Encouraging results from a Phase II clinical trial of Palbociclib for the treatment of advanced breast cancer patients were published this month in Clinical Cancer Research.
Palbociclib is an experimental oral drug that functions by inhibiting the cyclin-dependent kinase (CDK4/6), a key cell cycle protein involved in the transition G1-S phase, which is frequently dysregulated in breast cancer. The CDK4/6 kinase was shown to be responsible for the phosphorylation of retinoblastoma (Rb) protein, which plays a crucial role in the negative control of the cell cycle and in tumor progression.
In their study “CDK 4/6 Inhibitor Palbociclib (PD0332991) in Rb+ Advanced Breast Cancer: Phase II Activity, Safety, and Predictive Biomarker Assessment,” the research team tested palbociclib (PD0332991) in patients with advanced breast cancer positive for retinoblastoma (Rb) protein and with measurable disease. The patients had been previously submitted to several chemotherapy and hormonal regimens for metastatic disease. Palbociclib was given at 125 mg orally on days 1 to 21 on a cycle of 28 days. The drug was well tolerated and there was prolonged progression-free survival (PFS) in new patients responding to traditional endocrine treatments. Recently, the Food and Drug Administration (FDA) approved palbociclib for the treatment of patients with metastatic breast cancer that just started endocrine therapy.
The researchers observed a median PFS, the time before a tumor progressed or the patient died, of 3.7 months for patients treated with the drug. However, patients with hormone receptor-positive (HR+) or negative (HR-) breast cancer had different PFS: HR+ patients had significantly longer (5.1 months) progression-free survival when compared to HR-negative patients. Importantly, patients that had previously received at least two cycles of hormonal therapy, i.e. tumors that acquired endocrine resistance, and experienced significantly greater benefits.
“Combined with the promising results from other trials looking at the effectiveness of this drug, our results indicate that palbociclib can extend the duration of disease control and produce tumor shrinkage in patients with estrogen-receptor positive (ER+) breast cancer, without the debilitating side effects of chemotherapy,” said study author Dr. Angela DeMichele, in a news release.
“The drug was extremely well-tolerated in this trial, and the absence of symptoms commonly associated with cancer treatment, such as nausea, diarrhea, or pain was remarkable,” added Dr. Peter O’Dwyer. “Further, since dose reduction effectively restored normal neutrophil counts, safe administration of effective doses was easily accomplished.”
Dr. DeMichele along with Dr. Amy Clark, MD, a clinical instructor in the division of Hematology/Oncology, are currently performing studies in patients with ER-negative breast cancer treated with the combination of palbociclib with paclitaxel.
Dr. Clark explained that the use of palbociclib has many advantages since it can synchronize cells within the cell cycle and may increase the number of cells sensitive to traditional chemotherapeutic drugs. “Moreover, palbociclib may be effective in other types of cancer that operate by a similar mechanism. These trials are currently ongoing,” concluded Dr. Clark.