3 weeks for six cycles; the anthracycline regimen is AC followed by weekly paclitaxel (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 administered intravenously either every 3 weeks or every 2 weeks. The same regimen applied to the group that received additional trastuzumab.
The primary endpoint was to determine whether the addition of trastuzumab to chemotherapy improved invasive disease-free survival.
At a median follow-up of 46.1 months, 264 patients had IDFS events. The 5-year estimates for recurrence-free interval, distant recurrence–free interval, and overall survival were not statistically different for patients receiving trastuzumab compared with those not receiving trastuzumab.
There was no difference in outcomes for IHC 1+ (HR for IDFS 0.88, 95% CI, 0.63-1.22) or IHC 2+ (HR for IDFS 1.14 95% CI, 0.79-1.65).
“The retrospective outcome difference between local tested HER2 + and center tested HER2-low patients identified in two major adjuvant trials are not readily explained,” said Dr. Fehrenbacher. “There is no benefit with trastuzumab therapy in patients with a FISH ratio of less than 2 and IHC staining intensity of 1+ or 2+.
SOURCE: Fehrenbacher et al. GS1-02
SAN ANTONIO – Adding trastuzumab to the standard regimen for patients with early-stage breast cancer and low levels of HER2 does not improve outcomes, according to new findings presented at the San Antonio Breast Cancer Symposium.
In a randomized trial of more than 3,000 patients, the
Patients in both arms did well, explained lead study author Louis Fehrenbacher, MD, medical director of Kaiser Permanente Oncology Clinical Trials and an oncologist with the Kaiser Permanente Vallejo (Calif.) Medical Center. “But the primary endpoint of IDFS was not met and none of the secondary endpoints were met. No trends of efficacy were seen.”
Current guidelines classify a breast cancer as HER2 positive if immunohistochemistry testing shows high levels of HER2 protein, defined as IHC 3+, or increased copies of the HER2 gene in situ hybridization. Adding 1 year of treatment with trastuzumab to standard adjuvant chemotherapy has been found to significantly reduce cancer recurrence and to improve survival for patients with early-stage HER2-positive breast cancer.
However, data from some of the early trastuzumab clinical trials suggested that patients with HER2-low breast cancer may benefit from the HER2-targeted treatment as well.
In 2005, the “stunning” results from the NSABP B-31 trial, of trastuzumab used in HER2+ breast cancer, were presented at the annual meeting of the American Society of Clinical Oncology. The study criteria included having a FISH+ test greater than 2.0 or IHC 3+, and testing was initially performed at a local laboratory site. When testing was conducted by the NSABP, submitted tissue samples showed that 9.7% of patients were not HER2 IHC 3+ or FISH+ greater than 2.0.
There were 174 patients defined as HER2 low, and not HER2 +.
“When the analysis was performed looking at the benefit of using trastuzumab in these patients considered low, it was found that the result was essentially identical, the benefit was equal, and statistically there was no interaction between FISH testing of IHC testing,” said Dr. Fehrenbacher. “These results were bewildering as the hypothesis was that only the HER2 amplified patients would benefit.
Because of these results, the NCI [National Cancer Institute] and the NSABP [National Surgical Adjuvant Breast and Bowel Project] initiated another trial, the N9831, which also found the same benefit in patients who were HER2 low.
About 15% of breast cancers are HER2 positive and another 45% have low levels of HER2, but these patients are not currently treated with adjuvant trastuzumab. Therefore, the current study, the NSABP-B-47, was designed and conducted to see if these early results could be validated in a large, prospective, randomized trial.
The study included 3,270 patients with early-stage breast cancer that was either IHC 1+, IHC 2+, and/or ISH negative in the trial. The patients were randomized 1:1 to standard adjuvant chemotherapy with or without a year of trastuzumab.
The standard regimen consisted of either one of the two chemotherapy regimens, per physician choice: The non-anthracycline regimen is TC (docetaxel 75 mg/m2, cyclophosphamide 600 mg/m2) administered intravenously every 3 weeks for six cycles; the anthracycline regimen is AC followed by weekly paclitaxel (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 administered intravenously either every 3 weeks or every 2 weeks. The same regimen applied to the group that received additional trastuzumab.
The primary endpoint was to determine whether the addition of trastuzumab to chemotherapy improved invasive disease-free survival.
At a median follow-up of 46.1 months, 264 patients had IDFS events. The 5-year estimates for recurrence-free interval, distant recurrence–free interval, and overall survival were not statistically different for patients receiving trastuzumab compared with those not receiving trastuzumab.
There was no difference in outcomes for IHC 1+ (HR for IDFS 0.88, 95% CI, 0.63-1.22) or IHC 2+ (HR for IDFS 1.14 95% CI, 0.79-1.65).
