CDK4/6 Inhibitors Are Both Effective and Safe in Metastatic Hormone Receptor-Positive Breast Cancer

With 39 thousand cancer scientists attending, the ASCO 2018 Congress highlighted studies in metastatic hormone receptor -positive, HER2 receptor-negative breast cancer, where efficacy has been established for CDK4/6 inhibitors in these studies.

Our cells pass through various stages during proliferation. Mitotic division produces two daughter cells from one cell, and the sequence of events preparing for this is called the cell cycle . Proteins called cyclins provide the control step in this cell proliferation. Among these proteins, CDK 4/6 is known in hormone receptor-positive breast cancer to be responsible for resistance to hormonal treatments and, through excessive activity, can cause excessive cancer cell proliferation. Drugs that work by suppressing this protein are Targeted drugs; balbociclib (Ibrance) and ribociclib (Kisqali) were followed by a third-generation cyclin-dependent 4/6 kinase inhibitor, abemaciclib (Verzenio). All three drugs have demonstrated effectiveness in studies and received FDA approval for breast cancer treatment.

One of the best research methods for demonstrating a treatment’s effectiveness, evaluating all studies in the field together, is the meta-analysis method. At ASCO 2018, a meta-analysis evaluating CDK4/6 inhibitors in breast cancer that had spread throughout the body was reported.

This meta-analysis evaluated CD4/6 inhibitors in hormone receptor-positive / HER 2-negative metastatic breast cancer across 7 randomized trials. In a total of 3854 patients, adding a CDK4/6 inhibitor to hormone-suppressing treatment significantly improved the time until disease worsening (progression-free survival). The rate of disease worsening was shown to decrease by 50%.

When used as first-line treatment, these drugs also improved overall survival in addition to those benefits. CDK4/6 inhibitors were shown to benefit all patients using them, regardless of age, disease-free interval or sites of metastasis.

A subgroup analysis of MONALEESA-2 examining use of these highly effective drugs in older patients was also presented at the ASCO 2018 breast cancer session. MONALEESA enrolled patients with stage 4 hormone receptor-positive, HER2-negative disease, combining the hormone-suppressing drug letrozole with the CDK4/6 inhibitor ribociclib. By prolonging time until disease worsening by an additional 10 months, this study established its place in first-line treatment.

Patients over 65 in menopause, numbering 295 in this study, were reassessed. In newly diagnosed hormone-positive metastatic breast cancer, adding the CDK 4/6 inhibitor ribociclib to first-line hormone-suppressing treatment with letrozole did not impair health-related quality of life. On the contrary, it provided benefit particularly by reducing pain symptoms.

This study showed that we can also use these drugs safely in our patients over 65.

Conclusion

In light of all these studies, we know these drugs are clinically beneficial regardless of which hormone-suppressing drug they are combined with or the patient’s menopausal status. Their side effects are easily managed, and our patients can use them comfortably.

Questions still being explored include the best time to add these drugs to treatment, how resistance develops, and which treatment strategy should follow once resistance occurs. These questions remain under investigation. We will follow the results of these studies for you in the coming period.