Palbociclib in endocrine-resistant metastatic breast cancer patients: gene polymorphism- based study.

BACKGROUND

Despite the proven benefit of adding palbociclib to endocrine therapy (ET) as demonstrated in pivotal clinical trials (e.g., PALOMA-2 and PALOMA-3), many patients with hormone receptor-positive (HR+) and human epidermal growth factor-2-negative (HER2−) metastatic breast cancer (MBC) still experience early disease progression. This study aimed to identify predictive biomarkers for long-term response and evaluate the impact of adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1) gene polymorphisms in MBC patients who had progressed on prior ET.

METHODS

This prospective cohort study included 95 adult MBC patients treated with palbociclib. Demographic, laboratory, and therapeutic variables were analyzed. A genotyping assay was done using real-time polymerase chain reaction (RT-PCR).

RESULTS

Low Ki-67 expression (< 20%) and moderate-to-severe (grade 3/4) neutropenia were associated with longer progression-free survival (PFS) (p = 0.00 and p = 0.01, respectively). Regarding adverse effects, patients carrying the minor-T-allele (CT/TT) had a lower incidence of neutropenia compared to those with the CC genotype (33.3% vs. 66.7%, p = 0.03). Patients with a baseline absolute neutrophil count (ANC) < 3.6 × 10³/mm³ had higher rates of grade 3/4 neutropenia and dose interruptions/reductions (p = 0.00). In univariate logistic regression analysis, homozygous carriers of the ABCB1 CC genotype had a higher risk of grade 3/4 neutropenia (Odds ratio (OR) = 0.333, 95% confidence interval (CI) [0.121–0.920]; p = 0.03).

CONCLUSION

Ki-67 expression and grade 3/4 neutropenia were associated with PFS in MBC, suggesting their potential relevance to clinical outcomes. Additionally, pharmacogenetic polymorphisms may help explain interindividual variations in treatment safety.