Cyclin-dependent kinase inhibitor drugs- Palbociclib

Research that started with cancer viruses back in the 1970’s led to the development of new hope for patients with metastatic breast cancer.

The drug, produced by Pfizer, is called palbociclib or Ibrance. It inhibits two proteins called “cyclin-dependent-kinase 4 and cyclin-dependent-kinase 6”. Normally, CDK4/6 attach phosphate molecules on a protein called “Rb” which stops cells from dividing, like a ”brake”. CDK4/6 inactivate the Rb-brake so that the cell goes haywire, it divides uncontrollably. Hence the cancer. The palbociclib inhibits CDK4/6 and the Rb-brake is active again.

Early studies have shown that palbociclib was most effective when it was used in combination with anti estrogens like tamoxifen or aromatase inhibitors like letrozole in estrogen-receptor-positive (ER+) breast cancers. These studies tested palbociclib in women with ER+ / Her2-negative metastatic breast cancer. The results, recently published in November 2016 in the New England Journal of Medicine (375:1925, available online), showed that the median progression-free survival in the women who took palbociclib plus letrozole was 25 months, while in women on letrozole alone it was 14.5 months. This is good news, but there are side effects, especially a reduction in the white blood cells that fight infection. Adjusting the dose or stopping and restarting the drug can overcome this problem.

Kingston General Hospital has participated in palbociclib trials in metastatic breast cancer but the results are not available yet. A new study is about to start, looking at palbociclib in the adjuvant setting, ie when the cancer has not metastacised. The study is called the PALLAS trial. Palbociclib may have a role to play in preventing metastasis in triple negative breast cancers as well, and new studies are being developed in this area.

Palbociclib has received Health Canada approval, but as with all new drugs, it is the Provinces that pay for it. It is currently waiting to be reviewed by the Pan-Canadian Purchasing Alliance (PCPA) and then the provinces will decide on covering it, ie it will be some time before it is covered by OHIP. Pfizer however has a Patient Support Program to help patients cover the cost. The number is 1-844-616-6888. Also, some private insurance companies do cover it. That is, one way or the other, if it is the right drug for you, you can access it. Your oncologist is of course the best person to decide.

Dr. Leda Raptis, Ph.D. and Dr. Lois Shepherd, M.D.