Kubeczko Marcin, Gabryś Dorota, Gawkowska Marzena, Polakiewicz-Gilowska Anna, Cortez Alexander J, Krzywon Aleksandra, Woźniak Grzegorz, Latusek Tomasz, Leśniak Aleksandra, Świderska Katarzyna, Mianowska-Malec Marta, Łanoszka Barbara, Chomik Konstanty, Gajek Mateusz, Michalik Anna, Nowicka Elżbieta, Tarnawski Rafał, Rutkowski Tomasz, Jarząb Michał
Breast Cancer Center, Maria Sklodowska-Curie National Research Institute of Oncology, 44-102 Gliwice, Poland.
Department of Radiotherapy, Maria Sklodowska-Curie National Research Institute of Oncology, 44-102 Gliwice, Poland.
Cancers (Basel). 2023 Jan 22;15(3):690. doi: 10.3390/cancers15030690.
The addition of CDK4/6 inhibitors to endocrine therapy in advanced hormone receptor-positive HER2-negative breast cancer has led to practice-changing improvements in overall survival. However, data concerning the safety of CDK4/6i combination with radiotherapy (RT) are conflicting. A retrospective evaluation of 288 advanced breast cancer patients (pts) treated with CDK4/6i was performed, and 100 pts also received RT. Forty-six pts received 63 RT courses concurrently and fifty-four sequentially before CDK4/6i initiation (76 RT courses). Neutropenia was common (79%) and more frequent during and after concurrent RT than sequential RT (86% vs. 76%); however, CDK4/6i dose reduction rates were similar. In patients treated with CDK4/6i alone, the dose reduction rate was 42% (79 pts) versus 38% with combined therapy, and 5% discontinued treatment due to toxicity in the combined group. The risk of CDK4/6i dose reduction was correlated with neutropenia grade, RT performed within the first two CDK4/6i cycles, and more than one concurrent RT; a tendency was observed in concurrent bone irradiation. However, on multivariate regression analysis, only ECOG 1 performance status and severe neutropenia at the beginning of the second cycle were found to be associated with a higher risk of CDK4/6i dose reduction. This largest single-center experience published to date confirmed the acceptable safety profile of the CDK4/6i and RT combination without a significantly increased toxicity compared with CDK4/6i alone. However, one might delay RT for the first two CDK4/6i cycles, when myelotoxic AE are most common.
在晚期激素受体阳性、人表皮生长因子受体2阴性乳腺癌的内分泌治疗中添加细胞周期蛋白依赖性激酶4/6（CDK4/6）抑制剂，已使总生存期得到了改变临床实践的改善。然而，关于CDK4/6抑制剂与放疗（RT）联合使用安全性的数据相互矛盾。对288例接受CDK4/6抑制剂治疗的晚期乳腺癌患者进行了回顾性评估，其中100例患者也接受了放疗。46例患者在开始使用CDK4/6抑制剂之前同时接受了63个疗程的放疗，54例患者先后接受了放疗（76个疗程）。中性粒细胞减少很常见（79%），同时放疗期间及之后比序贯放疗更频繁（86%对76%）；然而，CDK4/6抑制剂的剂量降低率相似。在单独接受CDK4/6抑制剂治疗的患者中，剂量降低率为42%（79例），联合治疗组为38%，联合治疗组中有5%因毒性而停止治疗。CDK4/6抑制剂剂量降低的风险与中性粒细胞减少分级、在前两个CDK4/6抑制剂周期内进行放疗以及同时进行多个放疗疗程相关；在同时进行骨照射时观察到一种趋势。然而，多因素回归分析显示，只有东部肿瘤协作组（ECOG）1体力状况评分以及第二个周期开始时的严重中性粒细胞减少与CDK4/6抑制剂剂量降低的较高风险相关。迄今为止发表的这项最大规模的单中心经验证实，与单独使用CDK4/6抑制剂相比，CDK4/6抑制剂与放疗联合使用的安全性可接受，且毒性没有显著增加。然而，当骨髓毒性不良事件最常见时，可能需要在前两个CDK4/6抑制剂周期延迟放疗。
