engleski

Our experience with palbociclib

Clinical effi cacy of endocrine therapy (ET) is limited with the development of primary (de novo) and secondary resistence to ET. Cyclins and cyclin- dependent kinases (CDK) play a key role in cell signaling and their dysregulation is one of the mechanisms responsible for the development of endocrine resistance. Several clinical studies phase II and III (PALOMA1/TRIO18, PALOMA2 and 3) showed a signifi cant benefi t of the combination of CDK inhibitors (palbocicib, ribociklib, abemaciklib) plus ET. Thanks to Compassionate Use Program, in our institution treatment with palbociclib began on March 3, 2016. Since then, the program included 13 patients, seven have been so far treated (three patients in the course of active treatment) and fi ve patients had not yet begun treatment. The inclusion criteria are: hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer previously treated with a minimum of four therapy lines for metastatic disease. Before being included in the program our patients have previously received an average of fi ve lines of treatment for metastatic disease (4- 6). Palbociclib is taken orally once daily on a 28-day cycle consisting of 21 days on the drug and seven days off ; letrozole is taken orally once daily. Median age (range) is 61 years (49-72). Neutropenia is the most common adverse event. Dose interruption, dose reduction or delay in starting treatment cycles is not recommended for patients who develop grade I or II neutropenia. Three patients had neutropenia grade III, one febrile neutropenia and they were required to temporary discontinue treatment (3-23 days). The most common nonhematologic adverse events were grade I or II: fatigue (4), nausea (3) and diarrhea (2). The median duration of treatment is 15.35 weeks (3- 43.5). Based on our experience we can conclude that palbociclib, in combination with ET, is potentially an eff ective therapeutic option, with a consistent safety profi le, in the later lines of treatment luminal, HER2- negative breast cancer.

palbociclib, breast cancer, endocine therapy, metastatic

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