Division of Medical Oncology & Hematology, Department of Medicine, Princess Margaret Cancer Centre and the University of Toronto, Toronto, Ontario, Canada.
Division of Medical Oncology & Hematology, Department of Medicine, Princess Margaret Cancer Centre and the University of Toronto, Toronto, Ontario, Canada.
Cancer Treat Rev. 2020 Nov;90:102086. doi: 10.1016/j.ctrv.2020.102086. Epub 2020 Aug 17.
Palbociclib, ribociclib and abemaciclib have all been approved in combination with endocrine therapy in hormone-receptor positive, HER2 negative metastatic breast cancer. While the efficacy of these drugs appears similar, differences in safety and tolerability are apparent.
We searched PubMed and ASCO, ESMO and SABCS proceedings to identify randomized trials of palbociclib, ribociclib and abemaciclib. Data on common and serious adverse events (AE) were extracted for each approved drug. The odds ratio for each AE and the hazard ratio for progression-free survival were calculated relative to endocrine therapy alone. A network meta-analysis was then performed for each endocrine therapy backbone (aromatase inhibitor (AI) or fulvestrant) to compare ribociclib and abemaciclib to palbociclib.
8 trials were included in the analysis and comprised 2799 patients receiving cyclin-dependent kinase 4/6 inhibitors palbociclib: 873 patients; ribociclib: 1153 patients; abemaciclib: 773 patients. In 5 trials (1524 patients), the endocrine therapy backbone was an AI and in 3 trials (1275 patients) it was fulvestrant. Compared to palbociclib, ribociclib and abemaciclib showed significantly lower grade 3-4 neutropenia, but significantly higher GI toxicity. Treatment discontinuation was higher with abemaciclib than other drugs. Efficacy of the 3 drugs was similar. Compared to palbociclib, for AI backbone, the HR for PFS for ribociclib was 0.98 and for abemaciclib 1.02. For fulvestrant backbone, the HR were 0.88 and 0.93 respectively.
Palbociclib, ribociclib and abemaciclib have comparable efficacy, but differences in safety and tolerability. Abemaciclib has worse tolerability with significantly higher treatment discontinuation likely due to GI toxicity.
帕博西尼、瑞博西尼和阿贝西利均已被批准与内分泌治疗联合用于激素受体阳性、HER2 阴性转移性乳腺癌。虽然这些药物的疗效似乎相似，但在安全性和耐受性方面存在差异。
我们检索了 PubMed 以及 ASCO、ESMO 和 SABCS 会议记录，以确定帕博西尼、瑞博西尼和阿贝西利的随机试验。为每种已批准的药物提取常见和严重不良事件（AE）的数据。对于每种 AE 的优势比和无进展生存期的风险比均相对于单独的内分泌治疗进行计算。然后，对每个内分泌治疗骨干（芳香酶抑制剂（AI）或氟维司群）进行网络荟萃分析，以比较瑞博西尼和阿贝西利与帕博西尼。
8 项研究被纳入分析，共纳入 2799 例接受细胞周期蛋白依赖性激酶 4/6 抑制剂治疗的患者：帕博西尼 873 例；瑞博西尼 1153 例；阿贝西利 773 例。在 5 项试验（1524 例患者）中，内分泌治疗骨干为 AI，在 3 项试验（1275 例患者）中为氟维司群。与帕博西尼相比，瑞博西尼和阿贝西利的 3-4 级中性粒细胞减少症发生率显著降低，但胃肠道毒性显著增加。阿贝西利的停药率高于其他药物。这 3 种药物的疗效相似。与帕博西尼相比，对于 AI 骨干，瑞博西尼的 PFS 风险比为 0.98，阿贝西利为 1.02。对于氟维司群骨干，风险比分别为 0.88 和 0.93。
帕博西尼、瑞博西尼和阿贝西利的疗效相当，但在安全性和耐受性方面存在差异。阿贝西利的耐受性较差，停药率显著增加，可能与胃肠道毒性有关。
