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.