Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Division of Hematology/Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Br J Cancer. 2020 Sep;123(6):912-918. doi: 10.1038/s41416-020-0967-7. Epub 2020 Jul 9.
Palbociclib is highly active in oestrogen-receptor positive (ER+) metastatic breast cancer, but neutropenia is dose limiting. The goal of this study was to determine whether early neutropenia is associated with disease response to single-agent palbociclib.
Blood count and disease-response data were analysed from two Phase 2 clinical trials at different institutions using single-agent palbociclib: advanced solid tumours positive for retinoblastoma protein and advanced liposarcoma. The primary endpoint was PFS. The primary exposure variable was the nadir absolute neutrophil count (ANC) during the first two cycles of treatment.
One hundred and ninety-six patients (61 breast, 135 non-breast) were evaluated between the two trials. Development of any grade neutropenia was significantly associated with longer median PFS in both the breast cancer (HR 0.29, 95% CI 0.11-0.74, p = 0.010) and non-breast cancer (HR 0.57, 95% CI 0.38-0.85, p = 0.006) cohorts. Grade 3-4 neutropenia was significantly associated with prolonged PFS in the non-breast cohort (HR 0.57, 95% CI 0.38-0.85, p = 0.006) but not in the breast cohort (HR 0.87, 95% CI 0.51-1.47, p = 0.596). Multivariate analysis yielded similar results.
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.
Basket Trial: NCT01037790; Sarcoma Trial: NCT01209598.
帕博西尼在雌激素受体阳性（ER+）转移性乳腺癌中具有高度活性，但中性粒细胞减少是剂量限制因素。本研究的目的是确定早期中性粒细胞减少是否与单药帕博西尼治疗的疾病反应相关。
在两个不同机构的两项使用单药帕博西尼的 2 期临床试验中，分析了血液计数和疾病反应数据：视网膜母细胞瘤蛋白阳性的晚期实体瘤和晚期脂肪肉瘤。主要终点是无进展生存期（PFS）。主要暴露变量是治疗前两个周期的绝对中性粒细胞计数（ANC）的最低点。
在两项试验中，共评估了 196 名患者（61 名乳腺癌，135 名非乳腺癌）。在乳腺癌（HR 0.29，95%CI 0.11-0.74，p=0.010）和非乳腺癌（HR 0.57，95%CI 0.38-0.85，p=0.006）队列中，任何等级的中性粒细胞减少与较长的中位 PFS 显著相关。3-4 级中性粒细胞减少与非乳腺癌队列的 PFS 延长显著相关（HR 0.57，95%CI 0.38-0.85，p=0.006），但与乳腺癌队列无显著相关性（HR 0.87，95%CI 0.51-1.47，p=0.596）。多变量分析得出了类似的结果。
前两个周期的治疗相关中性粒细胞减少与延长的 PFS 显著相关，表明中性粒细胞减少可能是指导个体化帕博西尼剂量的有用药效学标志物。
篮子试验：NCT01037790；肉瘤试验：NCT01209598。
