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Neither fulvestrant alone nor fulvestrant plus anastrozole improved the endocrine-sensitive disease rate (ESDR) versus anastrozole alone as neoadjuvant endocrine therapy in postmenopausal women with locally advanced estrogen receptor-positive HER2-negative (ER+ HER2–) breast cancer in the phase 3 ALTERNATE trial.
The ESDRs were 22.7% in 431 evaluable patients randomized to receive fulvestrant alone, 20.5% in 434 patients who received fulvestrant + anastrozole, and 18.6% in 434 who received anastrozole alone, Cynthia X. Ma, MD, PhD, reported as part of the American Society of Clinical Oncology virtual scientific program.
, said Dr. Ma, a professor at Washington University in St. Louis.
Study subjects had a median age of 64 years, clinical stage II/III ER+ HER2– breast cancer, and were randomized 1:1:1 between February 2014 and November 2018 to receive 6 months of treatment with 500 mg of intramuscular fulvestrant given every 4 weeks following a loading dose, fulvestrant plus a 1 mg daily oral does of anastrozole, or anastrozole alone prior to breast conserving surgery.
The groups were similar with respect to baseline characteristics, and more than 70% were eligible for breast conserving surgery prior to the start of neoadjuvant therapy, Dr. Ma noted, adding that the treatments were well tolerated.
Grade 3 or 4 adverse events were rare, and the percentage of patients experiencing arthralgia, myalgia, or hot flashes was low and similar across arms, she said.
“Neoadjuvant therapy downstages the tumor and improves the rate of breast conserving surgery,” Dr. Ma said, adding that pathologic tumor size, nodal status, Ki67 level, and ER status of resected tumors after neoadjuvant therapy have been shown to be independent prognostic factors for relapse-free survival.
A modified preoperative endocrine prognostic index (mPEPI) of 0 (defined as pT1-2 pN0 Ki67< 2.7%) or pathologic complete response (pCR) is associated with low risk of recurrence without adjuvant chemotherapy. ESDR, defined as the combined mPEPI 0 rates and pCR rates, was a co-primary endpoint of the ALTERNATE trial.
The rationale for studying fulvestrant with or without anastrozole in this setting came from the FALCON and S0226 trials showing superiority of those treatments versus anastrozole monotherapy as first-line endocrine therapy in the metastatic setting, Dr. Ma explained.
In the ALTERNATE trial, Ki67 was tested centrally on biopsies acquired prior to therapy, at weeks 4 and 12, and at surgery. Those with Ki67 greater than 10% at week 4 (20.7% of patients overall) or at week 12 (an additional 1.3% overall) were triaged to receive neoadjuvant chemotherapy; a similar number of patients in each group met these criteria, Dr. Ma said.
Further, patients with mPEPI score of 0 at surgery, were recommended to continue their assigned endocrine therapy without chemotherapy for 1.5 years followed by anastrozole for a total of 5 years of endocrine therapy. Those with mPEPI scores above zero, received chemotherapy and physician’s choice of endocrine therapy.
Follow-up is planned for 10 years. A second primary endpoint will be the breast cancer–free interval in the adjuvant setting.
Among the 936 patients with week 4 Ki67 of 10% or less who completed NET and surgery, the ESDRs were similar across the arms: 31.7% for fulvestrant alone, 26.3% with fulvestrant plus anastrozole, and 28.0% with anastrozole alone, Dr. Ma said.
Week 4 Ki67 reductions from baseline also were similar across the arms.
Nearly all patients with Ki67 of 10% or less at baseline continued to have Ki67 less than 10% at week 4, and about two-thirds of those with Ki67 over 10% at baseline had Ki67 less than 10% at week 4, she said, noting that these findings were also similar across treatment arms.
These first results from the ALTERNATE trial show that fewer than 2% of patients treated with 6 months of neoadjuvant endocrine therapy progressed, likely as a result of the Ki67 triaging strategy, Dr. Ma said.
“Neoadjuvant chemotherapy outcomes for patients with week 4 Ki67 over 10% will be reported later,” she said. “Genomic and biomarker correlates, as well as, importantly, relapse-free survivals are also awaited.”
