Palbociclib (Ibrance, Pfizer), a new oral drug whose efficacy in combating breast cancer has been demonstrated alone and in combination with endocrine therapy, also has the potential to combat other types of cancer, according to research conducted at the Abramson Cancer Center of the University of Pennsylvania. The findings were published in JAMA Oncology.
Palbociclib targets the rapid division of tumor cells by inhibiting the activity of the enzymes CDK4 and CDK6, which propel cell division in most cancers. It is the first CDK4/6 inhibitor to be approved for the treatment of breast cancer.
“All living cells undergo cell division, and palbociclib’s unique capacity to halt the cell division process –– also known as the cell cycle –– therefore has potentially broad applicability,” said lead author Amy S. Clark, MD, MSCE. “Pairing palbociclib with other anticancer therapies, such as endocrine therapy, chemotherapy, and targeted therapy, can create a powerful combinatorial effect with real promise for addressing a variety of cancers.” For example, amplification of CDK4 is reported in a high percentage of melanomas and esophageal cancers.
Targeted therapy uses medications and other interventions to more accurately attack cancer cells, usually while doing no or little damage to normal cells.
“This drug has minor effects on normal cells other than neutrophils,” said senior author Peter J. O'Dwyer, MD. “In tumors, it can cause shrinkage, or more commonly, arrest of growth. As we discover new functions for the CDK4/6 target of this medicine, we are likely to use it in combinations to make other anticancer agents work better.”
In addition to inhibiting the cell cycle, palbociclib has been shown, for example, to alter several recently described non–cell-cycle functions of CDK4/6, a finding expected to expand its therapeutic role, O’Dwyer added.
Assessing 130 relevant publications in the literature, as well as interpreting their own continuing studies, the Penn investigators found that in addition to its safety and efficacy in fighting certain types of breast cancer, early trials of palbociclib have indicated potential effectiveness in cases of lymphoma, sarcoma, and teratoma –– tumors that, while rare, often affect younger patients.
A phase II study showed that, among 17 patients with previously treated mantle-cell lymphoma, palbociclib therapy resulted in one complete response and two partial responses. Although median progression-free survival (PFS) was four months, five patients had PFS that exceeded one year. Another phase II trial involving 29 sarcoma patients treated with palbociclib achieved a PFS rate of 66% at 12 weeks.
In addition, combining palbociclib with other anticancer agents is feasible, the authors say, and early results in myeloma and some solid tumors have led to more definitive studies.
In both breast and other cancer trials, palbociclib has been shown to be safe with once-daily dosing. Its main adverse effect is reversible neutropenia. The lower their neutrophil counts, the more vulnerable patients are to infectious diseases. In such cases, palbociclib is temporarily discontinued and reintroduced at a lower dose. Other adverse events included fatigue (33%), nausea (30%), diarrhea (18%), constipation (12%), and rash (12%).
Source: Penn Medicine; December 30, 2015.