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2 = 5 for additional AI therapy for postmenopausal HR+ breast cancer
SAN ANTONIO – Five years of additional therapy with anastrozole (Arimidex) was no more effective than 2 additional years following the standard 5 years of initial endocrine therapy in postmenopausal women with hormone receptor–positive (HR+) breast cancer, Austrian investigators reported.
In fact, the only thing that the additional years of the aromatase inhibitor (AI) anastrozole seemed to add was increased risk for fracture, said Michael Gnant, MD, from the Medical University of Vienna, on behalf of colleagues in the ABCSG-16 trial.
Previous trials have convincingly demonstrated the benefit of giving patients an AI for 5 years after 5 years of tamoxifen, but the optimal duration of extended adjuvant AI therapy is not known, Dr. Gnant said.
The ABCSG trialists recruited 3,484 postmenopausal women from with HR+, stage T1-3, node-negative or -positive, nonmetastatic breast cancer who had completed 4-6 years of endocrine therapy with either tamoxifen, an AI, or tamoxifen followed by an AI. The patients were randomly assigned at the end of initial endocrine therapy to either 2 years or 5 years of anastrozole.
As noted before, disease-free survival (DFS), the primary endpoint, was virtually identical between the treatment arms. The DFS rate at a median of 8.75 years after randomization – that is, approximately 14 years after diagnosis – was 71.1% among patients treated for 2 additional years, vs. 70.3% for patients treated for 5 extra years, translating into a hazard ratio of 1.007 and making the contest a statistical dead heat.
Similarly, there was no difference by anastrozole duration in the secondary endpoint of overall survival at 10 years, with respective rates of 85.3% vs. 84.9%, with a hazard ratio identical to that in the DFS analysis.
Where the 5-year schedule surpassed the 2-year schedule, however, was in apparent risk for fractures, which was 6.3% after 5 years of additional therapy, compared with 4.7% at 5 years among patients who received just 2 additional years of anastrozole. The hazard ratio associated with the difference was 1.353, but because the lower end of the 95% confidence interval was 1.00, the finding was of borderline significance (P = .053), Dr. Gnant acknowledged.
There are several ongoing translational studies that may help to identify specific molecular characteristics that could predict benefit from prolonged extended therapy in a given patient, “but for now we can conclude that 7 years are good enough for almost every patient with luminal breast cancer,” Dr. Gnant said at a briefing prior to his presentation of the study in an oral session.
“I do believe that for us as clinical scientists a negative trial is always disappointing, but I think the clinical take-home message can actually help to avoid unnecessary side effects for many, many women,” he added.
Asked at the briefing whether, given the identical survival curves between the two trial arms, additional therapy beyond 5 years was needed, Dr. Gnant replied “that was addressed by other trials. I think that the trials after tamoxifen are very clear: We have hazard ratios around 0.6 after tamoxifen, so some type of extension for adding aromatase inhibitors should be the standard of care.”
He noted that the optimal duration of additional therapy with an AI has not been known, because the trial that could have answered that question, the MA-17 trial, was halted and unblinded after just 2.5 years when an interim analysis showed superior survival with letrozole (Femara), compared with placebo.
More than 60% of patients in the placebo group in that trial were crossed over to letrozole, further muddying long-term follow-up results.
Carlos Arteaga, MD, director of the Harold C. Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center in Dallas, who moderated the briefing, agreed with Dr. Gnant that this ostensibly negative trial had good results for patients.
“I hope that we continue to see more de-escalation studies. I hope that as we combine AIs with CDK4/6 inhibitors, we may make therapy even shorter. I think we should do better than just extending and extending and extending. We have to come up with better ideas,” he said in an interview.
The ABCSG-16 study was supported by AstraZeneca. Dr. Gnant disclosed research funding, honoraria, and travel funding from that company and others. Dr. Arteaga disclosed consulting fees from AstraZeneca and other companies.
SOURCE: Gnant et al. SABCS 2017 Abstract GS3-01
SAN ANTONIO – Five years of additional therapy with anastrozole (Arimidex) was no more effective than 2 additional years following the standard 5 years of initial endocrine therapy in postmenopausal women with hormone receptor–positive (HR+) breast cancer, Austrian investigators reported.
In fact, the only thing that the additional years of the aromatase inhibitor (AI) anastrozole seemed to add was increased risk for fracture, said Michael Gnant, MD, from the Medical University of Vienna, on behalf of colleagues in the ABCSG-16 trial.
Previous trials have convincingly demonstrated the benefit of giving patients an AI for 5 years after 5 years of tamoxifen, but the optimal duration of extended adjuvant AI therapy is not known, Dr. Gnant said.
The ABCSG trialists recruited 3,484 postmenopausal women from with HR+, stage T1-3, node-negative or -positive, nonmetastatic breast cancer who had completed 4-6 years of endocrine therapy with either tamoxifen, an AI, or tamoxifen followed by an AI. The patients were randomly assigned at the end of initial endocrine therapy to either 2 years or 5 years of anastrozole.
As noted before, disease-free survival (DFS), the primary endpoint, was virtually identical between the treatment arms. The DFS rate at a median of 8.75 years after randomization – that is, approximately 14 years after diagnosis – was 71.1% among patients treated for 2 additional years, vs. 70.3% for patients treated for 5 extra years, translating into a hazard ratio of 1.007 and making the contest a statistical dead heat.
Similarly, there was no difference by anastrozole duration in the secondary endpoint of overall survival at 10 years, with respective rates of 85.3% vs. 84.9%, with a hazard ratio identical to that in the DFS analysis.
Where the 5-year schedule surpassed the 2-year schedule, however, was in apparent risk for fractures, which was 6.3% after 5 years of additional therapy, compared with 4.7% at 5 years among patients who received just 2 additional years of anastrozole. The hazard ratio associated with the difference was 1.353, but because the lower end of the 95% confidence interval was 1.00, the finding was of borderline significance (P = .053), Dr. Gnant acknowledged.
There are several ongoing translational studies that may help to identify specific molecular characteristics that could predict benefit from prolonged extended therapy in a given patient, “but for now we can conclude that 7 years are good enough for almost every patient with luminal breast cancer,” Dr. Gnant said at a briefing prior to his presentation of the study in an oral session.
“I do believe that for us as clinical scientists a negative trial is always disappointing, but I think the clinical take-home message can actually help to avoid unnecessary side effects for many, many women,” he added.
Asked at the briefing whether, given the identical survival curves between the two trial arms, additional therapy beyond 5 years was needed, Dr. Gnant replied “that was addressed by other trials. I think that the trials after tamoxifen are very clear: We have hazard ratios around 0.6 after tamoxifen, so some type of extension for adding aromatase inhibitors should be the standard of care.”
He noted that the optimal duration of additional therapy with an AI has not been known, because the trial that could have answered that question, the MA-17 trial, was halted and unblinded after just 2.5 years when an interim analysis showed superior survival with letrozole (Femara), compared with placebo.
More than 60% of patients in the placebo group in that trial were crossed over to letrozole, further muddying long-term follow-up results.
Carlos Arteaga, MD, director of the Harold C. Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center in Dallas, who moderated the briefing, agreed with Dr. Gnant that this ostensibly negative trial had good results for patients.
“I hope that we continue to see more de-escalation studies. I hope that as we combine AIs with CDK4/6 inhibitors, we may make therapy even shorter. I think we should do better than just extending and extending and extending. We have to come up with better ideas,” he said in an interview.
The ABCSG-16 study was supported by AstraZeneca. Dr. Gnant disclosed research funding, honoraria, and travel funding from that company and others. Dr. Arteaga disclosed consulting fees from AstraZeneca and other companies.
SOURCE: Gnant et al. SABCS 2017 Abstract GS3-01
SAN ANTONIO – Five years of additional therapy with anastrozole (Arimidex) was no more effective than 2 additional years following the standard 5 years of initial endocrine therapy in postmenopausal women with hormone receptor–positive (HR+) breast cancer, Austrian investigators reported.
In fact, the only thing that the additional years of the aromatase inhibitor (AI) anastrozole seemed to add was increased risk for fracture, said Michael Gnant, MD, from the Medical University of Vienna, on behalf of colleagues in the ABCSG-16 trial.
Previous trials have convincingly demonstrated the benefit of giving patients an AI for 5 years after 5 years of tamoxifen, but the optimal duration of extended adjuvant AI therapy is not known, Dr. Gnant said.
The ABCSG trialists recruited 3,484 postmenopausal women from with HR+, stage T1-3, node-negative or -positive, nonmetastatic breast cancer who had completed 4-6 years of endocrine therapy with either tamoxifen, an AI, or tamoxifen followed by an AI. The patients were randomly assigned at the end of initial endocrine therapy to either 2 years or 5 years of anastrozole.
As noted before, disease-free survival (DFS), the primary endpoint, was virtually identical between the treatment arms. The DFS rate at a median of 8.75 years after randomization – that is, approximately 14 years after diagnosis – was 71.1% among patients treated for 2 additional years, vs. 70.3% for patients treated for 5 extra years, translating into a hazard ratio of 1.007 and making the contest a statistical dead heat.
Similarly, there was no difference by anastrozole duration in the secondary endpoint of overall survival at 10 years, with respective rates of 85.3% vs. 84.9%, with a hazard ratio identical to that in the DFS analysis.
Where the 5-year schedule surpassed the 2-year schedule, however, was in apparent risk for fractures, which was 6.3% after 5 years of additional therapy, compared with 4.7% at 5 years among patients who received just 2 additional years of anastrozole. The hazard ratio associated with the difference was 1.353, but because the lower end of the 95% confidence interval was 1.00, the finding was of borderline significance (P = .053), Dr. Gnant acknowledged.
There are several ongoing translational studies that may help to identify specific molecular characteristics that could predict benefit from prolonged extended therapy in a given patient, “but for now we can conclude that 7 years are good enough for almost every patient with luminal breast cancer,” Dr. Gnant said at a briefing prior to his presentation of the study in an oral session.
“I do believe that for us as clinical scientists a negative trial is always disappointing, but I think the clinical take-home message can actually help to avoid unnecessary side effects for many, many women,” he added.
Asked at the briefing whether, given the identical survival curves between the two trial arms, additional therapy beyond 5 years was needed, Dr. Gnant replied “that was addressed by other trials. I think that the trials after tamoxifen are very clear: We have hazard ratios around 0.6 after tamoxifen, so some type of extension for adding aromatase inhibitors should be the standard of care.”