An invited discussant, Antonio C. Wolff, MD, professor of oncology at Johns Hopkins University, Baltimore, said that while the co-primary endpoint of ESDR in the study was not met, the results provide “a few important messages.”
First, the study showed that low Ki67 at baseline largely stays low at 4 weeks. High Ki67 at baseline frequently became low at week 4, he said.
“Finally, we must congratulate Dr. Ma and colleagues on showing that research biopsies for integral biomarker testing can happen across the [National Clinical Trials Network] throughout the U.S., including most community sites,” he said, adding “that alone is a major accomplishment.”
Dr. Wolff also noted that the 5-year relapse-free survival data for patients who achieve mPEPI 0 at surgery are “awaited with great interest.”
The ALTERNATE trial is funded by the Alliance Foundation, NCI Biomarker, Imaging and Quality of Life Studies Funding Program, Breast Cancer Research Foundation, Genentech,and AstraZeneca. Dr. Ma reported consulting or advisory roles with a variety of pharmaceutical companies, and research funding from pharmaceutical companies to her institution. Dr. Wolff reported relationships (consulting or advisory roles and research funding) with Ionis, Biomarin, Celldex, and patents or royalties (issued or pending) associated with methylation in breast cancer.
SOURCE: Ma C et al. ASCO 2020: Abstract 504.
Neither fulvestrant alone nor fulvestrant plus anastrozole improved the endocrine-sensitive disease rate (ESDR) versus anastrozole alone as neoadjuvant endocrine therapy in postmenopausal women with locally advanced estrogen receptor-positive HER2-negative (ER+ HER2–) breast cancer in the phase 3 ALTERNATE trial.
The ESDRs were 22.7% in 431 evaluable patients randomized to receive fulvestrant alone, 20.5% in 434 patients who received fulvestrant + anastrozole, and 18.6% in 434 who received anastrozole alone, Cynthia X. Ma, MD, PhD, reported as part of the American Society of Clinical Oncology virtual scientific program.
, said Dr. Ma, a professor at Washington University in St. Louis.
Study subjects had a median age of 64 years, clinical stage II/III ER+ HER2– breast cancer, and were randomized 1:1:1 between February 2014 and November 2018 to receive 6 months of treatment with 500 mg of intramuscular fulvestrant given every 4 weeks following a loading dose, fulvestrant plus a 1 mg daily oral does of anastrozole, or anastrozole alone prior to breast conserving surgery.
The groups were similar with respect to baseline characteristics, and more than 70% were eligible for breast conserving surgery prior to the start of neoadjuvant therapy, Dr. Ma noted, adding that the treatments were well tolerated.
Grade 3 or 4 adverse events were rare, and the percentage of patients experiencing arthralgia, myalgia, or hot flashes was low and similar across arms, she said.
“Neoadjuvant therapy downstages the tumor and improves the rate of breast conserving surgery,” Dr. Ma said, adding that pathologic tumor size, nodal status, Ki67 level, and ER status of resected tumors after neoadjuvant therapy have been shown to be independent prognostic factors for relapse-free survival.
A modified preoperative endocrine prognostic index (mPEPI) of 0 (defined as pT1-2 pN0 Ki67< 2.7%) or pathologic complete response (pCR) is associated with low risk of recurrence without adjuvant chemotherapy. ESDR, defined as the combined mPEPI 0 rates and pCR rates, was a co-primary endpoint of the ALTERNATE trial.
The rationale for studying fulvestrant with or without anastrozole in this setting came from the FALCON and S0226 trials showing superiority of those treatments versus anastrozole monotherapy as first-line endocrine therapy in the metastatic setting, Dr. Ma explained.
In the ALTERNATE trial, Ki67 was tested centrally on biopsies acquired prior to therapy, at weeks 4 and 12, and at surgery. Those with Ki67 greater than 10% at week 4 (20.7% of patients overall) or at week 12 (an additional 1.3% overall) were triaged to receive neoadjuvant chemotherapy; a similar number of patients in each group met these criteria, Dr. Ma said.
