Physicians Discover Palbociclib Effective in Cancers Beyond Those of the Breast

Earlier this year, the FDA approved palbociclib as frontline treatment for postmenopausal women with estrogen receptor-positive, HER2-negative metastatic breast cancer. An inhibitor of the cyclin-dependent kinase (CDK) 4/6 proteins, palbociclib halts the cell division cycle and prevent proliferation of the cancer cells. Now, a new report has identified potential use of this cell cycle inhibitor in a variety of other cancers.

Experts at the Abramson Cancer Center, University of Pennsylvania, conducted a literature review of preclinical and translational data and early- and late-phase clinical trials that evaluated palbociclib in diverse tumor types, published till March 1, 2015. Lead study author Amy S. Clarke, MD, MSCE, lead author on the paper believes, “All living cells undergo cell division and palbociclib's unique capacity to halt the cell division process therefore has potentially broad applicability.”

The following were the key findings of the review:

• Palbociclib is a potent and specific oral CDK 4/6 inhibitor that has strong preclinical data to support its activity in retinoblastoma protein—expressing tumors.
• Phase 1 trials have demonstrated safety, and phase 2 trials have shown single-agent activity in mantle-cell lymphoma, breast cancer, liposarcoma, and teratoma with reversible neutropenia as the main toxic effect.
• Addition of palbociclib to endocrine therapy improves progression-free survival in endocrine therapy—naïve and endocrine therapy–resistant metastatic settings.
• Combining palbociclib with other anti-cancer agents is feasible, and early results in myeloma and some solid tumors have led to more definitive studies.

Senior study author Peter J. O'Dwyer, MD, said, “This drug has minor effects on normal cells other than neutrophils (white blood cells. 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 anti-cancer agents work better.” Additionally, recent findings that palbociclib has targets beyond the cell cycle can expand could significantly expand its therapeutic role, O’Dwyer believes.

The safety records of palbociclib in breast cancer studies are quite encouraging, with the primary adverse effect being reversible neutropenia with a once-daily dosing. This can be overcome with temporary discontinuation of the drug and reintroducing it at a lower dose. Other side effects of palbociclib include fatigue, nausea, diarrhea, constipation, and rash.