He noted that the optimal duration of additional therapy with an AI has not been known, because the trial that could have answered that question, the MA-17 trial, was halted and unblinded after just 2.5 years when an interim analysis showed superior survival with letrozole (Femara), compared with placebo.
More than 60% of patients in the placebo group in that trial were crossed over to letrozole, further muddying long-term follow-up results.
Carlos Arteaga, MD, director of the Harold C. Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center in Dallas, who moderated the briefing, agreed with Dr. Gnant that this ostensibly negative trial had good results for patients.
“I hope that we continue to see more de-escalation studies. I hope that as we combine AIs with CDK4/6 inhibitors, we may make therapy even shorter. I think we should do better than just extending and extending and extending. We have to come up with better ideas,” he said in an interview.
The ABCSG-16 study was supported by AstraZeneca. Dr. Gnant disclosed research funding, honoraria, and travel funding from that company and others. Dr. Arteaga disclosed consulting fees from AstraZeneca and other companies.
SOURCE: Gnant et al. SABCS 2017 Abstract GS3-01
REPORTING FROM SABCS 2017
Key clinical point: Disease-free and overall survival were no different for women treated with 2 or 5 additional years of aromatase inhibitor therapy following 4-6 years of initial endocrine therapy.
Major finding: The hazard ratio for both DFS and OS with 5 additional years of anastrozole, compared with 2 years, was 1.007 and was not statistically significant.
Data source: Randomized phase 3 trial in 3,484 postmenopausal women with hormone receptor–positive breast cancer.
Disclosures: The ABCSG-16 study was supported by AstraZeneca. Dr. Gnant disclosed research funding, honoraria, and travel funding from that company and others. Dr. Arteaga disclosed consulting fees from AstraZeneca and other companies.
Source: Gnant et al. SABCS 2017 Abstract GS3-01
Shaping practice: Z1071 continues to redefine axillary management
SAN DIEGO – A 2013 breast cancer trial is changing the way lymph nodes are managed in women with node-positive disease who have an axillary pathologic complete response to neoadjuvant chemotherapy.
Emerging additional data support the initial theory of the American College of Surgeons Oncology Group (ACOSOG) Z1071 trial, said Judy C. Boughey, MD, FACS, at the American College of Surgeons Clinical Congress: Performing sentinel lymph node surgery after chemotherapy is an acceptable alternative for some women. This change in practice could bestow a profound long-term benefit on the approximately 40% of patients, who have an axillary pathologic complete response after neoadjuvant chemotherapy (NAC) – patients who otherwise might undergo an unnecessary axillary node exploration, which can lead to higher risk of lymphedema, said Dr. Boughey, head of surgical research at the Mayo Clinic, Rochester, Minn.
“About 20% of patients who are treated with chemotherapy for their breast cancer receive the chemotherapy prior to surgery. Of those who do receive neoadjuvant chemotherapy, probably half could benefit from this approach,” she said. “Lymphedema after axillary dissection is one of the situations patients are most concerned about. This approach is a great one when patients have a good chemotherapy response, and we want to reliably reassure ourselves that there’s no disease left in the axilla without automatically removing all the nodes. Of course, if there is any remaining disease in any of the lymph nodes, the current standard is still to remove all the nodes. This approach, however, optimizes management for patients who have the best response to chemotherapy.”
Neoadjuvant therapy success
Prechemotherapy nodal exploration was routine a decade or so ago and is what many surgeons were most comfortable with, Dr. Boughey said. “We know the false-negative rate, and chemotherapy doesn’t interfere with axillary staging. However, it means patients have to go through two surgeries, and, although the chemotherapy does not interfere with the procedure, if any of the sentinel nodes are positive and an axillary dissection is performed at the same setting, then systemic therapy will be delayed. However, most importantly, when the sentinel node is removed prior to chemotherapy, we lose the ability to assess axillary response to chemotherapy – which correlates with survival.”
The biggest drawback of axillary dissection is its potential for lifelong morbidity from lymphedema. “Women know about this. They worry about this, and they want to avoid it if at all possible,” Dr. Boughey said.
More effective, targeted chemotherapeutic agents have resulted in higher rates of eradication of disease with neoadjuvant treatment. So this leads to the question: Why not reassess nodes after treatment, when these drugs have had a chance to work? Doing so reduces the one-size-fits-all prescription of axillary dissection and, thus, the number of women with lasting adverse events.
Some early data supported this theory
In 2009, researchers at the MD Anderson Center reported that sentinel node surgery after chemotherapy in patients with node-negative breast cancer resulted in fewer positive sentinel nodes and decreased unnecessary axillary dissections. Node identification rates were about 98% whether the surgery came before or after treatment. The false-negative rate hovered around 5%. And there were significantly fewer axillary dissections with posttreatment surgery: 20% vs. 36% in women with T2 disease and 30% vs. 51% in those with T3 disease. Importantly, holding off on the surgery didn’t lead to higher local-regional failure rates or survival among the 3,746 women treated during 1994-2007.
The American College of Surgeons Oncology Group Z1071 trial was designed to explore this question in patients with node-positive breast cancer. The Z1071 trial enrolled 756 women who had clinical T0-T4, N1-N2, M0 breast cancer and received neoadjuvant chemotherapy. Patients underwent both sentinel lymph node surgery and axillary lymph node dissection following chemotherapy. The primary endpoint was the false-negative rate of sentinel lymph node surgery after chemotherapy in women who presented with cN1 disease and had at least two sentinel nodes resected; a rate of 10% lower was considered acceptable and would justify the approach.
Of the entire cohort, 40% had a complete pathologic nodal response rate. The sentinel node identification rate was nearly 93%. The false-negative rate among 525 women with two or more positive sentinel nodes, however, was 12.6% – short of the 10% rate investigators needed to deem the study a success, Dr. Boughey said.
But there were some positive findings in subgroup analyses. Among women who had nodes identified with a dual tracer (both dye and radioactive clipping), the false-negative rate dipped to 10.8%. It was just 9% in those who had more than two sentinel nodes identified.
A recent subanalysis of the Z1071 trial further refined these data. It looked at 170 of the patients with cN1 disease (32%) who had had a clip placed in the positive lymph node at the time of percutaneous biopsy and compared false-negative rates among them with rates in the 355 patients who were not clipped.
“When we looked at them, if the clipped node came out during the sentinel node surgery, then the false-negative rate dropped down to about 7%,” Dr. Boughey said. The comparator group pointed out the value of using a clip. The false-negative rate was 13% in patients who didn’t have a clip placed and 19% in the patients whose clip wasn’t retrieved until axillary dissection.
The results of Z1071 and its subanalyses have popularized nodal clipping, Dr. Boughey said. “When we ran Z1071, clipping wasn’t commonly being performed, but there has been a huge uptake in it now.”
Confirmatory data
Other recent studies confirm the feasibility of this approach in women who have clinically negative nodes after NAC.
In 2013, the German study SENTINA (sentinel-lymph-node biopsy in patients with breast cancer before and after neoadjuvant chemotherapy) explored the false-negative rate in women who had sentinel node biopsy before or after neoadjuvant chemotherapy. Overall, it found an unacceptably high false-negative rate of 14% in women with node positive disease who converted to clinically negative nodal status. However, when the analysis was limited to those cases with at least two sentinel nodes, the false-negative rate was less than 10%, once more suggesting a potential role for sentinel node surgery after neoadjuvant chemotherapy.
In 2015, the Sentinel Node Biopsy Following Neoadjuvant Chemotherapy (SN FNAC) study highlighted the potential effect of sentinel node surgery after NAC. The prospective study showed not only that the strategy was safe, with a false-negative rate around 8%, but also that it could have eliminated complete axillary dissection in about 30% of the cohort.
The study enrolled 153 women with biopsy-proven node-positive breast cancer (T0-3, N1-2) who underwent both sentinel node surgery and complete nodal dissection. Immunohistochemistry of the retrieved sentinel nodes was mandatory, and the presence of any tumor cells in the sentinel node rendered it positive.
The sentinel node retrieval rate was 88%, and the false-negative rate, 8.4%. The study also employed dual tracers of isotope and blue dye in a majority of patients; this was associated with a threefold decrease in the false-negative rate in those patients, dropping it to around 5%. “By using sentinel node biopsy after NAC, axillary node dissection could potentially be avoided in at least 30% of patients who present with node-positive breast cancer,” the study’s team concluded.
Long-term consequences?
It’s increasingly clear that for carefully selected patients, with robust NAC response, a postchemotherapy assessment can accurately assess nodal disease – especially if dual tracers are employed, several sentinel nodes examined, and the biopsy-proven positive node is resected. What isn’t clear yet is the long-term effect of this strategy, Dr. Boughey said.
“Five years ago, when Z1071 was first being reported, I would discuss it in terms of the controversy, and give the pros and cons,” she said. “But now that we have more information about this strategy under our belts, I feel much more confident. However, we still do not have information on patients with node-positive disease who have been treated with sentinel node only after neoadjuvant chemotherapy and followed for 5 or 10 years. That’s the piece we just can’t have, without time.”
Dr. Boughey had no relevant financial disclosures.
SOURCE: Boughey JC. Session PS108.
SAN DIEGO – A 2013 breast cancer trial is changing the way lymph nodes are managed in women with node-positive disease who have an axillary pathologic complete response to neoadjuvant chemotherapy.
Emerging additional data support the initial theory of the American College of Surgeons Oncology Group (ACOSOG) Z1071 trial, said Judy C. Boughey, MD, FACS, at the American College of Surgeons Clinical Congress: Performing sentinel lymph node surgery after chemotherapy is an acceptable alternative for some women. This change in practice could bestow a profound long-term benefit on the approximately 40% of patients, who have an axillary pathologic complete response after neoadjuvant chemotherapy (NAC) – patients who otherwise might undergo an unnecessary axillary node exploration, which can lead to higher risk of lymphedema, said Dr. Boughey, head of surgical research at the Mayo Clinic, Rochester, Minn.
“About 20% of patients who are treated with chemotherapy for their breast cancer receive the chemotherapy prior to surgery. Of those who do receive neoadjuvant chemotherapy, probably half could benefit from this approach,” she said. “Lymphedema after axillary dissection is one of the situations patients are most concerned about. This approach is a great one when patients have a good chemotherapy response, and we want to reliably reassure ourselves that there’s no disease left in the axilla without automatically removing all the nodes. Of course, if there is any remaining disease in any of the lymph nodes, the current standard is still to remove all the nodes. This approach, however, optimizes management for patients who have the best response to chemotherapy.”