Further, patients with mPEPI score of 0 at surgery, were recommended to continue their assigned endocrine therapy without chemotherapy for 1.5 years followed by anastrozole for a total of 5 years of endocrine therapy. Those with mPEPI scores above zero, received chemotherapy and physician’s choice of endocrine therapy.
Follow-up is planned for 10 years. A second primary endpoint will be the breast cancer–free interval in the adjuvant setting.
Among the 936 patients with week 4 Ki67 of 10% or less who completed NET and surgery, the ESDRs were similar across the arms: 31.7% for fulvestrant alone, 26.3% with fulvestrant plus anastrozole, and 28.0% with anastrozole alone, Dr. Ma said.
Week 4 Ki67 reductions from baseline also were similar across the arms.
Nearly all patients with Ki67 of 10% or less at baseline continued to have Ki67 less than 10% at week 4, and about two-thirds of those with Ki67 over 10% at baseline had Ki67 less than 10% at week 4, she said, noting that these findings were also similar across treatment arms.
These first results from the ALTERNATE trial show that fewer than 2% of patients treated with 6 months of neoadjuvant endocrine therapy progressed, likely as a result of the Ki67 triaging strategy, Dr. Ma said.
“Neoadjuvant chemotherapy outcomes for patients with week 4 Ki67 over 10% will be reported later,” she said. “Genomic and biomarker correlates, as well as, importantly, relapse-free survivals are also awaited.”
An invited discussant, Antonio C. Wolff, MD, professor of oncology at Johns Hopkins University, Baltimore, said that while the co-primary endpoint of ESDR in the study was not met, the results provide “a few important messages.”
First, the study showed that low Ki67 at baseline largely stays low at 4 weeks. High Ki67 at baseline frequently became low at week 4, he said.
“Finally, we must congratulate Dr. Ma and colleagues on showing that research biopsies for integral biomarker testing can happen across the [National Clinical Trials Network] throughout the U.S., including most community sites,” he said, adding “that alone is a major accomplishment.”
Dr. Wolff also noted that the 5-year relapse-free survival data for patients who achieve mPEPI 0 at surgery are “awaited with great interest.”
The ALTERNATE trial is funded by the Alliance Foundation, NCI Biomarker, Imaging and Quality of Life Studies Funding Program, Breast Cancer Research Foundation, Genentech,and AstraZeneca. Dr. Ma reported consulting or advisory roles with a variety of pharmaceutical companies, and research funding from pharmaceutical companies to her institution. Dr. Wolff reported relationships (consulting or advisory roles and research funding) with Ionis, Biomarin, Celldex, and patents or royalties (issued or pending) associated with methylation in breast cancer.
SOURCE: Ma C et al. ASCO 2020: Abstract 504.
Neither fulvestrant alone nor fulvestrant plus anastrozole improved the endocrine-sensitive disease rate (ESDR) versus anastrozole alone as neoadjuvant endocrine therapy in postmenopausal women with locally advanced estrogen receptor-positive HER2-negative (ER+ HER2–) breast cancer in the phase 3 ALTERNATE trial.
The ESDRs were 22.7% in 431 evaluable patients randomized to receive fulvestrant alone, 20.5% in 434 patients who received fulvestrant + anastrozole, and 18.6% in 434 who received anastrozole alone, Cynthia X. Ma, MD, PhD, reported as part of the American Society of Clinical Oncology virtual scientific program.
, said Dr. Ma, a professor at Washington University in St. Louis.
Study subjects had a median age of 64 years, clinical stage II/III ER+ HER2– breast cancer, and were randomized 1:1:1 between February 2014 and November 2018 to receive 6 months of treatment with 500 mg of intramuscular fulvestrant given every 4 weeks following a loading dose, fulvestrant plus a 1 mg daily oral does of anastrozole, or anastrozole alone prior to breast conserving surgery.
The groups were similar with respect to baseline characteristics, and more than 70% were eligible for breast conserving surgery prior to the start of neoadjuvant therapy, Dr. Ma noted, adding that the treatments were well tolerated.
