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. 

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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 ( 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