Neoadjuvant therapy success
Prechemotherapy nodal exploration was routine a decade or so ago and is what many surgeons were most comfortable with, Dr. Boughey said. “We know the false-negative rate, and chemotherapy doesn’t interfere with axillary staging. However, it means patients have to go through two surgeries, and, although the chemotherapy does not interfere with the procedure, if any of the sentinel nodes are positive and an axillary dissection is performed at the same setting, then systemic therapy will be delayed. However, most importantly, when the sentinel node is removed prior to chemotherapy, we lose the ability to assess axillary response to chemotherapy – which correlates with survival.”
The biggest drawback of axillary dissection is its potential for lifelong morbidity from lymphedema. “Women know about this. They worry about this, and they want to avoid it if at all possible,” Dr. Boughey said.
More effective, targeted chemotherapeutic agents have resulted in higher rates of eradication of disease with neoadjuvant treatment. So this leads to the question: Why not reassess nodes after treatment, when these drugs have had a chance to work? Doing so reduces the one-size-fits-all prescription of axillary dissection and, thus, the number of women with lasting adverse events.
Some early data supported this theory
In 2009, researchers at the MD Anderson Center reported that sentinel node surgery after chemotherapy in patients with node-negative breast cancer resulted in fewer positive sentinel nodes and decreased unnecessary axillary dissections. Node identification rates were about 98% whether the surgery came before or after treatment. The false-negative rate hovered around 5%. And there were significantly fewer axillary dissections with posttreatment surgery: 20% vs. 36% in women with T2 disease and 30% vs. 51% in those with T3 disease. Importantly, holding off on the surgery didn’t lead to higher local-regional failure rates or survival among the 3,746 women treated during 1994-2007.
The American College of Surgeons Oncology Group Z1071 trial was designed to explore this question in patients with node-positive breast cancer. The Z1071 trial enrolled 756 women who had clinical T0-T4, N1-N2, M0 breast cancer and received neoadjuvant chemotherapy. Patients underwent both sentinel lymph node surgery and axillary lymph node dissection following chemotherapy. The primary endpoint was the false-negative rate of sentinel lymph node surgery after chemotherapy in women who presented with cN1 disease and had at least two sentinel nodes resected; a rate of 10% lower was considered acceptable and would justify the approach.
Of the entire cohort, 40% had a complete pathologic nodal response rate. The sentinel node identification rate was nearly 93%. The false-negative rate among 525 women with two or more positive sentinel nodes, however, was 12.6% – short of the 10% rate investigators needed to deem the study a success, Dr. Boughey said.
But there were some positive findings in subgroup analyses. Among women who had nodes identified with a dual tracer (both dye and radioactive clipping), the false-negative rate dipped to 10.8%. It was just 9% in those who had more than two sentinel nodes identified.
A recent subanalysis of the Z1071 trial further refined these data. It looked at 170 of the patients with cN1 disease (32%) who had had a clip placed in the positive lymph node at the time of percutaneous biopsy and compared false-negative rates among them with rates in the 355 patients who were not clipped.
“When we looked at them, if the clipped node came out during the sentinel node surgery, then the false-negative rate dropped down to about 7%,” Dr. Boughey said. The comparator group pointed out the value of using a clip. The false-negative rate was 13% in patients who didn’t have a clip placed and 19% in the patients whose clip wasn’t retrieved until axillary dissection.
The results of Z1071 and its subanalyses have popularized nodal clipping, Dr. Boughey said. “When we ran Z1071, clipping wasn’t commonly being performed, but there has been a huge uptake in it now.”
Confirmatory data
Other recent studies confirm the feasibility of this approach in women who have clinically negative nodes after NAC.
In 2013, the German study SENTINA (sentinel-lymph-node biopsy in patients with breast cancer before and after neoadjuvant chemotherapy) explored the false-negative rate in women who had sentinel node biopsy before or after neoadjuvant chemotherapy. Overall, it found an unacceptably high false-negative rate of 14% in women with node positive disease who converted to clinically negative nodal status. However, when the analysis was limited to those cases with at least two sentinel nodes, the false-negative rate was less than 10%, once more suggesting a potential role for sentinel node surgery after neoadjuvant chemotherapy.
In 2015, the Sentinel Node Biopsy Following Neoadjuvant Chemotherapy (SN FNAC) study highlighted the potential effect of sentinel node surgery after NAC. The prospective study showed not only that the strategy was safe, with a false-negative rate around 8%, but also that it could have eliminated complete axillary dissection in about 30% of the cohort.
The study enrolled 153 women with biopsy-proven node-positive breast cancer (T0-3, N1-2) who underwent both sentinel node surgery and complete nodal dissection. Immunohistochemistry of the retrieved sentinel nodes was mandatory, and the presence of any tumor cells in the sentinel node rendered it positive.
The sentinel node retrieval rate was 88%, and the false-negative rate, 8.4%. The study also employed dual tracers of isotope and blue dye in a majority of patients; this was associated with a threefold decrease in the false-negative rate in those patients, dropping it to around 5%. “By using sentinel node biopsy after NAC, axillary node dissection could potentially be avoided in at least 30% of patients who present with node-positive breast cancer,” the study’s team concluded.
Long-term consequences?
It’s increasingly clear that for carefully selected patients, with robust NAC response, a postchemotherapy assessment can accurately assess nodal disease – especially if dual tracers are employed, several sentinel nodes examined, and the biopsy-proven positive node is resected. What isn’t clear yet is the long-term effect of this strategy, Dr. Boughey said.
“Five years ago, when Z1071 was first being reported, I would discuss it in terms of the controversy, and give the pros and cons,” she said. “But now that we have more information about this strategy under our belts, I feel much more confident. However, we still do not have information on patients with node-positive disease who have been treated with sentinel node only after neoadjuvant chemotherapy and followed for 5 or 10 years. That’s the piece we just can’t have, without time.”
Dr. Boughey had no relevant financial disclosures.
SOURCE: Boughey JC. Session PS108.
SAN DIEGO – A 2013 breast cancer trial is changing the way lymph nodes are managed in women with node-positive disease who have an axillary pathologic complete response to neoadjuvant chemotherapy.
Emerging additional data support the initial theory of the American College of Surgeons Oncology Group (ACOSOG) Z1071 trial, said Judy C. Boughey, MD, FACS, at the American College of Surgeons Clinical Congress: Performing sentinel lymph node surgery after chemotherapy is an acceptable alternative for some women. This change in practice could bestow a profound long-term benefit on the approximately 40% of patients, who have an axillary pathologic complete response after neoadjuvant chemotherapy (NAC) – patients who otherwise might undergo an unnecessary axillary node exploration, which can lead to higher risk of lymphedema, said Dr. Boughey, head of surgical research at the Mayo Clinic, Rochester, Minn.
“About 20% of patients who are treated with chemotherapy for their breast cancer receive the chemotherapy prior to surgery. Of those who do receive neoadjuvant chemotherapy, probably half could benefit from this approach,” she said. “Lymphedema after axillary dissection is one of the situations patients are most concerned about. This approach is a great one when patients have a good chemotherapy response, and we want to reliably reassure ourselves that there’s no disease left in the axilla without automatically removing all the nodes. Of course, if there is any remaining disease in any of the lymph nodes, the current standard is still to remove all the nodes. This approach, however, optimizes management for patients who have the best response to chemotherapy.”
Neoadjuvant therapy success
Prechemotherapy nodal exploration was routine a decade or so ago and is what many surgeons were most comfortable with, Dr. Boughey said. “We know the false-negative rate, and chemotherapy doesn’t interfere with axillary staging. However, it means patients have to go through two surgeries, and, although the chemotherapy does not interfere with the procedure, if any of the sentinel nodes are positive and an axillary dissection is performed at the same setting, then systemic therapy will be delayed. However, most importantly, when the sentinel node is removed prior to chemotherapy, we lose the ability to assess axillary response to chemotherapy – which correlates with survival.”
The biggest drawback of axillary dissection is its potential for lifelong morbidity from lymphedema. “Women know about this. They worry about this, and they want to avoid it if at all possible,” Dr. Boughey said.
More effective, targeted chemotherapeutic agents have resulted in higher rates of eradication of disease with neoadjuvant treatment. So this leads to the question: Why not reassess nodes after treatment, when these drugs have had a chance to work? Doing so reduces the one-size-fits-all prescription of axillary dissection and, thus, the number of women with lasting adverse events.
Some early data supported this theory
In 2009, researchers at the MD Anderson Center reported that sentinel node surgery after chemotherapy in patients with node-negative breast cancer resulted in fewer positive sentinel nodes and decreased unnecessary axillary dissections. Node identification rates were about 98% whether the surgery came before or after treatment. The false-negative rate hovered around 5%. And there were significantly fewer axillary dissections with posttreatment surgery: 20% vs. 36% in women with T2 disease and 30% vs. 51% in those with T3 disease. Importantly, holding off on the surgery didn’t lead to higher local-regional failure rates or survival among the 3,746 women treated during 1994-2007.
The American College of Surgeons Oncology Group Z1071 trial was designed to explore this question in patients with node-positive breast cancer. The Z1071 trial enrolled 756 women who had clinical T0-T4, N1-N2, M0 breast cancer and received neoadjuvant chemotherapy. Patients underwent both sentinel lymph node surgery and axillary lymph node dissection following chemotherapy. The primary endpoint was the false-negative rate of sentinel lymph node surgery after chemotherapy in women who presented with cN1 disease and had at least two sentinel nodes resected; a rate of 10% lower was considered acceptable and would justify the approach.
Of the entire cohort, 40% had a complete pathologic nodal response rate. The sentinel node identification rate was nearly 93%. The false-negative rate among 525 women with two or more positive sentinel nodes, however, was 12.6% – short of the 10% rate investigators needed to deem the study a success, Dr. Boughey said.
But there were some positive findings in subgroup analyses. Among women who had nodes identified with a dual tracer (both dye and radioactive clipping), the false-negative rate dipped to 10.8%. It was just 9% in those who had more than two sentinel nodes identified.
A recent subanalysis of the Z1071 trial further refined these data. It looked at 170 of the patients with cN1 disease (32%) who had had a clip placed in the positive lymph node at the time of percutaneous biopsy and compared false-negative rates among them with rates in the 355 patients who were not clipped.