“The retrospective outcome difference between local tested HER2 + and center tested HER2-low patients identified in two major adjuvant trials are not readily explained,” said Dr. Fehrenbacher. “There is no benefit with trastuzumab therapy in patients with a FISH ratio of less than 2 and IHC staining intensity of 1+ or 2+.
SOURCE: Fehrenbacher et al. GS1-02
SAN ANTONIO – Adding trastuzumab to the standard regimen for patients with early-stage breast cancer and low levels of HER2 does not improve outcomes, according to new findings presented at the San Antonio Breast Cancer Symposium.
In a randomized trial of more than 3,000 patients, the
Patients in both arms did well, explained lead study author Louis Fehrenbacher, MD, medical director of Kaiser Permanente Oncology Clinical Trials and an oncologist with the Kaiser Permanente Vallejo (Calif.) Medical Center. “But the primary endpoint of IDFS was not met and none of the secondary endpoints were met. No trends of efficacy were seen.”
Current guidelines classify a breast cancer as HER2 positive if immunohistochemistry testing shows high levels of HER2 protein, defined as IHC 3+, or increased copies of the HER2 gene in situ hybridization. Adding 1 year of treatment with trastuzumab to standard adjuvant chemotherapy has been found to significantly reduce cancer recurrence and to improve survival for patients with early-stage HER2-positive breast cancer.
However, data from some of the early trastuzumab clinical trials suggested that patients with HER2-low breast cancer may benefit from the HER2-targeted treatment as well.
In 2005, the “stunning” results from the NSABP B-31 trial, of trastuzumab used in HER2+ breast cancer, were presented at the annual meeting of the American Society of Clinical Oncology. The study criteria included having a FISH+ test greater than 2.0 or IHC 3+, and testing was initially performed at a local laboratory site. When testing was conducted by the NSABP, submitted tissue samples showed that 9.7% of patients were not HER2 IHC 3+ or FISH+ greater than 2.0.
There were 174 patients defined as HER2 low, and not HER2 +.
“When the analysis was performed looking at the benefit of using trastuzumab in these patients considered low, it was found that the result was essentially identical, the benefit was equal, and statistically there was no interaction between FISH testing of IHC testing,” said Dr. Fehrenbacher. “These results were bewildering as the hypothesis was that only the HER2 amplified patients would benefit.
Because of these results, the NCI [National Cancer Institute] and the NSABP [National Surgical Adjuvant Breast and Bowel Project] initiated another trial, the N9831, which also found the same benefit in patients who were HER2 low.
About 15% of breast cancers are HER2 positive and another 45% have low levels of HER2, but these patients are not currently treated with adjuvant trastuzumab. Therefore, the current study, the NSABP-B-47, was designed and conducted to see if these early results could be validated in a large, prospective, randomized trial.
The study included 3,270 patients with early-stage breast cancer that was either IHC 1+, IHC 2+, and/or ISH negative in the trial. The patients were randomized 1:1 to standard adjuvant chemotherapy with or without a year of trastuzumab.
The standard regimen consisted of either one of the two chemotherapy regimens, per physician choice: The non-anthracycline regimen is TC (docetaxel 75 mg/m2, cyclophosphamide 600 mg/m2) administered intravenously every 3 weeks for six cycles; the anthracycline regimen is AC followed by weekly paclitaxel (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 administered intravenously either every 3 weeks or every 2 weeks. The same regimen applied to the group that received additional trastuzumab.
The primary endpoint was to determine whether the addition of trastuzumab to chemotherapy improved invasive disease-free survival.
At a median follow-up of 46.1 months, 264 patients had IDFS events. The 5-year estimates for recurrence-free interval, distant recurrence–free interval, and overall survival were not statistically different for patients receiving trastuzumab compared with those not receiving trastuzumab.
There was no difference in outcomes for IHC 1+ (HR for IDFS 0.88, 95% CI, 0.63-1.22) or IHC 2+ (HR for IDFS 1.14 95% CI, 0.79-1.65).
“The retrospective outcome difference between local tested HER2 + and center tested HER2-low patients identified in two major adjuvant trials are not readily explained,” said Dr. Fehrenbacher. “There is no benefit with trastuzumab therapy in patients with a FISH ratio of less than 2 and IHC staining intensity of 1+ or 2+.
SOURCE: Fehrenbacher et al. GS1-02
REPORTING FROM SABCS 2017
Key clinical point: In contrast to earlier reports, trastuzumab does not improve outcomes in breast cancer patients with low HER2 levels.
Major finding: The 5-year invasive disease–free survival was 89.6% for those who received trastuzumab, compared with 89.2% for those who did not (HR 0.98 95% CI 0.77-1.26, P = .90).
Data source: Phase 3 randomized, prospective clinical trial of 3,720 heavily pretreated breast cancer patients with low HER2 levels.
Disclosures: The National Cancer Institute and Genentech supported the study. Dr. Fehrenbacher declared no conflicts of interest.
Source: Fehrenbacher et al. GS1-02.