Grade 3 or 4 adverse events were rare, and the percentage of patients experiencing arthralgia, myalgia, or hot flashes was low and similar across arms, she said.
“Neoadjuvant therapy downstages the tumor and improves the rate of breast conserving surgery,” Dr. Ma said, adding that pathologic tumor size, nodal status, Ki67 level, and ER status of resected tumors after neoadjuvant therapy have been shown to be independent prognostic factors for relapse-free survival.
A modified preoperative endocrine prognostic index (mPEPI) of 0 (defined as pT1-2 pN0 Ki67< 2.7%) or pathologic complete response (pCR) is associated with low risk of recurrence without adjuvant chemotherapy. ESDR, defined as the combined mPEPI 0 rates and pCR rates, was a co-primary endpoint of the ALTERNATE trial.
The rationale for studying fulvestrant with or without anastrozole in this setting came from the FALCON and S0226 trials showing superiority of those treatments versus anastrozole monotherapy as first-line endocrine therapy in the metastatic setting, Dr. Ma explained.
In the ALTERNATE trial, Ki67 was tested centrally on biopsies acquired prior to therapy, at weeks 4 and 12, and at surgery. Those with Ki67 greater than 10% at week 4 (20.7% of patients overall) or at week 12 (an additional 1.3% overall) were triaged to receive neoadjuvant chemotherapy; a similar number of patients in each group met these criteria, Dr. Ma said.
Further, patients with mPEPI score of 0 at surgery, were recommended to continue their assigned endocrine therapy without chemotherapy for 1.5 years followed by anastrozole for a total of 5 years of endocrine therapy. Those with mPEPI scores above zero, received chemotherapy and physician’s choice of endocrine therapy.
Follow-up is planned for 10 years. A second primary endpoint will be the breast cancer–free interval in the adjuvant setting.
Among the 936 patients with week 4 Ki67 of 10% or less who completed NET and surgery, the ESDRs were similar across the arms: 31.7% for fulvestrant alone, 26.3% with fulvestrant plus anastrozole, and 28.0% with anastrozole alone, Dr. Ma said.
Week 4 Ki67 reductions from baseline also were similar across the arms.
Nearly all patients with Ki67 of 10% or less at baseline continued to have Ki67 less than 10% at week 4, and about two-thirds of those with Ki67 over 10% at baseline had Ki67 less than 10% at week 4, she said, noting that these findings were also similar across treatment arms.
These first results from the ALTERNATE trial show that fewer than 2% of patients treated with 6 months of neoadjuvant endocrine therapy progressed, likely as a result of the Ki67 triaging strategy, Dr. Ma said.
“Neoadjuvant chemotherapy outcomes for patients with week 4 Ki67 over 10% will be reported later,” she said. “Genomic and biomarker correlates, as well as, importantly, relapse-free survivals are also awaited.”
An invited discussant, Antonio C. Wolff, MD, professor of oncology at Johns Hopkins University, Baltimore, said that while the co-primary endpoint of ESDR in the study was not met, the results provide “a few important messages.”
First, the study showed that low Ki67 at baseline largely stays low at 4 weeks. High Ki67 at baseline frequently became low at week 4, he said.
“Finally, we must congratulate Dr. Ma and colleagues on showing that research biopsies for integral biomarker testing can happen across the [National Clinical Trials Network] throughout the U.S., including most community sites,” he said, adding “that alone is a major accomplishment.”
Dr. Wolff also noted that the 5-year relapse-free survival data for patients who achieve mPEPI 0 at surgery are “awaited with great interest.”
The ALTERNATE trial is funded by the Alliance Foundation, NCI Biomarker, Imaging and Quality of Life Studies Funding Program, Breast Cancer Research Foundation, Genentech,and AstraZeneca. Dr. Ma reported consulting or advisory roles with a variety of pharmaceutical companies, and research funding from pharmaceutical companies to her institution. Dr. Wolff reported relationships (consulting or advisory roles and research funding) with Ionis, Biomarin, Celldex, and patents or royalties (issued or pending) associated with methylation in breast cancer.
SOURCE: Ma C et al. ASCO 2020: Abstract 504.
FROM ASCO 2020