In 2020, investigators presented the first efficacy results from the phase 3 WSG-ADAPT HR+/HER2- trial in patients with luminal early breast cancer.1
Among patients with up to 2 involved axillary nodes, endocrine therapy (ET) alone produced excellent long-term outcomes for those with intermediate genomic risk (21-gene recurrence score of 12-25) and a decrease in tumor cell proliferation (from baseline Ki-67 of >10% to <10%) after 2-4 weeks of ET.
At the time of the presentation, the investigators were asked about outcomes for patients with similar recurrence scores who did not have an early decrease in Ki-67 from pre-operative ET and for patients with a higher clinical or genomic risk of relapse.
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- trial, a substudy of the ADAPT trial (ClinicalTrials.gov Identifier: NCT01779206), actually consists of 2 treatment trials — a chemotherapy study and an ET study. Dr Gluz presented results from high-risk patients in the ET and chemotherapy studies together.
Patients were defined as having clinically high-risk breast cancer if their tumors were 2 cm or larger, had clinically involved axillary nodes, were judged to be histologic grade 3 on central review, or demonstrated baseline, centrally assessed, Ki-67 proliferation values 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.
High-risk patients with up to 3 positive lymph nodes and recurrence scores of 0-11 did not require post-ET assessment of Ki-67. They received ET alone.
ET alone was also given 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 without Ki-67 response, more than 4 positive lymph nodes, or very high-risk disease defined by additional clinical and pathological criteria.
Patients assigned to chemotherapy were randomly assigned to 1 of 2 dose-dense taxane/anthracycline regimens, followed by standard ET.
In all, there were 2335 patients assigned to chemotherapy-ET and 2356 patients assigned to ET alone. Among the patients assigned to chemotherapy, roughly 50% had involved axillary nodes, tumor size of 2 cm or larger, high-grade histology, and/or recurrence scores 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