College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
Department of Oncology, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital, Birmingham, UK.
J Oncol Pharm Pract. 2023 Dec;29(8):1825-1835. doi: 10.1177/10781552231163121. Epub 2023 Mar 22.
CDK4/6 inhibitors (ribociclib, palbociclib and abemaciclib) are 1st line therapy in metastatic breast cancer (MBC). No comparative data exists between agents regarding toxicity or efficacy.
A retrospective study was performed at our tertiary referral centre evaluating patients on a CDK4/6 inhibitor for MBC between July 2017 and December 2021. Toxicity was evaluated along with variability in full blood counts and liver function over the first 12 weeks of therapy.
Two hundred and seventeen patients were treated (palbociclib 59%, abemaciclib 25% and ribociclib 16%). 86% received the agent as 1st line therapy. Most patients were white women with a median age of 61 years (32-95) and ECOG 0/1. Twelve patients were switched to an alternative CDK4/6 inhibitor due to toxicity and two did not tolerate this. Toxicity profiles of agents were consistent with published trials. However, there was greater overlap in hepatitis, diarrhoea and bone marrow suppression. Blood results indicated a minimum of four weeks treatment before development of neutropenia. Forty percent of patients went onto have subsequent lines of therapy. The progression-free survival per agent was palbociclib 27.9 months (95% CI 23-32.5), ribociclib 29 months (95% CI 21.5-37.0) and abemaciclib 20.6 months (95% CI 15.0-26.0). The overall survival was palbociclib 38.0 months (95% CI 33.5-42.5), ribociclib 33.9 months (95% CI 26.7-41.1) and abemaciclib 27.3 months (95% CI 22.5-32.1).
Toxicity across CDK4/6 inhibitors overlaps. The optimal sequence of therapies post CDK4/6 inhibitors remains unknown but rechallenge with an alternative agent is possible.
CDK4/6 抑制剂（瑞博西利、哌柏西利和阿贝西利）是转移性乳腺癌（MBC）的一线治疗药物。目前尚无关于这些药物在毒性或疗效方面的比较数据。
我们在一家三级转诊中心进行了一项回顾性研究，评估了 2017 年 7 月至 2021 年 12 月期间接受 CDK4/6 抑制剂治疗的 MBC 患者。在治疗的前 12 周内，评估了毒性以及全血细胞计数和肝功能的变化。
共有 217 例患者接受治疗（哌柏西利 59%，阿贝西利 25%，瑞博西利 16%）。86%的患者将该药物作为一线治疗药物。大多数患者为白人女性，中位年龄为 61 岁（32-95 岁），ECOG 0/1。由于毒性，有 12 例患者改用了另一种 CDK4/6 抑制剂，有 2 例患者不能耐受该药物。三种药物的毒性谱与已发表的试验一致。然而，肝炎、腹泻和骨髓抑制之间的重叠更多。血液检查结果表明，在发生中性粒细胞减少症之前，至少需要四周的治疗时间。40%的患者随后接受了后续治疗。每种药物的无进展生存期分别为：哌柏西利 27.9 个月（95%CI 23-32.5），瑞博西利 29 个月（95%CI 21.5-37.0），阿贝西利 20.6 个月（95%CI 15.0-26.0）。总生存期分别为：哌柏西利 38.0 个月（95%CI 33.5-42.5），瑞博西利 33.9 个月（95%CI 26.7-41.1），阿贝西利 27.3 个月（95%CI 22.5-32.1）。
CDK4/6 抑制剂的毒性存在重叠。 CDK4/6 抑制剂治疗后的最佳治疗方案尚不清楚，但可以用另一种药物进行再挑战。