“When we looked at them, if the clipped node came out during the sentinel node surgery, then the false-negative rate dropped down to about 7%,” Dr. Boughey said. The comparator group pointed out the value of using a clip. The false-negative rate was 13% in patients who didn’t have a clip placed and 19% in the patients whose clip wasn’t retrieved until axillary dissection.
The results of Z1071 and its subanalyses have popularized nodal clipping, Dr. Boughey said. “When we ran Z1071, clipping wasn’t commonly being performed, but there has been a huge uptake in it now.”
Confirmatory data
Other recent studies confirm the feasibility of this approach in women who have clinically negative nodes after NAC.
In 2013, the German study SENTINA (sentinel-lymph-node biopsy in patients with breast cancer before and after neoadjuvant chemotherapy) explored the false-negative rate in women who had sentinel node biopsy before or after neoadjuvant chemotherapy. Overall, it found an unacceptably high false-negative rate of 14% in women with node positive disease who converted to clinically negative nodal status. However, when the analysis was limited to those cases with at least two sentinel nodes, the false-negative rate was less than 10%, once more suggesting a potential role for sentinel node surgery after neoadjuvant chemotherapy.
In 2015, the Sentinel Node Biopsy Following Neoadjuvant Chemotherapy (SN FNAC) study highlighted the potential effect of sentinel node surgery after NAC. The prospective study showed not only that the strategy was safe, with a false-negative rate around 8%, but also that it could have eliminated complete axillary dissection in about 30% of the cohort.
The study enrolled 153 women with biopsy-proven node-positive breast cancer (T0-3, N1-2) who underwent both sentinel node surgery and complete nodal dissection. Immunohistochemistry of the retrieved sentinel nodes was mandatory, and the presence of any tumor cells in the sentinel node rendered it positive.
The sentinel node retrieval rate was 88%, and the false-negative rate, 8.4%. The study also employed dual tracers of isotope and blue dye in a majority of patients; this was associated with a threefold decrease in the false-negative rate in those patients, dropping it to around 5%. “By using sentinel node biopsy after NAC, axillary node dissection could potentially be avoided in at least 30% of patients who present with node-positive breast cancer,” the study’s team concluded.
Long-term consequences?
It’s increasingly clear that for carefully selected patients, with robust NAC response, a postchemotherapy assessment can accurately assess nodal disease – especially if dual tracers are employed, several sentinel nodes examined, and the biopsy-proven positive node is resected. What isn’t clear yet is the long-term effect of this strategy, Dr. Boughey said.
“Five years ago, when Z1071 was first being reported, I would discuss it in terms of the controversy, and give the pros and cons,” she said. “But now that we have more information about this strategy under our belts, I feel much more confident. However, we still do not have information on patients with node-positive disease who have been treated with sentinel node only after neoadjuvant chemotherapy and followed for 5 or 10 years. That’s the piece we just can’t have, without time.”
Dr. Boughey had no relevant financial disclosures.
SOURCE: Boughey JC. Session PS108.
EXPERT ANALYSIS FROM THE ACS CLINICAL CONGRESS
VIDEO: CDK4/6, ET, LHRH combo improves PFS in premenopausal breast cancer
SAN ANTONIO – For premenopausal women with advanced hormone receptor–positive, HER2-negative breast cancer, the addition of the cyclin-dependent kinase (CDK) 4/6 inhibitor ribociclib (Kisqali) to endocrine therapy and goserelin was associated with a near doubling in progression-free survival (PFS), improvement in pain scores and a longer time to deterioration of quality of life scores.
Previous clinical trials have shown the advantage of adding a CDK4/6 inhibitor to standard aromatase inhibitor therapy in postmenopausal women, but the randomized phase 3 MONALEESA-7 trial is the first phase 3 study of an agent in this class in premenopausal women with breast cancer, and is the first randomized trial in this population in nearly 2 decades, notes Debu Tripathy, MD, from the University of Texas MD Anderson Cancer Center in Houston.
The median PFS for women treated with ribociclib plus endocrine therapy with either an aromatase inhibitor or tamoxifen plus the lutenizing hormone-releasing hormone agonist goserelin was 23.8 months, compared with 13 months for women treated with the same combination except for a ribociclib placebo.
In this video interview at the San Antonio Breast Cancer Symposium, Dr. Tripathy discusses the therapeutic benefits and quality of life improvements associated with adding ribociclib to endocrine therapy and ovarian suppression in this population.
The MONALEESA 7 trial was supported by Novartis. Dr. Tripathy disclosed steering committee consulting fees and institutional funding from the company.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
SAN ANTONIO – For premenopausal women with advanced hormone receptor–positive, HER2-negative breast cancer, the addition of the cyclin-dependent kinase (CDK) 4/6 inhibitor ribociclib (Kisqali) to endocrine therapy and goserelin was associated with a near doubling in progression-free survival (PFS), improvement in pain scores and a longer time to deterioration of quality of life scores.
Previous clinical trials have shown the advantage of adding a CDK4/6 inhibitor to standard aromatase inhibitor therapy in postmenopausal women, but the randomized phase 3 MONALEESA-7 trial is the first phase 3 study of an agent in this class in premenopausal women with breast cancer, and is the first randomized trial in this population in nearly 2 decades, notes Debu Tripathy, MD, from the University of Texas MD Anderson Cancer Center in Houston.
The median PFS for women treated with ribociclib plus endocrine therapy with either an aromatase inhibitor or tamoxifen plus the lutenizing hormone-releasing hormone agonist goserelin was 23.8 months, compared with 13 months for women treated with the same combination except for a ribociclib placebo.
In this video interview at the San Antonio Breast Cancer Symposium, Dr. Tripathy discusses the therapeutic benefits and quality of life improvements associated with adding ribociclib to endocrine therapy and ovarian suppression in this population.
The MONALEESA 7 trial was supported by Novartis. Dr. Tripathy disclosed steering committee consulting fees and institutional funding from the company.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
SAN ANTONIO – For premenopausal women with advanced hormone receptor–positive, HER2-negative breast cancer, the addition of the cyclin-dependent kinase (CDK) 4/6 inhibitor ribociclib (Kisqali) to endocrine therapy and goserelin was associated with a near doubling in progression-free survival (PFS), improvement in pain scores and a longer time to deterioration of quality of life scores.
Previous clinical trials have shown the advantage of adding a CDK4/6 inhibitor to standard aromatase inhibitor therapy in postmenopausal women, but the randomized phase 3 MONALEESA-7 trial is the first phase 3 study of an agent in this class in premenopausal women with breast cancer, and is the first randomized trial in this population in nearly 2 decades, notes Debu Tripathy, MD, from the University of Texas MD Anderson Cancer Center in Houston.
The median PFS for women treated with ribociclib plus endocrine therapy with either an aromatase inhibitor or tamoxifen plus the lutenizing hormone-releasing hormone agonist goserelin was 23.8 months, compared with 13 months for women treated with the same combination except for a ribociclib placebo.
In this video interview at the San Antonio Breast Cancer Symposium, Dr. Tripathy discusses the therapeutic benefits and quality of life improvements associated with adding ribociclib to endocrine therapy and ovarian suppression in this population.
The MONALEESA 7 trial was supported by Novartis. Dr. Tripathy disclosed steering committee consulting fees and institutional funding from the company.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
REPORTING FROM SABCS 2017
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
VIDEO: 5 years of additional AI no better than 2 in HR+ breast cancer
SAN ANTONIO – Clinical trials have shown a clear benefit for preventing breast cancer recurrence with aromatase inhibitor (AI) therapy following 5 years of tamoxifen. Yet the optimal duration for additional AI therapy following 5 years of endocrine therapy with tamoxifen, an AI, or sequential therapies is not known, according to Michael Gnant, MD, from the Medical University of Vienna.
In the ABCSG-16 trial, Dr. Gnant and his colleagues reported that 5 years of additional therapy with anastrozole (Arimidex) was no more effective than 2 additional years following the standard 5 years of initial endocrine therapy in postmenopausal women with hormone receptor–positive (HR+) breast cancer.
In this video interview at the San Antonio Breast Cancer Symposium, Dr. Gnant notes that, although some patients may still benefit from 5 years of additional therapy, the trial results suggest that most patients can be spared from such adverse events as risk for fractures associated with three additional and evidently unnecessary years of therapy.
The ABCSG-16 study was supported by AstraZeneca. Dr. Gnant disclosed research funding, honoraria, and travel funding from the company and others.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
SAN ANTONIO – Clinical trials have shown a clear benefit for preventing breast cancer recurrence with aromatase inhibitor (AI) therapy following 5 years of tamoxifen. Yet the optimal duration for additional AI therapy following 5 years of endocrine therapy with tamoxifen, an AI, or sequential therapies is not known, according to Michael Gnant, MD, from the Medical University of Vienna.
In the ABCSG-16 trial, Dr. Gnant and his colleagues reported that 5 years of additional therapy with anastrozole (Arimidex) was no more effective than 2 additional years following the standard 5 years of initial endocrine therapy in postmenopausal women with hormone receptor–positive (HR+) breast cancer.
In this video interview at the San Antonio Breast Cancer Symposium, Dr. Gnant notes that, although some patients may still benefit from 5 years of additional therapy, the trial results suggest that most patients can be spared from such adverse events as risk for fractures associated with three additional and evidently unnecessary years of therapy.
The ABCSG-16 study was supported by AstraZeneca. Dr. Gnant disclosed research funding, honoraria, and travel funding from the company and others.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
SAN ANTONIO – Clinical trials have shown a clear benefit for preventing breast cancer recurrence with aromatase inhibitor (AI) therapy following 5 years of tamoxifen. Yet the optimal duration for additional AI therapy following 5 years of endocrine therapy with tamoxifen, an AI, or sequential therapies is not known, according to Michael Gnant, MD, from the Medical University of Vienna.
In the ABCSG-16 trial, Dr. Gnant and his colleagues reported that 5 years of additional therapy with anastrozole (Arimidex) was no more effective than 2 additional years following the standard 5 years of initial endocrine therapy in postmenopausal women with hormone receptor–positive (HR+) breast cancer.
In this video interview at the San Antonio Breast Cancer Symposium, Dr. Gnant notes that, although some patients may still benefit from 5 years of additional therapy, the trial results suggest that most patients can be spared from such adverse events as risk for fractures associated with three additional and evidently unnecessary years of therapy.
