In 2020, researchers presented initial efficacy results from the Phase 3 WSG-ADAPT HR+/HER2- study in patients with early-stage luminal breast cancer.1
In patients with up to 2 affected axillary nodes, endocrine therapy (ET) alone resulted in excellent long-term outcomes in patients at intermediate genomic risk (21-gene recurrence score of 12-25) and a reduction in tumor cell proliferation (from baseline Ki-67 from >10% to <10%) after 2-4 weeks of ET.
At the time of presentation, investigators were asked about outcomes for patients with similar recurrence scores who did not experience early decline in Ki-67 due to preoperative ET and for patients at higher clinical or genomic risk of recurrence.
At the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, Oleg Gluz, MD, of Bethesda Evangelical Hospital in Duisburg, Germany, provided the answers.2
Protocol for high-risk patients
The WSG-ADAPT HR+/HER2- study, a substudy of the ADAPT study (ClinicalTrials.gov identifier: NCT01779206), actually consists of two treatment studies – a chemotherapy study and an ET study. Dr. Gluz jointly presented results from high-risk patients in the ET and chemotherapy trials.
Patients with clinically high-risk breast cancer were defined if their tumors were 2 cm or larger, had clinically involved axillary nodes, were histologic grade 3 on central examination, or had centrally assessed baseline Ki-67 proliferation greater than 15%.
Like the low- and intermediate-risk patients presented in 2020,1 The high-risk patients were initially treated with 2–4 weeks of standard ET before surgery or sequential core biopsy.
Post-ET assessment of Ki-67 was not required in high-risk patients with up to 3 positive lymph nodes and recurrence scores of 0–11. They received ET alone.
ET alone was also administered to patients with up to 3 positive lymph nodes and recurrence scores of 12–25 who were Ki-67 responders to neoadjuvant ET.
Patients who met any of the following criteria were assigned to chemotherapy plus ET: recurrence score greater than 25, recurrence score of 12-25 with no Ki-67 response, more than 4 positive lymph nodes, or very high-risk disease defined by additional clinical and pathologic criteria.
Patients undergoing chemotherapy were randomly assigned to one of two dose-dense taxane/anthracycline regimens followed by standard ET.
A total of 2,335 patients were assigned to chemotherapy ET and 2,356 patients were assigned to ET alone. Of the patients who underwent chemotherapy, approximately 50% had axillary nodules, a tumor size of 2 cm or larger, high-grade histology, and/or a recurrence score greater than 25.
The primary endpoint was invasive disease-free survival (iDFS), and the secondary endpoints were distant disease-free survival (dDFS) and overall survival.
This article originally appeared on Cancer Therapy Advisor
