Palbociclib Induced Neutropenia; Risk Factors and Treatment Outcome in Metastatic Breast Cancer Patients

Palbociclib is an orally active cyclin-dependent kinase (CDK) and is considered the standard treatment for hormone receptor (HR)-positive, (HER) negative metastatic breast cancer. The PALOMA studies' showed improvement in progression-free survival (PFS) compared to endocrine therapy alone but a non-significant trend towards improved overall survival (OS). MONALEESA and MONARCH suggest significantly improved OS with the addition of CDK inhibition. Neutropenia is considered the dose-limiting and most frequent adverse effect of CDK inhibitors resulting in frequent dose reductions and treatment interruptions that are potentially associated with a lack of efficiency. Grade III/IV neutropenia rates were 62-66% in the PALOMA studies. Some studies investigated the risk factors for the development of palbociclib-induced neutropenia. One concluded that no concomitant use of statins and high BMI were identified as significant predictors for the development of palbociclib-induced neutropenia. and another study also concluded that low baseline ANC, WBC, PLT, and BSA were associated with early grade III/IV neutropenia. Regarding treatment outcome, two Phase Two clinical trials concluded that the treatment-related neutropenia in the first two cycles was significantly and independently associated with prolonged PFS, suggesting that neutropenia may be a useful pharmacodynamic marker to guide individualised palbociclib dosing. However, another study concluded that limited dose modification may lead to longer PFS, without increasing toxicity, than the conventional dose scheme. A study of variable risk factors and treatment outcomes for palbociclib-induced neutropenia will be useful for careful monitoring leading to adapted therapy.