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

Study Overview
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Brief Summary
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Aim of the study to assess the neutropenia induced by Palbociclib in patient receiving Palbociclib in combination with hormonal treatment as first-line therapy in metastatic hormone receptor- positive HER2 negative breast cancer. To evaluate the risk factors for occurrence of neutropenia and treatment outcome as 2 years PFS and OS.

Detailed Description
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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.

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

Conditions
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Metastatic Breast Cancer

Intervention / Treatment
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* Drug: Palbociclib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological pathological confirmation of primary breast cancer or metastatic disease. Hormonal receptor-positive, HER2 negative. Metastatic breast cancer at presentation (Den novo) or recurrent. Patients did not receive any previous systemic therapy for metastatic disease. Performance status (ECOG) 0-2. Exclusion Criteria: Patient with co-morbidity Pregnant and breast lactating women
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 1<br>cases developed neutropenia Grade 0-2 with palbociclib administration | Drug: Palbociclib<br>* The investigator will follow the patients after starting treatment to follow and observe the outcome of the treatment side effects and risk factors<br>* Other names: Other drugs (hormonal treatment)+ denosumab;|
| 2<br>cases developed neutropenia Grade 3-4 with palbociclib administration | Drug: Palbociclib<br>* The investigator will follow the patients after starting treatment to follow and observe the outcome of the treatment side effects and risk factors<br>* Other names: Other drugs (hormonal treatment)+ denosumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigator will evaluate the patients and treatment characters in counts and percentage of developing high-grade neutropenia induced by palbociclib. | Investigator will record the patients and treatment characters in counts and percentage that associated with the occurrence of high-grade neutropenia. And then will compare the characters differences in patients with and without high grade neutropenia by uninitiated and multivariate statistical analysis. | 2 years | 
| assess treatment outcome as a progression free survival for palbociclib in patient with neutropenia | Measure the progression free survival | 2 years | 
| assess treatment outcome as overall survival for palbociclib in patient with neutropenia | Measure the overall survival | 2 years |