Safety and Efficacy of Palbociclib and Radiation Therapy in Patients With Metastatic Breast Cancer: Initial Results of a Novel Combination
Safety and Efficacy of Palbociclib and Radiation Therapy in Patients With Metastatic Breast Cancer: Initial Results of a Novel Combination
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DOI：
10.1016/j.adro.2019.03.011
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发表时间：
2019-07-01
影响因子：
2.3
通讯作者：
Rao, Ruta D.
中科院分区：
文献类型：
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作者：
Chowdhary, Mudit;Sen, Neilayan;Rao, Ruta D.
目的：Palbociclib是一种选择性细胞周期蛋白依赖性激酶4/6抑制剂，获批用于转移性ER+/HER 2-乳腺癌。临床前证据表明，Palbociclib与放射治疗（RT）联合使用时可能具有协同作用;然而，这种配对的毒性尚不清楚。我们报告了使用这种组合的初步结果。方法和材料：回顾性分析了2015年至2018年在我们机构接受palbociclib治疗的患者记录。纳入了与palbociclib同时或在palbociclib治疗14天内接受RT治疗症状性转移的患者。通过临床检查和随后的计算机断层扫描/磁共振成像评估局部治疗效果。根据不良事件通用术语标准第5.0版对毒性进行分级。结果：共有16名女性在接近palbociclib给药时间点接受姑息性RT。4例患者在RT前接受palbociclib治疗（25.0%），5例同时接受（31.3%），7例在RT后接受（43.8%）。从最接近palbociclib使用到RT的中位间隔为5天（范围，0-14）。以下部位按频率降序进行辐照：骨（11例中轴骨骼[9例椎骨和2例其他]; 4例骨盆; 3例肢体）、脑（4例：3例全脑RT和1例立体定向放射外科）和纵隔（1例）。中位和平均随访时间分别为14.7和17.6个月（范围：1.7-38.2）。所有患者的疼痛均得到缓解。在13例随访影像学可评价的患者中，未发现放射学局部失败。RT前4例（25.0%）、5例（31.3%）和1例（6.3%）患者出现白细胞减少、中性粒细胞减少和血小板减少。RT后，分别有5例（31.3%）、1例（6.3%）和3例（18.8%）患者出现白细胞减少、中性粒细胞减少和血小板减少。除2例（2级）血液学毒性外，其他所有血液学毒性均为1级。未观察到急性或晚期2+级皮肤、神经系统或胃肠道毒性。根据疾病部位、Palbociclib-RT时间关联或照射部位，毒性结果没有差异。结论：在接受Palbociclib治疗的患者中使用RT导致最低程度的2级毒性，没有3级+毒性。这项初步工作表明，接受palbociclib治疗的有症状的患者可以安全地接受放射治疗。(C)2019作者（S）爱思唯尔公司出版代表美国放射肿瘤学会。
Purpose: Palbociclib is a selective cyclin-dependent kinase 4/6 inhibitor approved for metastatic ER+/HER2- breast cancer. Preclinical evidence suggests a possible synergistic effect of palbociclib when combined with radiation therapy (RT); however, the toxicity of this pairing is unknown. We report preliminary results on the use of this combination.Methods and Materials: Records of patients treated with palbociclib at our institution from 2015 to 2018 were retrospectively reviewed. Patients who received RT for symptomatic metastases concurrently or within 14 days of palbociclib were included. Local treatment effect was assessed by clinical examination and subsequent computed tomography/magnetic resonance imaging. Toxicity was graded based on Common Terminology Criteria for Adverse Events version 5.0.Results: A total of 16 women received palliative RT in close temporal proximity to palbociclib administration. Four patients received palbociclib before RT (25.0%), 5 concurrently (31.3%), and 7 after RT (43.8%). The median interval from closest palbociclib use to RT was 5 days (range, 0-14). The following sites were irradiated in decreasing order of frequency: bone (11 axial skeleton [9 vertebra and 2 other]; 4 pelvis; 3 extremity), brain (4: 3 whole brain RT and 1 stereotactic radiosurgery), and mediastinum (1). The median and mean follow-up time is 14.7 and 17.6 months (range, 1.7-38.2). Pain relief was achieved in all patients. No radiographic local failure was noted in the 13 patients with evaluable follow-up imaging. Leukopenia, neutropenia, and thrombocytopenia were seen in 4 (25.0%), 5 (31.3%), and 1 (6.3%) patient before RT. After RT, 5 (31.3%), 1 (6.3%), and 3 (18.8%) patients were leukopenic, neutropenic, and thrombocytopenic, respectively. All but 2 (grade 2) hematologic toxicities were grade 1. No acute or late grade 2+ cutaneous, neurologic, or gastrointestinal toxicities were noted. Toxicity results did not differ based on disease site, palbociclib-RT temporal association, or irradiated site.Conclusions: The use of RT in patients receiving palbociclib resulted in minimal grade 2 and no grade 3+ toxicities. This preliminary work suggests that symptomatic patients receiving palbociclib may be safely irradiated. (C) 2019 The Author(s). Published by Elsevier Inc. on behalf of American Society for Radiation Oncology.