Palbociclib to Treat Breast Cancer

03 February, 2021
The commercialization of palbociclib has meant 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 to palbociclib in clinical trials.

Palbociclib is a targeted therapy marketed under the brand name Ibrance by Pfizer and is currently used to treat breast cancer. It’s the first selective inhibitor of enzymes called cyclin-dependent kinases 4 and 6 (CDK 4/6), approved in the USA.

Specialists currently use this targeted therapy as a first-line treatment in combination with hormone therapy, such as letrozole. They also use it in postmenopausal women with hormone receptor-positive and HER-2 negative metastatic breast cancer.

For the time being, physicians indicate it for this group of patients. Different clinical trials are investigating it to assess efficacy and safety in combination with hormonal therapy in other phases of cancer, such as earlier stages or as adjuvant therapy.

When did specialists approve palbociclib to treat breast cancer?

A breast cancer ribbon.

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

Since patients with metastatic breast cancer didn’t have any treatment for this disease and the study had positive results, specialists 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 confirmatory results from another phase 3 study support the accelerated approval of this drug, PALOMA-2. This study included 666 women with HER-2-negative, HR-positive metastatic breast cancer.

Specialists randomly assigned these women to two treatments, either palbociclib with letrozole or placebo with letrozole. Compared with placebo, palbociclib extended 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 an improvement when we compare it to the 44% of women with reduced tumor size with placebo treatment.

However, the timing of the analysis isn’t long enough to determine whether this therapy improves the overall survival of this type of patient. Therefore, the study is still open and specialists will continue to follow up with these patients to report on overall survival in the future.

How does palbociclib work in the body?

As we mentioned at the beginning of the article, it’s an enzyme inhibitor called cyclin-independent kinases CDK 4 and CDK 6. These cyclins are signaling pathways that lead to cell proliferation.

CDK 4/6 inactivates, through phosphorylation, a protein known as retinoblastoma. When inactivated, the protein can’t activate transcription factors and the cells divide.

Thus, when it inhibits these cyclins, retinoblastoma is active, i.e., it’s dephosphorylated and inhibits transcription factors, which ultimately causes the cells not to divide.

Also read: 3 Suggestions to Help You Face Breast Cancer

Adverse reactions to palbociclib in women with breast cancer

A woman checking for breast cancer.

Doctors administer this drug orally with an initial dose of 125 mg. However, depending on the adverse reactions the patient develops, they can reduce the dose to 100 mg or even to 75 mg if necessary.

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

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

Discover: Risk Factors for Mouth Cancer

Conclusion

Commercializing palbociclib has meant a great advance in health. Doctors use it to treat metastatic breast cancer. Likewise, there are other CDK 4/6 inhibitors, such as ribociclib, which have also shown similar results in clinical trials.

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

Don’t forget that prevention is one of the most important parts of the fight against breast cancer, as well as regular screening tests. Don’t miss regular check-ups!

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  • DeMichele, A., Clark, A. S., Tan, K. S., Heitjan, D. F., Gramlich, K., Gallagher, M., … O’Dwyer, P. (2015). CDK 4/6 Inhibitor palbociclib (PD0332991) in Rb+ advanced breast cancer: Phase II activity, safety, and predictive biomarker assessment. Clinical Cancer Research. https://doi.org/10.1158/1078-0432.CCR-14-2258
  • O’Leary, B., Finn, R. S., & Turner, N. C. (2016). Treating cancer with selective CDK4/6 inhibitors. Nature Reviews Clinical Oncology. https://doi.org/10.1038/nrclinonc.2016.26