Dr Ademuyiwa on the Sequencing of First-line CDK4/6 Inhibitors in HR+/HER2– Breast Cancer

Foluso Bisi Ademuyiwa, MD, MPH, MSCI, associate professor of medicine, Division of Oncology, Section of Breast Oncology, the Washington University School of Medicine, discusses the optimal sequencing of current CDK4/6 inhibitors in the first-line setting for hormone receptor (HR)–positive, HER2-negative breast cancer based on updated efficacy and safety data.

CDK4/6 inhibitors are now well established as the standard of care for patients with HR-positive, HER2-negative breast cancer in the first-line setting, Ademuyiwa begins. Although the CDK4/6 inhibitors palbociclib (Ibrance), ribociclib (Kisquali), and abemaciclib (Verzenio) are all currently approved by the FDA for use in this space, each agent is associated with slightly different survival and safety outcomes, Ademuyiwa states.

Recent clinical trials have shown that first-line ribociclib provides an overall survival (OS) benefit to patients in this population, Ademuyiwa explains. The final analysis of the phase 3 MONALEESA-2 (NCT01958021) and the MONALEESA-3 (NCT02422615) trials of ribociclib confirmed that the regimen provided both a progression-free survival and OS benefit when added to first-line ovarian function suppression.

In contrast, palbociclib or abemaciclib have yet to demonstrate the same result, Ademuyiwa continues. Interim findings from the phase 3 MONARCH-3 trial (NCT03155997) showed that abemaciclib plus endocrine therapy increased median OS compared with endocrine therapy alone, but these data were not statistically significant, although OS data we not yet fully mature.

Based on these data, ribociclib has become the preferred option for patients with advanced breast cancer in the first line over palbociclib and abemaciclib, Ademuyiwa states.

Additionally, each of the 3 CDK4/6 inhibitors has a slightly different safety profile, Ademuyiwa notes. For example, abemaciclib is associated with a higher incidence of gastrointestinal toxicities, whereas palbociclib and ribociclib produce more cytopenia, she explains. Rarely, ribociclib is also known to elicit electrocardiogram changes. Such differences in toxicity could be used to navigate the selection of CDK4/6 inhibitors in clinical practice, Ademuyiwa concludes.

Disclosures: Dr Ademuyiwa reports serving in a consultory or advisory role for Teladoc Health, Pfizer, AstraZeneca, Biotheranostics, Gilead, Cardinal Health; she received research funding from Pfizer, Astellas, and RNA Diagnostics