The ABCSG-16 study was supported by AstraZeneca. Dr. Gnant disclosed research funding, honoraria, and travel funding from the company and others.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
REPORTING FROM SABCS 2017
No evidence for perioperative AI benefit in early ER/PR+ breast cancer
SAN ANTONIO – Skip the perioperative aromatase inhibitor (AI) therapy in women with early stage hormone receptor-positive breast cancer, because it doesn’t make a difference in either time to recurrence or overall survival, British investigators advise.
Among nearly 4,500 women enrolled in the POETIC trial, time to recurrence (TTR) and overall survival (OS) were similar whether patients received AI therapy within 2 weeks of surgery or did not, reported John Robertson, MD, from the University of Nottingham, England, and his colleagues.
“There is no evidence of improved clinical outcome with perioperative aromatase inhibitor therapy,” he said at the San Antonio Breast Cancer Symposium.
The trial wasn’t all for naught, however, because it also provided further evidence that measuring Ki67 levels at baseline and at 2 weeks of therapy offer significant and independent prognostic information.
“If your baseline Ki67 is low, the prognosis is good, suggesting no need for 2 weeks of AI treatment and a second Ki67 measurement,” Dr. Robertson said.
However, if the Ki67 level is 10% or higher at baseline, a Ki67 measure after 2 weeks of AI therapy can be used to guide additional therapy.
“If the 2-week Ki67 is low, patients will do relatively well, with 8.4% recurrences, and may need no additional treatment beyond standard of care. If, however, your Ki67 at 2 weeks remains high, you have a poor prognosis with an almost 20% 5-year recurrence risk, and those patients should be considered for additional chemotherapy, and/or for trials looking at new agents,” he said.
POETIC was a randomized phase 3 trial in postmenopausal women with newly diagnosed estrogen– and progesterone receptor–positive invasive breast cancer. Patients were randomized on a 2:1 basis, respectively, to either perioperative therapy with an AI (letrozole or anastrozole) for 2 weeks, surgery, and an additional 2 weeks of AI treatment, or to surgery with no perioperative therapy within a 2-week window. Patients could receive further treatment in accordance with local practice.
Of 4,486 patients randomized, 4,480 were available for analysis, including 2,528 with both baseline and 2-week Ki67 in the perioperative therapy arm, and 678 with paired Ki67 readings in the no-therapy arm.
For the primary endpoint of TTR, the curves were superimposable, with 5-year TTR of 90.9% in the perioperative AI groups, and 90.3% in the no perioperative AI group, translating into an absolute difference of only 0.52%.
Similarly, there were no differences in OS at 5 years, at 89.0% vs. 89.5%, respectively (absolute difference, 0.51%), with survival curves virtually indistinguishable from one another.
The events contributing to TTR, including local or distant recurrence and breast cancer deaths were equally distributed between the trial arms.
For patients with high baseline Ki67 values (10% or greater) at both baseline and after 2 weeks of perioperative AI therapy, the 5-year absolute risk for recurrence was 19.6%, compared with 8.9% for those with high baseline but low 2-week Ki67 levels, and 4.5% for those with low levels at both time points. The hazard ratio for patients with high Ki67 at both time points was 2.22 (P less than .001).
The POETIC trial was supported by Cancer Research UK. Dr. Robertson did not report disclosure information.
SOURCE: Robertson J et al., Abstract GS1-03
SAN ANTONIO – Skip the perioperative aromatase inhibitor (AI) therapy in women with early stage hormone receptor-positive breast cancer, because it doesn’t make a difference in either time to recurrence or overall survival, British investigators advise.
Among nearly 4,500 women enrolled in the POETIC trial, time to recurrence (TTR) and overall survival (OS) were similar whether patients received AI therapy within 2 weeks of surgery or did not, reported John Robertson, MD, from the University of Nottingham, England, and his colleagues.
“There is no evidence of improved clinical outcome with perioperative aromatase inhibitor therapy,” he said at the San Antonio Breast Cancer Symposium.
The trial wasn’t all for naught, however, because it also provided further evidence that measuring Ki67 levels at baseline and at 2 weeks of therapy offer significant and independent prognostic information.
“If your baseline Ki67 is low, the prognosis is good, suggesting no need for 2 weeks of AI treatment and a second Ki67 measurement,” Dr. Robertson said.
However, if the Ki67 level is 10% or higher at baseline, a Ki67 measure after 2 weeks of AI therapy can be used to guide additional therapy.
“If the 2-week Ki67 is low, patients will do relatively well, with 8.4% recurrences, and may need no additional treatment beyond standard of care. If, however, your Ki67 at 2 weeks remains high, you have a poor prognosis with an almost 20% 5-year recurrence risk, and those patients should be considered for additional chemotherapy, and/or for trials looking at new agents,” he said.
POETIC was a randomized phase 3 trial in postmenopausal women with newly diagnosed estrogen– and progesterone receptor–positive invasive breast cancer. Patients were randomized on a 2:1 basis, respectively, to either perioperative therapy with an AI (letrozole or anastrozole) for 2 weeks, surgery, and an additional 2 weeks of AI treatment, or to surgery with no perioperative therapy within a 2-week window. Patients could receive further treatment in accordance with local practice.
Of 4,486 patients randomized, 4,480 were available for analysis, including 2,528 with both baseline and 2-week Ki67 in the perioperative therapy arm, and 678 with paired Ki67 readings in the no-therapy arm.
For the primary endpoint of TTR, the curves were superimposable, with 5-year TTR of 90.9% in the perioperative AI groups, and 90.3% in the no perioperative AI group, translating into an absolute difference of only 0.52%.
Similarly, there were no differences in OS at 5 years, at 89.0% vs. 89.5%, respectively (absolute difference, 0.51%), with survival curves virtually indistinguishable from one another.
The events contributing to TTR, including local or distant recurrence and breast cancer deaths were equally distributed between the trial arms.
For patients with high baseline Ki67 values (10% or greater) at both baseline and after 2 weeks of perioperative AI therapy, the 5-year absolute risk for recurrence was 19.6%, compared with 8.9% for those with high baseline but low 2-week Ki67 levels, and 4.5% for those with low levels at both time points. The hazard ratio for patients with high Ki67 at both time points was 2.22 (P less than .001).
The POETIC trial was supported by Cancer Research UK. Dr. Robertson did not report disclosure information.
SOURCE: Robertson J et al., Abstract GS1-03
SAN ANTONIO – Skip the perioperative aromatase inhibitor (AI) therapy in women with early stage hormone receptor-positive breast cancer, because it doesn’t make a difference in either time to recurrence or overall survival, British investigators advise.
Among nearly 4,500 women enrolled in the POETIC trial, time to recurrence (TTR) and overall survival (OS) were similar whether patients received AI therapy within 2 weeks of surgery or did not, reported John Robertson, MD, from the University of Nottingham, England, and his colleagues.
“There is no evidence of improved clinical outcome with perioperative aromatase inhibitor therapy,” he said at the San Antonio Breast Cancer Symposium.
The trial wasn’t all for naught, however, because it also provided further evidence that measuring Ki67 levels at baseline and at 2 weeks of therapy offer significant and independent prognostic information.
“If your baseline Ki67 is low, the prognosis is good, suggesting no need for 2 weeks of AI treatment and a second Ki67 measurement,” Dr. Robertson said.
However, if the Ki67 level is 10% or higher at baseline, a Ki67 measure after 2 weeks of AI therapy can be used to guide additional therapy.
“If the 2-week Ki67 is low, patients will do relatively well, with 8.4% recurrences, and may need no additional treatment beyond standard of care. If, however, your Ki67 at 2 weeks remains high, you have a poor prognosis with an almost 20% 5-year recurrence risk, and those patients should be considered for additional chemotherapy, and/or for trials looking at new agents,” he said.
POETIC was a randomized phase 3 trial in postmenopausal women with newly diagnosed estrogen– and progesterone receptor–positive invasive breast cancer. Patients were randomized on a 2:1 basis, respectively, to either perioperative therapy with an AI (letrozole or anastrozole) for 2 weeks, surgery, and an additional 2 weeks of AI treatment, or to surgery with no perioperative therapy within a 2-week window. Patients could receive further treatment in accordance with local practice.
Of 4,486 patients randomized, 4,480 were available for analysis, including 2,528 with both baseline and 2-week Ki67 in the perioperative therapy arm, and 678 with paired Ki67 readings in the no-therapy arm.
For the primary endpoint of TTR, the curves were superimposable, with 5-year TTR of 90.9% in the perioperative AI groups, and 90.3% in the no perioperative AI group, translating into an absolute difference of only 0.52%.
Similarly, there were no differences in OS at 5 years, at 89.0% vs. 89.5%, respectively (absolute difference, 0.51%), with survival curves virtually indistinguishable from one another.
The events contributing to TTR, including local or distant recurrence and breast cancer deaths were equally distributed between the trial arms.
For patients with high baseline Ki67 values (10% or greater) at both baseline and after 2 weeks of perioperative AI therapy, the 5-year absolute risk for recurrence was 19.6%, compared with 8.9% for those with high baseline but low 2-week Ki67 levels, and 4.5% for those with low levels at both time points. The hazard ratio for patients with high Ki67 at both time points was 2.22 (P less than .001).
The POETIC trial was supported by Cancer Research UK. Dr. Robertson did not report disclosure information.
SOURCE: Robertson J et al., Abstract GS1-03
REPORTING FROM SABCS 2017
Key clinical point: Perioperative aromatase inhibitor therapy did not offer a survival benefit in women with hormone receptor–positive early stage breast cancer.
Major finding: Both 5-year time to recurrence and overall survival rates were identical among women who received perioperative AI therapy and those who did not.
Data source: Randomized phase 3 trial with analysis of data on 4,480 women.
Disclosures: The POETIC trial was supported by Cancer Research UK. Dr. Robertson did not report disclosure information.
Source: Robertson J et al., Abstract GS1-03.
Dose intensification gets more mileage out of adjuvant chemo
SAN ANTONIO – Increasing the dose intensity of adjuvant chemotherapy for breast cancer by spacing cycles more closely or by giving drugs sequentially instead of concurrently improves outcomes, confirms a meta-analysis conducted by the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG).
