Dr Abdou on Treatment Sequencing With CDK4/6 Inhibitors in HR+/HER2– Breast Cancer

Yara Abdou, MD, assistant professor, medicine, Division of Oncology, Department of Medicine, University of North Carolina (UNC) School of Medicine, Lineberger Comprehensive Cancer Center, UNC Health, discusses treatment sequencing with CDK4/6 inhibitors across all lines of therapy in patients with hormone receptor (HR)–positive, HER2-negative breast cancer.

Abdou shares that she uses treatment with CDK4/6 inhibitors in the first-line setting in combination with endocrine therapy for patients with metastatic HR-positive/HER2-negative breast cancer. However, once the patients’ disease progresses on the CDK4/6 inhibitor, further questions need to be addressed, Abdou says. Whether patients should continue to receive a CDK4/6 inhibitor in the second-line setting beyond progression is unclear, Abdou notes.

Data from the phase 2 PACE trial (NCT03147287) in estrogen receptor–positive/HER2-negative breast cancer and the phase 2 PALMIRA trial (NCT03809988) in HR-positive/HER2-negative breast cancer***, answer this question, Abdou expands. Data derived from the phase 2 studies demonstrated no benefit associated with continuing palbociclib (Ibrance) in addition to second-line endocrine therapy vs endocrine therapy alone after patients’ disease had progressed on the agent, Abdou explains.

The findings from PACE and PALMIRA were different from the results of the phase 2 MAINTAIN trial (NCT02632045) in patients with HR-positive/HER2-negative breast cancer, Abdou continues. MAINTAIN demonstrated a PFS benefit when patients switched their endocrine therapy backbone from the one they used prior to trial enrollment and added the CDK4/6 inhibitor ribociclib (Kisqali), she emphasizes. Theconfounding datasets show that the field needs further data to properly determine the role of CDK4/6 inhibitors in the second line. Notably, the phase 3 monarchE trial (NCT03155997) is evaluating endocrine therapy with or without abemaciclib (Verzenio) following surgery in patients with breast cancer. This investigation is designed to answer this outstanding question within the breast cancer treatment landscape, Abdou concludes.