कैंसर विज्ञान एवं चिकित्सा

Palbociclib Associated with Endocrine Therapy in Patients with Metastatic Breast Cancer: Predictive Factors of Severe Early Hematological Toxicity

Abstract

Léa Vazquez, Julie Coussirou, Philippe Arvers, Jean François Rossi, Antoine Arnaud, Julien Grenier, Claire Simonin and Philippe Debourdeau

Objectives: The addition of palbociclib to endocrine therapy has been shown to improve disease free survival in hormone receptor positive metastatic breast cancer patients. This cyclin CDK4/6 inhibitor exposes patients to a grade 3 or 4 hematological toxicity leading to discontinuation or an arrest of treatment that is associate with a dose-reduction intensity and potentially a lack of efficiency. The aim of this study was to identify predictive factors of severe early hematotoxicity (ESHT).

Methods: This retrospective observational cohort study included patients who started with palbociclib in the Institut Sainte Catherine between December 1, 2016 and January 1, 2019 for the treatment of metastatic breast cancer. Individual data and particularly hematological toxicity were collected from electronic medical records. Severe early hematotoxicity was defined as the occurrence, during the first 3 cycles, of grade 4 or grade 3 hematological toxicity requiring a dosereduction of the drug.

Results: 181 patients (180 females) were included; median age was 67 years. 46 patients (25.4%) experienced an severe early hematotoxicity. Predictive factors of severe early hematotoxicity in multivariate analysis were a performance status (PS) of 2 or more (OR=3.77; 95% Cl; p=0.024) and lack of radiotherapy of bone metastasis in the previous year (OR=0.30; 95% Cl; p=0.003). Before palbociclib initiation, a neutrophil count below 3.37 G/L was predictive of severe early hematotoxicity with a sensibility of 76% and a specificity of 71%.

Conclusion: ECOG performance status, bone radiotherapy within the year and low baseline neutrophils count are associated with severe early hematotoxicity in palbociclib-treated metastatic breast cancer patients. These elements could be useful for a careful monitoring leading to adapted therapy.