On-treatment derived neutrophil-to-lymphocyte ratio and survival with palbociclib and endocrine treatment: analysis of a multicenter retrospective cohort and the PALOMA-2/3 study with immune correlates

Autor: Chang Gon Kim, Min Hwan Kim, Jee Hung Kim, Seul-Gi Kim, Gun Min Kim, Tae Yeong Kim, Won-Ji Ryu, Jee Ye Kim, Hyung Seok Park, Seho Park, Young Up Cho, Byeong Woo Park, Seung Il Kim, Joon Jeong, Joohyuk Sohn
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Breast Cancer Research, Vol 25, Iss 1, Pp 1-16 (2023)
Druh dokumentu: article
ISSN: 1465-542X
DOI: 10.1186/s13058-022-01601-4
Popis: Abstract Background Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors have been established as a standard treatment for hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC); however, predictive biomarkers with translational relevance have not yet been elucidated. Methods Data from postmenopausal women who received the CDK4/6 inhibitor palbociclib and letrozole for HR-positive, HER2-negative ABC from tertiary referral centers were analyzed (N = 221; exploratory cohort). Pre- and on-treatment neutrophil-to-lymphocyte ratio (NLR) and derived NLR (dNLR; neutrophil/[leukocyte-neutrophil]) were correlated with survival outcomes. Data from the PALOMA-2 (NCT01740427) and PALOMA-3 studies (NCT01942135) involving patients treated with endocrine treatment with or without palbociclib were also analyzed (validation cohort). Prospectively enrolled patients (N = 20) were subjected to immunophenotyping with circulating immune cells to explore the biological implications of immune cell dynamics. Results In the exploratory cohort, palbociclib administration significantly reduced leukocyte, neutrophil, and lymphocyte counts on day 1 of cycle 2. Although the baseline dNLR was not significantly associated with progression-free survival (PFS), higher on-treatment dNLRs were associated with worse PFS (hazard ratio = 3.337, P
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