Treatment of HR+/HER2– Breast Cancer with CDK4/6 Inhibitors: A Discussion on Evolution

The Evolution of CDK4/6 Inhibitor Treatment in Hormone Receptor-Positive/HER2-Negative Breast Cancer

Dr. Rita Nanda, an associate professor of medicine and director of the Breast Oncology Program at the University of Chicago Medicine, recently discussed the evolving landscape of treatment with CDK4/6 inhibitors for patients with hormone receptor (HR)-positive/HER2-negative breast cancer.

During a presentation at an OncLive® State of the Science Summit™ on breast cancer, Dr. Nanda highlighted the current state of care for these patients. She emphasized the importance of integrating CDK4/6 inhibitors into frontline therapy in combination with endocrine-based treatments. However, there are still questions about the appropriate next steps for patients who progress on CDK4/6 inhibitors, she noted.

Dr. Nanda also mentioned the emergence of new targeted therapies for specific patient subsets, such as those with ESR1 mutations or AKT pathway alterations. Clinical trials have produced varying results regarding the continuation of CDK4/6 inhibitors in the second-line setting. For example, the phase 2 PACE trial showed no benefit with continuing palbociclib (Ibrance) after progression on a prior CDK4/6 inhibitor, while the MAINTAIN study demonstrated some modest benefit with this approach.

Looking ahead, the results of the phase 3 postMONARCH trial are highly anticipated. This study explores the continuation of abemaciclib (Verzenio) plus fulvestrant (Faslodex) in the second-line HR-positive, HER2-negative metastatic breast cancer setting following progression on a CDK4/6 inhibitor and endocrine therapy. Dr. Nanda believes that the findings from this trial, expected to be presented at the 2024 ASCO Annual Meeting, could provide clarity on the role of continuing CDK4/6 inhibitors in this context.

For patients with ESR1 mutations, elacestrant (Orserdu) has emerged as a new treatment option. Additionally, the combination of capivasertib (Truqap) and fulvestrant is FDA approved for patients with AKT pathway alterations. Other targeted therapies, such as alpelisib (Piqray) and capivasertib, are available for patients with PIK3CA mutations. Despite these advancements, Dr. Nanda acknowledged that most patients do not have AKT pathway alterations or ESR1 mutations.

Dr. Nanda highlighted the importance of the ongoing monarchE trial, which aims to determine whether continuing CDK4/6 inhibitors is beneficial for patients without ESR1 mutations or AKT pathway alterations. The results of this trial are eagerly awaited to help guide treatment decisions in this population.