Novel therapies targeting CDK 4/6 have generated considerable excitement as treatments for patients with ER-positive metastatic breast cancer. The combination of the CDK 4/6 inhibitor palbociclib with letrozole demonstrated significantly improved clinical outcomes in the phase II PALOMA-1 trial.

To further explore palbociclib, a phase III trial combining the drug with letrozole was opened in February 2013. In December 2013, the trial had already accrued 25% of the necessary patients, notes Hope S. Rugo, MD. Additionally, a trial is exploring second-line palbociclib with fulvestrant in women with HR-positive metastatic breast cancer.

In addition to palbociclib, a number of other agents are being investigated across several clinical trials. The CDK 4/6 inhibitor LEE011 has demonstrated promising activity in patients with refractory ER-positive breast cancer, notes Denise A. Yardley, MD. In future clinical trials, this agent will be explored in combination with the alpha-specific PI3K inhibitor BYL719.

Adding to the excitement for this class of drugs, CDK 4/6 inhibitors may also be active in HER2-positive breast cancer, suggests Joyce A. O’Shaughnessy, MD. A study is planned that will explore LEE011 in combination with T-DM1 as a treatment for patients with HER2-positive metastatic breast cancer, O’Shaughnessy notes.