Dr Abdou on Sequencing CDK4/6 Inhibitors in HER2– Metastatic Breast Cancer

Yara Abdou, MD, assistant professor, medicine, Department of Medicine, Division of Oncology, University of North Carolina School of Medicine, discusses findings from the phase 2 MAINTAIN trial (NCT02632045) in patients with HER2-negative metastatic breast cancer, as well as the clinical implications of these trial results.

The MAINTAIN trial evaluated the efficacy of switching endocrine therapy and continuing a CDK4/6 inhibitor in patients with hormone receptor (HR)–positive, HER2-negative metastatic breast cancer whose disease had progressed on prior endocrine therapy and a CDK4/6 inhibitor. Patients enrolled in the trial switched to treatment with either exemestane [Aromasin] or fulvestrant [Faslodex] depending on which previous endocrine therapy they had received. They were then randomly assigned 1:1 to receive either the CDK4/6 inhibitor ribociclib (Kisqali) or placebo. In total, 86.5% and 11.7% of patients had previously received palbociclib and ribociclib, respectively. Patients who were randomly assigned to the ribociclib arm achieved a median progression-free survival (PFS) of 5.29 months (95% CI, 3.02-8.12) vs 2.76 months (95% CI, 2.66-3.25) in the placebo arm (HR, 0.57; 95% CI, 0.39-0.85; P = .006).

The findings from MAINTAIN contrasted those from the phase 2 PACE trial (NCT03147287). In this trial, patients with estrogen receptor–positive, HER2-negative metastatic breast cancer who received palbociclib plus fulvestrant after a prior CDK4/6 inhibitor and endocrine therapy did not experience a significant PFS benefit vs those who received fulvestrant alone. Of those enrolled on the trial, 90% of patients had received prior palbociclib and 4.5%, 4.1%, and 1.4% of patients had received prior ribociclib, abemaciclib (Verzenio), and palbociclib/ribociclib, respectively.

Contrasting findings between MAINTAIN and PACE indicate that switching CDK4/6 inhibitors post-progression may be the most effective treatment approach for patients with HR-positive, HER2-negative metastatic breast cancer who progressed on an initial CDK4/6 inhibitor, Abdou says. Differences between CDK4/6 inhibitors may also contribute to the data discrepancies that favor ribociclib over palbociclib in this setting, Abdou concludes.