A Network Meta-Analysis of Treatment-Related Adverse Events of Various CDK4/6 Inhibitors in Metastatic Breast Cancer

While showing comparable efficacy, the 3 approved CDK4/6 inhibitors differ in safety and tolerability profiles.

A standard of care in hormone receptor–positive, human epidermal growth factor receptor 2–negative metastatic breast cancer is CDK4/6 inhibitors used in combination with endocrine therapy. Approved agents, including palbociclib, ribociclib, and abemaciclib, have similar efficacy profiles but differ in terms of apparent safety and tolerability. Treatment-related adverse events of the 3 CDK4/6 inhibitors were analyzed and were carefully considered using a network meta-analysis.

Randomized trials of CDK4/6 inhibitors were identified by Alexandra Desnoyers, MD, Breast Cancer Fellow, Princess Margaret Cancer Centre, Toronto, Ontario, Canada, and colleagues who searched the American Society of Clinical Oncology and European Society for Medical Oncology proceedings as well as PubMed. For each approved CDK4/6 inhibitor, detailed information on treatment-emergent adverse events was obtained. Relative to endocrine therapy alone, the odds ratio for each treatment-related adverse event and the hazard ratio (HR) for progression-free survival (PFS) were computed.

To compare ribociclib and abemaciclib with palbociclib, a network meta-analysis was then performed for each endocrine therapy backbone (aromatase inhibitor or fulvestrant).

In the analysis, 7 randomized trials were included, totaling 2715 CDK4/6 inhibitor recipients. Of this total, 789 received palbociclib, 1153 received ribociclib, and 773 received abemaciclib.

In the analysis of 4 randomized trials totaling 1440 patients, endocrine therapy backbone was an aromatase inhibitor, and in 3 randomized trials totaling 1275 patients, the backbone was fulvestrant.

Ribociclib and abemaciclib were associated with lower grade 3/4 hematologic toxicity compared with palbociclib but were associated with higher gastrointestinal toxicity. Although the 3 CDK4/6 inhibitors demonstrated similar efficacy, abemaciclib had the highest rate of treatment discontinuation when compared with other CDK4/6 inhibitors.

The HR for PFS for ribociclib was 1.00 and 1.04 for abemaciclib, compared with palbociclib, for aromatase inhibitor backbone. The HRs were 0.88 and 0.93, respectively, for fulvestrant backbone.

Although the 3 available CDK4/6 inhibitors possess similar efficacy profiles, they differ in terms of safety and tolerability. The significantly higher treatment discontinuation rate of abemaciclib is likely associated with its worse tolerability profile and gastrointestinal toxicity.

Source: Desnoyers A, Nadler M, Kumar V, et al. Comparison of treatment-related adverse events (TRAE) of different CDK4/6 inhibitors (CDK4/6i) in metastatic breast cancer (MBC): a network meta-analysis. J Clin Oncol. 2020;38(15_suppl). Abstract e13052.