Results showed that depending on which specific strategy was used, women were 13%-18% less likely to experience recurrence and 11%-18% less likely to die from breast cancer if they were given dose-intensified chemotherapy instead of standard chemotherapy, he reported in a press briefing and a session at the San Antonio Breast Cancer Symposium.
“Shortening the interval between cycles and sequential administration of anthracycline and taxane chemotherapy reduces both recurrence and death from breast cancer,” Mr. Gray summarized. “The reductions are about 15%. They were seen in both estrogen receptor [ER]–positive and ER-negative disease and did not differ significantly by any other tumor or patient characteristics.”
“The beauty of this is these are the exact same drugs and, in many cases, similar doses. It’s just the schedule that changes,” commented press briefing moderator Virginia Kaklamani, MD, a professor of medicine in the division of hematology/oncology at the University of Texas Health Science Center San Antonio and a leader of the Breast Cancer Program at the UT Health San Antonio Cancer Center. “We used to give chemotherapy over 6 months, and with this approach, we can give it over 4 months, so the patients prefer it. The toxicity, with the growth factors for support, can be less. So everybody wins here.”
Study details
“We know that adjuvant chemotherapy can really help reduce recurrence and prevent breast cancer death. It reduces breast cancer death by about a third,” Mr. Gray noted, giving some background to the analysis. “We are still looking at ways to improve that even further. One of the approaches, which is based on cytokinetic modeling, is to try and increase the dose intensity of the chemotherapy.”
For the meta-analysis, the investigators identified trials that achieved dose intensification by reducing the interval between treatment cycles (a dose-dense approach) and/or by giving drugs sequentially rather than concurrently (allowing delivery of higher doses of each drug).
In all, seven trials, which included 10,004 women in total, tested chemotherapy given every 2 weeks (dose-dense chemotherapy) versus the same chemotherapy given every 3 weeks. Results showed that the former approach netted significantly lower risks of recurrence (rate ratio [RR], 0.83; P = .00004) and breast cancer mortality (RR, 0.86; P = .004), Mr. Gray reported. Absolute gains at 10 years were 4.3% and 2.8%, respectively. Findings were similar after adding five more trials, with another 5,508 women, that had some differences in chemotherapy treatments between arms.
Six trials, which included 11,028 women in total, tested sequential chemotherapy every 3 weeks versus concurrent chemotherapy every 3 weeks. Results showed similarly that the former strategy yielded lower risks of recurrence (RR, 0.87; P = .0006) and breast cancer death (RR, 0.89; P = .03). Absolute gains at 10 years were 3.2% and 2.1%, respectively.
Another six trials, which included a total of 6,532 women, tested sequential chemotherapy given every 2 weeks versus concurrent chemotherapy given every 3 weeks. Results here showed once again that the former yielded lower risks of recurrence (RR, 0.82; P = .0001) and breast cancer mortality (RR, 0.82; P = .001). Absolute gains at 10 years were 4.5% and 3.9%, respectively.
Finally, a pooled analysis of all trials showed that dose intensification reduced the risk of recurrence (RR, 0.85; P less than .00001) and breast cancer mortality (RR, 0.87; P less than .00001). Absolute gains at 10 years were 3.6% and 2.7%, respectively.
“That 13% reduction in breast cancer mortality may seem relatively modest, but given that taxane and anthracycline on a standard schedule reduces your chance of breast cancer death by a third, if you then reduce that by another 15%, then you have got almost 50% of breast cancer deaths by dose-dense taxane and anthracycline chemotherapy,” Mr. Gray pointed out. “So these little step-by-step improvements, it’s really important to identify them, and you get incremental gains which result in breast cancer deaths being about half of what they were 25 or 30 years ago.”
The proportional reduction in risk was similar whether tumors were ER positive or negative, but additional follow-up, especially for the positive tumors, will be important. “We do need longer follow-up in these trials, and sadly, many of the funding bodies are not providing funding for long-term follow-up,” he commented. “This is really valuable information, and we should be following these women up further, out to 20 years, given the long natural history of breast cancer.”
In terms of safety, the dose-intensification strategies were actually associated with lower risks of death without recurrence (RR, 0.85; P less than .02) and all-cause mortality (RR, 0.87; P less than .00001). Findings were similar when analyses focused on the first year of treatment.
Tolerability and toxicities of dose-intense regimens relative to standard regimens were not evaluated by the meta-analysis because these outcomes were reported differently across trials, according to Mr. Gray. However, the investigators did perform a systematic review of health-related quality of life studies that will be part of the final manuscript.
“We found surprisingly little extra toxicity” with the dose intensification, he reported. “It’s not very much considering the extra benefits we are getting. And when you know you are getting more benefit, it makes it easy to tolerate a drug.”
“In the U.S., people have moved toward the accelerated chemotherapy much more than they have in Europe. I think people have the mindset, ‘Well, we’ve always done it this way,’ ” Mr. Gray concluded. “This evidence being so clear and definite will help change that mindset. I wouldn’t be surprised if practice in the U.K. and many other parts of Europe doesn’t switch as a result of these very definite findings.”
SAN ANTONIO – Increasing the dose intensity of adjuvant chemotherapy for breast cancer by spacing cycles more closely or by giving drugs sequentially instead of concurrently improves outcomes, confirms a meta-analysis conducted by the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG).
Results showed that depending on which specific strategy was used, women were 13%-18% less likely to experience recurrence and 11%-18% less likely to die from breast cancer if they were given dose-intensified chemotherapy instead of standard chemotherapy, he reported in a press briefing and a session at the San Antonio Breast Cancer Symposium.
“Shortening the interval between cycles and sequential administration of anthracycline and taxane chemotherapy reduces both recurrence and death from breast cancer,” Mr. Gray summarized. “The reductions are about 15%. They were seen in both estrogen receptor [ER]–positive and ER-negative disease and did not differ significantly by any other tumor or patient characteristics.”
“The beauty of this is these are the exact same drugs and, in many cases, similar doses. It’s just the schedule that changes,” commented press briefing moderator Virginia Kaklamani, MD, a professor of medicine in the division of hematology/oncology at the University of Texas Health Science Center San Antonio and a leader of the Breast Cancer Program at the UT Health San Antonio Cancer Center. “We used to give chemotherapy over 6 months, and with this approach, we can give it over 4 months, so the patients prefer it. The toxicity, with the growth factors for support, can be less. So everybody wins here.”
Study details
“We know that adjuvant chemotherapy can really help reduce recurrence and prevent breast cancer death. It reduces breast cancer death by about a third,” Mr. Gray noted, giving some background to the analysis. “We are still looking at ways to improve that even further. One of the approaches, which is based on cytokinetic modeling, is to try and increase the dose intensity of the chemotherapy.”
For the meta-analysis, the investigators identified trials that achieved dose intensification by reducing the interval between treatment cycles (a dose-dense approach) and/or by giving drugs sequentially rather than concurrently (allowing delivery of higher doses of each drug).
In all, seven trials, which included 10,004 women in total, tested chemotherapy given every 2 weeks (dose-dense chemotherapy) versus the same chemotherapy given every 3 weeks. Results showed that the former approach netted significantly lower risks of recurrence (rate ratio [RR], 0.83; P = .00004) and breast cancer mortality (RR, 0.86; P = .004), Mr. Gray reported. Absolute gains at 10 years were 4.3% and 2.8%, respectively. Findings were similar after adding five more trials, with another 5,508 women, that had some differences in chemotherapy treatments between arms.
Six trials, which included 11,028 women in total, tested sequential chemotherapy every 3 weeks versus concurrent chemotherapy every 3 weeks. Results showed similarly that the former strategy yielded lower risks of recurrence (RR, 0.87; P = .0006) and breast cancer death (RR, 0.89; P = .03). Absolute gains at 10 years were 3.2% and 2.1%, respectively.
Another six trials, which included a total of 6,532 women, tested sequential chemotherapy given every 2 weeks versus concurrent chemotherapy given every 3 weeks. Results here showed once again that the former yielded lower risks of recurrence (RR, 0.82; P = .0001) and breast cancer mortality (RR, 0.82; P = .001). Absolute gains at 10 years were 4.5% and 3.9%, respectively.
Finally, a pooled analysis of all trials showed that dose intensification reduced the risk of recurrence (RR, 0.85; P less than .00001) and breast cancer mortality (RR, 0.87; P less than .00001). Absolute gains at 10 years were 3.6% and 2.7%, respectively.
“That 13% reduction in breast cancer mortality may seem relatively modest, but given that taxane and anthracycline on a standard schedule reduces your chance of breast cancer death by a third, if you then reduce that by another 15%, then you have got almost 50% of breast cancer deaths by dose-dense taxane and anthracycline chemotherapy,” Mr. Gray pointed out. “So these little step-by-step improvements, it’s really important to identify them, and you get incremental gains which result in breast cancer deaths being about half of what they were 25 or 30 years ago.”
The proportional reduction in risk was similar whether tumors were ER positive or negative, but additional follow-up, especially for the positive tumors, will be important. “We do need longer follow-up in these trials, and sadly, many of the funding bodies are not providing funding for long-term follow-up,” he commented. “This is really valuable information, and we should be following these women up further, out to 20 years, given the long natural history of breast cancer.”
In terms of safety, the dose-intensification strategies were actually associated with lower risks of death without recurrence (RR, 0.85; P less than .02) and all-cause mortality (RR, 0.87; P less than .00001). Findings were similar when analyses focused on the first year of treatment.
Tolerability and toxicities of dose-intense regimens relative to standard regimens were not evaluated by the meta-analysis because these outcomes were reported differently across trials, according to Mr. Gray. However, the investigators did perform a systematic review of health-related quality of life studies that will be part of the final manuscript.
“We found surprisingly little extra toxicity” with the dose intensification, he reported. “It’s not very much considering the extra benefits we are getting. And when you know you are getting more benefit, it makes it easy to tolerate a drug.”
“In the U.S., people have moved toward the accelerated chemotherapy much more than they have in Europe. I think people have the mindset, ‘Well, we’ve always done it this way,’ ” Mr. Gray concluded. “This evidence being so clear and definite will help change that mindset. I wouldn’t be surprised if practice in the U.K. and many other parts of Europe doesn’t switch as a result of these very definite findings.”
SAN ANTONIO – Increasing the dose intensity of adjuvant chemotherapy for breast cancer by spacing cycles more closely or by giving drugs sequentially instead of concurrently improves outcomes, confirms a meta-analysis conducted by the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG).
