Objective: To summarize the clinical use of palbociclib and evaluate its efficacy and safety in hormone-receptor (HR)-positive advanced breast cancer patients. Methods: We retrospectively analyzed data from 66 HR-positive metastatic breast cancer patients treated with palbociclib and endocrine therapy at the Department of Oncology in the First Affiliated Hospital with Nanjing Medical University between 2018 and 2020. We evaluated the factors affecting the efficacy of palbociclib using Kaplan-Meier method and Log-rank test for survival analysis and Cox regressions for multivariate analysis. Nomogram model was built for predicting prognosis among HR-positive breast cancer patients who received palbociclib. Concordance index (C-index) and calibration curve were used for internal validation to assess the predictive ability and conformity of the model. Results: Of the 66 patients treated with palbociclib, 33.3%(22), 42.4%(28) and 24.2%(16) patients were treated without endocrine therapy, first-line endocrine therapy, second-line or above endocrine therapy after recurrence, respectively. 36.4%(24) patients had hepatic metastasis, 16.7% (11) patients were sensitive to previous endocrine therapy, 27.3%(18/66) patients had primary resistance to endocrine therapy, while 56.1% (37) patients had secondary resistance to endocrine therapy. The overall response rate was 14.3% (95% CI: 6.7%, 25.4%) and clinical benefit rate was 58.7% (95% CI: 45.6%, 71.0%). Better clinical outcomes were associated with non-hepatic metastasis (P=0.001), sensitive/secondary resistant to previous endocrine therapy (P=0.004), no or only one line of chemotherapy for metastatic breast cancer (P=0.004), recent pathological confirmation of immunohistochemical analysis (P=0.025). Hepatic metastasis (P=0.005) and primary resistance to endocrine therapy (P=0.016) were the independent risk factors of progression free survival. The C-index of predictive probability for the nomogram constructed from the patient clinical characteristics (whether liver metastasis, whether primary endocrine resistance, lines of chemotherapy after metastasis, lines of endocrine therapy, number of metastatic sites, and time to last immunohistochemistry) to predict the progression-free survival at 6 and 12 months for patients was 69.7% and 72.1%, respectively. The most common adverse events were hematologic toxicities. Conclusions: Our report indicates that palbociclib combined with endocrine therapy for HR-positive recurrent metastatic breast cancer is effective and safe; patients with hepatic metastases and primary resistance to endocrine therapy have worse prognoses and are independent risk factors for progression after palbociclib therapy. The constructed nomogram could help predict the survival and guide the use of palbociclib.
目的： 评价真实世界中哌柏西利治疗激素受体(HR)阳性晚期乳腺癌的疗效和安全性。 方法： 回顾性分析南京医科大学第一附属医院2018—2020年接受哌柏西利联合内分泌治疗的66例HR阳性复发转移性乳腺癌患者的临床资料。生存分析采用Kaplan－Meier法和Log rank检验，多因素分析采用Cox回归模型，构建预测哌柏西利治疗HR阳性乳腺癌疾病进展风险的列线图模型，使用一致性指数(C－index)和校准曲线进行内部验证评估模型的预测能力和符合度。 结果： 66例患者中，复发转移后未经内分泌治疗、一线内分泌治疗、二线及以上内分泌治疗的患者分别占33.3% (22例)、42.4% (28例)、24.2% (16例)；肝转移者占36.4% (24例)；内分泌敏感患者占16.7%(11例)，原发内分泌耐药患者占27.3%(18例)，继发性内分泌耐药患者占56.1%(37例)。全组患者客观有效率为14.3%(95% CI：6.7%~25.4%)，临床获益率为58.7%(95% CI：45.6%~71.0%)。非肝转移(P＝0.001)、内分泌治疗敏感/继发耐药(P＝0.004)、复发转移后未行化疗或仅行一线化疗(P＝0.004)、哌柏西利治疗前最近一次免疫组化时间<3个月(P＝0.025)与更好的预后有关，肝转移(P＝0.005)及内分泌原发耐药(P＝0.016)是哌柏西利治疗后患者中位无进展生存时间(PFS)的独立危险因素。患者的临床特征(是否肝转移、是否内分泌原发耐药、转移后化疗线数、内分泌治疗线数、转移部位数目、最近一次免疫组化的时间)构建的列线图模型预测患者6个月和12个月无进展生存概率的C－index分别为69.7%和72.1%。哌柏西利相关的主要不良反应为血液学不良反应。 结论： 哌柏西利联合内分泌治疗HR阳性复发转移性乳腺癌疗效确切，安全性良好；肝转移和内分泌原发耐药的患者疗效欠佳，且是哌柏西利治疗后疾病进展的独立危险因素；预测哌柏西利治疗HR阳性乳腺癌疾病进展风险的列线图模型可用于辅助临床决策。.
Keywords: Breast neoplasms; CDK4/6 inhibitor; Nomogram; Palbociclib.