Palbociclib, a new oral treatment for certain types of breast cancer, demonstrates potential as a treatment for other types of cancer as well, according to a literature review and additional original research published in JAMA Oncology (doi:10.1001/jamaoncol.2015.4701).
Palbociclib targets rapid tumor cell division by inhibiting the enzymes CDK4 and CDK6, which propel cell division in most cancers. It is the first CDK4/6 inhibitor approved for the treatment of breast cancer, and is proven effective as a single agent and in combination with endocrine therapy.
“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 Amy S. Clark, MD, MSCE, an assistant professor of Hematology/Oncology at the University of Pennsylvania’s Perelman School of Medicine and the Abramson Cancer Center (ACC) in Philadelphia, and the lead author of the study. For example, melanomas and esophageal cancers often express a high amplification of CDK4.
“This drug has minor effects on normal cells other than neutrophils (white blood cells),” explained Peter J. O’Dwyer, MD, a professor of Hematology/Oncology at Penn and director of the Developmental Therapeutics Program at the ACC, and senior author of the study. “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.”
Palbociclib has been shown to alter several recently described non-cell cycle functions of CDK4/6, as well. This finding has the potential to expand the therapeutic role of this drug, O’Dwyer added.
In an assessment of 130 relevant publications in the literature, as well as data from their own studies, the team found that early trials of palbociclib demonstrated potential effectiveness for lymphoma, sarcoma, and teratoma, rare tumors that often afflict younger patients. Early results in trials for myeloma and some solid tumors have led to more definitive studies.
In a phase 2 trial showed involving 17 patients with previously treated mantle-cell lymphoma, palbociclib resulted in 1 complete response and 2 partial responses. Although median progression-free survival was 4 months, 5 patients achieved progression-free survival for more than 1 year. Another phase 2 trial involving 29 patients with sarcoma treated with palbociclib showed a progression-free survival of 66% at 12 weeks.
In both breast and other cancer trials, palbociclib is shown to be safe with once-daily dosing. Its main adverse effect is reversible neutropenia. Management involves temporarily discontinuing the drug, then reintroducing it at a lower dose. Other side effects included fatigue (33%), nausea (30%), diarrhea (18%), constipation (12%), and rash (12%).