Results showed that depending on which specific strategy was used, women were 13%-18% less likely to experience recurrence and 11%-18% less likely to die from breast cancer if they were given dose-intensified chemotherapy instead of standard chemotherapy, he reported in a press briefing and a session at the San Antonio Breast Cancer Symposium.
“Shortening the interval between cycles and sequential administration of anthracycline and taxane chemotherapy reduces both recurrence and death from breast cancer,” Mr. Gray summarized. “The reductions are about 15%. They were seen in both estrogen receptor [ER]–positive and ER-negative disease and did not differ significantly by any other tumor or patient characteristics.”
“The beauty of this is these are the exact same drugs and, in many cases, similar doses. It’s just the schedule that changes,” commented press briefing moderator Virginia Kaklamani, MD, a professor of medicine in the division of hematology/oncology at the University of Texas Health Science Center San Antonio and a leader of the Breast Cancer Program at the UT Health San Antonio Cancer Center. “We used to give chemotherapy over 6 months, and with this approach, we can give it over 4 months, so the patients prefer it. The toxicity, with the growth factors for support, can be less. So everybody wins here.”
Study details
“We know that adjuvant chemotherapy can really help reduce recurrence and prevent breast cancer death. It reduces breast cancer death by about a third,” Mr. Gray noted, giving some background to the analysis. “We are still looking at ways to improve that even further. One of the approaches, which is based on cytokinetic modeling, is to try and increase the dose intensity of the chemotherapy.”
For the meta-analysis, the investigators identified trials that achieved dose intensification by reducing the interval between treatment cycles (a dose-dense approach) and/or by giving drugs sequentially rather than concurrently (allowing delivery of higher doses of each drug).
In all, seven trials, which included 10,004 women in total, tested chemotherapy given every 2 weeks (dose-dense chemotherapy) versus the same chemotherapy given every 3 weeks. Results showed that the former approach netted significantly lower risks of recurrence (rate ratio [RR], 0.83; P = .00004) and breast cancer mortality (RR, 0.86; P = .004), Mr. Gray reported. Absolute gains at 10 years were 4.3% and 2.8%, respectively. Findings were similar after adding five more trials, with another 5,508 women, that had some differences in chemotherapy treatments between arms.
Six trials, which included 11,028 women in total, tested sequential chemotherapy every 3 weeks versus concurrent chemotherapy every 3 weeks. Results showed similarly that the former strategy yielded lower risks of recurrence (RR, 0.87; P = .0006) and breast cancer death (RR, 0.89; P = .03). Absolute gains at 10 years were 3.2% and 2.1%, respectively.
Another six trials, which included a total of 6,532 women, tested sequential chemotherapy given every 2 weeks versus concurrent chemotherapy given every 3 weeks. Results here showed once again that the former yielded lower risks of recurrence (RR, 0.82; P = .0001) and breast cancer mortality (RR, 0.82; P = .001). Absolute gains at 10 years were 4.5% and 3.9%, respectively.
Finally, a pooled analysis of all trials showed that dose intensification reduced the risk of recurrence (RR, 0.85; P less than .00001) and breast cancer mortality (RR, 0.87; P less than .00001). Absolute gains at 10 years were 3.6% and 2.7%, respectively.
“That 13% reduction in breast cancer mortality may seem relatively modest, but given that taxane and anthracycline on a standard schedule reduces your chance of breast cancer death by a third, if you then reduce that by another 15%, then you have got almost 50% of breast cancer deaths by dose-dense taxane and anthracycline chemotherapy,” Mr. Gray pointed out. “So these little step-by-step improvements, it’s really important to identify them, and you get incremental gains which result in breast cancer deaths being about half of what they were 25 or 30 years ago.”
The proportional reduction in risk was similar whether tumors were ER positive or negative, but additional follow-up, especially for the positive tumors, will be important. “We do need longer follow-up in these trials, and sadly, many of the funding bodies are not providing funding for long-term follow-up,” he commented. “This is really valuable information, and we should be following these women up further, out to 20 years, given the long natural history of breast cancer.”
In terms of safety, the dose-intensification strategies were actually associated with lower risks of death without recurrence (RR, 0.85; P less than .02) and all-cause mortality (RR, 0.87; P less than .00001). Findings were similar when analyses focused on the first year of treatment.
Tolerability and toxicities of dose-intense regimens relative to standard regimens were not evaluated by the meta-analysis because these outcomes were reported differently across trials, according to Mr. Gray. However, the investigators did perform a systematic review of health-related quality of life studies that will be part of the final manuscript.
“We found surprisingly little extra toxicity” with the dose intensification, he reported. “It’s not very much considering the extra benefits we are getting. And when you know you are getting more benefit, it makes it easy to tolerate a drug.”
“In the U.S., people have moved toward the accelerated chemotherapy much more than they have in Europe. I think people have the mindset, ‘Well, we’ve always done it this way,’ ” Mr. Gray concluded. “This evidence being so clear and definite will help change that mindset. I wouldn’t be surprised if practice in the U.K. and many other parts of Europe doesn’t switch as a result of these very definite findings.”
REPORTING FROM SABCS 2017
Key clinical point:
Major finding: Compared with standard chemotherapy, dose-intense chemotherapy using various strategies reduced the risk of recurrence (rate ratio, 0.85; P less than .00001) and breast cancer mortality (RR, 0.87; P less than .00001).
Data source: A meta-analysis of individual patient data from 25 randomized trials among 34,122 women with early-stage breast cancer.
Disclosures: Mr. Gray disclosed that he had no relevant conflicts of interest.
Ribociclib plus standard of care improves PFS in premenopausal HR+/HER2-negative breast cancer
SAN ANTONIO – For premenopausal women with advanced hormone receptor–positive, HER2-negative breast cancer, the addition of the CDK4/6 inhibitor ribociclib (Kisqali) to endocrine therapy and goserelin was associated with a near doubling in progression-free survival (PFS), improvement in pain scores and a longer time to deterioration of quality of life (Qol) scores, investigators reported.
The hazard ratio for the ribociclib-based combination was 0.553 (P less than .0001), he reported at the San Antonio Breast Cancer Symposium.
“The treatment benefit was seen across all subgroups, and also regardless of the endocrine partner, either tamoxifen or aromastase inhibitors,” he said.
The combination of ribociclib with goserelin and either tamoxifen or a nonsteroidal AI is a potential new treatment option for premenopausal women with hormone receptor–positive, HER2-negative advanced breast cancer, regardless of the disease-free interval or the endocrine partner, he said in a media briefing and in an oral session.
In the United States, approximately 19% of invasive breast cancers are diagnosed in women aged 49 years or younger, and in the Asia/Pacific region, the proportion of patients aged younger than 50 years with invasive breast cancer may be as high as 42%, Dr. Tripathy said.
The need for new therapeutic approaches in this population is clear, with the last randomized clinical trial focused solely on women with advanced premenopausal breast being published 17 years ago, he pointed out.
Given the efficacy of adding ribociclib to standard AI therapy in postmenopausal women with advanced HR+/HER2- breast cancer as seen in the MONALEESA-2 trial, the MONALEESA-7 investigators looked at the same combination as first-line therapy in premenopausal women with similar disease features.
In the trial, 672 pre- or perimenopausal women with HR+/HER2– advanced breast cancer with no prior endocrine therapy for advanced disease and no more than one line of chemotherapy for advanced disease were enrolled. The patients were stratified by the presence of liver/lung metastases, prior chemotherapy, and prior endocrine partner, tamoxifen or nonsteroidal AI, and then randomly assigned to the ribociclib 600 mg/day for 3 weeks, followed by 1-week off, plus tamoxifen or AI and goserelin, or the same combination and schedule with placebo.
Of the 672 patients enrolled, a total of 335 patients assigned to ribociclib and 337 assigned to placebo received treatment.
Investigator-assessed progression-free survival was the primary endpoint, as noted before. The findings were supported by an analysis of the data by a blinded independent review committee, which determined the median PFS to not have been reached in the ribociclib arm, compared with 11.1 months in the placebo arm, with a hazard ratio of 0.427, and a 95% confidence interval showing statistical significance.
The secondary endpoint of overall response rate (ORR) was also significantly better with ribociclib among the entire patient population (40.9% vs. 29.7%; P = .00098), and in patients with measurable disease (50.9% vs. 36.4%; P = .000317).
An analysis of PFS by endocrine agent (tamoxifen or AI) showed similar hazard ratios with each class of agent combined with ribociclib.
Hematologic adverse events occurred in 75.8% of all patients on ribociclib, compared with 7.7% of those on placebo. In the CDK4/6 inhibitor arm, 50.7% of patients had grade 3 neutropenia, and 9.9% had grade 4. Febrile neutropenia occurred in 2.1% of patients on ribociclib, compared with 0.6% of patients on placebo.
Nonhematologic adverse events were generally similar between the trial arms, with the exception of more frequent nausea with ribociclib.
Ribociclib also was associated with significantly better patient-reported outcomes, including longer time to deterioration of QoL scores, and better improvement in pain scores from baseline.
“For me, I would now be very comfortable giving these women an aromatase inhibitor plus goserelin and riboclicib,” she said in an interview.
SABCS fixture Steven “Vogl, New York” Vogl, MD, a medical oncologist in private practice in New York, commented after Dr. Tripathy’s presentation that, “I think that this is a momentous study, and I think it should immediately change the standard of care for symptomatic young women with metastatic breast cancer. More of them get better, and they stay better longer. These are people who we’re trying to buy some good life for, before the inevitable happens.”
The MONALEESA 7 trial was supported by Novartis. Dr. Tripathy disclosed steering committee consulting fees and institutional funding from the company. Dr. Kaklamani reported serving as a consultant to Novartis. Dr. Vogl reported no conflicts of interest.
SAN ANTONIO – For premenopausal women with advanced hormone receptor–positive, HER2-negative breast cancer, the addition of the CDK4/6 inhibitor ribociclib (Kisqali) to endocrine therapy and goserelin was associated with a near doubling in progression-free survival (PFS), improvement in pain scores and a longer time to deterioration of quality of life (Qol) scores, investigators reported.
The hazard ratio for the ribociclib-based combination was 0.553 (P less than .0001), he reported at the San Antonio Breast Cancer Symposium.
“The treatment benefit was seen across all subgroups, and also regardless of the endocrine partner, either tamoxifen or aromastase inhibitors,” he said.
