Palbociclib In The Treatment Of Breast Cancer

Palbociclib is a targeted therapy that is marketed under the brand name Ibrance from the Pfizer laboratory. It is the first selective inhibitor of enzymes called cyclin-dependent kinases 4 and 6 (CDK 4/6), approved in the USA.

This targeted therapy is currently used as the first line of treatment in combination with hormone therapy, such as letrozole. It is used in postmenopausal women with estrogen receptor-positive and HER-2-negative metastatic breast cancer.

At the moment, it is indicated for this group of patients because it is being investigated in different clinical trials to assess the efficacy and safety in combination with hormonal therapy in other phases of cancer, such as earlier stages or as adjuvant therapy.

When was palbociclib approved?

Palbociclib was approved in a different way than usual. Its approval was expedited, based on data from a phase 2 study called PALOMA-1.

As patients with metastatic breast cancer had no treatment for this disease and the study results were positive, it was decided to approve it without waiting for the results of a phase 3 study. Palbociclib doubled progression-free survival compared to letrozole alone.

However, the accelerated approval of this drug is supported by the confirmatory results of another phase 3 study, PALOMA-2. In this study, 666 women with RH-positive and HER-2-negative metastatic breast cancer participated.

These women were randomized to two arms: palbociclib with letrozole or placebo with letrozole. Compared with placebo, palbociclib extended the median progression-free survival by almost 10 months, from 15 months in the placebo group to almost 25 months in the palbociclib group.

In addition, more than half of the patients who were receiving this drug had a significant reduction in tumor size after treatment. This is a great improvement compared to the 44% of women who reduced tumor size with placebo treatment.

However, the analysis time is not sufficient to determine whether this therapy improves the overall survival of these types of patients. For this reason, the study is not yet closed and the follow-up of these patients continues to inform about general survival in the future.

How does palbociclib work on the body?

As we mentioned at the beginning of the article, it is a drug that inhibits enzymes known as independent cyclin kinases CDK 4 and CDK 6. These cyclins are signaling pathways that lead to cell proliferation.

CDK 4/6 inactivate, through phosphorylation, a protein known as retinoblastoma. Being inactive, the protein cannot activate transcription factors and cells divide.

Therefore, when these cyclins are inhibited, retinoblastoma is active, that is, it is dephosphorylated and inhibits transcription factors, which ultimately prevents cells from dividing.

Adverse reactions of palbociclib

This medicine is administered orally with a starting dose of 125 mg. However, depending on the adverse reactions that the patient develops, the dose can be reduced to 100 mg or even 75 mg if necessary.

Permanent treatment discontinuation due to an adverse reaction occurred in 8% of patients treated with palbociclib and letrozole. The most frequent adverse reactions and, therefore, the most characteristic of treatment with this medicine are:

• Neutropenia: it is a decrease in neutrophils, which are a type of white blood cell. Normally, if it is grade 3, it usually disappears when the dose of the drug is reduced.
• Fatigue.
• Anemia.
• Leukopenia : decrease in white blood cells.
• Infections
• Diarrhea.
• Loss of appetite

Conclution

The commercialization of palbociclib has represented a great advance in the treatment of metastatic breast cancer. Likewise, there are other CDK 4/6 inhibitors, such as ribociclib, which have also shown similar results in clinical trials.

Today, new indications for this drug are being investigated .  For example, the treatment of early cancer or the treatment of the first isolated locoregional recurrence of breast cancer.

Do not forget that prevention is one of the most important parts of the fight against breast cancer, as well as regular screening tests. Do not stop going for a check-up regularly!