New class of metastatic breast cancer drugs has less side-effects

An exciting new class of drugs for treating metastatic breast cancer, known as cyclin-dependent kinase (CDK) inhibitors, are confirmed to have manageable side-effects and be well tolerated, according to a new comprehensive study.

The excitement surrounding CDK inhibitors is due to their great potential for treating the most common type of breast cancer known as hormone receptor-positive (HR+) metastatic breast cancer, in which the cancer cells express hormone receptors.

International clinical trials have shown that CDK inhibitors have the potential to change the landscape of management of HR+ breast cancer, significantly lengthening the time that metastatic breast cancer can be controlled for some women.

Availability of CDK inhibitors

The three main CDK inhibitors palbociclib (Ibrance), ribociclib (Kisqali) and abemaciclib are in varying phases of development and availability. All three have been designated as ‘breakthrough therapies’ by the US Food and Drug Administration.

The FDA approved palbociclib in February 2015 and ribociclib in March 2017. Abemaciclib is currently undergoing Phase 3 trials.

In Australia, palbociclib was approved for sale by Therapeutic Goods Administration (TGA) in Australia in May 2017. While this is a positive step for women with metastatic breast cancer, it has not been approved for inclusion on the Pharmaceutical Benefits Scheme (the PBS) and is very expensive.

How CDK inhibitors work

A major hallmark of cancer cells is their ability to multiply rapidly; CDK inhibitors interfere with this process by blocking the activity of enzymes known as CDKs, particularly CDK 4 and CDK 6, that help to regulate cell division. For effectively treating breast cancer, CDK inhibitors are usually combined with endocrine therapy (such as fulvestrant), which works by preventing hormones from binding with their respective receptors on the cancer cells.

CDK inhibitors are now being investigated for their ability to treat various other cancers, including lung cancer, prostate cancer and ovarian cancer, so their effectiveness and excellent safety profile could eventually prove to have benefit in diseases besides breast cancer.

What the study says on side-effects

The research team reviewed all the publicly available studies conducted on the three main CDK inhibitors, palbociclib, ribociclib and abemaciclib. For palbociclib and ribociclib, the most common side effect was a low level of white blood cells, a condition known as neutropenia, which can increase a woman’s chance of infection. This makes sense, because CDK inhibitors are known to affect the division of blood cells in the bone marrow, including white blood cells. However, since the impact on white blood cells is temporary and dose-dependent, the counts usually return to normal by interrupting treatment or lowering the dosage.

Various other, less common side effects are sometimes also seen with CDK inhibitors, including nausea and hair loss, but they’re usually mild and can often be treated by reducing the dose and taking regular breaks from treatment.