Real-World Predictors of Severe Neutropenia Associated with Palbociclib and Endocrine Therapy for Metastatic Breast Cancer in Japanese Patients

• Published in: Biological & pharmaceutical bulletin Vol. 46; no. 8; pp. 1105 - 1111
• Main Authors: Takada, Shinya, Maeda, Hideki, Umehara, Kengo, Kuwahara, Sayuri, Yamamoto, Mitsugu, Tomioka, Nobumoto, Watanabe, Kenichi, Mino, Kozo
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 01.08.2023; Japan Science and Technology Agency
• Subjects: age-adjusted Charlson comorbidity index; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Comorbidity; Cyclin-dependent kinase; Cyclin-dependent kinase 4; cyclin-dependent kinase 4/6 inhibitor; Cyclin-dependent kinases; East Asian People; Endocrine therapy; Female; Humans; Kinases; Leukocytes (neutrophilic); Metastases; Metastasis; Neutropenia; Neutropenia - chemically induced; Neutropenia - drug therapy; Neutrophils; palbociclib; Prospective Studies; Receptor, ErbB-2; Retrospective Studies; Risk factors; severe neutropenia; breast cancer; age-adjusted Charlson comorbidity index; cyclin-dependent kinase 4/6 inhibitor; palbociclib; severe neutropenia
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.b23-00187

Therapy for patients of metastatic breast cancer based on palbociclib, a cyclin-dependent kinase 4/6 inhibitor, has been approved in Japan. However, the risk factors for palbociclib-induced severe neutropenia in Japanese patients are rarely reported. Hence, the present study is aimed to identify the risk factors for adverse events requiring palbociclib dose reduction or discontinuation, and to identify the factors necessary to identify a more stable strategy for treatment continuation. This retrospective cohort analysis included patients with advanced breast cancer treated with 125 mg/d palbociclib. We demonstrated that severe neutropenia required significant dose reduction or therapy cessation. Most (77%) of the patients had severe neutropenia within the three courses. Risk factors for grade 3 or higher included low neutrophil counts (< 3250 /µL) before treatment [odds ratio (OR) = 9.10, 95% confidence interval (CI) (2.80–29.41), p < 0.001] and high age-adjusted Charlson comorbidity index (> 9) [OR = 1.64, 95% CI (1.09–2.48), p = 0.018]. Thus, low baseline neutrophil counts and high values for Age-adjusted Charlson comorbidity index are prospective predictive markers for palbociclib-induced severe neutropenia.