Dr Nanda on the Evolution of CDK4/6 Inhibitor Treatment in HR+/HER2– Breast Cancer

Rita Nanda, MD, associate professor, medicine, director, Breast Oncology Program, University of Chicago, UChicago Medicine, discusses the evolution of treatment with CDK4/6 inhibitors in patients with hormone receptor (HR)–positive/HER2-negative breast cancer.

The current state of care for patients with HR-positive/HER2-negative breast cancer was discussed in a presentation at an OncLive® State of the Science Summit™ on breast cancer, with a focus on integrating CDK4/6 inhibitors into frontline therapy in combination with endocrine-based treatments, Nanda begins. However, there remains a question about next steps after patients progress on CDK4/6 inhibitors, she adds. New targeted therapies have emerged for patient subsets, such as those with ESR1 mutations or AKTpathway alterations, Nanda states.

Trials have yielded varied results regarding the continuation of CDK4/6 inhibitors in the second-line setting, Nanda continues. The phase 2 PACE trial (NCT03147287) demonstrated no benefit with continuing palbociclib (Ibrance) after progression on a prior CDK4/6 inhibitor in patients with HR-positive/HER2-negative metastatic breast cancer. However, the phase 2 MAINTAIN study (NCT02632045) showed modest benefit with this treatment approach in this patient population. Expectations are high for the phase 3 postMONARCH trial (NCT05169567), primary findings from which will be presented at the 2024 ASCO Annual Meeting, according to Nanda. postMONARCH is a robust randomized study exploring 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, Nanda explains, noting that this trial's results could provide clarity on the role of continuing CDK4/6 inhibitors in this context.

For patients with ESR1 mutations, elacestrant (Orserdu) is now a treatment option, and the combination of capivasertib (Truqap) and fulvestrant is FDA approved for patients with AKT pathway alterations, she expands. Furthermore, alpelisib (Piqray) and capivasertib are available for patients with PIK3CA mutations, Nanda states. Despite these advancements, most patients lack AKT pathway alterations or ESR1 mutations, Nanda notes.

The monarchE trial is anticipated to shed light on whether continuing CDK4/6 inhibitors is beneficial for patients without ESR1 mutations or AKT pathway alterations, Nanda says. This trial's findings are eagerly awaited to guide treatment decisions in this setting, Nanda concludes.