The combination of ribociclib with goserelin and either tamoxifen or a nonsteroidal AI is a potential new treatment option for premenopausal women with hormone receptor–positive, HER2-negative advanced breast cancer, regardless of the disease-free interval or the endocrine partner, he said in a media briefing and in an oral session.
In the United States, approximately 19% of invasive breast cancers are diagnosed in women aged 49 years or younger, and in the Asia/Pacific region, the proportion of patients aged younger than 50 years with invasive breast cancer may be as high as 42%, Dr. Tripathy said.
The need for new therapeutic approaches in this population is clear, with the last randomized clinical trial focused solely on women with advanced premenopausal breast being published 17 years ago, he pointed out.
Given the efficacy of adding ribociclib to standard AI therapy in postmenopausal women with advanced HR+/HER2- breast cancer as seen in the MONALEESA-2 trial, the MONALEESA-7 investigators looked at the same combination as first-line therapy in premenopausal women with similar disease features.
In the trial, 672 pre- or perimenopausal women with HR+/HER2– advanced breast cancer with no prior endocrine therapy for advanced disease and no more than one line of chemotherapy for advanced disease were enrolled. The patients were stratified by the presence of liver/lung metastases, prior chemotherapy, and prior endocrine partner, tamoxifen or nonsteroidal AI, and then randomly assigned to the ribociclib 600 mg/day for 3 weeks, followed by 1-week off, plus tamoxifen or AI and goserelin, or the same combination and schedule with placebo.
Of the 672 patients enrolled, a total of 335 patients assigned to ribociclib and 337 assigned to placebo received treatment.
Investigator-assessed progression-free survival was the primary endpoint, as noted before. The findings were supported by an analysis of the data by a blinded independent review committee, which determined the median PFS to not have been reached in the ribociclib arm, compared with 11.1 months in the placebo arm, with a hazard ratio of 0.427, and a 95% confidence interval showing statistical significance.
The secondary endpoint of overall response rate (ORR) was also significantly better with ribociclib among the entire patient population (40.9% vs. 29.7%; P = .00098), and in patients with measurable disease (50.9% vs. 36.4%; P = .000317).
An analysis of PFS by endocrine agent (tamoxifen or AI) showed similar hazard ratios with each class of agent combined with ribociclib.
Hematologic adverse events occurred in 75.8% of all patients on ribociclib, compared with 7.7% of those on placebo. In the CDK4/6 inhibitor arm, 50.7% of patients had grade 3 neutropenia, and 9.9% had grade 4. Febrile neutropenia occurred in 2.1% of patients on ribociclib, compared with 0.6% of patients on placebo.
Nonhematologic adverse events were generally similar between the trial arms, with the exception of more frequent nausea with ribociclib.
Ribociclib also was associated with significantly better patient-reported outcomes, including longer time to deterioration of QoL scores, and better improvement in pain scores from baseline.
“For me, I would now be very comfortable giving these women an aromatase inhibitor plus goserelin and riboclicib,” she said in an interview.
SABCS fixture Steven “Vogl, New York” Vogl, MD, a medical oncologist in private practice in New York, commented after Dr. Tripathy’s presentation that, “I think that this is a momentous study, and I think it should immediately change the standard of care for symptomatic young women with metastatic breast cancer. More of them get better, and they stay better longer. These are people who we’re trying to buy some good life for, before the inevitable happens.”
The MONALEESA 7 trial was supported by Novartis. Dr. Tripathy disclosed steering committee consulting fees and institutional funding from the company. Dr. Kaklamani reported serving as a consultant to Novartis. Dr. Vogl reported no conflicts of interest.
SAN ANTONIO – For premenopausal women with advanced hormone receptor–positive, HER2-negative breast cancer, the addition of the CDK4/6 inhibitor ribociclib (Kisqali) to endocrine therapy and goserelin was associated with a near doubling in progression-free survival (PFS), improvement in pain scores and a longer time to deterioration of quality of life (Qol) scores, investigators reported.
The hazard ratio for the ribociclib-based combination was 0.553 (P less than .0001), he reported at the San Antonio Breast Cancer Symposium.
“The treatment benefit was seen across all subgroups, and also regardless of the endocrine partner, either tamoxifen or aromastase inhibitors,” he said.
The combination of ribociclib with goserelin and either tamoxifen or a nonsteroidal AI is a potential new treatment option for premenopausal women with hormone receptor–positive, HER2-negative advanced breast cancer, regardless of the disease-free interval or the endocrine partner, he said in a media briefing and in an oral session.
In the United States, approximately 19% of invasive breast cancers are diagnosed in women aged 49 years or younger, and in the Asia/Pacific region, the proportion of patients aged younger than 50 years with invasive breast cancer may be as high as 42%, Dr. Tripathy said.
The need for new therapeutic approaches in this population is clear, with the last randomized clinical trial focused solely on women with advanced premenopausal breast being published 17 years ago, he pointed out.
Given the efficacy of adding ribociclib to standard AI therapy in postmenopausal women with advanced HR+/HER2- breast cancer as seen in the MONALEESA-2 trial, the MONALEESA-7 investigators looked at the same combination as first-line therapy in premenopausal women with similar disease features.
In the trial, 672 pre- or perimenopausal women with HR+/HER2– advanced breast cancer with no prior endocrine therapy for advanced disease and no more than one line of chemotherapy for advanced disease were enrolled. The patients were stratified by the presence of liver/lung metastases, prior chemotherapy, and prior endocrine partner, tamoxifen or nonsteroidal AI, and then randomly assigned to the ribociclib 600 mg/day for 3 weeks, followed by 1-week off, plus tamoxifen or AI and goserelin, or the same combination and schedule with placebo.
Of the 672 patients enrolled, a total of 335 patients assigned to ribociclib and 337 assigned to placebo received treatment.
Investigator-assessed progression-free survival was the primary endpoint, as noted before. The findings were supported by an analysis of the data by a blinded independent review committee, which determined the median PFS to not have been reached in the ribociclib arm, compared with 11.1 months in the placebo arm, with a hazard ratio of 0.427, and a 95% confidence interval showing statistical significance.
The secondary endpoint of overall response rate (ORR) was also significantly better with ribociclib among the entire patient population (40.9% vs. 29.7%; P = .00098), and in patients with measurable disease (50.9% vs. 36.4%; P = .000317).
An analysis of PFS by endocrine agent (tamoxifen or AI) showed similar hazard ratios with each class of agent combined with ribociclib.
Hematologic adverse events occurred in 75.8% of all patients on ribociclib, compared with 7.7% of those on placebo. In the CDK4/6 inhibitor arm, 50.7% of patients had grade 3 neutropenia, and 9.9% had grade 4. Febrile neutropenia occurred in 2.1% of patients on ribociclib, compared with 0.6% of patients on placebo.
Nonhematologic adverse events were generally similar between the trial arms, with the exception of more frequent nausea with ribociclib.
Ribociclib also was associated with significantly better patient-reported outcomes, including longer time to deterioration of QoL scores, and better improvement in pain scores from baseline.
“For me, I would now be very comfortable giving these women an aromatase inhibitor plus goserelin and riboclicib,” she said in an interview.
SABCS fixture Steven “Vogl, New York” Vogl, MD, a medical oncologist in private practice in New York, commented after Dr. Tripathy’s presentation that, “I think that this is a momentous study, and I think it should immediately change the standard of care for symptomatic young women with metastatic breast cancer. More of them get better, and they stay better longer. These are people who we’re trying to buy some good life for, before the inevitable happens.”
The MONALEESA 7 trial was supported by Novartis. Dr. Tripathy disclosed steering committee consulting fees and institutional funding from the company. Dr. Kaklamani reported serving as a consultant to Novartis. Dr. Vogl reported no conflicts of interest.
REPORTING FROM SABCS 2017
Key clinical point: Adding a CDK4/6 inhibitor to endocrine therapy and ovarian suppression significantly improves progression-free survival of advanced breast cancer in premenopausal and postmenopausal women.
Major finding: Median PFS with ribociclib, an aromatase inhibitor or tamoxifen plus goserelin was 23.8 months, compared with 13 months for women treated with ribociclib placebo.
Data source: Randomized phase 3 trial in 672 pre- or perimenopausal women with HR+/HER2– advanced breast cancer.
Disclosures: The MONALEESA 7 trial was supported by Novartis. Dr. Tripathy disclosed steering committee consulting fees and institutional funding from the company. Dr. Kaklamani reported serving as a consultant to Novartis. Dr. Vogl reported no conflicts of interested.
VIDEO: Dr. Matteo Lambertini answers questions on temporary ovarian suppression
SAN ANTONIO – A meta-analysis of five trials among 873 premenopausal women with early breast cancer finds that temporarily suppressing ovarian function with a gonadotropin-releasing hormone analog during chemotherapy helps preserve fertility, reducing risk of premature ovarian insufficiency by 62% and nearly doubling the posttreatment pregnancy rate. In an interview at the San Antonio Breast Cancer Symposium, lead investigator Matteo Lambertini, MD, of the Institut Jules Bordet in Brussels, Belgium, discussed subgroup findings, the risk-benefit profile, and appropriate patient selection, as well as avenues for future research in this area.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
SAN ANTONIO – A meta-analysis of five trials among 873 premenopausal women with early breast cancer finds that temporarily suppressing ovarian function with a gonadotropin-releasing hormone analog during chemotherapy helps preserve fertility, reducing risk of premature ovarian insufficiency by 62% and nearly doubling the posttreatment pregnancy rate. In an interview at the San Antonio Breast Cancer Symposium, lead investigator Matteo Lambertini, MD, of the Institut Jules Bordet in Brussels, Belgium, discussed subgroup findings, the risk-benefit profile, and appropriate patient selection, as well as avenues for future research in this area.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
SAN ANTONIO – A meta-analysis of five trials among 873 premenopausal women with early breast cancer finds that temporarily suppressing ovarian function with a gonadotropin-releasing hormone analog during chemotherapy helps preserve fertility, reducing risk of premature ovarian insufficiency by 62% and nearly doubling the posttreatment pregnancy rate. In an interview at the San Antonio Breast Cancer Symposium, lead investigator Matteo Lambertini, MD, of the Institut Jules Bordet in Brussels, Belgium, discussed subgroup findings, the risk-benefit profile, and appropriate patient selection, as well as avenues for future research in this area.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
REPORTING FROM SABCS 2017
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.