Kim Ji-Yeon, Oh Jung Min, Park Yeon Hee, Ahn Jin Seok, Im Young-Hyuck
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
Front Oncol. 2021 Oct 21;11:759150. doi: 10.3389/fonc.2021.759150. eCollection 2021.
In this study, we evaluated clinical parameters to predict the primary resistance of palbociclib in combination with endocrine therapy as the first-line treatment in patients with hormone receptor (HR)+, human epidermal growth factor receptor 2 (HER2)- metastatic breast cancer (MBC). We performed a data analysis of patients diagnosed with HR+, HER2-MBC who received palbociclib plus letrozole as the first-line treatment in the metastatic setting from the clinical data warehouse in Samsung Medical Center. In this study, 305 patients were included in the final data analysis. The median follow-up duration was 31 months, and we observed 123 cases of disease progression. The median progression-free survival (PFS) was 28.7 months, and 38 patients (12.5%) had less than a 6-month PFS. The multivariate analysis suggested that primary resistance to adjuvant endocrine therapy (ET) (hazard ratio: 1.91), presence of liver metastasis (hazard ratio: 2.17), initial elevation of serum CA-15-3 (hazard ratio: 1.99), weak positivity of estrogen receptor (ER) (hazard ratio: 2.28), Ki-67 3+ or 4+ (hazard ratios: 2.58 and 10.28), and presence of mutation (hazard ratio: 9.59) were associated with a short PFS duration. A further prediction model was developed with data from 256 patients and 33 cases of disease progression in 6 months. This model included five factors-primary resistance to adjuvant ET (odds ratio, OR: 1.14), liver metastasis (OR: 1.56), initial CA-15-3 elevation (OR: 1.51), weak ER expression (OR: 2.22), and BRCA2 mutation (OR: 2.85)-and the area under the receiver operating characteristic curve was 0.842 (95% CI: 0.775, 0.909; < 0.001). Finally, we divided them into four risk groups according to the prediction model with the five risk factors. These four groups had different PFS ( < 0.001) and primary resistance of palbociclib with letrozole [OR of group 2 group 1 (ref): 2.18 ( = 0.002), OR of group 3: 3.91 ( < 0.001), and OR of group 4: 4.25 ( < 0.001)]. We developed a prediction model of primary resistance to palbociclib with letrozole as the first-line treatment for HR+, HER2-MBC. Our prediction model might be helpful for considering the first-line treatment strategies. Further well-designed clinical trials would be warranted to validate our prediction model.
在本研究中，我们评估了临床参数，以预测哌柏西利联合内分泌治疗作为激素受体（HR）阳性、人表皮生长因子受体2（HER2）阴性转移性乳腺癌（MBC）患者一线治疗时的原发性耐药情况。我们对三星医疗中心临床数据仓库中诊断为HR阳性、HER2阴性MBC且在转移情况下接受哌柏西利加来曲唑作为一线治疗的患者进行了数据分析。本研究最终纳入305例患者进行数据分析。中位随访时间为31个月，我们观察到123例疾病进展。中位无进展生存期（PFS）为28.7个月，38例患者（12.5%）的PFS少于6个月。多变量分析表明，辅助内分泌治疗（ET）的原发性耐药（风险比：1.91）、肝转移的存在（风险比：2.17）、血清CA - 15 - 3的初始升高（风险比：1.99）、雌激素受体（ER）弱阳性（风险比：2.28）、Ki - 67 3 +或4 +（风险比：2.58和10.28）以及突变的存在（风险比：9.59）与较短的PFS持续时间相关。利用来自256例患者的数据和6个月内33例疾病进展情况建立了进一步的预测模型。该模型包括五个因素——辅助ET的原发性耐药（比值比，OR：1.14）、肝转移（OR：1.56）、初始CA - 15 - 3升高（OR：1.51）、ER弱表达（OR：2.22）和BRCA2突变（OR：2.85），受试者操作特征曲线下面积为0.842（95%CI：0.775，0.909；P < 0.001）。最后，我们根据具有五个风险因素的预测模型将患者分为四个风险组。这四个组的PFS不同（P < 0.001），且哌柏西利联合来曲唑的原发性耐药情况不同[第2组与第1组（参照）的OR：2.18（P = 0.002），第3组的OR：3.91（P < 于0.001），第4组的OR：4.25（P < 0.001）]。我们建立了HR阳性、HER2阴性MBC患者一线治疗时对哌柏西利联合来曲唑原发性耐药的预测模型。我们的预测模型可能有助于考虑一线治疗策略。有必要进行进一步设计良好的临床试验来验证我们的预测模型。
