Dr Desai on Research Informing Upfront CDK 4/6 Inhibitor Use in HR+/HER2– Breast Cancer

"There [are several] pivotal trials for [ribociclib, abemaciclib, and palbociclib] in metastatic HR-positive, HER2-negative breast cancer…all of [which] show a consistent improvement in progression-free survival [PFS]. [Accordingly], all 3 of these drugs are approved in the metastatic setting."

Neelam Desai, MD, a breast medical oncologist and hematologist at the Atrium Health Levine Cancer Institute, highlighted the current body of research supporting upfront use of CDK 4/6 inhibitors in combination with endocrine therapy for patients with metastatic hormone receptor. (HR)–positive, HER2-negative breast cancer.

Desai noted that multiple pivotal trials have guided the choice among the three approved CDK4/6 inhibitors for metastatic HR-positive, HER2-negative breast cancer.

These include the phase 3 PALOMA-2 trial (NCT01740427), the phase 2 PARSIFAL trial (NCT02491983), and the phase 2 Young-PEARL trial (NCT02592746) for palbociclib (Ibrance); the MONALEESA trials evaluating ribociclib (Kisqali), and the phase 3 MONARCH 3 trial (NCT02246621) evaluating abemaciclib (Verzenio).

All of these studies demonstrated a consistent and statistically significant progression-free survival (PFS) benefit, Desai reported. Beyond PFS, the studies investigating ribociclib also demonstrated a statistically significant improvement in overall survival (OS) vs the control regimen. Although the MONARCH 3 trial for abemaciclib did not meet the threshold for statistical significance in its OS end point, it nevertheless presented a clinically meaningful OS benefit of 13.1 months, Desai added.

Similarly, studies evaluating palbociclib did not show a statistically significant improvement in OS, a result that has drawn some criticism regarding the methodology of data collection, Desai noted. However, she pointed out that real-world studies have since provided evidence of improvement in both PFS and OS with palbociclib. These findings collectively reinforce the established role of all 3 CDK 4/6 inhibitors, which are fully approved for use in the metastatic setting, as a cornerstone of treatment for this specific patient population, Desai concluded.