Adaptive neoadjuvant endocrine therapy screens out prime population of ribociclib intensive adjuvant therapy

Area of Science:

• Oncology
• Pharmacology
• Clinical Trials

Background:

• The NATALEE trial evaluated adjuvant ribociclib for hormone receptor-positive/human epidermal growth factor receptor-2-negative (HR+/HER2-) advanced breast cancer.
• A 4.9% absolute invasive disease-free survival benefit was observed at 3 years with ribociclib.
• Primary resistance to ribociclib occurs in a subset of intermediate-risk patients, limiting treatment efficacy.

Purpose of the Study:

• To address the challenge of identifying patients who will benefit most from intensive adjuvant ribociclib therapy.
• To explore the potential of adaptive neoadjuvant endocrine therapy (NET) as a screening tool.

Main Methods:

• Analysis of data from the NATALEE trial, focusing on the intermediate-risk HR+/HER2- subgroup.
• Discussion of the role of adaptive neoadjuvant endocrine therapy in patient selection.

Main Results:

• Ribociclib provides a significant, but not universal, benefit in the intermediate-risk HR+/HER2- population.
• Some patients exhibit primary resistance to ribociclib, gaining minimal benefit from the therapy.
• The cost-effectiveness and toxicity of a 3-year ribociclib course warrant careful consideration for all intermediate-risk patients.

Conclusions:

• A 3-year course of ribociclib may not be optimal for all intermediate-risk HR+/HER2- breast cancer patients.
• Adaptive neoadjuvant endocrine therapy shows promise for selecting patients who are most likely to respond to intensive adjuvant ribociclib treatment.
• Further research is needed to refine patient selection strategies for adjuvant therapies.